The 2023 MDPI Annual Report has
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29 pages, 754 KiB  
Article
Calcium, Phosphate, and Vitamin D in Children and Adolescents with Chronic Diseases: A Cross-Sectional Study
by Marlene Fabiola Escobedo-Monge, Pilar Bahillo-Curieses, Joaquín Parodi-Román, María Antonieta Escobedo-Monge, Pedro Alonso-López and José Manuel Marugán-Miguelsanz
Nutrients 2024, 16(9), 1349; https://doi.org/10.3390/nu16091349 (registering DOI) - 29 Apr 2024
Abstract
Chronic diseases may affect the nutritional status of children and adolescents. Calcium (Ca), phosphorus (P), and vitamin D (Vit-D) are crucial nutrients for their growth and development. Proper diagnosis and treatment are critical components of personalized and precision medicine. Hence, we conducted a [...] Read more.
Chronic diseases may affect the nutritional status of children and adolescents. Calcium (Ca), phosphorus (P), and vitamin D (Vit-D) are crucial nutrients for their growth and development. Proper diagnosis and treatment are critical components of personalized and precision medicine. Hence, we conducted a cross-sectional and comparative study to evaluate Ca, P, and Vit-D levels in their non-skeletal functions and their association with health and nutritional biomarkers in children and adolescents with diverse chronic conditions. We performed anthropometric, body composition, clinical evaluation, biochemical analysis, and dietary survey methods. A total of 78 patients (1–19 years, 43 females, 42 children) took part in this study. Overall, 24, 30, and 24 participants were obese, undernourished, and eutrophic, respectively. Results found that 74% and 35% of individuals had deficient Vit-D and Ca intake, respectively. Most cases were normocalcemic. Results also found that 47% of the subjects had Vit-D deficiency (VDD), 37% were insufficient, and 37% had hypophosphatemia. Of the 46% and 31% of patients with VDD and insufficient levels, 19% and 11% were hypophosphatemic, respectively. Calcium, P, and Vit-D levels were associated with anthropometric parameters, body mass index, body composition, physical activity, diet, growth hormones, and the immune, liver, and kidney systems. These results show the coincident risk of altered Ca, P, and Vit-D metabolism in children and adolescents with chronic diseases. Full article
(This article belongs to the Special Issue Nutritional Status in Children and Adolescents with Chronic Diseases)
16 pages, 5827 KiB  
Article
Preparation and Performance Study of HTPB-g-(PNIPAM/PEG) Thermoresponsive Polymer Brush
by Pengzhi Bi, Xiuzhong Zhu, Li Tian, Jinbang Han, Wanbin Zhang and Tong Wang
Polymers 2024, 16(9), 1248; https://doi.org/10.3390/polym16091248 (registering DOI) - 29 Apr 2024
Abstract
In recent years, a great deal of work has been devoted to the development of thermoresponsive polymers that can be made into new types of smart materials. In this paper, a branched polymer, HTPB-g-(PNIPAM/PEG), with polyolefin chain segments as the backbone [...] Read more.
In recent years, a great deal of work has been devoted to the development of thermoresponsive polymers that can be made into new types of smart materials. In this paper, a branched polymer, HTPB-g-(PNIPAM/PEG), with polyolefin chain segments as the backbone and having polyethylene glycol (PEG) and poly(N-isopropylacrylamide) (PNIPAM) as side chains was synthesized by ATRP and click reactions using N3-HTPB-Br as the macroinitiator. This initiator was designed and synthesized using hydroxyl-terminated polybutadiene (HTPB) as the substrate. The temperature-responsive behavior of the branched polymer was investigated. The lower critical solution temperature (LCST) of the branched polymer was determined by ultraviolet and visible spectrophotometry (UV-vis) and was found to be 35.2 °C. The relationship between the diameter size of micelles and temperature was determined by dynamic light scattering (DLS). It was found that the diameter size changed at 36 °C, which was nearly consistent with the result obtained by UV-vis. The results of the study indicate that HTPB-g-(PNIPAM/PEG) is a temperature-responsive polymer. At room temperature, the polymer can self-assemble into composite micelles, with the main chain as the core and the branched chain as the shell. When the temperature was increased beyond LCST, the polyolefin main chain along with the PNIPAM branched chain assembled to form the nucleus, and the PEG branched chain constituted the shell. Full article
(This article belongs to the Special Issue Feature Papers in Smart and Functional Polymers)
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12 pages, 2350 KiB  
Article
Ketogenic Diet Protects from Experimental Colitis in a Mouse Model Regardless of Dietary Fat Source
by Lotta Luiskari, Jere Lindén, Markku Lehto, Hanne Salmenkari and Riitta Korpela
Nutrients 2024, 16(9), 1348; https://doi.org/10.3390/nu16091348 (registering DOI) - 29 Apr 2024
Abstract
While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets influences intestinal health. The objective of this study was to investigate how the source of dietary fat of [...] Read more.
