bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Extremely Low-Frequency Electromagnetic Fields on Inflammation and Performance-Related Indices in Trained Athletes: A Double-Blinded Crossover Study
Authors: Markus Irit , Ohayon Evyatar , Constantini Keren , Geva-Kleinberger Keren , Ibrahim Rawan , Ruban Angela , Gepner Yftach
Published: August 2023

Previous investigations have demonstrated the therapeutic advantages of extremely low-frequency electromagnetic fields (ELF-EMFs) in mitigating inflammation and influencing biological processes. We aimed to shed light on the effects of ELF-EMF on recovery rate following high-intensity exercise. Nine male athletes (26.7 ± 6.0 years; 69.6 ± 7.7 kg, VO2peak 57.3 ± 6.8 mL/kg/min) completed five visits in a double-blinded crossover design, performing two consecutive testing days, following a ventilatory thresholds assessment. Following 62 min of high-intensity cycling, participants lay on an ELF-EMF mattress under active (A) and non-active (NA) conditions, immediately post protocol and during the night. Physical performance and blood markers were assessed at baseline and at 60 min (60 P) and 24 h (24 H) post-protocol. The A-condition demonstrated a notable reduction in interleukin-10 (IL-10) concentrations (mean difference = −88%, p = 0.032) and maximal isometric strength of the quadriceps muscles (mean difference = ~8%, p = 0.045) compared to the NA-condition between 60 P and 24 H. In a sensitivity analysis, the A-condition revealed that younger athletes who possessed lower fat mass experienced attenuated inflammation and biochemical responses and improved physical performance. In conclusion, ELF-EMF showed no significant overall effects on performance and inflammation after intense cycling among athletes. Post-hoc analysis revealed modest benefits of ELF-MLF, suggesting a context-dependent impact. Further research with a larger sample size and multiple sessions is needed to confirm the recovery potential of ELF-EMF.
Neutrophils and the Systemic Inflammatory Response Syndrome (SIRS)
Authors: Sikora Janusz P. , Karawani Jakub , Sobczak Jarosław
Published: August 2023

We are not entirely able to understand, assess, and modulate the functioning of the immune system in clinical situations that lead to a systemic inflammatory response. In the search for diagnostic and treatment strategies (which are still far from perfect), it became very important to study the pathogenesis and participation of endogenous inflammation mediators. This study attempts to more precisely establish the role of neutrophils in individual phenomena occurring during an inflammatory and anti-inflammatory reaction, taking into account their cidal, immunoregulatory, and reparative abilities. Pro- and anticoagulatory properties of endothelium in systemic inflammatory response syndrome (SIRS) are emphasised, along with the resulting clinical implications (the application of immunotherapy using mesenchymal stem/stromal cells (MSCs) or IL-6 antagonists in sepsis and COVID-19 treatment, among others). Special attention is paid to reactive oxygen species (ROS), produced by neutrophils activated during “respiratory burst” in the course of SIRS; the protective and pathogenic role of these endogenous mediators is highlighted. Moreover, clinically useful biomarkers of SIRS (neutrophil extracellular traps, cell-free DNA, DAMP, TREMs, NGAL, miRNA, selected cytokines, ROS, and recognised markers of endothelial damage from the group of adhesins by means of immunohistochemical techniques) related to the neutrophils are presented, and their role in the diagnosing and forecasting of sepsis, burn disease, and COVID-19 is emphasised. Finally, examples of immunomodulation of sepsis and antioxidative thermal injury therapy are presented.
Integrated Metabolome and Transcriptome Analyses Reveal Amino Acid Biosynthesis Mechanisms during the Physiological Maturity of Grains in Yunnan Hulled Wheat (Triticum aestivum ssp. yunnanense King)
Authors: Zhang Chuanli , Zhang Ping , Zhang Xuesong , Wang Qianchao , Liu Junna , Li Li , Cheng Shunhe , Qin Peng
Published: August 2023

