bluuebunny/crossref_metadata_2025 huggingface dataset:
Anemia among Syrian Refugee Children Aged 6 to 23 Months Living in Greater Beirut, Lebanon, including the Voices of Mothers’ and Local Healthcare Staff: A Mixed-Methods Study
Authors: Jeremias Theresa , Abou-Rizk Joana , Burgard Leonie , Entenmann Isa , Nasreddine Lara , Jomaa Lamis , Hwalla Nahla , Frank Jan , Scherbaum Veronika
Published: January 2023

Globally, the prevalence of anemia among children during the period of complementary feeding is high. A cross-sectional, mixed-methods study was conducted to examine the main determinants of anemia among Syrian refugee children aged 6 to 23 months (n = 215) and to illuminate the knowledge, attitudes and perceptions of their mothers and Lebanese healthcare staff on its causes and available treatment options. 42% of the children and 20% of their mothers were anemic. Determinants of child anemia were the mother having anemia or not knowing that fish/seafood is a source of iron; the child having been acutely ill the last two weeks or receiving cow’s milk, but not consuming iron-rich infant formula, added fats/oils, or fruits in the previous 24 hours. Several Syrian mothers knew some causes of anemia and named dizziness as a leading symptom but did not mention flesh foods as a key source of heme iron. They reported financial constraints in accessing iron-rich foods and supplements. Lebanese doctors largely gave appropriate dietary advice and prescribed iron supplements as treatment. Multisectoral interventions are needed that combine medical and financial support with nutrition counseling for mothers to reduce the high burden of anemia among young children living in a multiple crises situation.
Parallel Synthesis of Aurones Using a Homogeneous Scavenger
Authors: Taylor Zachary E. , Handy Scott T.
Published: January 2023

The ability to synthesize arrays of related compounds quickly and with good purity has become critical for a rapid exploration of their properties for biological or material applications. While a number of methods have been developed to enable this combinatorial synthesis, the existing options were not readily appliable to the synthesis of aurones using the simple Knoevenagel condensation approach. In order to avoid the time, expense, and lowered yields associated with flash column chromatography, we developed a scavenging approach for their synthesis. This method uses an excess of aldehyde to ensure complete conversion to aurones, followed by selective removal of the remaining aldehyde using a simple, inexpensive scavenger – isoniazid – and subsequent extraction with dilute acid, to produce the desired compounds with good purity under operationally simple conditions. This approach is expected to be applicable to many other reactions involving aldehydes as one of the reactants.
Direct Photon Production in Heavy-Ion Collisions: Theory and Experiment
Authors: Blau Dmitry , Peresunko Dmitri
Published: January 2023

Direct photons provide a possibility to test properties of hot matter created in proton–proton (pp), proton–nucleus (p–A) or nucleus–nucleus (A–A) collisions. As they are created in charged particles’ scatterings and freely escape the hot region, they provide a tool to test all stages of the collision: the scattering of the partons of incoming nucleons, pre-equilibrium evolution and collective expansion of hot quark–gluon matter created in nucleus–nucleus collisions. Comparing direct photon production in pp, p–A and A–A collisions, one can check the scaling with the number of binary collisions expected at a high transverse momentum range and obtain insight into the hot and cold hadronic matter properties with soft photons. The collective elliptic flow of direct photons is a unique possibility to trace the collective flow formation and space–time evolution of the fireball. We review the experimental results on direct photon production in pp, p–A and A–A collisions at the Super Proton Synchroton (SPS), the Relativistic Heavy Ion Collider (RHIC) and the Large Hadron Collider (LHC) energies and discuss an agreement of theoretical predictions with measurements. Finally, we present predictions of direct photon spectra and collective flow for lower energy collisions expected at the Nuclotron-based Ion Collider fAcility (NICA) and the Facility for Antiproton and Ion Research (FAIR).
Monogeneans from Catfishes in Lake Tanganyika. II: New Infection Site, New Record, and Additional Details on the Morphology of the Male Copulatory Organ of Gyrodactylus transvaalensis Prudhoe and Hussey, 1977
Authors: Mushagalusa Mulega Archimède , Van Steenberge Maarten , Kmentová Nikol , Muterezi Bukinga Fidel , Rahmouni Imane , Masilya Pascal Mulungula , Benhoussa Abdelaziz , Pariselle Antoine , Vanhove Maarten P. M.
Published: January 2023

The ichthyofauna of Lake Tanganyika consists of 12 families of fish of which five belong to Siluriformes (catfishes). Studies on Siluriformes and their parasites in this lake are very fragmentary. The present study was carried out to help fill the knowledge gap on the monogeneans infesting the siluriform fishes of Lake Tanganyika in general and, more particularly, Clarias gariepinus. Samples of gills of Clarias gariepinus (Clariidae) were examined for ectoparasites. We identified the monogenean Gyrodactylus transvaalensis (Gyrodactylidae). This is the first time this parasite was found infecting gills. We are the first to observe a large spine in the male copulatory organ of this species and to provide measurements of its genital spines; this completes the description of the male copulatory organ, which is important in standard monogenean identification. This is the first monogenean species reported in C. gariepinus at Lake Tanganyika and the third known species on a representative of Siluriformes of this lake. It brings the total number of species of Gyrodactylus recorded in Lake Tanganyika to four. Knowing that other locations where this species has been reported are geographically remote from Lake Tanganyika, we propose a “failure to diverge” phenomenon for G. transvaalensis.
Antimicrobial-Loaded Polyacrylamide Hydrogels Supported on Titanium as Reservoir for Local Drug Delivery
Authors: Sille Irene E. , Pissinis Diego E. , Fagali Natalia S. , Ghilini Fiorela , Urrutia María Noel , Schilardi Patricia L.
Published: January 2023