While ketogenic diets (KDs) may have potential as adjunct treatments for gastrointestinal diseases, there is little knowledge on how the fat source of these diets influences intestinal health. The objective of this study was to investigate how the source of dietary fat of KD influences experimental colitis. We fed nine-week-old male C57BL/6J mice (n = 36) with a low-fat control diet or KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) for four weeks and then induced colitis with dextran sodium sulfate (DSS). To compare the diets, we analyzed macroscopic and histological changes in the colon, intestinal permeability to fluorescein isothiocyanate−dextran (FITC–dextran), and the colonic expression of tight junction proteins and inflammatory markers. While the effects were more pronounced with LA-KD, both KDs markedly alleviated DSS-induced histological lesions. LA-KD prevented inflammation-related weight loss and the shortening of the colon, as well as preserved Il1b and Tnf expression at a healthy level. Despite no significant between-group differences in permeability to FITC–dextran, LA-KD mitigated changes in tight junction protein expression. Thus, KDs may have preventive potential against intestinal inflammation, with the level of the effect being dependent on the dietary fat source. Full article
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18 pages, 1047 KiB  
Article
Expression and Localization Profiles of Tight Junction Proteins in Immune Cells Depend on Their Activation Status
by Lena Voges, Franziska Weiß, Ana-Teresa Branco, Michael Fromm and Susanne M. Krug
Int. J. Mol. Sci. 2024, 25(9), 4861; https://doi.org/10.3390/ijms25094861 (registering DOI) - 29 Apr 2024
Abstract
The ability of the immune system to combat pathogens relies on processes like antigen sampling by dendritic cells and macrophages migrating through endo- and epithelia or penetrating them with their dendrites. In addition, other immune cell subtypes also migrate through the epithelium after [...] Read more.
The ability of the immune system to combat pathogens relies on processes like antigen sampling by dendritic cells and macrophages migrating through endo- and epithelia or penetrating them with their dendrites. In addition, other immune cell subtypes also migrate through the epithelium after activation. For paracellular migration, interactions with tight junctions (TJs) are necessary, and previous studies reported TJ protein expression in several immune cells. Our investigation aimed to characterize, in more detail, the expression profiles of TJ proteins in different immune cells in both naïve and activated states. The mRNA expression analysis revealed distinct expression patterns for TJ proteins, with notable changes, mainly increases, upon activation. At the protein level, LSR appeared predominant, being constitutively present in naïve cell membranes, suggesting roles as a crucial interaction partner. Binding experiments suggested the presence of claudins in the membrane only after stimulation, and claudin-8 translocation to the membrane occurred after stimulation. Our findings suggest a dynamic TJ protein expression in immune cells, implicating diverse functions in response to stimulation, like interaction with TJ proteins or regulatory roles. While further analysis is needed to elucidate the precise roles of TJ proteins, our findings indicate important non-canonical functions of TJ proteins in immune response. Full article
(This article belongs to the Special Issue The Tight Junction and Its Proteins: From Structure to Pathologies)
14 pages, 1640 KiB  
Article
Structural and Dynamic Features of the Recognition of 8-oxoguanosine Paired with an 8-oxoG-clamp by Human 8-oxoguanine-DNA Glycosylase
by Maria V. Lukina, Polina V. Zhdanova and Vladimir V. Koval
Curr. Issues Mol. Biol. 2024, 46(5), 4119-4132; https://doi.org/10.3390/cimb46050253 (registering DOI) - 29 Apr 2024
Abstract
8-oxoguanine (oxoG) is formed in DNA by the action of reactive oxygen species. As a highly mutagenic and the most common oxidative DNA lesion, it is an important marker of oxidative stress. Human 8-oxoguanine-DNA glycosylase (OGG1) is responsible for its prompt removal in [...] Read more.
8-oxoguanine (oxoG) is formed in DNA by the action of reactive oxygen species. As a highly mutagenic and the most common oxidative DNA lesion, it is an important marker of oxidative stress. Human 8-oxoguanine-DNA glycosylase (OGG1) is responsible for its prompt removal in human cells. OGG1 is a bifunctional DNA glycosylase with N-glycosylase and AP lyase activities. Aspects of the detailed mechanism underlying the recognition of 8-oxoguanine among numerous intact bases and its subsequent interaction with the enzyme’s active site amino acid residues are still debated. The main objective of our work was to determine the effect (structural and thermodynamic) of introducing an oxoG-clamp in model DNA substrates on the process of 8-oxoG excision by OGG1. Towards that end, we used DNA duplexes modeling OGG1-specific lesions: 8-oxoguanine or an apurinic/apyrimidinic site with either cytidine or the oxoG-clamp in the complementary strand opposite to the lesion. It was revealed that there was neither hydrolysis of the N-glycosidic bond at oxoG nor cleavage of the sugar–phosphate backbone during the reaction between OGG1 and oxoG-clamp-containing duplexes. Possible structural reasons for the absence of OGG1 enzymatic activity were studied via the stopped-flow kinetic approach and molecular dynamics simulations. The base opposite the damage was found to have a critical effect on the formation of the enzyme–substrate complex and the initiation of DNA cleavage. The oxoG-clamp residue prevented the eversion of the oxoG base into the OGG1 active site pocket and impeded the correct convergence of the apurinic/apyrimidinic site of DNA and the attacking nucleophilic group of the enzyme. An obtained three-dimensional model of the OGG1 complex with DNA containing the oxoG-clamp, together with kinetic data, allowed us to clarify the role of the contact of amino acid residues with DNA in the formation of (and rearrangements in) the enzyme–substrate complex. Full article
(This article belongs to the Special Issue DNA Damage and Repair in Health and Diseases)
14 pages, 967 KiB  
Article
Temperature Effects on Expression Levels of hsp Genes in Eggs and Second-Stage Juveniles of Meloidogyne hapla Chitwood, 1949
by Łukasz Flis, Tadeusz Malewski and Renata Dobosz
Int. J. Mol. Sci. 2024, 25(9), 4867; https://doi.org/10.3390/ijms25094867 (registering DOI) - 29 Apr 2024
Abstract
Meloidogyne hapla is one of the most important nematode pathogens. It is a sedentary, biotrophic parasite of plants that overwinters in the soil or in diseased roots. The development of M. hapla is temperature dependent. Numerous studies have been performed on the effect [...] Read more.
