bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Mtb GlmU Uridyltransferase Domain Inhibitors by Ligand-Based and Structure-Based Drug Design Approaches
Authors: Singh Manvi , Kempanna Priya , Bharatham Kavitha
Published: April 2022

Targeting enzymes that play a role in the biosynthesis of the bacterial cell wall has long been a strategy for antibacterial discovery. In particular, the cell wall of Mycobacterium tuberculosis (Mtb) is a complex of three layers, one of which is Peptidoglycan, an essential component providing rigidity and strength. UDP-GlcNAc, a precursor for the synthesis of peptidoglycan, is formed by GlmU, a bi-functional enzyme. Inhibiting GlmU Uridyltransferase activity has been proven to be an effective anti-bacterial, but its similarity with human enzymes has been a deterrent to drug development. To develop Mtb selective hits, the Mtb GlmU substrate binding pocket was compared with structurally similar human enzymes to identify selectivity determining factors. Substrate binding pockets and conformational changes upon substrate binding were analyzed and MD simulations with substrates were performed to quantify crucial interactions to develop critical pharmacophore features. Thereafter, two strategies were applied to propose potent and selective bacterial GlmU Uridyltransferase domain inhibitors: (i) optimization of existing inhibitors, and (ii) identification by virtual screening. The binding modes of hits identified from virtual screening and ligand growing approaches were evaluated further for their ability to retain stable contacts within the pocket during 20 ns MD simulations. Hits that are predicted to be more potent than existing inhibitors and selective against human homologues could be of great interest for rejuvenating drug discovery efforts towards targeting the Mtb cell wall for antibacterial discovery.
Dictyophora Polysaccharide Attenuates As-Mediated PINK1/Parkin Pathway-Induced Mitophagy in L-02 Cell through Scavenging ROS
Authors: Hu Ting , Lu Ju , Wu Changyan , Duan Tianxiao , Luo Peng
Published: April 2022

Arsenic (As) is common in the human living environment and a certain amount of exposure to As can lead to liver damage; this toxic effect has been proved to be closely related to intracellular PINK1/Parkin pathway-mediated mitophagy. Dictyophora is an edible fungus that extracts polysaccharides with antioxidant and hepatoprotective effects. In the present study, we demonstrated that As induced the onset of mitophagy in hepatocytes by stimulating cellular production of ROS to activate PINK1/Parkin, and the extent of damage increased with increased As-induced toxicity. Dictyophora polysaccharide (DIP) has the ability to scavenge intracellular ROS, which can inhibit oxidative stress injury and inhibit the PINK/Parkin pathway through its receptors or efficacious proteins, thus preventing mitochondrial autophagy and alleviating the hepatotoxicity of As. In conclusion, our results indicate that DIP can reduce As-induced PINK1/Parkin pathway-mediated hepatic mitophagy through scavenging ROS and exert hepatoprotective effects, providing experimental data and theoretical basis for the development of medicinal value of Dictyophora as a dual-use food and medicinal fungus.
Engineering Plasmonic Environments for 2D Materials and 2D-Based Photodetectors
Authors: Li Jianmei , Liu Jingyi , Guo Zirui , Chang Zeyu , Guo Yang
Published: April 2022

Two-dimensional layered materials are considered ideal platforms to study novel small-scale optoelectronic devices due to their unique electronic structures and fantastic physical properties. However, it is urgent to further improve the light–matter interaction in these materials because their light absorption efficiency is limited by the atomically thin thickness. One of the promising approaches is to engineer the plasmonic environment around 2D materials for modulating light–matter interaction in 2D materials. This method greatly benefits from the advances in the development of nanofabrication and out-plane van der Waals interaction of 2D materials. In this paper, we review a series of recent works on 2D materials integrated with plasmonic environments, including the plasmonic-enhanced photoluminescence quantum yield, strong coupling between plasmons and excitons, nonlinear optics in plasmonic nanocavities, manipulation of chiral optical signals in hybrid nanostructures, and the improvement of the performance of optoelectronic devices based on composite systems.
Catalytic and Stoichiometric Baeyer–Villiger Oxidation Mediated by Nonheme Peroxo-Diiron(III), Acylperoxo, and Iodosylbenzene Iron(III) Intermediates
Authors: Lakk-Bogáth Dóra , Szávuly Miklós István , Török Patrik , Kaizer József
Published: April 2022

In this paper we describe a detailed mechanistic studies on the [FeII(PBO)2(CF3SO3)2] (1), [FeII(PBT)2(CF3SO3)2] (2), and [FeII(PBI)3](CF3SO3)2 (3)-catalyzed (PBO = 2-(2′-pyridyl)benzoxazole, PBT = 2-(2′-pyridyl)benzthiazole, PBI = 2-(2′-pyridyl)benzimidazole) Baeyer–Villiger oxidation of cycloketones by dioxygen with cooxidation of aldehydes and peroxycarboxylic acids, including the kinetics on the reactivity of (μ-1,2-peroxo)diiron(III), acylperoxo- and iodosylbenzene-iron(III) species as key intermediates.
Synthesis and Evaluation of Serinolamide Derivatives as Sphingosine-1-Phosphate-1 (S1P1) Receptor Agonists
Authors: Park Sun Jun , Kim Jushin , Kim Jaehwan , Kim Yoowon , Lee Elijah Hwejin , Kim Hyeon Jeong , Kim Siwon , Kim Byungeun , Kim Rium , Choi Ji Won , Park Jong-Hyun , Park Ki Duk
Published: April 2022