Arthroplasty is a highly successful treatment to restore the function of a joint. The contamination of the implant via bacterial adhesion is the first step toward the development of device-associated infections. The emerging concern about antimicrobial resistance resulted in a growing interest to develop alternative therapeutic strategies. Thus, the increment in the incidence of bacterial periprosthetic infections, the complexity of treating infections caused by organisms growing in biofilms, together with the rise in antibiotic resistant bacteria, expose the need to design novel surfaces that provide innovative solutions to these rising problems. The aim of this work is to develop a coating on titanium (Ti) suitable for inhibiting bacterial adhesion and proliferation, and hence, biofilm formation on the surface. We have successfully prepared polyacrylamide hydrogels containing the conventional antibiotic ampicillin (AMP), silver nanoparticles (AgNPs), and both, AMP and AgNPs. The release of the antibacterial agents from the gelled to aqueous media resulted in an excellent antibacterial action of the loaded hydrogels against sessile S. aureus. Moreover, a synergic effect was achieved with the incorporation of both AMP and AgNPs in the hydrogel, which highlights the importance of combining antimicrobial agents having different targets. The polyacrylamide hydrogel coating on the Ti surface was successfully achieved, as it was demonstrated by FTIR, contact angle, and AFM measurements. The modified Ti surfaces having the polyacrylamide hydrogel film containing AgNPs and AMP retained the highest antibacterial effect against S. aureus as it was found for the unsupported hydrogels. The modified surfaces exhibit an excellent cytocompatibility, since healthy, flattened MC3T3-E1 cells spread on the surfaces were observed. In addition, similar macrophage RAW 264.7 adhesion was found on all the surfaces, which could be related to a low macrophage activation. Our results indicate that AMP and AgNP-loaded polyacrylamide hydrogel films on Ti are a good alternative for designing efficient antibacterial surfaces having an excellent cytocompatibility without inducing an exacerbated immune response. The approach emerges as a superior alternative to the widely used direct adsorption of therapeutic agents on surfaces, since the antimicrobial-loaded hydrogel coatings open the possibility of modulating the concentration of the antimicrobial agents to enhance bacterial killing, and then, reducing the risk of infections in implantable materials.
Morphological and Molecular Identification of Dactylogyrus gobiocypris (Monogenea: Dactylogyridae) on Gills of a Model Fish, Gobiocypris rarus (Cypriniformes: Gobionidae)
Authors: Cheng Jiangwen , Zou Hong , Li Ming , Wang Jianwei , Wang Guitang , Li Wenxiang
Published: January 2023

The rare minnow Gobiocypris rarus is an ideal model organism for toxicological research. Dactylogyrus species are usually found on the gills of this rare minnow in laboratory farming systems. Dactylogyrid infection may change the sensibility of fish to toxicants and affect toxicological evaluations. In the present study, dactylogyrid infection was investigated, and species of Dactylogyrus collected from rare minnows were determined. Based on the observed ‘D. wunderi’ type anchors, with a shorter outer root and elongated inner root, and accessory piece consisting of two parts, the dactylogyrids were identified as D. gobiocypris. A partial 18S-ITS1 rDNA sequence was firstly sequenced, and the highest sequence identity (86.7%) was to D. cryptomeres. Phylogenetic analysis revealed that D. gobiocypris formed a clade with D. squameus, D. finitimus, and D. cryptomeres, all of which have been recorded in the family Gobionidae. Histopathology analysis indicated that a heavy burden of D. gobiocypris caused necrosis of gill filaments. Inflammatory responses, such as tumefaction and hyperaemia, were also observed on gills with severe dactylogyrid infection. Supplementary morphological characteristics and 18S-ITS1 rDNA sequence provided basic data for identification of this parasite species.
Supporting the Aspecific Physiological Defenses of Upper Airways against Emerging SARS-CoV-2 Variants
Authors: Cegolon Luca , Mastrangelo Giuseppe , Bellizzi Saverio , Filon Francesca Larese , Salata Cristiano
Published: January 2023

The rapid rollout of COVID-19 vaccines in 2021 sparked general optimism toward controlling the severe form of the disease, preventing hospitalizations and COVID-19-associated mortality, and the transmissibility of SARS-CoV-2 infection [...]
Far-UVC Radiation for Disinfecting Hands or Gloves?
Authors: Hessling Martin , Sicks Ben , Lau Bernhard
Published: January 2023

