bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Different Dietary Ratios of Soluble Carbohydrate-to-Neutral Detergent Fiber on Rumen Barrier Function and Inflammation in Dumont Lambs
Authors: Li Shufang , Ma Tian , An Yawen , Zhang Yu , Yang Xiaodong , Gao Aiwu , Wang Hairong
Published: June 2024

Appropriate soluble carbohydrate (SCHO)-to-NDF ratios in the diet are essential for rumen health. The effects of different SCHO-to-NDF ratios (1.0, 1.5, and 2.0) on rumen barrier function and inflammation in Dumont lambs (n = 18, 6 replicates per treatment) was investigated. The SCHO:NDF ratio was altered by replacing the forage (Leynus chinensis) with corn grain. With an increase in the proportion of SCHO, the final body weight (FBW), average daily gain (ADG), soluble carbohydrate intake (SCHOI), and LPS level increased; and the neutral detergent fiber intake (NDFI), ruminal papillae height, papillae area, and pH decreased (p < 0.05, plin < 0.05). The medium CHO:NDF group had increased claudin-1 mRNA (p < 0.05, plin = 0.005, pquad = 0.003) and protein (p < 0.05, pquad < 0.001) levels; the high CHO:NDF group had increased occludin mRNA and protein (p < 0.05, plin = 0.001) levels. The level of the anti-inflammatory cytokine IL-10 was significantly greater in the medium CHO:NDF group than in the high CHO:NDF group (p < 0.05, pquad < 0.001). With an increase in the ratio of SCHO, the mRNA level and concentration of the proinflammatory cytokines IL-1β, IL-6, and TNF-α linearly increased (p < 0.05, plin < 0.05), and those in the high CHO:NDF group were significantly greater than those in the low CHO:NDF group. The levels of phosphorylated p65 (plin = 0.003), IκB-α (plin < 0.001), and JNK (plin = 0.001) increased linearly, and those in the high CHO:NDF group were significantly greater than those in the other two groups (p < 0.05). Therefore, when the SCHO-to-NDF ratio was increased to 1.5, the rumen epithelium was not affected, but when the ratio was increased to 2.0, NF-κB and MAPK were activated in the rumen epithelium, leading to impaired barrier function and inflammation. The suitable NFC:NDF ratio for the short-term fattening of Dumont lambs was found to be 1.50.
Prevalence of Gastrointestinal Parasites in Small Ruminant Farms in Southern Spain
Authors: Rufino-Moya Pablo José , Zafra Leva Rafael , Gonçalves Reis Lilian , Acosta García Isabel , Ruiz Di Genova Diego , Sánchez Gómez Almudena , García García Francisco , Martínez-Moreno Francisco J.
Published: June 2024

The primary population of small ruminants in Spain is concentrated in the southern region, a critical area for the country’s livestock production. Indirect economic losses can occur when this livestock is affected by gastrointestinal parasites. This study aimed to determine the prevalence of these parasites in small ruminant herds (159 sheep and 39 goats) through coprological analyses and conducted a survey on farmers’ management practices related to gastrointestinal parasite control. The survey results revealed some important aspects: monitoring through coprological analyses is not a common practice; veterinarians are not typically involved in deworming plans; anthelmintic treatment in adults is often applied twice a year in sheep and once a year in goats; and finally, drug rotation was higher in sheep farms. Coprological analyses showed Eimeria spp. as the most common parasitic infection, followed by Strongyles infection. Other parasites like Moniezia spp., Trichuris spp., and D. dendriticum were less important, although their prevalence was higher in sheep than goats. This constitutes the first report on the epidemiological status of gastrointestinal parasites in small ruminants in southern Spain. Based on the survey findings, the introduction of certain management measures on farms could potentially mitigate parasite infections.
Establishing a Reference Interval for Fibroblast Growth Factor (FGF)-23 in Cats
Authors: Lapsina Sandra , von Luckner Jennifer , Nagler Nicole , Müller Simon Franz , Müller Elisabeth , Schäfer Ingo
Published: June 2024

Fibroblast growth factor (FGF)-23 is a phosphaturic hormone. An association between increasing FGF-23 levels and progression of chronic kidney disease (CKD) was documented in cats, dogs, and humans. The information regarding reference intervals (RIs) of FGF-23 in cats is limited. We aimed to establish RIs in a large cohort of clinically healthy cats and to investigate correlations with sex and age. A total of 118 cats with unremarkable complete blood count and serum chemistry profile were included. Clinically sick cats, cats with concurrent diseases, suspicion of CKD, or receiving renal diets were excluded. FGF-23 concentrations were measured with the FGF-23 ELISA Kit. RIs were calculated using the reference interval advisor software 2.1 (Microsoft Excel). FGF-23 concentrations were correlated with sex and age. The RI for FGF-23 concentrations spanned 85.8 to 387.0 pg/mL (90% confidence interval: lower limit 40.5 to 103.9 pg/mL, upper limit: 354.6 to 425.0 pg/mL). No significant relationships (r2 = 0.044) were detected with age (p = 0.081) or sex (p = 0.191). Other studies of the same diagnostic assay calculated RIs of 56 to 700 pg/mL in 79 cats and <336 pg/mL in 108 cats, and in concordance with the present study, did not detect any correlation with sex or age.
Myocarditis in an FIP-Diseased Cat with FCoV M1058L Mutation: Clinical and Pathological Changes
Authors: Guarnieri Chiara , Bertola Luca , Ferrari Luca , Quintavalla Cecilia , Corradi Attilio , Di Lecce Rosanna
Published: June 2024