Yunnan hulled wheat (YHW) possesses excellent nutritional characteristics; however, the precise amino acid (AA) composition, contents, and molecular mechanisms underlying AA biosynthesis in YHW grains remain unclear. In this study, we aimed to perform metabolomic and transcriptomic profiling to identify the composition and genetic factors regulating AA biosynthesis during the physiological maturation of grains of two YHW genotypes, Yunmai and Dikemail, with high and low grain protein contents, respectively. A total of 40 and 14 differentially accumulated amino acids (AAs) or AA derivatives were identified between the waxy grain (WG) and mature grain (MG) phenological stages of Yunmai and Dikemail, respectively. The AA composition differed between WG and MG, and the abundance of AAs—especially that of essential AAs—was significantly higher in WG than in MG (only 38.74–58.26% of WG). Transcriptome analysis revealed differential regulation of structural genes associated with the relatively higher accumulation of AAs in WG. Weighted gene co-expression network analysis and correlation analyses of WG and MG indicated differences in the expression of clusters of genes encoding both upstream elements of AA biosynthesis and enzymes that are directly involved in AA synthesis. The expression of these genes directly impacted the synthesis of various AAs. Together, these results contribute to our understanding of the mechanism of AA biosynthesis during the different developmental stages of grains and provide a foundation for further research to improve the nutritional value of wheat products.
BAP31 Knockout in Macrophages Affects CD4+T Cell Activation through Upregulation of MHC Class II Molecule
Authors: Zhao Bo , Sun Lijun , Yuan Qing , Hao Zhenzhen , An Fei , Zhang Wanting , Zhu Xiaoshuang , Wang Bing
Published: August 2023

The differentiation of CD4+T cells is a crucial component of the immune response. The spleen and thymus, as immune organs, are closely associated with the differentiation and development of T cells. Previous studies have suggested that BAP31 may play a role in modulating T cell activation, but the specific impact of BAP31 on T cells through macrophages remains uncertain. In this study, we present evidence that BAP31 macrophage conditional knockout (BAP31-MCKO) mice display an enlarged spleen and thymus, accompanied by activated clustering and disrupted differentiation of CD4+T cells. In vitro co-culture studies were conducted to investigate the impact of BAP31-MCKO on the activation and differentiation of CD4+T cells. The examination of costimulatory molecule expression in BMDMs and RAW 264.7 cells, based on the endoplasmic reticulum function of BAP31, revealed an increase in the expression of antigen presenting molecules, particularly MHC-II molecule, in the absence of BAP31 in BMDMs or RAW264.7 cells. These findings suggest that BAP31 plays a role in the activation and differentiation of CD4+T cells by regulating the MHC class II molecule on macrophages. These results provide further support for the importance of BAP31 in developing interaction between macrophages and CD4+T cells.
Epigenetic Downregulation of Hsa-miR-193b-3p Increases Cyclin D1 Expression Level and Cell Proliferation in Human Meningiomas
Authors: Kober Paulina , Mossakowska Beata Joanna , Rusetska Natalia , Baluszek Szymon , Grecka Emilia , Konopiński Ryszard , Matyja Ewa , Oziębło Artur , Mandat Tomasz , Bujko Mateusz
Published: August 2023

Meningiomas are common intracranial tumors in adults. Abnormal microRNA (miRNA) expression plays a role in their pathogenesis. Change in miRNA expression level can be caused by impaired epigenetic regulation of miRNA-encoding genes. We found the genomic region covering the MIR193B gene to be DNA hypermethylated in meningiomas based on analysis of genome-wide methylation (HumanMethylation450K Illumina arrays). Hypermethylation of MIR193B was also confirmed via bisulfite pyrosequencing. Both hsa-miR-193b-3p and hsa-miR-193b-5p are downregulated in meningiomas. Lower expression of hsa-miR-193b-3p and higher MIR193B methylation was observed in World Health Organization (WHO) grade (G) II/III tumors as compared to GI meningiomas. CCND1 mRNA was identified as a target of hsa-miR-193b-3p as further validated using luciferase reporter assay in IOMM-Lee meningioma cells. IOMM-Lee cells transfected with hsa-miR-193b-3p mimic showed a decreased cyclin D1 level and lower cell viability and proliferation, confirming the suppressive nature of this miRNA. Cyclin D1 protein expression (immunoreactivity) was higher in atypical than in benign meningiomas, accordingly to observations of lower hsa-miR-193b-3p levels in GII tumors. The commonly observed hypermethylation of MIR193B in meningiomas apparently contributes to the downregulation of hsa-miR-193b-3p. Since hsa-miR-193b-3p regulates proliferation of meningioma cells through negative regulation of cyclin D1 expression, it seems to be an important tumor suppressor in meningiomas.
Screening, Synthesis and Biochemical Characterization of SARS-CoV-2 Protease Inhibitors
Authors: Bagdonas Martynas , Čerepenkaitė Kamilė , Mickevičiūtė Aurelija , Kananavičiūtė Rūta , Grybaitė Birutė , Anusevičius Kazimieras , Rukšėnaitė Audronė , Kojis Tautvydas , Gedgaudas Marius , Mickevičius Vytautas , Matulis Daumantas , Zubrienė Asta , Matulienė Jurgita
Published: August 2023