Sphingosine-1-phosphate-1 (S1P1) receptor agonists are well-known drugs for treating multiple sclerosis (MS) caused by autoreactive lymphocytes that attack the myelin sheath. Therefore, an effective therapeutic strategy is to reduce the lymphocytes in the blood by inducing S1P1 receptor internalization. We synthesized serinolamide A, a natural product of the sea, and performed S1P1 receptor internalization assay to evaluate functionally antagonistic S1P1 receptor agonist activity. In order to synthesize derivatives with better efficacy than serinolamide A and B, new derivatives were synthesized by introducing the phenyl ring moiety of fingolimod. Among them, compounds 19 and 21 had superior S1P1 agonistic effects to serinolamide. We also confirmed that compound 19 effectively inhibited lymphocyte outflow in peripheral lymphocyte count (PLC) assay.
The Shapes of Sulfonamides: A Rotational Spectroscopy Study
Authors: Vigorito Annalisa , Calabrese Camilla , Maris Assimo , Loru Donatella , Peña Isabel , Sanz M. Eugenia , Melandri Sonia
Published: April 2022

Benzenesulfonamides are a class of molecules of extreme interest in the biochemical field because many of them are active against a variety of diseases. In this work, the pharmacophoric group benzensulfonamide, its derivatives para-toluensulfonamide and ortho-toluensulfonamide, and the bioactive molecule sulfanilamide, were investigated using rotational spectroscopy to determine their conformations and the influence of different substituents on their structures. For all species, the hyperfine structure due to the 14N atom was analyzed, and this provided crucial information for the unambiguous identification of the observed conformation of all molecules. In addition, for ortho-toluensulfonamide, the vibration–rotation hyperfine structure related to the methyl torsion was analyzed, and the methyl group rotation barrier was determined. For benzensulfonamide, partial rS and r0 structures were established from the experimental rotational constants of the parent and two deuterated isotopic species. In all compounds except ortho-toluensulfonamide, the amino group of the sulfonamide group lies perpendicular to the benzene plane with the aminic hydrogens eclipsing the oxygen atoms. In ortho-toluensulfonamide, where weak attractive interactions occur between the nitrogen lone pair and the methyl hydrogen atoms, the amino group lies in a gauche orientation, retaining the eclipsed configuration with respect to the SO2 frame. A comparison of the geometrical arrangements found in the PDB database allowed us to understand that the bioactive conformations are different from those found in isolated conditions. The conformations within the receptor are reached with an energy cost, which is balanced by the interactions established in the receptor.
Research Update of Emergent Sulfur Quantum Dots in Synthesis and Sensing/Bioimaging Applications
Authors: Ning Keke , Sun Yujie , Liu Jiaxin , Fu Yao , Ye Kang , Liang Jiangong , Wu Yuan
Published: April 2022

Due to their unique optical property, low toxicity, high hydrophilicity, and low cost, sulfur quantum dots (SQDs), an emerging luminescent nanomaterial, have shown great potential in various application fields, such as sensing, bioimaging, light emitting diode, catalysis, and anti-bacteria. This minireview updates the synthetic methods and sensing/bioimaging applications of SQDs in the last few years, followed by discussion of the potential challenges and prospects in their synthesis and sensing/bioimaging applications, with the purpose to provide some useful information for researchers in this field.
Human Estrogen Receptor Alpha Antagonists, Part 3: 3-D Pharmacophore and 3-D QSAR Guided Brefeldin A Hit-to-Lead Optimization toward New Breast Cancer Suppressants
Authors: Kurtanović Nezrina , Tomašević Nevena , Matić Sanja , Proia Elenora , Sabatino Manuela , Antonini Lorenzo , Mladenović Milan , Ragno Rino
Published: April 2022

The estrogen receptor α (ERα) is an important biological target mediating 17β-estradiol driven breast cancer (BC) development. Aiming to develop innovative drugs against BC, either wild-type or mutated ligand-ERα complexes were used as source data to build structure-based 3-D pharmacophore and 3-D QSAR models, afterward used as tools for the virtual screening of National Cancer Institute datasets and hit-to-lead optimization. The procedure identified Brefeldin A (BFA) as hit, then structurally optimized toward twelve new derivatives whose anticancer activity was confirmed both in vitro and in vivo. Compounds as SERMs showed picomolar to low nanomolar potencies against ERα and were then investigated as antiproliferative agents against BC cell lines, as stimulators of p53 expression, as well as BC cell cycle arrest agents. Most active leads were finally profiled upon administration to female Wistar rats with pre-induced BC, after which 3DPQ-12, 3DPQ-3, 3DPQ-9, 3DPQ-4, 3DPQ-2, and 3DPQ-1 represent potential candidates for BC therapy.
Preparation of Zeolitic Imidazolate Framework-8-Based Nanofiber Composites for Carbon Dioxide Adsorption
Authors: Chiang Yu-Chun , Chin Wei-Ting
Published: April 2022