Meloidogyne hapla is one of the most important nematode pathogens. It is a sedentary, biotrophic parasite of plants that overwinters in the soil or in diseased roots. The development of M. hapla is temperature dependent. Numerous studies have been performed on the effect of temperature on the development of M. hapla, but only a few of them analyzed the heat shock protein (hsp) genes. The aim of the study was to perform expression profiling of eight hsp genes (Mh-hsp90, Mh-hsp1, Mh-hsp4, Mh-hsp6, Mh-hsp60, Mh-dnj19, Mh-hsp43, and Mh-hsp12.2) at two development stages of M. hapla, i.e., in eggs and second-stage juveniles (J2). The eggs and J2 were incubated under cold stress (5 °C), heat stress (35 °C, 40 °C), and non-stress (10 °C, 20 °C, and 30 °C) conditions. Expression profiling was performed by qPCR. It was demonstrated that only two genes, Mh-hsp60 and Mh-dnj19, have been upregulated by heat and cold stress at both development stages. Heat stress upregulated the expression of more hsp genes than cold stress did. The level of upregulation of most hsp genes was more marked in J2 than in eggs. The obtained results suggest that the Mh-hsp90 and Mh-hsp1 genes can be used as bioindicators of environmental impacts on nematodes of the Meloidogyne genus. Full article
12 pages, 540 KiB  
Article
Clinical Features and Patient Outcomes in Infective Endocarditis with Surgical Indication: A Single-Centre Experience
by Fausto Pizzino, Umberto Paradossi, Giancarlo Trimarchi, Giovanni Benedetti, Federica Marchi, Sara Chiappino, Mattia Conti, Gianluca Di Bella, Michele Murzi, Silvia Di Sibio, Giovanni Concistrè, Giacomo Bianchi and Marco Solinas
J. Cardiovasc. Dev. Dis. 2024, 11(5), 138; https://doi.org/10.3390/jcdd11050138 (registering DOI) - 29 Apr 2024
Abstract
Background: Infective endocarditis (IE) is marked by a heightened risk of embolic events (EEs), uncontrolled infection, or heart failure (HF). Methods: Patients with IE and surgical indication were enrolled from October 2015 to December 2018. The primary endpoint consisted of a composite of [...] Read more.
Background: Infective endocarditis (IE) is marked by a heightened risk of embolic events (EEs), uncontrolled infection, or heart failure (HF). Methods: Patients with IE and surgical indication were enrolled from October 2015 to December 2018. The primary endpoint consisted of a composite of major adverse events (MAEs) including all-cause death, hospitalizations, and IE relapses. The secondary endpoint was all-cause death. Results: A total of 102 patients (66 ± 14 years) were enrolled: 50% with IE on prosthesis, 33% with IE-associated heart failure (IE-aHF), and 38.2% with EEs. IE-aHF and EEs were independently associated with MAEs (HR 1.9, 95% CI 1.1–3.4, p = 0.03 and HR 2.1, 95% CI 1.2–3.6, p = 0.01, respectively) and Kaplan–Meier survival curves confirmed a strong difference in MAE-free survival of patients with EEs and IE-aHF (p < 0.01 for both). IE-aHF (HR 4.3, 95% CI 1.4–13, p < 0.01), CRP at admission (HR 5.6, 95% CI 1.4–22.2, p = 0.01), LVEF (HR 0.9, 95% CI 0.9–1, p < 0.05), abscess (HR 3.5, 95% CI 1.2–10.6, p < 0.05), and prosthetic detachment (HR 4.6, 95% CI 1.5–14.1, p < 0.01) were independently associated with the all-cause death endpoint. Conclusions: IE-aHF and EEs were independently associated with MAEs. IE-aHF was also independently associated with the secondary endpoint. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
27 pages, 3244 KiB  
Article
Seamless Modeling of Direct and Indirect Aerosol Effects during April 2020 Wildfire Episode in Ukraine
by Mykhailo Savenets, Valeriia Rybchynska, Alexander Mahura, Roman Nuterman, Alexander Baklanov, Markku Kulmala and Tuukka Petäjä
Atmosphere 2024, 15(5), 550; https://doi.org/10.3390/atmos15050550 (registering DOI) - 29 Apr 2024
Abstract
Wildfires frequently occur in Ukraine during agricultural open-burning seasons in spring and autumn. High aerosol concentrations from fire emissions can significantly affect meteorological processes via direct and indirect aerosol effects. To study these impacts, we selected a severe wildfire episode from April 2020 [...] Read more.
Wildfires frequently occur in Ukraine during agricultural open-burning seasons in spring and autumn. High aerosol concentrations from fire emissions can significantly affect meteorological processes via direct and indirect aerosol effects. To study these impacts, we selected a severe wildfire episode from April 2020 in the Chornobyl Exclusion Zone (CEZ) and its surrounding area as a case study. We employed the Enviro-HIRLAM modeling system to simulate reference (REF) meteorological conditions, along with direct (DAE), indirect (IDAE), and combined (COMB) aerosol effects. In our simulations, black carbon (BC) and organic carbon (OC) comprised 70–80% of all aerosol mass in the region, represented in two layers of higher concentrations: one near the surface and the other 3–4 km above the surface. Our simulations showed that the inclusion of aerosol effects into the modeling framework led to colder (up to −3 °C) and drier (relative humidity drop up to −20%) conditions near the surface. We also observed localized changes in cloudiness, precipitation (mainly redistribution), and wind speed (up to ±4 m/s), particularly during the movement of atmospheric cold fronts. Larger uncertainties were observed in coarser model simulations when direct aerosol effects were considered. Quantifying the aerosol effects is crucial for predicting and promptly detecting changes that could exacerbate unfavorable weather conditions and wildfires. Such knowledge is essential for improving the effectiveness of emergency response measures. Full article
(This article belongs to the Section Aerosols)
16 pages, 1858 KiB  
Article
Evolutionary Adaptation of an RNA Bacteriophage to Repeated Freezing and Thawing Cycles
by Mara Laguna-Castro, Alicia Rodríguez-Moreno and Ester Lázaro
Int. J. Mol. Sci. 2024, 25(9), 4863; https://doi.org/10.3390/ijms25094863 (registering DOI) - 29 Apr 2024
Abstract
Bacteriophage fitness is determined by factors influencing both their replication within bacteria and their ability to maintain infectivity between infections. The latter becomes particularly crucial under adverse environmental conditions or when host density is low. In such scenarios, the damage experienced by viral [...] Read more.