An 8-month-old intact male domestic shorthair cat was referred to the Emergency Service of the Veterinary Teaching Hospital (VTH) of the Department of Veterinary Science of the University of Parma (Italy) from the Parma municipal multi-cat shelter, during the winter season (January 2023), for lethargy, anorexia, hypothermia, and hypoglycemia. At the VTH, upon cardiologic examination, an increase in heart rate, under normal blood pressure conditions, was detected. Signalment, clinical history, basal metabolic panel (BMP), ultrasound investigations, and cytological findings were all consistent with a diagnosis of feline infectious peritonitis (FIP). FIP was confirmed in the effusive abdominal fluid by a molecular genetic test (real-time PCR for feline coronavirus RNA). The molecular genetic investigation also detected an FCoV S gene single-nucleotide mutation: biotype M1058L. At necropsy, an effusive collection was recorded in the abdomen, thoracic cavity, and pericardium sac. White parenchymal nodules, of about 1 mm diameter, were found on the surface and deep in the lungs, liver, kidneys, and heart. Histopathology revealed the typical FIP pyogranulomatous vasculitis and IHC confirmed the presence of the FIP virus (FIPV) antigen. The most relevant histopathological finding was the myocarditis/myocardial necrosis associated with the presence of the S gene-mutated FCoV (M1058L biotype). This is the first case of myocarditis in a cat positive for the FCoV/FIP M1058L biotype. Further studies are necessary to support the mutated FCoV M1058L biotype, as an uncommon, but possible, causative pathogen of myocarditis in FCoV/FIP-positive cats. Studies including several FCoV/FIP M1058L-positive cases could allow us to make a correlation with heart gross pathology, histopathology, and immunolocalization of the FCoV/FIP M1058L biotype in the myocardium. The investigation will potentially allow us to determine the effective tropism of the FCoV/FIP M1058L biotype for myocardiocytes or whether myocardiocyte lesions are evident in the presence of concomitant causes related to the patient, its poor condition, or external environmental distress such as cold season, and whether the aforementioned concomitant events are correlated.
Exploring the Impact of Antibiotics on Fever Recovery Time and Hospital Stays in Children with Viral Infections: Insights from Advanced Data Analysis
Authors: Al Qahtani Mohammed , AlFulayyih Saleh Fahad , Al Baridi Sarah Saleh , Alomar Sara Amer , Alshammari Ahmed Nawfal , Albuaijan Reem Jassim , Uddin Mohammed Shahab
Published: June 2024

Background: Antibiotic overuse in pediatric patients with upper respiratory tract infections (UR-TIs) raises concerns about antimicrobial resistance. This study examines the impact of antibiotics on hospital stay duration and fever resolution in pediatric patients diagnosed with viral infections via a multiplex polymerase chain reaction (PCR) respiratory panel. Methods: In the pediatric ward of Imam Abdulrahman Bin Faisal Hospital, a retrospective cohort analysis was conducted on pediatric patients with viral infections confirmed by nasopharyngeal aspirates from October 2016 to December 2021. Cohorts receiving antibiotics versus those not receiving them were balanced using the gradient boosting machine (GBM) technique for propensity score matching. Results: Among 238 patients, human rhinovirus/enterovirus (HRV/EV) was most common (44.5%), followed by respiratory syncytial virus (RSV) (18.1%). Co-infections occurred in 8.4% of cases. Antibiotic administration increased hospital length of stay (LOS) by an average of 2.19 days (p-value: 0.00). Diarrhea reduced LOS by 2.26 days, and higher albumin levels reduced LOS by 0.40 days. Fever and CRP levels had no significant effect on LOS. Time to recovery from fever showed no significant difference between antibiotic-free (Abx0) and antibiotic-received (Abx1) groups (p-value: 0.391), with a hazard ratio of 0.84 (CI: 0.57–1.2). Conclusions: Antibiotics did not expedite recovery but were associated with longer hospital stays in pediatric patients with acute viral respiratory infections. Clinicians should exercise caution in prescribing antibiotics to pediatric patients with confirmed viral infections, especially when non-critical.
Antimicrobial Stewardship: A Correct Management to Reduce Sepsis in NICU Settings
Authors: Notarbartolo Veronica , Badiane Bintu Ayla , Insinga Vincenzo , Giuffrè Mario
Published: June 2024

The discovery of antimicrobial drugs has led to a significant increase in survival from infections; however, they are very often prescribed and administered, even when their use is not necessary and appropriate. Newborns are particularly exposed to infections due to the poor effectiveness and the immaturity of their immune systems. For this reason, in Neonatal Intensive Care Units (NICUs), the use of antimicrobial drugs is often decisive and life-saving, and it must be started promptly to ensure its effectiveness in consideration of the possible rapid evolution of the infection towards sepsis. Nevertheless, the misuse of antibiotics in the neonatal period leads not only to an increase in the development and wide spreading of antimicrobial resistance (AMR) but it is also associated with various short-term (e.g., alterations of the microbiota) and long-term (e.g., increased risk of allergic disease and obesity) effects. It appears fundamental to use antibiotics only when strictly necessary; specific decision-making algorithms and electronic calculators can help limit the use of unnecessary antibiotic drugs. The aim of this narrative review is to summarize the right balance between the risks and benefits of antimicrobial therapy in NICUs; for this purpose, specific Antimicrobial Stewardship Programs (ASPs) in neonatal care and the creation of a specific antimicrobial stewardship team are requested.
A Novel Bacteriophage Infecting Multi-Drug- and Extended-Drug-Resistant Pseudomonas aeruginosa Strains
Authors: Santamaría-Corral Guillermo , Pagán Israel , Aguilera-Correa John Jairo , Esteban Jaime , García-Quintanilla Meritxell
Published: June 2024