(1) Background: Far-UVC radiation in the spectral range 200–230 nm has, according to previous findings, a strong antimicrobial effect on pathogens, but exhibits hardly any harmful effect on human skin. Therefore, the present study will discuss whether such radiation could also be suitable for hand disinfection in the healthcare sector. (2) Methods: Hands and gloves were microbially contaminated and exposed to radiation from a 222 nm krypton-chloride-excimer lamp. The applied doses were 23 mJ/cm2 and 100 mJ/cm2, respectively. Irradiated and non-irradiated hands and gloves were pressed onto agar plates and colonies were counted and compared after 24 h of incubation. For comparison, we also treated hands and gloves with a commercial liquid alcohol-based disinfectant. (3) Results: On the hand, the 23 mJ/cm2 resulted in the reduction of the observed colonies on the agar plates by one log level. For the gloves irradiated with 100 mJ/cm2, a colony reduction of 1.3 log levels was recorded. In the comparative experiments with the commercial disinfectant, a colony reduction of 1.9 and approximately one log level was observed on hand and gloves, respectively. (4) Conclusion: In both cases, far-UVC radiation provided a considerable reduction in microorganisms. However, compared to published far-UVC irradiation results in suspensions, the disinfection success on hands and gloves was rather low. With regard to the irradiation limits currently existing in the European Union, multiple daily hand disinfection with far-UVC radiation is actually legally not possible at present, but the thresholds are currently under discussion and could change in the future. Far-UVC disinfection of hands in gloves seems theoretically possible if attention is paid to potential perforations in the gloves.
Presence of Anaplasma phagocytophilum Ecotype I in UK Ruminants and Associated Zoonotic Risk
Authors: Bianchessi Laura , Rocchi Mara Silvia , Maley Madeleine , Allen Kayleigh , Ballingall Keith , Turin Lauretta
Published: January 2023

Anaplasma phagocytophilum is the causative agent of tick-borne fever in sheep, pasture fever in cattle, and granulocytic anaplasmosis in humans. The increasing prevalence and transboundary spread of A. phagocytophilum in livestock, ticks, and wildlife in the UK poses a potential zoonotic risk that has yet to be estimated. Several ecotypes of A. phagocytophilum show variable zoonotic potential. To evaluate the possible risk associated with the transmission of A. phagocytophilum from ruminants to humans, the ecotype was determined by sequencing the groEL gene from 71 positive blood and tissue samples from UK ruminants. Thirty-four groEL sequences were obtained, fourteen of which were identified in multiple samples. Of the 13 nucleotide polymorphisms identified through pairwise comparison, all corresponded to synonymous substitutions. The subsequent phylogenetic estimation of the relationship with other European/world isolates indicated that all the groEL sequences clustered with other ecotype I sequences. The presence of ecotype I closely reflects that observed in ruminants in continental Europe and suggests a lower risk of zoonotic transmission from this reservoir.
In Vivo Pharmacodynamics of Calophyllum soulattri as Antiobesity with In Silico Molecular Docking and ADME/Pharmacokinetic Prediction Studies
Authors: Fajriaty Inarah , Ih Hariyanto , Fidrianny Irda , Kurniati Neng Fisheri , Reynaldi Muhammad Andre , Adnyana I Ketut , Rommy Rommy , Kurniawan Fransiska , Tjahjono Daryono Hadi
Published: January 2023

This study aims to determine the antiobesity activity of Calophyllum soulattri leaves extract (CSLE) on high fat diet-fed rats (HFD) and to predict the molecular docking and pharmacokinetics of selected compounds of Calophyllum soulattri to fat mass and obesity-associated protein (FTO). Daily body weight, organ, carcass fat (renal and anal), body mass index, total cholesterol, and total triglyceride levels were observed after CSLE was given orally for 50 days. Furthermore, body mass index of a CSLE dose of 50 mg/kgbw, 100 mg/kgbw and orlistat (120 mg/kgbw) group are 0.68, 0.57 and 0.52, respectively. The total body weight of the CLSE dose of 100 mg/kgbw group showed the lowest percentage change, followed by a CLSE dose of 50 mg/kgbw compared to the normal and positive control group. The carcass fat index of CSLE dose of 100 mg/kgbw was not significantly different from orlistat, which was in line with its total cholesterol level and triglyceride (p < 0.05). The binding affinity of selected compounds from Calophyllum soulattri (friedelin, caloxanthone B, macluraxanthone, stigmasterol, trapezifolixanthone, dombakinaxanthone, and brasixanthone B) to FTO are –8.27, –9.74, –8.48, –9.34, –8.85, –8.68 and –9.39 kcal/mol, which are better than that of orlistat at –4.80 kcal/mol. The molecular dynamics simulation showed that the interaction between Caloxanthone B compounds and obesity receptors was relatively stable. Lipinski’s rule determined the absorption percentage of all compounds above 90% with good drug-likeness. The results showed the potential of CSLE as an antiobesity drug candidate.
In Vivo Imaging and Kinetic Modeling of Novel Glycogen Synthase Kinase-3 Radiotracers [11C]OCM-44 and [18F]OCM-50 in Non-Human Primates
Authors: Smart Kelly , Zheng Ming-Qiang , Holden Daniel , Felchner Zachary , Zhang Li , Han Yanjiang , Ropchan Jim , Carson Richard E. , Vasdev Neil , Huang Yiyun
Published: January 2023

Glycogen synthase kinase 3 (GSK-3) is a potential therapeutic target for a range of neurodegenerative and psychiatric disorders. The goal of this work was to evaluate two leading GSK-3 positron emission tomography (PET) radioligands, [11C]OCM-44 and [18F]OCM-50, in non-human primates to assess their potential for clinical translation. A total of nine PET scans were performed with the two radiotracers using arterial blood sampling in adult rhesus macaques. Brain regional time-activity curves were extracted and fitted with one- and two-tissue compartment models using metabolite-corrected arterial input functions. Target selectivity was assessed after pre-administration of the GSK-3 inhibitor PF-04802367 (PF-367, 0.03–0.25 mg/kg). Both radiotracers showed good brain uptake and distribution throughout grey matter. [11C]OCM-44 had a free fraction in the plasma of 3% at baseline and was metabolized quickly. The [11C]OCM-44 volume of distribution (VT) values in the brain increased with time; VT values from models fitted to truncated 60-min scan data were 1.4–2.9 mL/cm3 across brain regions. The plasma free fraction was 0.6% for [18F]OCM-50 and VT values (120-min) were 0.39–0.87 mL/cm3 in grey matter regions. After correcting for plasma free fraction increases during blocking scans, reductions in regional VT indicated >80% target occupancy by 0.1 mg/kg of PF-367 for both radiotracers, supporting target selectivity in vivo. [11C]OCM-44 and [18F]OCM-50 warrant further evaluation as radioligands for imaging GSK-3 in the brain, though radio-metabolite accumulation may confound image analysis.
A Dietary Plant Extract Formulation Helps Reduce Flea Populations in Cats: A Double-Blind Randomized Study
Authors: Banuls Damien , Brun Jessie , Blua Jean-Louis , Cadiergues Marie Christine
Published: January 2023