The severe acute respiratory syndrome-causing coronavirus 2 (SARS-CoV-2) papain-like protease (PLpro) and main protease (Mpro) play an important role in viral replication events and are important targets for anti-coronavirus drug discovery. In search of these protease inhibitors, we screened a library of 1300 compounds using a fluorescence thermal shift assay (FTSA) and identified 53 hits that thermally stabilized or destabilized PLpro. The hit compounds structurally belonged to two classes of small molecules: thiazole derivatives and symmetrical disulfide compounds. Compound dissociation constants (Kd) were determined using an enzymatic inhibition method. Seven aromatic disulfide compounds were identified as efficient PLpro inhibitors with Kd values in the micromolar range. Two disulfides displayed six-fold higher potency for PLpro (Kd = 0.5 µM) than for Mpro. The disulfide derivatives bound covalently to both proteases, as confirmed through mass spectrometry. The identified compounds can serve as lead compounds for further chemical optimization toward anti-COVID-19 drugs.
Continuous Wet Spinning of Regenerated Silk Fibers from Spinning Dopes Containing 4% Fibroin Protein
Authors: Wöltje Michael , Isenberg Kristin L. , Cherif Chokri , Aibibu Dilbar
Published: August 2023

The wet spinning of fibers from regenerated silk fibroin has long been a research goal. Due to the degradation of the molecular structure of the fibroin protein during the preparation of the regenerated silk fibroin solution, fibroin concentrations with at least 10% protein content are required to achieve sufficient viscosity for wet spinning. In this study, a spinning dope formulation of regenerated silk fibroin is presented that shows a rheological behavior similar to that of native silk fibroin isolated from the glands of B. mori silkworm larvae. In addition, we present a wet-spinning process that enables, for the first time, the continuous wet spinning of regenerated silk fibroin with only 4% fibroin protein content into an endless fiber. Furthermore, the tensile strength of these wet-spun regenerated silk fibroin fibers per percentage of fibroin is higher than that of all continuous spinning approaches applied to regenerated and native silk fibroin published so far.
Fibres and Colorectal Cancer: Clinical and Molecular Evidence
Authors: Celiberto Francesca , Aloisio Adriana , Girardi Bruna , Pricci Maria , Iannone Andrea , Russo Francesco , Riezzo Giuseppe , D’Attoma Benedetta , Ierardi Enzo , Losurdo Giuseppe , Di Leo Alfredo
Published: August 2023

Colorectal cancer (CRC) is one of the leading causes of mortality for cancer in industrialized countries. The link between diet and CRC is well-known, and presumably CRC is the type of cancer which is most influenced by dietary habits. In Western countries, an inadequate dietary intake of fibers is endemic, and this could be a driving factor in the increase of CRC incidence. Indeed, several epidemiologic studies have elucidated an inverse relationship between daily fiber intake and risk of CRC. Long-term prognosis in CRC survivors is also dependent on dietary fibers. Several pathogenetic mechanisms may be hypothesized. Fibers may interfere with the metabolism of bile acids, which may promote colon carcinogenesis. Further, fibers are often contained in vegetables which, in turn, contain large amounts of antioxidant agents like resveratrol, polyphenols, or phytoestrogens. Moreover, fibers can be digested by commensal flora, thus producing compounds such as butyrate, which exerts an antiproliferative effect. Finally, fibers may modulate gut microbiota, whose composition has shown to be associated with CRC onset. In this regard, dietary interventions based on high-fiber-containing diets are ongoing to prevent CRC development, especially in patients with high potential for this type of tumor. Despite the fact that outcomes are preliminary, encouraging results have been observed.
Inflammation and Digestive Cancer
Authors: Waldum Helge , Fossmark Reidar
Published: August 2023