In this study, polyacrylonitrile (PAN)-based activated nanofiber composites, which were embedded inside zeolitic imidazolate framework-8 (ZIF-8) crystals or ZIF-8-derived carbons (ZDC-850), were fabricated using an electrospinning process, to serve as CO2 adsorbents. The adsorbents were characterized using various techniques. The degree of crystallinity of ZDC-850 totally changed compared to that of ZIF-8. For nanofiber composites, the timing of the ligand decomposition of ZIF-8 significantly affected the material properties. The Zn metals in the ZIF-8/PAN or ZDC-850/PAN could be embedded and protected by the PAN fibers from excess volatilization in the following treatments: ZIF-8 had significant pore volumes in the range of 0.9–1.3 nm, but ZDC-850 and ZIF-8/PAN exhibited a distinct peak at approximately 0.5 nm. The CO2 adsorption capacities at 25 °C and 1 atm followed the order: ZIF-8/PAN (4.20 mmol/g) > ZDC-850 (3.50 mmol/g) > ZDC-850/PAN (3.38 mmol/g) > PAN (2.91 mmol/g) > ZIF-8 (0.88 mmol/g). The slope in the log–linear plot of isosteric heat of adsorption was highly associated with CO2 adsorption performance. Under 1 atm at 25 °C, for Zn metal active sites inside the pores, the pores at approximately 0.5 nm and in C-N (amines) groups could promote CO2 adsorption. At low CO2 pressures, for a good CO2 adsorbent, the carbon content in the adsorbent should be higher than a threshold value. Under this condition, the percentage of ultra-micropore and micropore volumes, as well as the functional groups, such as the quaternary or protonated N (amines), N=C (imines or pyridine-type N), C-OH, and -COOH groups, should be considered as significant factors for CO2 adsorption.
Monodisperse and Nanometric-Sized Calcium Carbonate Particles Synthesis Optimization
Authors: Persano Francesca , Nobile Concetta , Piccirillo Clara , Gigli Giuseppe , Leporatti Stefano
Published: April 2022

Calcium carbonate (CaCO3) particles represent an appealing choice as a drug delivery system due to their biocompatibility, biodegradability, simplicity and cost-effectiveness of manufacturing, and stimulus-responsiveness. Despite this, the synthesis of CaCO3 particles with controlled size in the nanometer range via a scalable manufacturing method remains a major challenge. Here, by using a co-precipitation technique, we investigated the impact on the particle size of different synthesis parameters, such as the salt concentration, reaction time, stirring speed, and temperature. Among them, the salt concentration and temperature resulted in having a remarkable effect on the particle size, enabling the preparation of well-dispersed spherical nanoparticles with a size below 200 nm. Upon identification of optimized synthesis conditions, the encapsulation of the antitumoral agent resveratrol into CaCO3 nanoparticles, without significantly impacting the overall size and morphology, has been successfully achieved.
Serum, Dietary, and Supplemental Vitamin D Levels and Insulin Resistance in 6294 Randomly Selected, Non-Diabetic U.S. Adults
Authors: Tucker Larry A.
Published: April 2022

The primary aim of this study was to determine the associations between serum, dietary, and supplemental vitamin D levels and insulin resistance in 6294 non-diabetic U.S. adults. A total of 8 years of data from the 2011–2018 National Health and Nutrition Examination Survey (NHANES) and a cross-sectional design were utilized to answer the research questions. Serum vitamin D levels were quantified using high-performance liquid chromatography–tandem mass spectrometry. Dietary and supplemental vitamin D intakes were assessed using the average of two 24 h dietary recalls taken 3–10 days apart. The homeostatic model assessment (HOMA), based on fasting glucose and fasting insulin levels, was employed to index insulin resistance. Demographic covariates were age, sex, race, and year of assessment. Differences in physical activity, body mass index (BMI), cigarette smoking, body weight, season, and energy intake were also controlled statistically. Serum levels of vitamin D differed significantly, and in a dose–response order, across quartiles of HOMA-IR, after adjusting for year, age, sex, and race (F = 30.3, p < 0.0001) and with all the covariates controlled (F = 5.4, p = 0.0029). Dietary vitamin D levels differed similarly across HOMA-IR quartiles, but to a lesser extent, respectively (F = 8.1, p = 0.0001; F = 2.9, p = 0.0437). Likewise, supplemental vitamin D levels also differed across the HOMA-IR quartiles, respectively (F = 3.5, p = 0.0205; F = 3.3, p = 0.0272). With all the covariates controlled, the odds of having insulin resistance were significantly greater for those in the lowest quartile of serum and supplemental vitamin D intake compared to the other quartiles combined. In conclusion, in this nationally representative sample, serum, dietary, and supplemental vitamin D were each predictive of insulin resistance, especially in those with low serum levels and those with no supplemental intake of vitamin D.
Critical Role of Maternal Selenium Nutrition in Neurodevelopment: Effects on Offspring Behavior and Neuroinflammatory Profile
Authors: Ajmone-Cat Maria Antonietta , De Simone Roberta , Tartaglione Anna Maria , Di Biase Antonella , Di Benedetto Rita , D’Archivio Massimo , Varì Rosaria , Ricceri Laura , Aureli Federica , Iacoponi Francesca , Raggi Andrea , Cubadda Francesco , Fairweather-Tait Susan J. , Calamandrei Gemma , Minghetti Luisa
Published: April 2022

Research in both animals and humans shows that some nutrients are important in pregnancy and during the first years of life to support brain and cognitive development. Our aim was to evaluate the role of selenium (Se) in supporting brain and behavioral plasticity and maturation. Pregnant and lactating female rats and their offspring up to postnatal day 40 were fed isocaloric diets differing in Se content—i.e., optimal, sub-optimal, and deficient—and neurodevelopmental, neuroinflammatory, and anti-oxidant markers were analyzed. We observed early adverse behavioral changes in juvenile rats only in sub-optimal offspring. In addition, sub-optimal, more than deficient supply, reduced basal glial reactivity in sex dimorphic and brain-area specific fashion. In female offspring, deficient and sub-optimal diets reduced the antioxidant Glutathione peroxidase (GPx) activity in the cortex and in the liver, the latter being the key organ regulating Se metabolism and homeostasis. The finding that the Se sub-optimal was more detrimental than Se deficient diet may suggest that maternal Se deficient diet, leading to a lower Se supply at earlier stages of fetal development, stimulated homeostatic mechanisms in the offspring that were not initiated by sub-optimal Se. Our observations demonstrate that even moderate Se deficiency during early life negatively may affect, in a sex-specific manner, optimal brain development.
Genetic Diversity and Haplotype Analysis of Cattle Hydatid Cyst Isolates Using Mitochondrial Markers in Turkey
Authors: Kesik Harun Kaya , Celik Figen , Kilinc Seyma Gunyakti , Simsek Sami , Ahmed Haroon , Shen Yujuan , Cao Jianping
Published: April 2022