Bacteriophage fitness is determined by factors influencing both their replication within bacteria and their ability to maintain infectivity between infections. The latter becomes particularly crucial under adverse environmental conditions or when host density is low. In such scenarios, the damage experienced by viral particles could lead to the loss of infectivity, which might be mitigated if the virus undergoes evolutionary optimization through replication. In this study, we conducted an evolution experiment involving bacteriophage Qβ, wherein it underwent 30 serial transfers, each involving a cycle of freezing and thawing followed by replication of the surviving viruses. Our findings show that Qβ was capable of enhancing its resistance to this selective pressure through various adaptive pathways that did not impair the virus replicative capacity. Notably, these adaptations predominantly involved mutations located within genes encoding capsid proteins. The adapted populations exhibited higher resistance levels than individual viruses isolated from them, and the latter surpassed those observed in single mutants generated via site-directed mutagenesis. This suggests potential interactions among mutants and mutations. In conclusion, our study highlights the significant role of extracellular selective pressures in driving the evolution of phages, influencing both the genetic composition of their populations and their phenotypic properties. Full article
(This article belongs to the Section Molecular Microbiology)
13 pages, 401 KiB  
Article
Exome Sequencing for the Diagnostics of Osteogenesis Imperfecta in Six Russian Patients
by Yulia S. Koshevaya, Mariia E. Turkunova, Anastasia O. Vechkasova, Elena A. Serebryakova, Maxim Yu. Donnikov, Svyatoslav I. Papanov, Alexander N. Chernov, Lev N. Kolbasin, Lyudmila V. Kovalenko, Andrey S. Glotov and Oleg S. Glotov
Curr. Issues Mol. Biol. 2024, 46(5), 4106-4118; https://doi.org/10.3390/cimb46050252 (registering DOI) - 29 Apr 2024
Abstract
Osteogenesis imperfecta (OI) is a group of inherited disorders of connective tissue that cause significant deformities and fragility in bones. Most cases of OI are associated with pathogenic variants in collagen type I genes and are characterized by pronounced polymorphisms in clinical manifestations [...] Read more.
Osteogenesis imperfecta (OI) is a group of inherited disorders of connective tissue that cause significant deformities and fragility in bones. Most cases of OI are associated with pathogenic variants in collagen type I genes and are characterized by pronounced polymorphisms in clinical manifestations and the absence of clear phenotype–genotype correlation. The objective of this study was to conduct a comprehensive molecular–genetic and clinical analysis to verify the diagnosis of OI in six Russian patients with genetic variants in the COL1A1 and COL1A2 genes. Clinical and laboratory data were obtained from six OI patients who were observed at the Medical Genetics Center in Saint Petersburg from 2016 to 2023. Next-generation sequencing on MGISEQ G400 (MGI, China) was used for DNA analysis. The GATK bioinformatic software (version 4.5.0.0) was used for variant calling and hard filtering. Genetic variants were verified by the direct automatic sequencing of PCR products using the ABI 3500X sequencer. We identified six genetic variants, as follows pathogenic c.3505G>A (p. Gly1169Ser), c.769G>A (p.Gly257Arg), VUS c.4123G>A (p.Ala1375Thr), and c.4114A>T (p.Asn1372Tyr) in COL1A1; and likely pathogenic c.2035G>A (p.Gly679Ser) and c.739-2A>T in COL1A2. In addition, clinical cases are presented due to the presence of the c.4114A>T variant in the COL1A2 gene. Molecular genetics is essential for determining different OI types due to the high similarity across various types of the disease and the failure of unambiguous diagnosis based on clinical manifestations alone. Considering the variable approaches to OI classification, an integrated strategy is required for optimal patient management. Full article
(This article belongs to the Collection Bioinformatics Approaches to Biomedicine)
16 pages, 1274 KiB  
Article
The Genetic Landscape of Antimicrobial Resistance Genes in Enterococcus cecorum Broiler Isolates
by Yue Huang, Filip Boyen, Gunther Antonissen, Nick Vereecke and Filip Van Immerseel
Antibiotics 2024, 13(5), 409; https://doi.org/10.3390/antibiotics13050409 (registering DOI) - 29 Apr 2024
Abstract
Enterococcus cecorum is associated with bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Prophylactic treatment with antimicrobials is common in the poultry industry, and, in the case of outbreaks, antimicrobial treatment is needed. In this study, the minimum inhibitory concentrations (MICs) and epidemiological cutoff [...] Read more.