The prevalence of carbapenem-resistant P. aeruginosa has dramatically increased over the last decade, and antibiotics alone are not enough to eradicate infections caused by this opportunistic pathogen. Phage therapy is a fresh treatment that can be administered under compassionate use, particularly against chronic cases. However, it is necessary to thoroughly characterize the virus before therapeutic application. Our work describes the discovery of the novel sequenced bacteriophage, vB_PaeP-F1Pa, containing an integrase, performs a phylogenetical analysis, describes its stability at a physiological pH and temperature, latent period (40 min), and burst size (394 ± 166 particles per bacterial cell), and demonstrates its ability to infect MDR and XDR P. aeruginosa strains. Moreover, this novel bacteriophage was able to inhibit the growth of bacteria inside preformed biofilms. The present study offers a road map to analyze essential areas for successful phage therapy against MDR and XDR P. aeruginosa infections, and shows that a phage containing an integrase is also able to show good in vitro results, indicating that it is very important to perform a genomic analysis before any clinical use, in order to prevent adverse effects in patients.
Antimicrobial Resistance of Listeria monocytogenes Strains Isolated in Food and Food-Processing Environments in Italy
Authors: Rippa Antonio , Bilei Stefano , Peruzy Maria Francesca , Marrocco Maria Grazia , Leggeri Patrizia , Bossù Teresa , Murru Nicoletta
Published: June 2024

Listeria monocytogenes, along with various other pathogenic bacteria, may show resistance against a broad spectrum of antibiotics. Evaluating the extent of resistance in harmful microorganisms like Listeria monocytogenes holds significant importance in crafting novel therapeutic strategies to mitigate or combat the rise of infections stemming from antibiotic-resistant bacteria. The present work aims to investigate the occurrence of antimicrobial resistance among Listeria monocytogenes strains in meat products (n = 173), seafood (n = 54), dairy products (n = 19), sauces (n = 2), confectionary products (n = 1), ready-to-eat rice dishes (n = 1), and food-processing environments (n = 19). A total of 269 Listeria monocytogenes strains belonging to eight different serovars were tested against 10 antimicrobials. In the classes of antibiotics, most of the strains were resistant antibiotics belonging to the family of β-lactams (92.94%). High proportions of L. monocytogenes isolates were resistant to oxacillin (88.48%), followed by fosfomycin (85.87%) and flumenique (78.44%). The lowest level of resistance was observed against gentamycin (1.49%). A total of 235 strains (n = 87.36%) showed a profile of multidrug resistance. In conclusion, a high occurrence of resistant and multidrug-resistant strains of Listeria monocytogenes was observed among the examined serotypes isolated from different food sources. This understanding enables the adoption of suitable measures to avert contamination and the spread of resistant bacteria via food.
Vitamin E Attenuates Red-Light-Mediated Vasodilation: The Benefits of a Mild Oxidative Stress
Authors: Keszler Agnes , Weihrauch Dorothee , Lindemer Brian , Broeckel Grant , Lohr Nicole L.
Published: June 2024

Red light (670 nm) energy controls vasodilation via the formation of a transferable endothelium-derived nitric oxide (NO)-precursor-containing substance, its intracellular traffic, and exocytosis. Here we investigated the underlying mechanistic effect of oxidative stress on light-mediated vasodilation by using pressure myography on dissected murine arteries and immunofluorescence on endothelial cells. Treatment with antioxidants Trolox and catalase decreased vessel dilation. In the presence of catalase, a lower number of exosomes were detected in the vessel bath. Light exposure resulted in increased cellular free radical levels. Mitochondrial reactive oxygen species were also more abundant but did not alter cellular ATP production. Red light enhanced the co-localization of late exosome marker CD63 and cellular S-nitrosoprotein to a greater extent than high glucose, suggesting that a mild oxidative stress favors the localization of NO precursor in late exosomes. Exocytosis regulating protein Rab11 was more abundant after irradiation. Our findings conclude that red-light-induced gentle oxidative stress facilitates the dilation of blood vessels, most likely through empowering the traffic of vasodilatory substances. Application of antioxidants disfavors this mechanism.
Osthole Suppresses Cell Growth of Prostate Cancer by Disrupting Redox Homeostasis, Mitochondrial Function, and Regulation of tiRNAHisGTG
Authors: Song Jisoo , Ham Jiyeon , Song Gwonhwa , Lim Whasun
Published: June 2024