Chronic inflammation is linked to carcinogenesis, particularly in the digestive organs, i.e., the stomach, colon, and liver. The mechanism of this effect has, however, only partly been focused on. In this review, we focus on different forms of chronic hepatitis, chronic inflammatory bowel disease, and chronic gastritis, conditions predisposing individuals to the development of malignancy. Chronic inflammation may cause malignancy because (1) the cause of the chronic inflammation is itself genotoxic, (2) substances released from the inflammatory cells may be genotoxic, (3) the cell death induced by the inflammation induces a compensatory increase in proliferation with an inherent risk of mutation, (4) changes in cell composition due to inflammation may modify function, resulting in hormonal disturbances affecting cellular proliferation. The present review focuses on chronic gastritis (Helicobacter pylori or autoimmune type) since all four mechanisms may be relevant to this condition. Genotoxicity due to the hepatitis B virus is an important factor in hepatocellular cancer and viral infection can similarly be central in the etiology and malignancy of inflammatory bowel diseases. Helicobacter pylori (H. pylori) is the dominating cause of chronic gastritis and has not been shown to be genotoxic, so its carcinogenic effect is most probably due to the induction of atrophic oxyntic gastritis leading to hypergastrinemia.
A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut
Authors: Wang Yi , He Chengwei , Xin Shuzi , Liu Xiaohui , Zhang Sitian , Qiao Boya , Shang Hongwei , Gao Lei , Xu Jingdong
Published: August 2023

Intestinal diseases have always posed a serious threat to human health, with inflammatory bowel disease (IBD) being one of them. IBD is an autoimmune disease characterized by chronic inflammation, including ulcerative colitis (UC) and Crohn’s disease (CD). The “alarm” cytokine IL-33, which is intimately associated with Th2 immunity, is a highly potent inflammatory factor that is considered to have dual functions—operating as both a pro-inflammatory cytokine and a transcriptional regulator. IL-33 has been shown to play a crucial role in both the onset and development of IBD. Therefore, this review focuses on the pathogenesis of IBD, the major receptor cell types, and the activities of IL-33 in innate and adaptive immunity, as well as its underlying mechanisms and conflicting conclusions in IBD. We have also summarized different medicines targeted to IL-33-associated diseases. Furthermore, we have emphasized the role of IL-33 in gastrointestinal cancer and parasitic infections, giving novel prospective therapeutic utility in the future application of IL-33.
New Insights into Photobiomodulation of the Vaginal Microbiome—A Critical Review
Authors: Santos Fernanda P. , Carvalhos Carlota A. , Figueiredo-Dias Margarida
Published: August 2023

The development of new technologies such as sequencing has greatly enhanced our understanding of the human microbiome. The interactions between the human microbiome and the development of several diseases have been the subject of recent research. In-depth knowledge about the vaginal microbiome (VMB) has shown that dysbiosis is closely related to the development of gynecologic and obstetric disorders. To date, the progress in treating or modulating the VMB has lagged far behind research efforts. Photobiomodulation (PBM) uses low levels of light, usually red or near-infrared, to treat a diversity of conditions. Several studies have demonstrated that PBM can control the microbiome and improve the activity of the immune system. In recent years, increasing attention has been paid to the microbiome, mostly to the gut microbiome and its connections with many diseases, such as metabolic disorders, obesity, cardiovascular disorders, autoimmunity, and neurological disorders. The applicability of PBM therapeutics to treat gut dysbiosis has been studied, with promising results. The possible cellular and molecular effects of PBM on the vaginal microbiome constitute a theoretical and promising field that is starting to take its first steps. In this review, we will discuss the potential mechanisms and effects of photobiomodulation in the VMB.
Common miRNAs of Osteoporosis and Fibromyalgia: A Review
Authors: Philippe Soline , Delay Marine , Macian Nicolas , Morel Véronique , Pickering Marie-Eva
Published: August 2023