Enterococcus cecorum is associated with bacterial chondronecrosis with osteomyelitis (BCO) in broilers. Prophylactic treatment with antimicrobials is common in the poultry industry, and, in the case of outbreaks, antimicrobial treatment is needed. In this study, the minimum inhibitory concentrations (MICs) and epidemiological cutoff (ECOFF) values (COWT) for ten antimicrobials were determined in a collection of E. cecorum strains. Whole-genome sequencing data were analyzed for a selection of these E. cecorum strains to identify resistance determinants involved in the observed phenotypes. Wild-type and non-wild-type isolates were observed for the investigated antimicrobial agents. Several antimicrobial resistance genes (ARGs) were detected in the isolates, linking phenotypes with genotypes for the resistance to vancomycin, tetracycline, lincomycin, spectinomycin, and tylosin. These detected resistance genes were located on mobile genetic elements (MGEs). Point mutations were found in isolates with a non-wild-type phenotype for enrofloxacin and ampicillin/ceftiofur. Isolates showing non-wild-type phenotypes for enrofloxacin had point mutations within the GyrA, GyrB, and ParC proteins, while five amino acid changes in penicillin-binding proteins (PBP2x superfamily) were observed in non-wild-type phenotypes for the tested β-lactam antimicrobials. This study is one of the first that describes the genetic landscape of ARGs within MGEs in E. cecorum, in association with phenotypical resistance determination. Full article
(This article belongs to the Special Issue Antibiotics Resistance in Animals and the Environment)
29 pages, 1863 KiB  
Article
Distinctive Nucleic Acid Recognition by Lysine-Embedded Phenanthridine Peptides
by Josipa Matić, Patryciusz Piotrowski, Lucija Vrban, Renata Kobetić, Robert Vianello, Ivona Jurić, Ivana Fabijanić, Margareta Pernar Kovač, Anamaria Brozovic, Ivo Piantanida, Carsten Schmuck and Marijana Radić Stojković
Int. J. Mol. Sci. 2024, 25(9), 4866; https://doi.org/10.3390/ijms25094866 (registering DOI) - 29 Apr 2024
Abstract
Three new phenanthridine peptide derivatives (19, 22, and 23) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions [...] Read more.
Three new phenanthridine peptide derivatives (19, 22, and 23) were synthesized to explore their potential as spectrophotometric probes for DNA and RNA. UV/Vis and circular dichroism (CD) spectra, mass spectroscopy, and computational analysis confirmed the presence of intramolecular interactions in all three compounds. Computational analysis revealed that compounds alternate between bent and open conformations, highlighting the latter’s crucial influence on successful polynucleotide recognition. Substituting one glycine with lysine in two regioisomers (22, 23) resulted in stronger binding interactions with DNA and RNA than for a compound containing two glycines (19), thus emphasizing the importance of lysine. The regioisomer with lysine closer to the phenanthridine ring (23) exhibited a dual and selective fluorimetric response with non-alternating AT and ATT polynucleotides and induction of triplex formation from the AT duplex. The best binding constant (K) with a value of 2.5 × 107 M−1 was obtained for the interaction with AT and ATT polynucleotides. Furthermore, apart from distinguishing between different types of ds-DNA and ds-RNA, the same compound could recognize GC-rich DNA through distinct induced CD signals. Full article
(This article belongs to the Special Issue Computational, Structural and Spectroscopic Studies of Macromolecules)
15 pages, 711 KiB  
Article
Effect of Peanut Butter Intake on Sleep Health in Firefighters: A Randomized Controlled Trial
by Tiffany J. Oberther, Andrew R. Moore, Austin A. Kohler, David H. Shuler, Nicole Peritore and Angelia M. Holland-Winkler
Int. J. Environ. Res. Public Health 2024, 21(5), 571; https://doi.org/10.3390/ijerph21050571 (registering DOI) - 29 Apr 2024
Abstract
Sleep is often impaired in firefighters due to the psychologically and physiologically intense nature of their work and working shift schedules. Peanut butter is affordable and a substantial source of monounsaturated fatty acids, which may aid sleep health. Thus, this study sought to [...] Read more.
Sleep is often impaired in firefighters due to the psychologically and physiologically intense nature of their work and working shift schedules. Peanut butter is affordable and a substantial source of monounsaturated fatty acids, which may aid sleep health. Thus, this study sought to determine if a daily serving of peanut butter consumed before bedtime for seven weeks altered sleep quality and quantity among full-time firefighters. Forty firefighters (peanut butter group = 20; control group = 20) participated in this eight-week randomized controlled trial. All participants completed a subjective questionnaire on mood, focus, and alertness twice daily and wore an Actigraph wristwatch to measure sleep variables, including latency, efficiency, time in bed, time asleep, wake after sleep onset, number of awakenings, and time spent awake. After a baseline week, the peanut butter group consumed two tablespoons of peanut butter two hours prior to bedtime for seven weeks. Compared to the control group, the peanut butter group did not demonstrate significant changes (p > 0.05) in sleep measures or subjective feelings of mood, focus, or alertness after consuming peanut butter for seven weeks. Therefore, peanut butter as a source of peanuts did not alter sleep quality or quantity in this group of firefighters. ClinicalTrials.gov NCT06364202. Full article
11 pages, 1208 KiB  
Article
Evaluating Agility in Pre-Adolescent Basketball: A Comparative Analysis of CODAT, IAT, and RAT
by Gökhan Deliceoğlu, Okan İbiş and Erkan Tortu
Appl. Sci. 2024, 14(9), 3815; https://doi.org/10.3390/app14093815 (registering DOI) - 29 Apr 2024
Abstract
Background: In basketball, agility is essential, characterized by the ability to change direction swiftly and accelerate. Traditional tests like the Illinois Agility Test (IAT) and the Reactive Agility Test (RAT) may not fully capture the agility demands specific to basketball. Purpose: This study [...] Read more.