Echinococcus granulosus sensu lato (s.l.) causes cystic echinococcosis in ungulates and humans. The current study was designed to find the genetic diversity and haplotypic profiles of hydatid cysts from the lungs of cattle in three provinces in eastern Turkey. Individual cyst isolates (n = 60) were collected from infected cattle lungs after slaughter and then samples were stored in ethanol (70%) until further use. From each isolate, total gDNA was extracted from the cysts’ germinal layers. A partial (875 bp) mt-CO1 gene was amplified by PCR and sequenced unidirectionally. The final size of the trimmed sequences was 530 bp for 60 sequences. Sequence and haplotype analyses were performed, followed by phylogenetic analyses. According to BLAST searches, all sequences were detected as E. granulosus s.s. (G1 and G3 strains). Forty-nine point mutations were identified. In addition, five conserved fragments were detected in all sequences. The haplotype analysis diagram showed E. granulosus s.s. haplotypes organized in a star-like configuration. The haplotypes were characterized by 1–17 mutations compared with the fundamental focal haplotype. Thirty-three haplotypes were determined in 60 samples of which 17 (28.3%) belonged to the main haplotype (Hap_06). The mt-CO1 sequences revealed 49 polymorphic sites, 34.5% (20/49) of which were informative according to parsimony analysis.
Surgical Strikes on Host Defenses: Role of the Viral Protease Activity in Innate Immune Antagonism
Authors: Chin Chue Vin , Saeed Mohsan
Published: April 2022

As a frontline defense mechanism against viral infections, the innate immune system is the primary target of viral antagonism. A number of virulence factors encoded by viruses play roles in circumventing host defenses and augmenting viral replication. Among these factors are viral proteases, which are primarily responsible for maturation of viral proteins, but in addition cause proteolytic cleavage of cellular proteins involved in innate immune signaling. The study of these viral protease-mediated host cleavages has illuminated the intricacies of innate immune networks and yielded valuable insights into viral pathogenesis. In this review, we will provide a brief summary of how proteases of positive-strand RNA viruses, mainly from the Picornaviridae, Flaviviridae and Coronaviridae families, proteolytically process innate immune components and blunt their functions.
Unveiling the Multitarget Anti-Alzheimer Drug Discovery Landscape: A Bibliometric Analysis
Authors: Sampietro Anna , Pérez-Areales F. Javier , Martínez Paula , Arce Elsa M. , Galdeano Carles , Muñoz-Torrero Diego
Published: April 2022

Multitarget anti-Alzheimer agents are the focus of very intensive research. Through a comprehensive bibliometric analysis of the publications in the period 1990–2020, we have identified trends and potential gaps that might guide future directions. We found that: (i) the number of publications boomed by 2011 and continued ascending in 2020; (ii) the linked-pharmacophore strategy was preferred over design approaches based on fusing or merging pharmacophores or privileged structures; (iii) a significant number of in vivo studies, mainly using the scopolamine-induced amnesia mouse model, have been performed, especially since 2017; (iv) China, Italy and Spain are the countries with the largest total number of publications on this topic, whereas Portugal, Spain and Italy are the countries in whose scientific communities this topic has generated greatest interest; (v) acetylcholinesterase, β-amyloid aggregation, oxidative stress, butyrylcholinesterase, and biometal chelation and the binary combinations thereof have been the most commonly pursued, while combinations based on other key targets, such as tau aggregation, glycogen synthase kinase-3β, NMDA receptors, and more than 70 other targets have been only marginally considered. These results might allow us to spot new design opportunities based on innovative target combinations to expand and diversify the repertoire of multitarget drug candidates and increase the likelihood of finding effective therapies for this devastating disease.
Importance of Spray–Wall Interaction and Post-Deposition Liquid Motion in the Transport and Delivery of Pharmaceutical Nasal Sprays
Authors: Kolanjiyil Arun V. , Alfaifi Ali , Aladwani Ghali , Golshahi Laleh , Longest Worth
Published: April 2022

Nasal sprays, which produce relatively large pharmaceutical droplets and have high momentum, are primarily used to deliver locally acting drugs to the nasal mucosa. Depending on spray pump administration conditions and insertion angles, nasal sprays may interact with the nasal surface in ways that creates complex droplet–wall interactions followed by significant liquid motion after initial wall contact. Additionally, liquid motion can occur after deposition as the spray liquid moves in bulk along the nasal surface. It is difficult or impossible to capture these conditions with commonly used computational fluid dynamics (CFD) models of spray droplet transport that typically employ a deposit-on-touch boundary condition. Hence, an updated CFD framework with a new spray–wall interaction (SWI) model in tandem with a post-deposition liquid motion (PDLM) model was developed and applied to evaluate nasal spray delivery for Flonase and Flonase Sensimist products. For both nasal spray products, CFD revealed significant effects of the spray momentum on surface liquid motion, as well as motion of the surface film due to airflow generated shear stress and gravity. With Flonase, these factors substantially influenced the final resting place of the liquid. For Flonase Sensimist, anterior and posterior liquid movements were approximately balanced over time. As a result, comparisons with concurrent in vitro experimental results were substantially improved for Flonase compared with the traditional deposit-on-touch boundary condition. The new SWI-PDLM model highlights the dynamicenvironment that occurs when a nasal spray interacts with a nasal wall surface and can be used to better understand the delivery of current nasal spray products as well as to develop new nasal drug delivery strategies with improved regional targeting.
Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy
Authors: Galdopórpora Juan M. , Martinena Camila , Bernabeu Ezequiel , Riedel Jennifer , Palmas Lucia , Castangia Ines , Manca Maria Letizia , Garcés Mariana , Lázaro-Martinez Juan , Salgueiro Maria Jimena , Evelson Pablo , Tateosian Nancy Liliana , Chiappetta Diego Andres , Moretton Marcela Analia
Published: April 2022