There is a growing demand for natural products to be used to control fleas in pets. A prospective, double-blind, randomized, placebo-controlled study evaluated the efficacy of the biological plant-based food supplement Bioticks® (thyme, rosemary, lemon balm, fenugreek, wormwood, and lemongrass extracts) as a flea control product in naturally flea-infested cats with an indoor–outdoor lifestyle. Ten cats were used as placebo controls (group A). Ten other cats were fed the same daily diet but supplemented with Bioticks® (group B). Fleas were counted by combing at D0 and D0 + 14 days, then one, two, three, four, and five months after the start of this study. No flea treatment was administered, and no environmental changes were made for six months prior to the start and throughout this study. The product was well-tolerated. The mean flea population in group B progressively and steadily decreased to reach 3.3 ± 2.1 at month five. At the same time and under similar maintenance conditions, the average flea population in group A remained stable (14.3 ± 2.5) until the fifth month. The percentages of efficacy (Abbott formula) in group B compared to group A was 27%, 20%, 52%, 66%, and 77%, respectively, at one, two, three, four, and five months after the start of this study.
Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics
Authors: Kumar Rachna M. , Kumar Hitesh , Bhatt Tanvi , Jain Rupshee , Panchal Kanan , Chaurasiya Akash , Jain Vikas
Published: January 2023

Cancer is one of the major causes of mortality, globally. Cancerous cells invade normal cells and metastasize to distant sites with the help of the lymphatic system. There are several mechanisms involved in the development and progression of cancer. Several treatment strategies including the use of phytoconstituents have evolved and been practiced for better therapeutic outcomes against cancer. Fisetin is one such naturally derived flavone that offers numerous pharmacological benefits, i.e., antioxidant, anti-inflammatory, antiangiogenic, and anticancer properties. It inhibits the rapid growth, invasiveness, and metastasis of tumors by hindering the multiplication of cancer cells, and prompts apoptosis by avoiding cell division related to actuation of caspase-9 and caspase-8. However, its poor bioavailability associated with its extreme hydrophobicity hampers its clinical utility. The issues related to fisetin delivery can be addressed by adapting to the developmental aspects of nanomedicines, such as formulating it into lipid or polymer-based systems, including nanocochleates and liposomes. This review aims to provide in-depth information regarding fisetin as a potential candidate for anticancer therapy, its properties and various formulation strategies.
Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase
Authors: Wu I-Ting , Kuo Chan-Yen , Su Ching-Hui , Lan Yu-Hsuan , Hung Chin-Chuan
Published: January 2023

Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. Fluorescence substrate efflux assays, multidrug resistance 1 (MDR1) shift assays, P-gp ATPase activity assays, Western blotting, and docking simulation were performed. The potential of the test compounds for MDR reversal and the associated molecular mechanisms were investigated through cell viability assay, cell cycle analysis, apoptosis assay, and further determining the combination index. Results demonstrated that pinostrobin and tectochrysin were not the substrates of P-gp, nor did they affect the expression of this transporter. Both compounds noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp. Furthermore, they resensitized MDR cancer cells to chemotherapeutic drugs, such as vincristine, paclitaxel, and docetaxel; thus, they exhibited strong MDR reversal effects. Our findings indicate that pinostrobin and tectochrysin are effective P-gp inhibitors and promising candidates for resensitizing MDR cancer cells.
Design, Synthesis and Phenotypic Profiling of Simplified Gedatolisib Analogues
Authors: Costa Caroline Marques Xavier , Aparecida-Silva Cristiane , Gamba Luis Eduardo Reina , de Melo Thalita Neves , Barbosa Gisele , Moraes Junior Manoel Oliveira de , de Oliveira Victoria Regina Thomaz , de Amorim Carolinne Souza , Moraes João A. , Barreiro Eliezer Jesus , Lima Lídia Moreira
Published: January 2023

Targeted antitumour therapy has revolutionized the treatment of several types of tumours. Among the validated targets, phosphatidylinositol-3 kinase (PI3K) deserves to be highlighted. Several PI3K inhibitors have been developed for the treatment of cancer, including gedatolisib (4). This inhibitor was elected as a prototype and molecular modifications were planned to design a new series of simplified gedatolisib analogues (5a-f). The analogues were synthesised, and the comparative cytotoxic activity profile was studied in phenotypic models employing solid and nonadherent tumour cell lines. Compound 5f (LASSBio-2252) stood out as the most promising of the series, showing good aqueous solubility (42.38 μM (pH = 7.4); 39.33 μM (pH = 5.8)), good partition coefficient (cLogP = 2.96), cytotoxic activity on human leukemia cell lines (CCRF-CEM, K562 and MOLT-4) and an excellent metabolic stability profile in rat liver microsomes (t1/2 = 462 min; Clapp = 0.058 mL/min/g). The ability of 5f to exert its cytotoxic effect through modulation of the PI3K pathway was demonstrated by flow cytometry analysis in a comparative manner to gedatolisib.
Bacterial Cellulose-Based Materials as Dressings for Wound Healing
Authors: Horue Manuel , Silva Jhonatan Miguel , Berti Ignacio Rivero , Brandão Larissa Reis , Barud Hernane da Silva , Castro Guillermo R.
Published: January 2023