Prostate cancer remains a significant global health concern, posing a substantial threat to men’s well-being. Despite advancements in treatment modalities, the progression of prostate cancer still presents challenges, warranting further exploration of novel therapeutic strategies. In this study, osthole, a natural coumarin derivative, inhibited cell viability in cancer cells but not in the normal prostate cell line. Moreover, osthole disrupted cell cycle progression. Furthermore, osthole reduces mitochondrial respiration with mitochondrial membrane potential (ΔΨm) depolarization and reactive oxygen species (ROS) generation, indicating mitochondrial dysfunction. In particular, osthole-induced ROS generation was reduced by N-acetyl-L-cysteine (NAC) in prostate cancer. In addition, using calcium inhibitors (2-APB and ruthenium red) and endoplasmic reticulum (ER) stress inhibitor (4-PBA), we confirmed that ER stress-induced calcium overload by osthole causes mitochondrial dysfunction. Moreover, we verified that the osthole-induced upregulation of tiRNAHisGTG expression is related to mechanisms that induce permeabilization of the mitochondrial membrane and calcium accumulation. Regarding intracellular signaling, osthole inactivated the PI3K and ERK pathways while activating the expression of the P38, JNK, ER stress, and autophagy-related proteins. In conclusion, the results suggest that osthole can be used as a therapeutic or adjuvant treatment for the management of prostate cancer.
The Interplay between Nitrosative Stress, Inflammation, and Antioxidant Defense in Patients with Lichen Planus
Authors: Tampa Mircea , Nicolae Ilinca , Ene Corina Daniela , Mitran Cristina Iulia , Mitran Madalina Irina , Matei Clara , Georgescu Simona Roxana
Published: June 2024

Background: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune reaction. However, other pathogenic pathways complement these mechanisms. Recent studies highlight the involvement of nitrosative stress in the pathogenesis of chronic inflammatory skin diseases. Current data on its role in the pathogenesis of LP are scarce. Methods: In this article, we investigated nitrosative stress in 40 cutaneous LP (CLP) patients compared to 40 healthy subjects using serum markers including nitrosative stress markers—direct nitrite, total nitrite, nitrate and symmetric dimethylarginine (SDMA), total antioxidant status (TAS), and hsCRP, a marker of inflammation, and analyzed the relationship between nitrosative stress, antioxidant defense, and inflammation to offer new insights into the role of the NO pathway in LP pathogenesis. Results: We identified significantly higher serum levels of direct nitrite, total nitrite, nitrate, SDMA and hsCRP, and significantly lower levels of TAS in CLP patients versus controls. There were significant negative correlations between the serum levels of TAS and significantl positive correlations between the serum levels of hsCRP and the analyzed nitrosative stress markers in patients with CLP. Conclusion: Our results indicate an increased level of nitrosative stress in LP patients that correlates with a pro-inflammatory status and altered antioxidant defense.
Empagliflozin Alleviates Carfilzomib-Induced Cardiotoxicity in Mice by Modulating Oxidative Stress, Inflammatory Response, Endoplasmic Reticulum Stress, and Autophagy
Authors: George Mina Y. , Dabour Mohamed S. , Rashad Eman , Zordoky Beshay N.
Published: June 2024

Carfilzomib is an irreversible proteasome inhibitor used for multiple myeloma patients. However, carfilzomib treatment is associated with cardiovascular complications. Empagliflozin, an Sodium Glucose Co-transporter 2 inhibitor (SGLT-2) inhibitor, is an oral antidiabetic drug with proven antioxidant and anti-inflammatory properties. The aim of the present study was to determine the cardioprotective effects of empagliflozin against carfilzomib-induced cardiotoxicity. C57BL/6 mice were randomly divided into four groups: control, empagliflozin, carfilzomib, and carfilzomib + empagliflozin. Empagliflozin prevented carfilzomib-induced cardiotoxicity by ameliorating histological alterations, CK-MB, and troponin-I. Moreover, it inhibited carfilzomib-induced oxidative damage and inflammation via its action on catalase activity, reduced glutathione levels and superoxide dismutase activity, and reduced nuclear factor-κB (p65) and cytokine levels. Mechanistically, empagliflozin abrogated endoplasmic reticulum stress induced by carfilzomib, as evidenced by the effect on the Glucose Regulated Protein-78 (GRP-78)/Activating Transcription Factor 6 (ATF6)/C/EBP homologous protein (CHOP) axis. Intriguingly, carfilzomib significantly induced autophagy, an effect that was further enhanced by empagliflozin, evidenced by increased LC3B and beclin-1 mRNA expression and reduced p62 expression. The effect of empagliflozin on apoptosis was confirmed by reduced expression of active caspase-3. Importantly, empagliflozin did not alter the cytotoxic effect of carfilzomib on human U266B1 multiple myeloma cells. our findings suggest that empagliflozin may provide a new therapeutic strategy to mitigate carfilzomib-induced cardiotoxicity in multiple myeloma patients.
Effects of MnTBAP on Porcine Semen Cryopreservation and Capacitation
Authors: Kim Eunji , Yu Il-Jeoung , Lee Joohyeong , Jeon Yubyeol
Published: June 2024