A significant clinical association between osteoporosis (OP) and fibromyalgia (FM) has been shown in the literature. Given the need for specific biomarkers to improve OP and FM management, common miRNAs might provide promising tracks for future prevention and treatment. The aim of this review is to identify miRNAs described in OP and FM, and dysregulated in the same direction in both pathologies. The PubMed database was searched until June 2023, with a clear mention of OP, FM, and miRNA expression. Clinical trials, case–control, and cross-sectional studies were included. Gray literature was not searched. Out of the 184 miRNAs found in our research, 23 are shared by OP and FM: 7 common miRNAs are dysregulated in the same direction for both pathologies (3 up-, 4 downregulated). The majority of these common miRNAs are involved in the Wnt pathway and the cholinergic system and a possible link has been highlighted. Further studies are needed to explore this relationship. Moreover, the harmonization of technical methods is necessary to confirm miRNAs shared between OP and FM.
The Effect of Skeletal Muscle-Specific Creatine Treatment on ALS NMJ Integrity and Function
Authors: Badu-Mensah Agnes , Guo Xiufang , Mendez Roxana , Parsaud Hemant , Hickman James J.
Published: August 2023

Although skeletal muscle (hSKM) has been proven to be actively involved in Amyotrophic Lateral Sclerosis (ALS) neuromuscular junction (NMJ) dysfunction, it is rarely considered as a pharmacological target in preclinical drug discovery. This project investigated how improving ALS hSKM viability and function effects NMJ integrity. Phenotypic ALS NMJ human-on-a-chip models developed from patient-derived induced pluripotent stem cells (iPSCs) were used to study the effect of hSKM-specific creatine treatment on clinically relevant functional ALS NMJ parameters, such as NMJ numbers, fidelity, stability, and fatigue index. Results indicated comparatively enhanced NMJ numbers, fidelity, and stability, as well as reduced fatigue index, across all hSKM-specific creatine-treated systems. Immunocytochemical analysis of the NMJs also revealed improved post-synaptic nicotinic Acetylcholine receptor (AChR) clustering and cluster size in systems supplemented with creatine relative to the un-dosed control. This work strongly suggests hSKM as a therapeutic target in ALS drug discovery. It also demonstrates the need to consider all tissues involved in multi-systemic diseases, such as ALS, in drug discovery efforts. Finally, this work further establishes the BioMEMs NMJ platform as an effective means of performing mutation-specific drug screening, which is a step towards personalized medicine for rare diseases.
Positive Effects of the Nutraceutical Association of Lycopene and Selenium in Experimental Varicocele
Authors: Freni Jose , Pallio Giovanni , Marini Herbert Ryan , Micali Antonio , Irrera Natasha , Romeo Carmelo , Puzzolo Domenico , Mannino Federica , Minutoli Letteria , Pirrotta Igor , Scarfone Alessandro , Antonuccio Pietro
Published: August 2023

Many natural substances commonly found in healthy diets have been studied for their potential to reduce male infertility associated with varicocele. A positive role of selenium (Se) or lycopene alone was demonstrated in experimental varicocele, while no data are available on their association. One group of male Sprague–Dawley rats was sham operated and daily treated with Se (3 mg/kg, i.p.), lycopene (1 mg/kg, i.p.), or their association. A second group underwent surgery to induce varicocele. Sham and half of the varicocele animals were sacrificed after twenty-eight days, while the residual animals were treated for one more month and then sacrificed. In varicocele animals, testosterone levels and testes weight were reduced, Hypoxia Inducible Factor-1α (HIF-1α) expression was absent in the tubules and increased in Leydig cells, caspare-3 was increased, seminiferous epithelium showed evident structural changes, and many apoptotic germ cells were demonstrated with TUNEL assay. The treatment with lycopene or Se alone significantly increased testis weight and testosterone levels, reduced apoptosis and caspase-3 expression, improved the tubular organization, decreased HIF-1α positivity of Leydig cells, and restored its tubular positivity. Lycopene or Se association showed a better influence on all biochemical and morphological parameters. Therefore, the nutraceutical association of lycopene plus Se might be considered a possible therapeutic tool, together with surgery, in the treatment of male infertility. However, long-term experimental and clinical studies are necessary to evaluate sperm quantity and quality.
Degree of Hydrolysis Regulated by Enzyme Mediation of Wheat Gluten Fibrillation: Structural Characterization and Analysis of the Mechanism of Action
Authors: Zhang Huijuan , Lv Shihao , Ren Feiyue , Liu Jie , Wang Jing
Published: August 2023