Bacterial cellulose (BC) is produced by several microorganisms as extracellular structures and can be modified by various physicochemical and biological strategies to produce different cellulosic formats. The main advantages of BC for biomedical applications can be summarized thus: easy moldability, purification, and scalability; high biocompatibility; and straightforward tailoring. The presence of a high amount of free hydroxyl residues, linked with water and nanoporous morphology, makes BC polymer an ideal candidate for wound healing. In this frame, acute and chronic wounds, associated with prevalent pathologies, were addressed to find adequate therapeutic strategies. Hence, the main characteristics of different BC structures—such as membranes and films, fibrous and spheroidal, nanocrystals and nanofibers, and different BC blends, as well as recent advances in BC composites with alginate, collagen, chitosan, silk sericin, and some miscellaneous blends—are reported in detail. Moreover, the development of novel antimicrobial BC and drug delivery systems are discussed.
CD13-Mediated Pegylated Carboxymethyl Chitosan-Capped Mesoporous Silica Nanoparticles for Enhancing the Therapeutic Efficacy of Hepatocellular Carcinoma
Authors: Liu Jinhu , Mu Weiwei , Gao Tong , Fang Yuxiao , Zhang Na , Liu Yongjun
Published: January 2023

Liver cancer, especially hepatocellular carcinoma, is an important cause of cancer-related death, and its incidence is increasing worldwide. Nano drug delivery systems have shown great promise in the treatment of cancers. In order to improve their therapeutic efficacy, it is very important to realize the high accumulation and effective release of drugs at the tumor site. In this manuscript, using doxorubicin (DOX) as a model drug, CD13-targeted mesoporous silica nanoparticles coated with NGR-peptide-modified pegylated carboxymethyl chitosan were constructed (DOX/MSN-CPN). DOX/MSN-CPN comprises a spherical shape with an obvious capping structure and a particle size of 125.01 ± 1.52 nm. With a decrease in pH, DOX/MSN-CPN showed responsive desorption from DOX/MSN-CPN and pH-responsive release of DOX was observed. Meanwhile, DOX/MSN-CPN could be efficiently absorbed through NGR-mediated internalization in vitro and could efficiently deliver DOX to tumor tissues with long accumulation times in vivo, suggesting good active targeting properties. Moreover, significant tumor inhibition has been observed in antitumor studies in vivo. This study provides a strategy of utilizing DOX/MSN-CPN as a nano-platform for drug delivery, which has superb therapeutic efficacy and safety for the treatment of hepatocellular carcinoma both in vivo and in vitro.
Characteristics of Environmental Klebsiella pneumoniae and Klebsiella oxytoca Bacteriophages and Their Therapeutic Applications
Authors: Weber-Dąbrowska Beata , Żaczek Maciej , Łobocka Małgorzata , Łusiak-Szelachowska Marzanna , Owczarek Barbara , Orwat Filip , Łodej Norbert , Skaradzińska Aneta , Łaczmański Łukasz , Martynowski Dariusz , Kaszowska Marta , Górski Andrzej
Published: January 2023

In recent years, multidrug-resistant (MDR) strains of Klebsiella pneumoniae have spread globally, being responsible for the occurrence and severity of nosocomial infections. The NDM-1-kp, VIM-1 carbapenemase-producing isolates as well as extended-spectrum beta lactamase-producing (ESBL) isolates along with Klebsiella oxytoca strains have become emerging pathogens. Due to the growing problem of antibiotic resistance, bacteriophage therapy may be a potential alternative to combat such multidrug-resistant Klebsiella strains. Here, we present the results of a long-term study on the isolation and biology of bacteriophages active against K. pneumoniae, as well as K. oxytoca strains. We evaluated biological properties, morphology, host specificity, lytic spectrum and sensitivity of these phages to chemical agents along with their life cycle parameters such as adsorption, latent period, and burst size. Phages designated by us, vB_KpnM-52N (Kpn52N) and VB_KpnM-53N (Kpn53N), demonstrated relatively broad lytic spectra among tested Klebsiella strains, high burst size, adsorption rates and stability, which makes them promising candidates for therapeutic purposes. We also examined selected Klebsiella phages from our historical collection. Notably, one phage isolated nearly 60 years ago was successfully used in purulent cerebrospinal meningitis in a new-born and has maintained lytic activity to this day. Genomic sequences of selected phages were determined and analyzed. The phages of the sequenced genomes belong to the Slopekvirus and Jiaodavirus genus, a group of phages related to T4 at the family level. They share several features of T4 making them suitable for antibacterial therapies: the obligatorily lytic lifestyle, a lack of homologs of known virulence or antibiotic resistance genes, and a battery of enzymes degrading host DNA at infection.
Adherence to Acromegaly Treatment and Analysis of the Related Factors—A Real-World Study in Bulgaria
Authors: Kamusheva Maria , Vandeva Silvia , Mitov Konstantin , Parvanova Alexina , Pesheva Marina , Ganov Nikolay , Rusenova Yanitsa , Marinov Lyubomir , Getova Violeta , Elenkova Atanaska , Petrova Guenka
Published: January 2023