Antioxidants protect cellular function and structure by neutralizing the oxidative stress caused by increased reactive oxygen species (ROS) during sperm freezing. Studies on cryopreservation using various antioxidants have demonstrated encouraging results. Many studies have used antioxidants to increase the efficiency of sperm freezing and to improve the success rate of artificial insemination and pregnancy. Manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) is a newly synthesized antioxidant with positive effects on sperm morphology and capacitation in humans, rams, and stallions. In this study, porcine semen was treated with 0, 50, 100, and 150 μM of MnTBAP based on a Tris–egg-yolk extender and frozen to determine whether MnTBAP can assist the status of sperm during cryopreservation. First, motility was assessed using the computer-assisted sperm analysis (CASA) system, with the 100 μM treatment group showing the highest motile rate (66.8%) compared with that of the other groups (control, 51.1%; 50 μM and 150 μM, 59.6%); therefore, the remaining analyses were conducted comparing the two groups (control vs. 100 μM group; p < 0.01). Second, fluorescence staining was applied to examine the control and 100 μM groups using fluorescence microscopy. The viability (41.7% vs. 62.4%) and the acrosome integrity (77.9% vs. 86.4%) differed significantly (p < 0.05). In addition, the mitochondrial membrane potential (MMP) was 46.5% vs. 51.9%; the fragmentation rate, estimated using the Sperm-sus-Halomax kit, was 63.4% vs. 57.4%; and the detected caspase activity was 30.1% vs. 22.9%. These tended to be higher in the treated group but did not differ significantly. Third, measurements using FACSLyric revealed that the 100 μM treatment group exhibited a state of elevated normal lipid arrangement within the plasma membrane and diminished levels of apoptosis and ROS (p < 0.01). We assessed the expression of genes relevant to antioxidant effectiveness using real-time RT-qPCR. Our findings indicated significant alterations in the expression levels of various mRNA species, with the exception of NOX5 (p < 0.05). Finally, the straws were dissolved and used to treat matured denuded oocytes to investigate the effect on fertilization and embryo development in vitro. The cleavage rate was (77.6% vs. 84.1%), and the blastocyst rate was 9.7% vs. 11.4% (p < 0.05). In conclusion, these results suggest that MnTBAP positively affected sperm freeze–thawing, improving the fertilization capacity, and leading to increased embryo development.
Identification of New, Translatable ProtectomiRs against Myocardial Ischemia/Reperfusion Injury and Oxidative Stress: The Role of MMP/Biglycan Signaling Pathways
Authors: Szabados Tamara , Molnár Arnold , Kenyeres Éva , Gömöri Kamilla , Pipis Judit , Pósa Bence , Makkos András , Ágg Bence , Giricz Zoltán , Ferdinandy Péter , Görbe Anikó , Bencsik Péter
Published: June 2024

Introduction: Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here, we hypothesized that cardiac MMP and BGN signaling are involved in the protective effects of ICon. Methods: A reverse target-microRNA prediction was performed by using the miRNAtarget™ 2.0 software to identify human microRNAs with a possible regulatory effect on MMP and BGN, such as on related genes. To validate the identified 1289 miRNAs in the predicted network, we compared them to two cardioprotective miRNA omics datasets derived from pig and rat models of MIRI in the presence of ICons. Results: Among the experimentally measured miRNAs, we found 100% sequence identity to human predicted regulatory miRNAs in the case of 37 porcine and 24 rat miRNAs. Upon further analysis, 42 miRNAs were identified as MIRI-associated miRNAs, from which 24 miRNAs were counter-regulated due to ICons. Conclusions: Our findings highlight 24 miRNAs that potentially regulate cardioprotective therapeutic targets associated with MMPs and BGN in a highly translatable porcine model of acute myocardial infarction.
The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect
Authors: Yao Siyuan , Kasargod Aanchal , Chiu Richard , Torgerson Taylor R. , Kupiec-Weglinski Jerzy W. , Dery Kenneth J.
Published: June 2024

Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels of oxidative stress (OxS) that occur in response to hepatic ischemia/reperfusion injury (IRI) and metabolic diseases of the liver. Antisense oligonucleotides (ASOs) are an emerging class of gene expression modulators that target RNA molecules by Watson–Crick binding specificity, leading to RNA degradation, splicing modulation, and/or translation interference. Here, we review ASO inhibitor/activator strategies to modulate transcription and translation that control the expression of enzymes, transcription factors, and intracellular sensors of DNA damage. Several small-interfering RNA (siRNA) drugs with N-acetyl galactosamine moieties for the liver have recently been approved. Preclinical studies using short-activating RNAs (saRNAs), phosphorodiamidate morpholino oligomers (PMOs), and locked nucleic acids (LNAs) are at the forefront of proof-in-concept therapeutics. Future research targeting intracellular OxS-related pathways in the liver may help realize the promise of precision medicine, revolutionizing the customary approach to caring for and treating individuals afflicted with liver-specific conditions.
Co-Microencapsulation of Cushuro (Nostoc sphaericum) Polysaccharide with Sacha Inchi Oil (Plukenetia huayllabambana) and Natural Antioxidant Extracts
Authors: Chasquibol Nancy , Sotelo Axel , Tapia Mateo , Alarcón Rafael , Goycoolea Francisco , Perez-Camino María del Carmen
Published: June 2024

Cushuro (Nostoc sphaericum) polysaccharide was used to co-microencapsulate sacha inchi oil, natural antioxidant extracts from the oleoresin of charapita chili peppers (Capsicum frutescens L.) and grape orujo (Vitis vinifera L.). Encapsulation efficiency, moisture, particle size, morphology, oxidative stability, shelf-life, solubility, essential fatty acid profile, sterol content and antioxidant capacity were evaluated. The formulations with grape orujo extract showed higher oxidative stability (4908 ± 184 h), antioxidant capacity (4835.33 ± 40.02 µg Trolox/g ms), higher phenolic contents (960.11 ± 53.59 µg AGE/g ms) and a smaller particle size (7.55 µm) than the other formulations, as well as good solubility and a low moisture content. Therefore, grape orujo extracts can be used as natural antioxidants. The fatty acid composition (ω-3) remained quite stable in all the formulations carried out, which also occurred for sterols and tocopherols. In combination with gum arabic, grape orujo extract offered oxidative protection to sacha inchi oil during the first week of storage.
Neuroinflammation and Lysosomal Abnormalities Characterise the Essential Role for Oxidation Resistance 1 in the Developing and Adult Cerebellum
Authors: Bucknor Eboni M. V. , Johnson Errin , Efthymiou Stephanie , Alvi Javeria R. , Sultan Tipu , Houlden Henry , Maroofian Reza , Karimiani Ehsan G. , Finelli Mattéa J. , Oliver Peter L.
Published: June 2024