Among respiratory infections, tuberculosis was the second deadliest infectious disease in 2020 behind COVID-19. Inhalable nanocarriers offer the possibility of actively targeting anti-tuberculosis drugs to the lungs, especially to alveolar macrophages (cellular reservoirs of the Mycobacterium tuberculosis). Our strategy was based on the development of a mannose-decorated micellar nanoformulation based in Soluplus® to co-encapsulate rifampicin and curcumin. The former is one of the most effective anti-tuberculosis first-line drugs, while curcumin has demonstrated potential anti-mycobacterial properties. Mannose-coated rifampicin (10 mg/mL)–curcumin (5 mg/mL)-loaded polymeric micelles (10% w/v) demonstrated excellent colloidal properties with micellar size ~108 ± 1 nm after freeze-drying, and they remain stable under dilution in simulated interstitial lung fluid. Drug-loaded polymeric micelles were suitable for drug delivery to the deep lung with lung accumulation, according to the in vitro nebulization studies and the in vivo biodistribution assays of radiolabeled (99mTc) polymeric micelles, respectively. Hence, the nanoformulation did not exhibit hemolytic potential. Interestingly, the addition of mannose significantly improved (5.2-fold) the microbicidal efficacy against Mycobacterium tuberculosis H37Rv of the drug-co-loaded systems in comparison with their counterpart mannose-free polymeric micelles. Thus, this novel inhaled nanoformulation has demonstrated its potential for active drug delivery in pulmonary tuberculosis therapy.
Liposome-Encapsulated Tobramycin and IDR-1018 Peptide Mediated Biofilm Disruption and Enhanced Antimicrobial Activity against Pseudomonas aeruginosa
Authors: Alzahrani Nouf M. , Booq Rayan Y. , Aldossary Ahmad M. , Bakr Abrar A. , Almughem Fahad A. , Alfahad Ahmed J. , Alsharif Wijdan K. , Jarallah Somayah J. , Alharbi Waleed S. , Alsudir Samar A. , Alyamani Essam J. , Tawfik Essam A. , Alshehri Abdullah A.
Published: April 2022

The inadequate eradication of pulmonary infections and chronic inflammation are significant complications in cystic fibrosis (CF) patients, who usually suffer from persistent and frequent lung infections caused by several pathogens, particularly Pseudomonas aeruginosa (P. aeruginosa). The ability of pathogenic microbes to protect themselves from biofilms leads to the development of an innate immune response and antibiotic resistance. In the present work, a reference bacterial strain of P. aeruginosa (PA01) and a multidrug-resistant isolate (MDR 7067) were used to explore the microbial susceptibility to three antibiotics (ceftazidime, imipenem, and tobramycin) and an anti-biofilm peptide (IDR-1018 peptide) using the minimum inhibition concentration (MIC). The most effective antibiotic was then encapsulated into liposomal nanoparticles and the IDR-1018 peptide with antibacterial activity, and the ability to disrupt the produced biofilm against PA01 and MDR 7067 was assessed. The MIC evaluation of the tobramycin antibacterial activity showed an insignificant effect on the liposomes loaded with tobramycin and liposomes encapsulating tobramycin and IDR-1018 against both P. aeruginosa strains to free tobramycin. Nevertheless, the biofilm formation was significantly reduced (p < 0.05) at concentrations of ≥4 μg/mL and ≤32 μg/mL for PA01 and ≤32 μg/mL for MDR 7067 when loading tobramycin into liposomes, with or without the anti-biofilm peptide compared to the free antibiotic, empty liposomes, and IDR-1018-loaded liposomes. A tobramycin concentration of ≤256 µg/mL was safe when exposed to a lung carcinoma cell line upon its encapsulation into the liposomal formulation. Tobramycin-loaded liposomes could be a potential candidate for treating lung-infected animal models owing to the high therapeutic efficacy and safety profile of this system compared to the free administration of the antibiotic.
Clinical Impact of Implementing a Nurse-Led Adverse Drug Reaction Profile in Older Adults Prescribed Multiple Medicines in UK Primary Care: A Study Protocol for a Cluster-Randomised Controlled Trial
Authors: Logan Vera , Bamsey Alexander , Carter Neil , Hughes David , Turner Adam , Jordan Sue
Published: April 2022

(1) Aims: Adverse drug reactions (ADRs) particularly affect older people prescribed multiple medicines. The professional bodies of nursing, medicine and pharmacy have issued guidelines on identification and management of ADRs; however, ADRs continue to account for ~10% unplanned hospital admissions in the UK. Current methods of ADR identification and management could be improved by multidisciplinary collaboration involving nurses. The aim of this study is to examine the impact of implementing the nurse-led Adverse Drug Reaction (ADRe) Profile in UK primary care. (2) Design: A pragmatic cluster-randomised controlled trial (RCT) followed by qualitative interviews in a sequential mixed-methods study. (3) Methods: For the cluster RCT, 60 patients aged ≥65 prescribed ≥5 regular medicines for long-term conditions will be recruited, 10 in each of 6 general practices. The intervention arm (n = 30) will complete the ADRe Profile, whilst the control participants (n = 30) continue to receive usual, standard care. Primary outcomes will include clinical impact on patients, benefit and prescription changes. On completion of the RCT, participants will be invited to semi-structured qualitative interviews, to evaluate the impact of the ADRe Profile from stakeholders’ perspectives, and to describe the contextual factors relevant to ADRe implementation. (4) Results: The findings of this study will evaluate the effectiveness of the ADRe Profile in identifying and resolving potential ADRs in primary care. Trial registration: This study was registered in ClinicalTrials.gov, registration number NCT04663360, date of registration—29 November 2021 (date of initial registration: 26 November 2020), protocol version 2, dated 8 January 2021.
Broadband Time-Delay and Chirp Compensator for X-ray Pulses
Authors: Braig Christoph , Erko Alexei
Published: April 2022