The purpose was to assess the level of medication adherence (MA) and related factors among individuals with acromegaly. The secondary goal was to assess the quality of life of patients and whether and how it correlates with the level of adherence. A prospective one-year study was conducted among patients with acromegaly diagnosed, treated, and monitored in the reference center for rare endocrine diseases in Bulgaria in 2021. Clinical data, patients reported outcomes, and health economics data were collected to define the predictors of non-adherence to medicines. Medication adherence level was assessed through a free Morisky–Green 4-item questionnaire. A total of 179 patients with acromegaly were observed. Approximately 62% were female, 50% were between 41 and 60 years, and the mean age at diagnosis was 40.4 years. The response rate to the questionnaires was 53% (n = 95; mean age 53.5 years, 73% female and 26% male). Patients with high levels of MA reported higher median values for the 36-Item Short Form Health Survey (SF-36) in comparison with those with low levels: 65.5 vs. 48.5 (p = 0.017). Similar results for EQ-5D-3L (3-level EuroQol 5D version) values and the level of MA were found: 0.656 vs. 0.796 (p = 0.0123). A low level of adherence was revealed in 34.7% of the patients, with no difference among different age groups. A significant positive determinant for adherence was years lived with acromegaly (OR = 5.625, 95% CI 1.7401–18.1832, p = 0.0039), as shorter duration was related to higher odds for high level of adherence. The current study demonstrates the importance of MA assessment for patients with acromegaly in Bulgaria. The medication adherence to the prescribed therapy among the observed group of patients with acromegaly varied as the percentage of adherent patients was around 65%. Still, there are low-adherent patients, and the responsible factors should be further investigated.
Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses
Authors: Donkor Michael , Choe Jamie , Reid Danielle Marie , Quinn Byron , Pulse Mark , Ranjan Amalendu , Chaudhary Pankaj , Jones Harlan P.
Published: January 2023

Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)—nasal nano-vaccine—significantly reduced lung colonization by intravenous challenge of an extra-pulmonary tumor. Protection against tumor-cell lung colonization was linked to the induction of localized mucosal-associated effector and resident memory T cells as well as increased bronchiolar alveolar lavage-fluid IgA and serum IgG antibody responses. The nasal nano-vaccine-induced T-cell-mediated antitumor mucosal immune response was shown to increase tumor-specific production of IFN-γ and granzyme B by lung-derived CD8+ T cells. These findings demonstrate that our engineered nasal nano-vaccine has the potential to be used as a prophylactic approach prior to the seeding of tumors in the lungs, and thereby prevent overt lung metastases from existing extra pulmonary tumors.
Composition-Property Relationships of pH-Responsive Poly[(2-vinylpyridine)-co-(butyl methacrylate)] Copolymers for Reverse Enteric Coatings
Authors: Brewer Kyle , Blencowe Anton
Published: January 2023

The taste-masking of bitter-tasting active pharmaceutical ingredients is key to ensuring patient compliance when producing oral pharmaceutical formulations. This is generally achieved via the incorporation of pH-responsive, reverse enteric polymers, that prevent the dissolution of the formulation in the oral environment, but rapidly mediate it within the gastric environment. Reverse enteric polymers are commonly applied as coatings on oral dosage forms via spray atomisation (e.g., fluidised-bed spray coating), and generally exhibit the most efficient taste-masking. However, currently used reverse enteric coatings require high mass gains (% w/w) during coating to mediate taste-masking, and thereby exhibit delayed release within the gastric environment. Therefore, there remains a need for the development of new reverse enteric coatings, that can efficiently taste-mask at low mass gains and maintain rapid release characteristics within the gastric environment. Herein we report the synthesis and evaluation of a series of addition copolymers of 2-vinylpyridine and butyl methacrylate, methyl methacrylate and isobornyl methacrylate. The thermal, solubility, and water absorption properties of the copolymers were effectively tuned by altering the mol% fraction of the constitutive monomers. Based on their physical properties, selected copolymers were preliminarily evaluated for their compatibility with fluidised-bed spray coating, and effectiveness as taste-masking reverse enteric coatings. The copolymers poly[(2-vinylpyridine)-co-(butyl methacrylate)] (mol% ratio 40:60) and poly[(2-vinylpyridine)-co-(butyl methacrylate)-co-(methyl methacrylate)] (mol% ratio 40:50:10) were found to exhibit excellent taste-masking properties following fluidised-bed spray coating onto Suglets® sugar spheres. Suglets® bearing a film coating of either copolymer (5.2–6.5% w/w mass gain) were found to effectively impede the release of a model drug formulation for up to 72 h in a simulated salivary environment, and rapidly release it (<10 min) within a simulated gastric environment. The results demonstrated the potential of poly[(2-vinylpyridine)-co-(butyl methacrylate)] copolymers to form effectively taste-masked, reverse enteric dosage forms, and suggested that these copolymers may provide improved performance compared to currently available polymers.
Exosomes: The Role in Tumor Tolerance and the Potential Strategy for Tumor Therapy
Authors: Lv Yun , Du Xiaobo , Tang Wenqiang , Yang Qian , Gao Feng
Published: January 2023