Background: In basketball, agility is essential, characterized by the ability to change direction swiftly and accelerate. Traditional tests like the Illinois Agility Test (IAT) and the Reactive Agility Test (RAT) may not fully capture the agility demands specific to basketball. Purpose: This study aimed to introduce the Change of Direction and Acceleration Test (CODAT), designed specifically for young basketball players. It evaluates CODAT’s effectiveness by comparing it with IAT and RAT through comprehensive analysis. Methods: We assessed 87 pre-adolescent male basketball players, aged 9 to 13 years, with an average biological age of 11.2 years and an average estimated Peak Height Velocity (PHV) of 12.5 ± 0.5 years, using CODAT, IAT, and RAT. We employed regression analysis and the Bland–Altman method to determine CODAT’s reliability and validity. Results: The findings indicate that CODAT offers superior reliability and validity in measuring basketball-specific agility. Consistent scores highlight its potential as an effective tool for agility assessment in basketball training and talent identification. Conclusions: CODAT represents a significant advancement in agility assessment for young basketball players, advocating for its integration into sports science practices to better address the specialized demands of basketball agility. Full article
(This article belongs to the Special Issue Advances in Sports, Exercise and Health)
14 pages, 425 KiB  
Review
Therapeutic Implications of Phenolic Acids for Ameliorating Inflammatory Bowel Disease
by Yanan Lu and Xue Han
Nutrients 2024, 16(9), 1347; https://doi.org/10.3390/nu16091347 (registering DOI) - 29 Apr 2024
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder, and its complex etiology makes prevention and treatment challenging. Research on new drugs and treatment strategies is currently a focal point. Phenolic acids are widely present in plant-based diets and have demonstrated the [...] Read more.
Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder, and its complex etiology makes prevention and treatment challenging. Research on new drugs and treatment strategies is currently a focal point. Phenolic acids are widely present in plant-based diets and have demonstrated the potential to alleviate colitis due to their powerful antioxidant and anti-inflammatory properties. In this review, we provide an overview of the structures and main dietary sources of phenolic acids, encompassing benzoic acid and cinnamic acid. Additionally, we explore the potential of phenolic acids as a nutritional therapy for preventing and treating IBD. In animal and cell experiments, phenolic acids effectively alleviate IBD induced by drug exposure or genetic defects. The mechanisms include improving intestinal mucosal barrier function, reducing oxidative stress, inhibiting excessive activation of the immune response, and regulating the balance of the intestinal microbiota. Our observation points towards the need for additional basic and clinical investigations on phenolic acids and their derivatives as potential novel therapeutic agents for IBD. Full article
(This article belongs to the Section Nutrition and Metabolism)
13 pages, 432 KiB  
Article
ALDRESS: A Retrospective Pilot Study to Develop a Pharmacological Causality Algorithm for Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
by Stefan Stewart, Arturo Gómez López de las Huertas, María Jiménez-González, Antonio J. Carcas, Alberto M. Borobia and Elena Ramírez
J. Clin. Med. 2024, 13(9), 2622; https://doi.org/10.3390/jcm13092622 (registering DOI) - 29 Apr 2024
Abstract
Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe form of drug hypersensitivity reaction characterized by significant morbidity, mortality, and long-term sequelae, coupled with limited therapeutic avenues. Accurate identification of the causative drug(s) is paramount for acute management, [...] Read more.
Background: The drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome represents a severe form of drug hypersensitivity reaction characterized by significant morbidity, mortality, and long-term sequelae, coupled with limited therapeutic avenues. Accurate identification of the causative drug(s) is paramount for acute management, exploration of safe therapeutic alternatives, and prevention of future occurrences. However, the absence of a standardized diagnostic test and a specific causality algorithm tailored to DRESS poses a significant challenge in its clinical management. Methods: We conducted a retrospective case–control study involving 37 DRESS patients to validate a novel causality algorithm, the ALDRESS, designed explicitly for this syndrome, comparing it against the current standard algorithm, SEFV. Results: The ALDRESS algorithm showcased superior performance, exhibiting an 85.7% sensitivity and 93% specificity with comparable negative predictive values (80.6% vs. 97%). Notably, the ALDRESS algorithm yielded a substantially higher positive predictive value (75%) compared to SEFV (51.40%), achieving an overall accuracy rate of 92%. Conclusions: Our findings underscore the efficacy of the ALDRESS algorithm in accurately attributing causality to drugs implicated in DRESS syndrome. However, further validation studies involving larger, diverse cohorts are warranted to consolidate its clinical utility and broaden its applicability. This study lays the groundwork for a refined causality assessment tool, promising advancements in the diagnosis and management of DRESS syndrome. Full article
(This article belongs to the Section Pharmacology)
21 pages, 1869 KiB  
Article
Neuroreceptor Inhibition by Clozapine Triggers Mitohormesis and Metabolic Reprogramming in Human Blood Cells
by Karin Fehsel, Marie-Luise Bouvier, Loredana Capobianco, Paola Lunetti, Bianca Klein, Marko Oldiges, Marc Majora and Stefan Löffler
Cells 2024, 13(9), 762; https://doi.org/10.3390/cells13090762 (registering DOI) - 29 Apr 2024
Abstract
The antipsychotic drug clozapine demonstrates superior efficacy in treatment-resistant schizophrenia, but its intracellular mode of action is not completely understood. Here, we analysed the effects of clozapine (2.5–20 µM) on metabolic fluxes, cell respiration, and intracellular ATP in human HL60 cells. Some results [...] Read more.