Loss-of-function mutations in the TLDc family of proteins cause a range of severe childhood-onset neurological disorders with common clinical features that include cerebellar neurodegeneration, ataxia and epilepsy. Of these proteins, oxidation resistance 1 (OXR1) has been implicated in multiple cellular pathways related to antioxidant function, transcriptional regulation and cellular survival; yet how this relates to the specific neuropathological features in disease remains unclear. Here, we investigate a range of loss-of-function mouse model systems and reveal that constitutive deletion of Oxr1 leads to a rapid and striking neuroinflammatory response prior to neurodegeneration that is associated with lysosomal pathology. We go on to show that neuroinflammation and cell death in Oxr1 knockouts can be completely rescued by the neuronal expression of Oxr1, suggesting that the phenotype is driven by the cell-intrinsic defects of neuronal cells lacking the gene. Next, we generate a ubiquitous, adult inducible knockout of Oxr1 that surprisingly displays rapid-onset ataxia and cerebellar neurodegeneration, establishing for the first time that the distinctive pathology associated with the loss of Oxr1 occurs irrespective of developmental stage. Finally, we describe two new homozygous human pathogenic variants in OXR1 that cause neurodevelopmental delay, including a novel stop-gain mutation. We also compare functionally two missense human pathogenic mutations in OXR1, including one newly described here, that cause different clinical phenotypes but demonstrate partially retained neuroprotective activity against oxidative stress. Together, these data highlight the essential role of Oxr1 in modulating neuroinflammatory and lysosomal pathways in the mammalian brain and support the hypothesis that OXR1 protein dosage may be critical for pathological outcomes in disease.
Artesunate Exerts Organ- and Tissue-Protective Effects by Regulating Oxidative Stress, Inflammation, Autophagy, Apoptosis, and Fibrosis: A Review of Evidence and Mechanisms
Authors: Zhu Mingtao , Wang Yu , Han Jianwei , Sun Yanping , Wang Shuang , Yang Bingyou , Wang Qiuhong , Kuang Haixue
Published: June 2024

The human body comprises numerous organs and tissues operating in synchrony, it facilitates metabolism, circulation, and overall organismal function. Consequently, the well-being of our organs and tissues significantly influences our overall health. In recent years, research on the protective effects of artesunate (AS) on various organ functions, including the heart, liver, brain, lungs, kidneys, gastrointestinal tract, bones, and others has witnessed significant advancements. Findings from in vivo and in vitro studies suggest that AS may emerge as a newfound guardian against organ damage. Its protective mechanisms primarily entail the inhibition of inflammatory factors and affect anti-fibrotic, anti-aging, immune-enhancing, modulation of stem cells, apoptosis, metabolic homeostasis, and autophagy properties. Moreover, AS is attracting a high level of interest because of its obvious antioxidant activities, including the activation of Nrf2 and HO-1 signaling pathways, inhibiting the release of reactive oxygen species, and interfering with the expression of genes and proteins associated with oxidative stress. This review comprehensively outlines the recent strides made by AS in alleviating organismal injuries stemming from various causes and protecting organs, aiming to serve as a reference for further in-depth research and utilization of AS.
Selenium as a Modulator of Redox Reactions in the Prevention and Treatment of Cardiovascular Diseases
Authors: Leszto Klaudia , Biskup Laura , Korona Klaudia , Marcinkowska Weronika , Możdżan Maria , Węgiel Andrzej , Młynarska Ewelina , Rysz Jacek , Franczyk Beata
Published: June 2024

Cardiovascular diseases stand as the predominant global cause of mortality, exerting a profound impact on both life expectancy and its quality. Given their immense public health burden, extensive efforts have been dedicated to comprehending the underlying mechanisms and developing strategies for prevention and treatment. Selenium, a crucial participant in redox reactions, emerges as a notable factor in maintaining myocardial cell homeostasis and influencing the progression of cardiovascular disorders. Some disorders, such as Keshan disease, are directly linked with its environmental deficiency. Nevertheless, the precise extent of its impact on the cardiovascular system remains unclear, marked by contradictory findings in the existing literature. High selenium levels have been associated with an increased risk of developing hypertension, while lower concentrations have been linked to heart failure and atrial fibrillation. Although some trials have shown its potential effectiveness in specific groups of patients, large cohort supplementation attempts have generally yielded unsatisfactory outcomes. Consequently, there persists a significant need for further research aimed at delineating specific patient cohorts and groups of diseases that would benefit from selenium supplementation.
Not Everyone Chooses Profit (If It Is too Tiring): What Behavioral and EEG Data Tell Us
Authors: Balconi Michela , Acconito Carlotta , Angioletti Laura
Published: June 2024