Drug and radiotherapy resistance is the primary cause of treatment failure and poor prognosis in patients with tumors. Exosomes are extracellular vesicles loaded with substances such as nucleic acids, lipids, and proteins that transmit information between cells. Studies have found that exosomes are involved in tumor therapy resistance through drug efflux, promotion of drug resistance phenotypes, delivery of drug-resistance-related molecules, and regulation of anti-tumor immune responses. Based on their low immunogenicity and high biocompatibility, exosomes have been shown to reduce tumor therapy resistance by loading nucleic acids, proteins, and drugs inside xosomes or expressing tumor-specific antigens, target peptides, and monoclonal antibodies on their phospholipid bimolecular membranes. Consequently, future research on genetically engineered exosomes is expected to eliminate resistance to tumor treatment, improving the overall prognosis of patients with tumors.
Unveiling the Anti-Biofilm Property of Hydroxyapatite on Pseudomonas aeruginosa: Synthesis and Strategy
Authors: MubarakAli Davoodbasha , Arunachalam Kannappan , Lakshmanan Murugan , Badar Bazigha , Kim Jung-Wan , Lee Sang-Yul
Published: January 2023

Biofilm-related nosocomial infections may cause a wide range of life-threatening infections. In this regard, Pseudomonas aeruginosa biofilm is becoming a serious health burden due to its capability to develop resistance to natural and synthetic drugs. The utilization of nanoparticles that inhibit biofilm formation is one of the major strategies to control infections caused by biofilm-forming pathogens. Hydroxyapatite (HA) is a synthetic ceramic material having properties similar to natural bones. Herein, a co-precipitation method followed by microwave treatment was used to synthesize HA nanoparticles (HANPs). The resulting HANPs were characterized using X-ray diffraction and transmission electron microscopy. Then, their antibiofilm properties against P. aeruginosa ATCC 10145 were examined in vitro. The needle-shaped HANPs were 30 and 90 nm long in width and length, respectively. The synthesized HANPs inhibited the biofilm formation of P. aeruginosa ATCC 10145 in a concentration-dependent manner, which was validated by light and confocal laser scanning microscopy. Hence, this study demonstrated that HANPs could be used to control the biofilm-related infections of P. aeruginosa.
Application of Antiviral, Antioxidant and Antibacterial Glycyrrhiza glabra L., Trifolium pratense L. Extracts and Myristica fragrans Houtt. Essential Oil in Microcapsules
Authors: Kazlauskaite Jurga Andreja , Matulyte Inga , Marksa Mindaugas , Lelesius Raimundas , Pavilonis Alvydas , Bernatoniene Jurga
Published: January 2023

Viruses and bacteria can disrupt normal human functions; therefore, ways to use the beneficial properties of plants to promote health are constantly being researched. Plant materials that accumulate biologically active compounds can be used to create a new pharmaceutical form. This study aimed to investigate the biological activity of selected plant extracts and essential oil and to produce microcapsules. The main compounds in extracts and essential oil were determined using chromatographic methods, antioxidant activity was evaluated spectrophotometrically, antimicrobial activity was assessed by monitoring the growth of nine pathogens, and the antiviral effect on infected bird cells with coronavirus was evaluated. Trifolium pratense L. extract had the highest antioxidant (26.27 ± 0.31 and 638.55 ± 9.14 µg TE/g dw by the DPPH and ABTS methods, respectively) and antiviral activity (56 times decreased titre of virus). Liquorice extract expressed antibacterial activity against Gram-positive pathogens and the highest antioxidant activity using the FRAP method (675.71 ± 4.61 mg FS/g dw). Emulsion stability depended on excipients and their amount. Microcapsules with extracts and essential oil were 1.87 mm in diameter, and their diameter after swelling was increased more than two times in intestinal media, while less than 0.5 times in gastric media.
Generating High-Power, Frequency Tunable Coherent THz Pulse in an X-ray Free-Electron Laser for THz Pump and X-ray Probe Experiments
Authors: Kang Yin , Wang Zhen , Zhang Kaiqing , Feng Chao
Published: January 2023

Precisely synchronized X-ray and strong-field coherent terahertz (THz) enable the coherent THz excitation of many fundamental modes (THz pump) and the capturing of X-ray dynamic images of matter (X-ray probe), while the generation of such a light source is still a challenge for most existing techniques. In this paper, a novel X-ray free-electron laser based light source is proposed to produce a synchronized high-powered X-ray pulse and strong field, widely frequency tunable coherent THz pulse simultaneously. The technique adopts a frequency beating laser modulated electron bunch with a Giga-electron-volt beam energy to generate an X-ray pulse and a THz pulse sequentially by passing two individual undulator sections with different magnetic periods. Theoretical analysis and numerical simulations are carried out using the beam parameters of the Shanghai soft X-ray free-electron laser facility. The results show that the technique can generate synchronized 4 nm X-ray radiation with a peak power of 1.89 GW, and narrow-band THz radiation with a pulse energy of 1.62 mJ, and the frequency of THz radiation can be continuously tuned from 0.1 to 40 THz. The proposed technique can be used for THz pump and X-ray probe experiments for dynamic research on the interaction between THz pulse and matter at a femtosecond time scale.
Interactions of Atomistic Nitrogen Optical Centers during Bulk Femtosecond Laser Micromarking of Natural Diamond
Authors: Rimskaya Elena , Kriulina Galina , Kuzmin Evgeny , Kudryashov Sergey , Danilov Pavel , Kirichenko Alexey , Rodionov Nikolay , Khmelnitskii Roman , Chen Jiajun
Published: January 2023