A new type of aberration-corrected time-delay compensating monochromator (TDCM) for soft X-rays is presented. Composed of two identical reflection zone plates (RZPs) on spherical substrates and an intermediate flat mirror for band-pass selection, the TDCM can operate in a wide energy range of about ±20% around the design energy of 410eV. Assuming a source size of 50μm and an angular acceptance of 1 mrad, the spectral resolving power may reach 6×102, at a pulse length as short as 4.3femtoseconds(fs). In the case of μm-sized sources, the resolution can be better than 0.1eV and the sub-fs regime could become accessible. The overall transmission efficiency varies within (4.2–6.0)% across the energy range (310–510) eV. In the complementary mode, chirped-pulse compression works as well. Depending on the properties of the source, simulations predict an up to 9-fold reduction in pulse duration, whereas ≤50% of the peak intensity is maintained.
Chemical Composition, Enantiomeric Distribution and Anticholinesterase and Antioxidant Activity of the Essential Oil of Diplosthephium juniperinum
Authors: Salinas Melissa , Calva James , Cartuche Luis , Valarezo Eduardo , Armijos Chabaco
Published: April 2022

The aim of this study was to extract and identify the chemical compounds of Diplosthephium juniperinum essential oil (EO) from Ecuador and to assess its anticholinesterase and antioxidant properties. The EO chemical composition was determined by GC–MS. A total of 74 constituents of EO were identified, representing 97.27% in DB-5ms and 96.06% in HP-INNOWax of the total EO. The major constituents (>4.50%) identified were: α-pinene (21.52, 22.04%), geranyl acetate (10.54, 7.78%), silphiper-fol-5-ene (8.67, 7.38%), α-copaene (8.26, 8.18%), 7-epi-silphiperfol-5-ene (4.93, 5.95%), and germacrene D (4.91, 6.00%). Enantioselective analysis of the volatile fraction of D. juniperinum showed: (+)-α-pinene as a pure enantiomer and 5 pairs of enantiomeric compounds. Among them, (−)-β-Pinene and (−)-Germacrene D presented a high enantiomeric excess of 93.23 and 84.62%, respectively, while (−)-α-Thujene, (−)-Sabinene and (S)-4-Terpineol with a lower enantiomeric excess of 56.34, 47.84 and 43.11%, respectively. A moderate inhibitory effect was observed for Acetylcholinesterase (AChE) and Butyrylcholinesterase (BuChE) enzymes with IC50 values of 67.20 ± 7.10 and 89.00 ± 9.90 µg/mL, respectively. A lower antioxidant potential was observed for the EO measured through DPPH and ABTS radical scavenging assays with SC50 values of 127.03 and >1000 µg/mL, respectively. To the best of our knowledge, this is the first report of the chemical composition, enantiomeric distribution and, anticholinesterase and antioxidant potential of the EO of D. juniperinum. As future perspective, further in-vivo studies could be conducted to confirm the anticholinesterase potential of the EO.
Germacrene A Synthases for Sesquiterpene Lactone Biosynthesis Are Expressed in Vascular Parenchyma Cells Neighboring Laticifers in Lettuce
Authors: Kwon Moonhyuk , Hodgins Connor L. , Haslam Tegan M. , Roth Susan A. , Nguyen Trinh-Don , Yeung Edward C. , Ro Dae-Kyun
Published: April 2022

Sesquiterpene lactone (STL) and natural rubber (NR) are characteristic isoprenoids in lettuce (Lactuca sativa). Both STL and NR co-accumulate in laticifers, pipe-like structures located along the vasculature. NR-biosynthetic genes are exclusively expressed in laticifers, but cell-type specific expression of STL-biosynthetic genes has not been studied. Here, we examined the expression pattern of germacrene A synthase (LsGAS), which catalyzes the first step in STL biosynthesis in lettuce. Quantitative PCR and Illumina read mapping revealed that the transcripts of two GAS isoforms (LsGAS1/LsGAS2) are expressed two orders of magnitude (~100–200) higher in stems than laticifers. This result implies that the cellular site for LsGAS1/2 expression is not in laticifers. To gain more insights, promoters of LsGAS1/2 were cloned and fused to β-glucuronidase (GUS), followed by transformations of lettuce with these promoter-GUS constructs. In in situ GUS assays, the GUS expression driven by the LsGAS1/2 promoters was tightly associated with vascular bundles. High-resolution microsections showed that GUS signals are not present in laticifers but are detected in the vascular parenchyma cells neighboring the laticifers. These results suggest that expression of LsGAS1/2 occurs in the parenchyma cells neighboring laticifers, while the resulting STL metabolites accumulate in laticifers. It can be inferred that active metabolite-trafficking occurs from the parenchyma cells to laticifers in lettuce.
Insecticidal Effect of Wild-Grown Mentha pulegium and Rosmarinus officinalis Essential Oils and Their Main Monoterpenes against Culex pipiens (Diptera: Culicidae)
Authors: Ramzi Amal , El Ouali Lalami Abdelhakim , Ez zoubi Yassine , Assouguem Amine , Almeer Rafa , Najda Agnieszka , Ullah Riaz , Ercisli Sezai , Farah Abdellah
Published: April 2022