The impact of different degrees of hydrolysis (DHs) on fibrillation when trypsin mediates wheat gluten (WG) fibrillation has not been thoroughly investigated. This study discussed the differences in amyloid fibrils (AFs) formed from wheat gluten peptides (WGPs) at various DH values. The results from Thioflavin T (ThT) fluorescence analysis indicated that WGPs with DH6 were able to form the most AFs. Changes in Fourier Transform Infrared (FTIR) absorption spectra and secondary structure also suggested a higher degree of fibrillation in DH6 WGPs. Analysis of surface hydrophobicity and ζ-potential showed that DH6 AFs had the highest surface hydrophobicity and the most stable water solutions. Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM) images revealed the best overall morphology of DH6 AFs. These findings can offer valuable insights into the development of a standardized method for preparing wheat gluten amyloid fibrils.
The Role of Aryl Hydrocarbon Receptor in the Endothelium: A Systematic Review
Authors: Guerra-Ojeda Sol , Suarez Andrea , Valls Alicia , Verdú David , Pereda Javier , Ortiz-Zapater Elena , Carretero Julián , Mauricio Maria D. , Serna Eva
Published: August 2023

Activation of the aryl hydrocarbon receptor (AhR) has been shown to be important in physiological processes other than detoxification, including vascular homeostasis. Although AhR is highly expressed in the endothelium, its function has been poorly studied. This systematic review aims to summarise current knowledge on the AhR role in the endothelium and its cardiovascular implications. We focus on endogenous AhR agonists, such as some uremic toxins and other agonists unrelated to environmental pollutants, as well as studies using AhR knockout models. We conclude that AhR activation leads to vascular oxidative stress and endothelial dysfunction and that blocking AhR signalling could provide a new target for the treatment of vascular disorders such as cardiovascular complications in patients with chronic kidney disease or pulmonary arterial hypertension.
Exploratory Study Analyzing the Urinary Peptidome of T2DM Patients Suggests Changes in ECM but Also Inflammatory and Metabolic Pathways Following GLP-1R Agonist Treatment
Authors: Lohia Sonnal , Siwy Justyna , Mavrogeorgis Emmanouil , Eder Susanne , Thöni Stefanie , Mayer Gert , Mischak Harald , Vlahou Antonia , Jankowski Vera
Published: August 2023

Type II diabetes mellitus (T2DM) accounts for approximately 90% of all diabetes mellitus cases in the world. Glucagon-like peptide-1 receptor (GLP-1R) agonists have established an increased capability to target directly or indirectly six core defects associated with T2DM, while the underlying molecular mechanisms of these pharmacological effects are not fully known. This exploratory study was conducted to analyze the effect of treatment with GLP-1R agonists on the urinary peptidome of T2DM patients. Urine samples of thirty-two T2DM patients from the PROVALID study (“A Prospective Cohort Study in Patients with T2DM for Validation of Biomarkers”) collected pre- and post-treatment with GLP-1R agonist drugs were analyzed by CE-MS. In total, 70 urinary peptides were significantly affected by GLP-1R agonist treatment, generated from 26 different proteins. The downregulation of MMP proteases, based on the concordant downregulation of urinary collagen peptides, was highlighted. Treatment also resulted in the downregulation of peptides from SERPINA1, APOC3, CD99, CPSF6, CRNN, SERPINA6, HBA2, MB, VGF, PIGR, and TTR, many of which were previously found to be associated with increased insulin resistance and inflammation. The findings indicate potential molecular mechanisms of GLP-1R agonists in the context of the management of T2DM and the prevention or delaying of the progression of its associated diseases.
Biomarkers of Oxidative Stress in Diabetes Mellitus with Diabetic Nephropathy Complications
Authors: Goycheva Petya , Petkova-Parlapanska Kamelia , Georgieva Ekaterina , Karamalakova Yanka , Nikolova Galina
Published: August 2023