Background: A more rewarding choice, even if it requires more effort, is usually preferred by individuals; yet, in some cases, individuals choose less profitable and less tiring options. This study explored the behavioral and electrophysiological (EEG) correlates of healthy adults performing a task, designed to investigate the decision-making process behind the selection of more effortful (but highly monetarily rewarding) and less effortful (but less monetarily rewarding) options. Methods: A sample of 20 healthy adults (mean age = 46.40) performed the decision-making task, while behavioral data and EEG frequency bands (delta, theta, alpha, and beta) were collected. The Maximization Scale (MS) was administered to evaluate individuals’ differences in the tendency to maximize their choices. Results: the results showed a general preference for selecting more compared to less effortful options, while no significant differences were obtained for the response times. Individuals who score higher on the MS High Standards subscale are more inclined to choose less effortful options; conversely, those with lower scores are more likely to choose a more effortful and rewarding option. However, no significant correlations were found between the behavioral data and the alternative search, or the decision difficulty subscales of the MS. EEG findings reported a significant interaction effect Choice × Electrode in delta, theta, alpha and beta bands. Specifically, the choice of less effortful options is associated with a higher increase in delta, theta, alpha, and beta band power in the right temporoparietal area (TP10) and by a lower activation of delta and theta in the contralateral site (TP9). The delta band decreased in left frontal area (AF7) during the task for the less versus more effortful options. Conclusions: Overall, despite more effortful and more monetarily rewarding options seeming to be the most rational ones to choose, less effortful choices are associated with specific EEG correlates, suggesting that there is a perceived advantage in avoiding automatisms, delaying gratification, and maximizing future possibilities.
An Artificial Neural Network-Based Data-Driven Embedded Controller Design for a Pneumatic Artificial Muscle-Actuated Pressing Unit
Authors: Engin Mustafa , Duymazlar Okan , Engin Dilşad
Published: June 2024

Obtaining mathematical models of nonlinear cyber–physical systems for use in controller design is both difficult and time consuming. In this paper, an ANN-based method is proposed to design a controller for a nonlinear system that does not require a mathematical model. The developed ANN-based control algorithm is implemented directly on a real-time field controller, and its performance is evaluated without the use of auxiliary devices, such as PCs or workstations. By executing machine learning algorithms on local devices or embedded systems, edge artificial intelligence (Edge AI) with transfer learning gives priority to processing data at the source, minimizing the necessity for continuous connectivity to remote servers. The control algorithm was developed using the Matlab Simulink environment. The first and second ANNs were cascaded, wherein the first ANN computes the appropriate pressure signal for the given displacement, while the second predicts the force based on the pressure value from the first ANN. Subsequently, the ANN-based control algorithm was converted to SCL code using the Simulink PLC Coder and deployed on the PLC for operation. The algorithm was tested using two different scenarios. The conducted tests demonstrated the successful prediction of pressure signals corresponding to the targeted displacement values and accurate estimation of force values. Experimental work was carried out on PAM manipulators as a nonlinear model application, and the obtained results were discussed.
Inversion of Chlorophyll-a Concentration in Wuliangsu Lake Based on OGolden-DBO-XGBoost
Authors: Zhou Hao , Fu Xueliang , Li Honghui
Published: June 2024

Chlorophyll-a (Chl-a) concentration is one of the important indicators in water bodies for assessing the ecological health of water quality. In this paper, an OGolden-DBO-XGBoost Chl-a concentration inversion model is proposed using Wuliangsu Lake as the study area, and by combining the Sentinel-2 remote-sensing satellite images and measured Chl-a concentration data in Wuliangsu Lake, the XGBoost model is optimized using the hybrid-strategy-improved dung beetle optimization algorithm (OGolden-DBO), and an OGolden-DBO-XGBoost Chl-a concentration inversion model. The OGolden-DBO-XGBoost model’s coefficients of determination (R2s) were 0.8936 and 0.8850 on the training set and test set, according to the results. The root mean squared errors (RMSEs) were 3.1353 and 2.9659 μg/L, and the mean absolute errors (MAEs) were 1.8918 and 2.4282 μg/L. The model performed well and provided a strong support for the detection of Chl-a concentration in Wuliangsu Lake.
An Investigation of Fly Ash and Slag Processing and Fiber Production Using Plasma Technology
Authors: Kavaliauskas Žydrūnas , Kėželis Romualdas , Grigaitienė Viktorija , Milieška Mindaugas , Valinčius Vitas , Uscila Rolandas , Kriūkienė Rita , Baltušnikas Arūnas
Published: June 2024

As the world’s population grows and resource consumption rises, there will be an increase in household waste and, consequently, the fly ash and slag from after the incineration of this waste need to be properly recycled or used as secondary raw materials in other industries. The authors of this work propose an innovative technology that has not yet been studied much in the literature; the obtained slag and fly ash are processed by plasma technology, and from those, fiber is formed. As shown by SEM studies, the raw material (before plasma–chemical treatment) consists of irregularly shaped granules or rod-shaped microforms. EDS studies show that both the original material and the products obtained after plasma–chemical processing are composed of various metal elements, but they make up a significantly small part, as the predominant elements are C, O, Cl, Si, and Ca. BET studies show that when the fiber is obtained with a plasma torch power of 55.5; 55.6 and 74 kW, respectively, the specific surface area is 11.9; 8.5 and 3 m2/g. It is worth noting that the raw material obtained after plasma–chemical processing is sufficiently clean and harmless to the environment, so it can be used as a secondary raw material, e.g., for the production of thermal insulation, in the production of catalysts, as a component in the production of concrete, or in other industries.
A Study of Cavitation Erosion in Artificial Submerged Water Jets
Authors: Li Haonan , Chen Jiawang , Guo Jin , Zhu Hai , Lin Yuan , Ge Han
Published: June 2024