Micromarks were formed in bulk natural IaAB-type diamond laser-inscribed by 515 nm 0.3 ps femtosecond laser pulses focused by a 0.25 NA micro-objective at variable pulse energies in sub-picosecond visible-range laser regimes. These micromarks were characterized at room temperature (25 °C) by stationary 3D confocal photoluminescence (PL) microspectroscopy at 405 nm and 532 nm excitation wavelengths. The acquired PL spectra exhibit the increasing pulse-energy-dependent yield in the range of 550–750 nm (NV0, NV− centers) at the expense of the simultaneous reciprocal reduction in the blue–green (490–570 nm, H-band centers) PL yield. The detailed analysis indicates low-energy intensity rise for H-band centers as an intermediate product of vacancy-mediated dissociation of B1 and B2 centers, with H4 centers converting to H3 and NV centers at higher pulse energies, while the laser exposure effect demonstrates the same trend. These results will help solve the problem of direct laser writing technology, which is associated with the writing of micromarks in bulk natural diamond, and promising three-dimensional micro-electrooptical and photonic devices in physics and electronics.
Correction: Asaba, K.; Miyamoto, T. System Level Requirement Analysis of Beam Alignment and Shaping for Optical Wireless Power Transmission System by Semi–Empirical Simulation. Photonics 2022, 9, 452
Authors: Asaba Kaoru , Miyamoto Tomoyuki
Published: January 2023

In the original publication [...]
Real-Time Chlorophyll-a Pigment Monitoring of Chlamydomonas reinhardtii in a Controlled Environment Using Pulsed LED Fluorescence LiDAR System
Authors: Cadondon Jumar G. , Vallar Edgar A. , Shiina Tatsuo , Galvez Maria Cecilia D.
Published: January 2023

The real-time chlorophyll-a pigment monitoring of C. reinhardtii is studied using our developed LED fluorescence light detection and ranging (LiDAR) system. It features a portable set-up that uses a pulsed LED module with an excitation wavelength of 385 nm. We were able to monitor the different growth phases of C. reinhardtii with specific cultivation parameters. The developed fluorescence LiDAR system showed the linear correlation of its chlorophyll-a signal with the optical density and EEM fluorescence measurements at 680 nm emission wavelength. Water quality and weather parameters were also measured, which explains the variation in the growth dynamics of C. reinhardtii during the sampling period. The results from the monitoring demonstrated a different technique that can be used in estimating algal biomass in the environment.
Cyanobacteria-Based Bioprocess for Cosmetic Products—Cyanobium sp. as a Novel Source of Bioactive Pigments
Authors: Pagels Fernando , Guedes A. Catarina , Vicente António A. , Vasconcelos Vitor
Published: January 2023

As a producer of pigments with known bioactive potential, cyanobacteria are a great source of active ingredients for cosmetics (i.e., carotenoids and phycobiliproteins). Multiple phases in the cyanobacteria-based bioprocess led to the obtention of these compounds. The marine Cyanobium sp. LEGE 06113 has been proposed as a promising source for pigments for cosmetic uses, and it has been optimized in the past few years in terms of production, extraction, and application of pigment extracts. This report aims at providing an overview of the cyanobacteria-based bioprocess, regarding optimization strategies, consolidating into a proposed bioprocess for this cyanobacterium. The optimization of Cyanobium sp. included strategies regarding its production (culture medium, light, temperature, pH and salinity) and extraction (successive solvent extraction and ohmic heating). After the optimization, the two pigment-rich extracts (carotenoids and phycobiliproteins) were assessed in terms of their cosmetic potential and compatibility as an ingredient. Finally, aiming a scale-up proposal, life cycle assessment (LCA) was used as tool for a sustainable process. Ultimately, the proposed process gives the possibility to obtain two stable cosmetic ingredients from the same biomass and applied as anti-agent agents, especially due to their high anti-hyaluronidase capacity. Moreover, there remain challenges and information regarding novel cosmetic ingredient regulations were also discussed.
Electron as a Tiny Mirror: Radiation from a Worldline with Asymptotic Inertia
Authors: Good Michael R. R. , Ong Yen Chin
Published: January 2023

We present a moving mirror analog of the electron, whose worldline possesses asymptotic constant velocity with corresponding Bogoliubov β coefficients that are consistent with finite total emitted energy. Furthermore, the quantum analog model is in agreement with the total energy obtained by integrating the classical Larmor power.
Heating and Cooling in Transversely Oscillating Coronal Loops Powered by Broadband, Multi-Directional Wave Drivers
Authors: Howson Thomas , De Moortel Ineke
Published: January 2023

Recent studies have identified the potential for coronal wave heating to balance radiative losses in a transversely oscillating low-density loop undergoing resonant absorption, phase mixing and the Kelvin–Helmholtz instability. This result relied on a continuous, resonant oscillatory driver acting on one of the loop footpoints and similar setups with non-resonant driving produce insufficient heating. Here, we consider broadband and multi-directional drivers with power in both resonant and non-resonant frequencies. Using three-dimensional magnetohydrodynamic simulations, we impose transverse, continuous velocity drivers at the footpoints of a coronal loop, which is dense in comparison to the background plasma. We include the effects of optically thin radiation and a uniform background heating term that maintains the temperature of the external plasma but is insufficient to balance energy losses within the loop. For both broadband and multi-directional drivers, we find that the energy dissipation rates are sufficient to balance the average energy losses throughout the simulation volume. Resonant components of the wave driver efficiently inject energy into the system and these frequencies dominate the energetics. Although the mean radiative losses are balanced, the loop core cools in all cases as the wave heating rates are locally insufficient, despite the relatively low density considered here.