The antipsychotic drug clozapine demonstrates superior efficacy in treatment-resistant schizophrenia, but its intracellular mode of action is not completely understood. Here, we analysed the effects of clozapine (2.5–20 µM) on metabolic fluxes, cell respiration, and intracellular ATP in human HL60 cells. Some results were confirmed in leukocytes of clozapine-treated patients. Neuroreceptor inhibition under clozapine reduced Akt activation with decreased glucose uptake, thereby inducing ER stress and the unfolded protein response (UPR). Metabolic profiling by liquid-chromatography/mass-spectrometry revealed downregulation of glycolysis and the pentose phosphate pathway, thereby saving glucose to keep the electron transport chain working. Mitochondrial respiration was dampened by upregulation of the F0F1-ATPase inhibitory factor 1 (IF1) leading to 30–40% lower oxygen consumption in HL60 cells. Blocking IF1 expression by cotreatment with epigallocatechin-3-gallate (EGCG) increased apoptosis of HL60 cells. Upregulation of the mitochondrial citrate carrier shifted excess citrate to the cytosol for use in lipogenesis and for storage as triacylglycerol in lipid droplets (LDs). Accordingly, clozapine-treated HL60 cells and leukocytes from clozapine-treated patients contain more LDs than untreated cells. Since mitochondrial disturbances are described in the pathophysiology of schizophrenia, clozapine-induced mitohormesis is an excellent way to escape energy deficits and improve cell survival. Full article
(This article belongs to the Section Cellular Metabolism)
25 pages, 780 KiB  
Review
CNS Resident Innate Immune Cells: Guardians of CNS Homeostasis
by Luca Muzio and Jessica Perego
Int. J. Mol. Sci. 2024, 25(9), 4865; https://doi.org/10.3390/ijms25094865 (registering DOI) - 29 Apr 2024
Abstract
 Although the CNS has been considered for a long time an immune-privileged organ, it is now well known that both the parenchyma and non-parenchymal tissue (meninges, perivascular space, and choroid plexus) are richly populated in resident immune cells. The advent of more [...] Read more.
 Although the CNS has been considered for a long time an immune-privileged organ, it is now well known that both the parenchyma and non-parenchymal tissue (meninges, perivascular space, and choroid plexus) are richly populated in resident immune cells. The advent of more powerful tools for multiplex immunophenotyping, such as single-cell RNA sequencing technique and upscale multiparametric flow and mass spectrometry, helped in discriminating between resident and infiltrating cells and, above all, the different spectrum of phenotypes distinguishing border-associated macrophages. Here, we focus our attention on resident innate immune players and their primary role in both CNS homeostasis and pathological neuroinflammation and neurodegeneration, two key interconnected aspects of the immunopathology of multiple sclerosis.  Full article
(This article belongs to the Special Issue Molecular Mechanism in Multiple Sclerosis and Related Disorders 2.0)
18 pages, 3090 KiB  
Article
Statistical Reliability Assessment with Generalized Intuitionistic Fuzzy Burr XII Distribution
by Abdul Kalam, Weihu Cheng, Dionisis Stefanatos and Sayed Kifayat Shah
Processes 2024, 12(5), 915; https://doi.org/10.3390/pr12050915 (registering DOI) - 29 Apr 2024
Abstract
Intuitionistic fuzzy sets provide a viable framework for modelling lifetime distribution characteristics, particularly in scenarios with measurement imprecision. This is accomplished by utilizing membership and non-membership degrees to accurately express the complexities of data uncertainty. Nonetheless, the complexities of some cases necessitate a [...] Read more.
Intuitionistic fuzzy sets provide a viable framework for modelling lifetime distribution characteristics, particularly in scenarios with measurement imprecision. This is accomplished by utilizing membership and non-membership degrees to accurately express the complexities of data uncertainty. Nonetheless, the complexities of some cases necessitate a more advanced approach of imprecise data, motivating the use of generalized intuitionistic fuzzy sets (GenIFSs). The use of GenIFSs represents a flexible modeling strategy that is characterized by the careful incorporation of an extra level of hesitancy, which effectively clarifies the underlying ambiguity and uncertainty present in reliability evaluations. The study employs a methodology based on generalized intuitionistic fuzzy distributions to thoroughly examine the uncertainty related to the parameters and reliability characteristics present in the Burr XII distribution. The goal is to provide a more accurate evaluation of reliability measurements by addressing the inherent ambiguity in the distribution’s shape parameter. Various reliability measurements, such as reliability, hazard rate, and conditional reliability functions, are derived for the Burr XII distribution. This extensive analysis is carried out within the context of the generalized intuitionistic fuzzy sets paradigm, improving the understanding of the Burr XII distribution’s reliability measurements and providing important insights into its performance for the study of various types of systems. To facilitate understanding and point to practical application, the findings are shown graphically and contrasted across various cut-set values using a valuable numerical example. Full article
(This article belongs to the Section Process Control and Monitoring)
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20 pages, 524 KiB  
Article
Extending Undirected Graph Techniques to Directed Graphs via Category Theory
by Sebastian Pardo-Guerra, Vivek Kurien George, Vikash Morar, Joshua Roldan and Gabriel Alex Silva
Mathematics 2024, 12(9), 1357; https://doi.org/10.3390/math12091357 (registering DOI) - 29 Apr 2024
Abstract
We use Category Theory to construct a `bridge’ relating directed graphs with undirected graphs, such that the notion of direction is preserved. Specifically, we provide an isomorphism between the category of simple directed graphs and a category we call `prime graphs category’; this [...] Read more.