The artificially submerged cavitation water jet is effectively utilized by ejecting a high-pressure water stream into a low-pressure water stream through concentric nozzles and utilizing the cavitation phenomenon generated by the shear layer formed between the two streams. In this study, we investigated the cavitation characteristics of artificially submerged cavitation water jets by combining numerical simulations and erosion experiments. The results indicate that an appropriate standoff distance can generate more cavitation clouds on the workpiece surface, and the erosion characteristics of the artificially submerged cavitation water jet are most pronounced at a dimensionless standoff distance of SD = 30. The shear effect formed between the two jets plays a crucial role in generating initial cavitation bubbles within the flow field of the artificially submerged cavitation water jet. Moreover, increasing the convergent angle between the two jets can significantly enhance the cavitation effect between them and lead to a more substantial cavitation effect. Simultaneously, increasing the pressure of the high-pressure inner nozzle also contributes to enhancing the cavitation effect of the artificially submerged cavitation water jet.
Impact Wear Behavior of the Valve Cone Surface after Plasma Alloying Treatment
Authors: Luo Changzeng , Yao Yajun , Wei Dongbo , Lin Muyao , Zhang Pingze , Qu Shengguan
Published: June 2024

Valves are prone to wear under harsh environments, such as high temperatures and reciprocating impacts, which has become one of the most severe factors reducing the service life of engines. As a lightweight ceramic, CrN is considered an excellent protective material with high-temperature strength and resistance to wear. In this study, a CrN coating was applied onto the valve cone surface via double-layer glow plasma surface metallurgy technology. The formation process, microstructure, phase composition, hardness, and adhesion strength were analyzed in detail. Impact wear tests were conducted on the valve using a bench test device. The SEM and EDS results showed that the CrN coating evolved from an island-like form to a dense, cell-shaped surface structure. The thickness of the coating was approximately 46 μm and could be divided into a deposition layer and a diffusion layer, from the outer to the inner sections. The presence of element gradients within the diffusion layer proved that the coating and substrate were metallurgically bonded. The adhesion strength of the CrN coating measured via scratch method was as high as 72 N. The average Vickers hardness of the valve cone surface increased from 377.1 HV0.5 to 903.1 HV0.5 following the plasma alloying treatment. After 2 million impacts at 12,000 N and 650 °C, adhesive wear emerged as the primary wear mode of the CrN coating, with an average wear depth of 42.93 μm and a wear amount of 23.49 mg. Meanwhile, the valve substrate exhibited a mixed wear mode of adhesive wear and abrasive wear, with an average wear depth of 118.23 μm and a wear amount of 92.66 mg, being 63.7% and 74.6% higher than those of the coating. Thus, the CrN coating showed excellent impact wear resistance, which contributed to the enhancement of the service life of the valve in harsh environments.
An Intelligent Human–Machine Interface Architecture for Long-Term Remote Robot Handling in Fusion Reactor Environments
Authors: Benito Tamara , Barrientos Antonio
Published: June 2024

This paper addresses the intricate challenge posed by remote handling (RH) operations in facilities with operational lifespans surpassing 30 years. The extended RH task horizon necessitates a forward-looking strategy to accommodate the continuous evolution of RH equipment. Confronted with diverse and evolving hardware interfaces, a critical requirement emerges for a flexible and adaptive software architecture based on changing situations and past experiences. The paper explores the inherent challenges associated with sustaining and upgrading RH equipment within an extended operational context. In response to this challenge, a groundbreaking, flexible, and maintainable human–machine interface (HMI) architecture named MAMIC is designed, guaranteeing seamless integration with a diverse range of RH equipment developed over the years. Embracing a modular and extensible design, the MAMIC architecture facilitates the effortless incorporation of new equipment without compromising system integrity. Moreover, by adopting this approach, nuclear facilities can proactively steer the evolution of RH equipment, guaranteeing sustained performance and compliance throughout the extended operational lifecycle. The proposed adaptive architecture provides a scalable and future-proof solution, addressing the dynamic landscape of remote handling technology for decades.
Does Exposure to Burning and Heated Tobacco Affect the Abundance of Perio-Pathogenic Species in the Subgingival Biofilm?
Authors: Mišković Ivana , Kuiš Davor , Špalj Stjepan , Pupovac Aleksandar , Mohar-Vitezić Bojana , Prpić Jelena
Published: June 2024

This study investigated the impact of tobacco exposure, specifically through heating and burning, on periodontopathogens in the subgingival microbiome among clinically healthy individuals and those diagnosed with periodontitis. The sample comprised 66 subjects (26–56 years, median 38 yrs; 64% females) classified as non-smokers, classic cigarette smokers, and tobacco heating system (THS) smokers (each N = 22). Full-mouth periodontal examination was performed, and 330 paper-point samples from periodontal pockets were collected. Next-generation sequencing of 16S rRNA genes was conducted to identify the composition of subgingival microbiome. Periodontitis prevalence among the groups was ranked as THS (41%) < non-smokers (44%) < cigarette smokers (68%), without statistically significant differences between the groups. The number of perio-pathogenic species was higher in subjects with periodontitis compared to those without (median 7 vs. 6 species; p = 0.005) but without significant differences between exposure groups: non-smokers (6) = smokers (6) < THS (6.5). When combining exposure and periodontal status, each smoker group had more perio-pathogenic species than non-smokers: non-smokers without periodontitis (5) < smokers without periodontitis (5.5) < THS without periodontitis (6); non-smokers with periodontitis (6.5) < THS with periodontitis (7) = smokers with periodontitis (7). Multiple linear regression indicated periodontitis as the sole predictor of perio-pathogenic species quantity, irrespective of the type of tobacco consumption, sex, age, or oral hygiene (R2 = 0.163; p = 0.005). In conclusion, the quantity of perio-pathogenic species in the subgingival microbiome was more influenced by periodontitis than by exposure to tobacco smoke, regardless of whether it was heated or burned.