The present study investigates the insecticidal effect of plant extract such as Mentha pulegium and Rosmarinus officinalis essential oils and some of their major compounds; these plants are well known for their many biological activities. The fumigant toxicity was evaluated, using glass jars, against female adults of Culex pipiens that constitute a mosquito vector of important diseases such as the West Nile virus. The adulticidal test showed that both essential oils and monoterpenes presented an insecticidal effect better than the chemical insecticide (Deltamethrin). The highest mortality percentages for the two essential oils have occurred at 312.5 µL/L air (between 56.14 ± 1.7% and 97.71 ± 3.03% after 24 h and 48 h of treatment). Moreover, all tested monoterpenes (carvone, R(+)-pulegone, 1,8-cineole, camphor and α-pinene) have produced high mortalities that varied depending on the time of the treatment and the concentrations used. Lethal concentrations (LC50) obtained for the essential oils and the main compounds have also varied according to the exposure time. M. pulegium and R. officinalis essential oil exhibited the lowest LC50 values after 24 h (72.94 and 222.82 µL/L air, respectively) and after 48 h (25.43 and 55.79 µL/L air, respectively) while the pure molecules revealed the lowest LC50 values after 48 h (between 84.96 and 578.84 µL/L air). This finding proves that the two essential oils and their main compounds have an insecticidal potential, which could help to develop natural toxic fumigants that may be used as an eco-friendly alternative in integrated and sustainable vector management.
Analysis of Nutrient-Specific Response of Maize Hybrids in Relation to Leaf Area Index (LAI) and Remote Sensing
Authors: Szabó Atala , Mousavi Seyed Mohammad Nasir , Bojtor Csaba , Ragán Péter , Nagy János , Vad Attila , Illés Árpád
Published: April 2022

Leaf area index (LAI) indicates the leaf area per ground surface area occupied by a crop. Various methods are used to measure LAI, which is unitless and varies according to species and environmental conditions. This experiment was carried out in three different nitrogen ranges (control, 120 kg N ha−1, and 300 kg N ha−1) + PK nutrient levels, with five replications used for leaf area measurement on seven different maize hybrids. Hybrids had different moisture, protein, oil, and starch contents. N (1, 2) + PK treatments had a desirable effect on protein, starch, and yield. P0217 LAI had a minimal response at these fertiliser levels. LAI for Sushi peaked at different dates between control and fertiliser treatments. This result showed that Sushi has an excellent capacity for LAI. LAI values on 15 June 2020 showed minimum average values for all hybrids, and it had a maximum average values on 23 July 2020. LAI had maximum performance between the average values treatments in Sushi, Armagnac, Loupiac, and DKC4792 on 15 June 2020. This study also provides insights for examining variably applied N doses using crop sensors and UAV remote-sensing platforms.
Analysis of Comparative Transcriptome and Positively Selected Genes Reveal Adaptive Evolution in Leaf-Less and Root-Less Whisk Ferns
Authors: Xia Zengqiang , Liu Li , Wei Zuoying , Wang Faguo , Shen Hui , Yan Yuehong
Published: April 2022

While roots and leaves have evolved independently in lycophytes, ferns and seed plants, there is still confusion regarding the morphological evolution of ferns, especially in whisk ferns, which lack true leaves and roots and instead only exhibit leaf-like appendages and absorptive rhizoids. In this study, analyses of comparative transcriptomics on positively selected genes were performed to provide insights into the adaptive evolution of whisk fern morphologies. Significantly clustered gene families specific to whisk ferns were mainly enriched in Gene Ontology (GO) terms “binding proteins” and “transmembrane transporter activity”, and positive selection was detected in genes involved in transmembrane transporter activities and stress response (e.g., sodium/hydrogen exchanger and heat shock proteins), which could be related to the adaptive evolution of tolerance to epiphytic environments. The analysis of TF/TR gene family sizes indicated that some rapidly evolving gene families (e.g., the GRF and the MADS-MIKC families) related to the development of morphological organs were commonly reduced in whisk ferns and ophioglossoid ferns. Furthermore, the WUS homeobox-containing (WOX) gene family and the knotted1-like homeobox (KNOX) gene family, both associated with root and leaf development, were phylogenetically conserved in whisk ferns and ophioglossoid ferns. In general, our results suggested that adaptive evolution to epiphytic environments might have occurred in whisk ferns. We propose that the simplified and reduced leaf and root system in whisk ferns is the result of reduction from the common ancestor of whisk ferns and ophioglossoid ferns, rather than an independent origin.
A New Analytical Model for Deflection of Concrete Beams Reinforced by BFRP Bars and Steel Fibres under Cyclic Loading
Authors: Zhu Haitang , Li Zongze , Chen Qun , Cheng Shengzhao , Li Chuanchuan , Zhou Xiangming
Published: April 2022