We use Category Theory to construct a `bridge’ relating directed graphs with undirected graphs, such that the notion of direction is preserved. Specifically, we provide an isomorphism between the category of simple directed graphs and a category we call `prime graphs category’; this has as objects labeled undirected bipartite graphs (which we call prime graphs), and as morphisms undirected graph morphisms that preserve the labeling (which we call prime graph morphisms). This theoretical bridge allows us to extend undirected graph techniques to directed graphs by converting the directed graphs into prime graphs. To give a proof of concept, we show that our construction preserves topological features when applied to the problems of network alignment and spectral graph clustering. Full article
14 pages, 2007 KiB  
Article
Construction of Cultivated Land Ecological Network Based on Supply and Demand of Ecosystem Services and MCR Model: A Case Study of Shandong Province, China
by Yifan Xu, Yuepeng Liu, Qian Sun and Wei Qi
Sustainability 2024, 16(9), 3745; https://doi.org/10.3390/su16093745 (registering DOI) - 29 Apr 2024
Abstract
The research on the ecological protection of cultivated land has gradually become a focus and frontier of cultivated land protection. Constructing an ecological network of a cultivated land system is important to improve the effect of cultivated land ecological protection. In this study, [...] Read more.
The research on the ecological protection of cultivated land has gradually become a focus and frontier of cultivated land protection. Constructing an ecological network of a cultivated land system is important to improve the effect of cultivated land ecological protection. In this study, the supply-demand ratio of five ecosystem services was calculated from 2000 to 2020 in Shandong Province, a major grain-producing area in China. The morphological spatial pattern analysis (MSPA) model was used to construct the minimum cumulative resistance (MCR) model. The conclusions of the study are as follows: (1) the areas with a higher supply and demand ratio of various ecosystem services of cultivated land in Shandong Province are distributed in southern and southwestern areas. (2) The ecological source of cultivated land in Shandong Province has decreased by about 7000 km2 from 2000 to 2020, and the fragmentation trend is obvious. (3) The total length of the ecological corridors is 798.5 km2. The majority of these corridors are located in central and southern Shandong. The ideas and conclusions of this study are important for the formulation of ecological protection policies for regional cultivated land systems. Full article
13 pages, 538 KiB  
Review
Prevalence of and Contributors to Food Insecurity among College Athletes: A Scoping Review
by Jamie Pacenta, Brooke E. Starkoff, Elizabeth K. Lenz and Amanda Shearer
Nutrients 2024, 16(9), 1346; https://doi.org/10.3390/nu16091346 (registering DOI) - 29 Apr 2024
Abstract
Given the financial demands of attending college, the transition to new living situations, abrupt changes in social support, and overall lifestyle adjustments, college students are at an increased risk of food insecurity (FI) compared to the general population. Collegiate athletes experience an even [...] Read more.
Given the financial demands of attending college, the transition to new living situations, abrupt changes in social support, and overall lifestyle adjustments, college students are at an increased risk of food insecurity (FI) compared to the general population. Collegiate athletes experience an even greater risk of FI as a result of greater time commitments and energy demands associated with their sports. This heightened vulnerability poses a tremendous threat to student-athletes’ academic and athletic achievements. This study aims to address the prevalence and primary determinants of FI among collegiate athletes while providing potential solutions to navigate and alleviate the effects of diminished food security among this demographic. To address these aims, a total of 18 articles were selected from both peer-reviewed and gray literature. The U.S. Household Food Security Survey Module (US-HFSSM) survey tools were predominantly utilized across universities throughout the United States to gather data on FI. Student-athletes reported experiencing FI across various regions of the United States, including universities in the northeastern states (n = 5), the southwest region (n = 3), the southeast region (n = 3), the northwest (n = 1), and the Midwest (n = 1). Overall, FI prevalence rates ranged from 9.9% to 65%, and the most significant contributors included limited financial resources, time management, meal plans, and housing location/amenities. These findings highlight a need for screening, education, and interventions to address FI among collegiate athletes. Full article
(This article belongs to the Special Issue Public Health, Nutritional Behavior and Nutritional Status)
14 pages, 785 KiB  
Article
Exploration of Genome-Wide Recombination Rate Variation Patterns at Different Scales in Pigs
by Zuoquan Chen, Meng Zhou, Yingchun Sun, Xi Tang, Zhiyan Zhang and Lusheng Huang
Animals 2024, 14(9), 1345; https://doi.org/10.3390/ani14091345 (registering DOI) - 29 Apr 2024
Abstract
Meiotic recombination is a prevalent process in eukaryotic sexual reproduction organisms that plays key roles in genetic diversity, breed selection, and species evolution. However, the recombination events differ across breeds and even within breeds. In this study, we initially computed large-scale population recombination [...] Read more.
Meiotic recombination is a prevalent process in eukaryotic sexual reproduction organisms that plays key roles in genetic diversity, breed selection, and species evolution. However, the recombination events differ across breeds and even within breeds. In this study, we initially computed large-scale population recombination rates of both sexes using approximately 52 K SNP genotypes in a total of 3279 pigs from four different Chinese and Western breeds. We then constructed a high-resolution historical recombination map using approximately 16 million SNPs from a sample of unrelated individuals. Comparative analysis of porcine recombination events from different breeds and at different resolutions revealed the following observations: Firstly, the 1Mb-scale pig recombination maps of the same sex are moderately conserved among different breeds, with the similarity of recombination events between Western pigs and Chinese indigenous pigs being lower than within their respective groups. Secondly, we identified 3861 recombination hotspots in the genome and observed medium- to high-level correlation between historical recombination rates (0.542~0.683) and estimates of meiotic recombination rates. Third, we observed that recombination hotspots are significantly far from the transcription start sites of pig genes, and the silico–predicted PRDM9 zinc finger domain DNA recognition motif is significantly enriched in the regions of recombination hotspots compared to recombination coldspots, highlighting the potential role of PRDM9 in regulating recombination hotspots in pigs. Our study analyzed the variation patterns of the pig recombination map at broad and fine scales, providing a valuable reference for genomic selection breeding and laying a crucial foundation for further understanding the molecular mechanisms of pig genome recombination. Full article

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