Basalt-fiber-reinforced plastic-bars-reinforced concrete beams (i.e., BFRP-RC beams) usually possess significant deformations compared to reinforced concrete beams due to the FRP bars having a lower Young’s modulus. This paper investigates the effects of adding steel fibers into BFRP-RC beams to reduce their deflection. Ten BFRP-RC beams were prepared and tested to failure via four-point bending under cyclic loading. The experimental variables investigated include steel-fiber volume fraction and shape, BFRP reinforcement ratio, and concrete strength. The influences of steel fibers on ultimate moment capacity, service load moment, and deformation of the BFRP-RC beams were investigated. The results reveal that steel fibers significantly improved the ultimate moment capacity and service load moment of the BFRP-RC beams. The deflection and residual deflection of the BFRP-RC beams reinforced with 1.5% by volume steel fibers were 48.18% and 30.36% lower than their counterpart of the BFRP-RC beams without fibers. Under the same load, the deflection of the beams increased by 11% after the first stage of three loading and unloading cycles, while the deflection increased by only 8% after three unloading and reloading cycles in the second and third stages. Finally, a new analytical model for the deflection of the BFRP-RC beams with steel fibers under cyclic loading was established and validated by the experiment results from this study. The new model yielded better results than current models in the literature.
The Influence of Accelerated Carbonation on Physical and Mechanical Properties of Hemp-Fibre-Reinforced Alkali-Activated Fly Ash and Fly Ash/Slag Mortars
Authors: Merta Ildiko , Poletanovic Bojan , Dragas Jelena , Carevic Vedran , Ignjatovic Ivan , Komljenovic Miroslav
Published: April 2022

The physical and mechanical properties of hemp-fibre-reinforced alkali-activated (AA) mortars under accelerated carbonation were evaluated. Two matrices of different physical and chemical properties, i.e., a low Ca-containing and less dense one with fly ash (FA) and a high Ca-containing and denser one with FA and granulated blast furnace slag (GBFS), were reinforced with fibres (10 mm, 0.5 vol% and 1.0 vol%). Under accelerated carbonation, due to the pore refinement resulting from alkali and alkaline earth salt precipitation, AA hemp fibre mortars markedly (20%) decreased their water absorption. FA-based hemp mortars increased significantly their compressive and flexural strength (40% and 34%, respectively), whereas in the denser FA/GBFS matrix (due to the hindered CO2 penetration, i.e., lower chemical reaction between CO2 and pore solution and gel products), only a slight variation (±10%) occurred. Under accelerated carbonation, embrittlement of the fibre/matrix interface and of the whole composite occurred, accompanied by increased stiffness, decreased deformation capacity and loss of the energy absorption capacity under flexure. FA-based matrices exhibited more pronounced embrittlement than the denser FA/GBFS matrices. A combination of FA/GBFS-based mortar reinforced with 0.5 vol% fibre dosage ensured an optimal fibre/matrix interface and stress transfer, mitigating the embrittlement of the material under accelerated carbonation.
RPL Neutron Dosimetry in n-γ Fields in Comparison with Polymer Detectors Type CR-39
Authors: Salem Youbba Ould , Elazhar Halima , Traore Issiaka , Riffaud Jonathan , Nourreddine Abdelmjid
Published: April 2022

Previously we characterized radiophotoluminescent (RPL) detectors for measuring both fast and thermal neutrons for personal monitoring. The linear response and angular dependence, which satisfies the ISO 21909 standard makes their application possible in neutron dosimetry. The polymer CR-39 track detectors remain one of the most used dosimeters where neutron radiations are to be measured, but the visualization process is time consuming. The difference between results obtained by RPL and CR-39 has been discussed mainly for fast neutrons. The present study has also looked at thermal neutron dosimetry, where we found few results in the literature for CR-39. Our measurements demonstrate that RPL detectors can be advantageously incorporated into a dosimeter to measure thermal neutrons.
Accelerated Discovery of the Polymer Blends for Cartilage Repair through Data-Mining Tools and Machine-Learning Algorithm
Authors: Mairpady Anusha , Mourad Abdel-Hamid I. , Mozumder Mohammad Sayem
Published: April 2022

In designing successful cartilage substitutes, the selection of scaffold materials plays a central role, among several other important factors. In an empirical approach, the selection of the most appropriate polymer(s) for cartilage repair is an expensive and time-consuming affair, as traditionally it requires numerous trials. Moreover, it is humanly impossible to go through the huge library of literature available on the potential polymer(s) and to correlate the physical, mechanical, and biological properties that might be suitable for cartilage tissue engineering. Hence, the objective of this study is to implement an inverse design approach to predict the best polymer(s)/blend(s) for cartilage repair by using a machine-learning algorithm (i.e., multinomial logistic regression (MNLR)). Initially, a systematic bibliometric analysis on cartilage repair has been performed by using the bibliometrix package in the R program. Then, the database was created by extracting the mechanical properties of the most frequently used polymers/blends from the PoLyInfo library by using data-mining tools. Then, an MNLR algorithm was run by using the mechanical properties of the polymers, which are similar to the cartilages, as the input and the polymer(s)/blends as the predicted output. The MNLR algorithm used in this study predicts polyethylene/polyethylene-graftpoly(maleic anhydride) blend as the best candidate for cartilage repair.
Carbohydrate-Binding Modules of Potential Resources: Occurrence in Nature, Function, and Application in Fiber Recognition and Treatment
Authors: Liu Yena , Wang Peipei , Tian Jing , Seidi Farzad , Guo Jiaqi , Zhu Wenyuan , Xiao Huining , Song Junlong
Published: April 2022

Great interests have recently been aroused in the independent associative domain of glycoside hydrolases that utilize insoluble polysaccharides-carbohydrate-binding module (CBM), which responds to binding while the catalytic domain reacts with the substrate. In this mini-review, we first provide a brief introduction on CBM and its subtypes including the classifications, potential sources, structures, and functions. Afterward, the applications of CBMs in substrate recognition based on different types of CBMs have been reviewed. Additionally, the progress of CBMs in paper industry as a new type of environmentally friendly auxiliary agent for fiber treatment is summarized. At last, other applications of CBMs and the future outlook have prospected. Due to the specificity in substrate recognition and diversity in structures, CBM can be a prosperous and promising ‘tool’ for wood and fiber processing in the future.