The present study aimed to investigate and compare biomarkers of oxidative stress and the activity of antioxidant enzymes in the plasma of patients with different stages of diabetic nephropathy. For this purpose, we studied (1) the levels of reactive oxygen species and reactive nitrogen species as oxidative stress parameters, (2) lipid and protein oxidation, (3) the activity of antioxidant enzymes, and (4) cytokine production. Patients with type 2 diabetes mellitus were divided into three groups according to the loss of renal function: patients with compensated diabetes mellitus with normal renal function DMT2N0 measured as an estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2, a group with decompensated diabetes mellitus with complication diabetic nephropathy and mild-to-moderate loss of renal function DMT2N1 (eGFR < 60 mL/min/1.73 m2: 59–45 mL/min/1.73 m2), and a decompensated diabetes mellitus with diabetic nephropathy group with moderate-to-severe loss of renal function DMT2N2 (eGFR > 30 mL/min/1.73 m2: 30–44 mL/min/1.73 m2). All results were compared with healthy volunteers. The results showed that patients with diabetic nephropathy had significantly higher levels of ROS, cytokine production, and end products of lipid and protein oxidation compared to healthy volunteers. Furthermore, patients with diabetic nephropathy had depleted levels of nitric oxide (NO), an impaired NO synthase (NOS) system, and reduced antioxidant enzyme activity (p < 0.05). These findings suggest that patients with impaired renal function are unable to compensate for oxidative stress. The decreased levels of NO radicals in patients with advanced renal complications may be attributed to damage NO availability in plasma. The study highlights the compromised oxidative status as a contributing factor to impaired renal function in patients with decompensated type 2 diabetes mellitus. The findings of this study have implications for understanding the pathogenesis of diabetic nephropathy and the role of oxidative stress and chronic inflammation in its development. The assessment of oxidative stress levels and inflammatory biomarkers may aid in the early detection and prediction of diabetic complications.
Formal Template-Based Generation of Attack–Defence Trees for Automated Security Analysis
Authors: Bryans Jeremy , Liew Lin Shen , Nguyen Hoang Nga , Sabaliauskaite Giedre , Shaikh Siraj Ahmed
Published: August 2023

Systems that integrate cyber and physical aspects to create cyber-physical systems (CPS) are becoming increasingly complex, but demonstrating the security of CPS is hard and security is frequently compromised. These compromises can lead to safety failures, putting lives at risk. Attack Defense Trees with sequential conjunction (ADS) are an approach to identifying attacks on a system and identifying the interaction between attacks and the defenses that are present within the CPS. We present a semantic model for ADS and propose a methodology for generating ADS automatically. The methodology takes as input a CPS system model and a library of templates of attacks and defenses. We demonstrate and validate the effectiveness of the ADS generation methodology using an example from the automotive domain.
Linked Data Interfaces: A Survey
Authors: Bernasconi Eleonora , Ceriani Miguel , Di Pierro Davide Di , Ferilli Stefano , Redavid Domenico
Published: August 2023

In the era of big data, linked data interfaces play a critical role in enabling access to and management of large-scale, heterogeneous datasets. This survey investigates forty-seven interfaces developed by the semantic web community in the context of the Web of Linked Data, displaying information about general topics and digital library contents. The interfaces are classified based on their interaction paradigm, the type of information they display, and the complexity reduction strategies they employ. The main purpose to be addressed is the possibility of categorizing a great number of available tools so that comparison among them becomes feasible and valuable. The analysis reveals that most interfaces use a hybrid interaction paradigm combining browsing, searching, and displaying information in lists or tables. Complexity reduction strategies, such as faceted search and summary visualization, are also identified. Emerging trends in linked data interface focus on user-centric design and advancements in semantic annotation methods, leveraging machine learning techniques for data enrichment and retrieval. Additionally, an interactive platform is provided to explore and compare data on the analyzed tools. Overall, there is no one-size-fits-all solution for developing linked data interfaces and tailoring the interaction paradigm and complexity reduction strategies to specific user needs is essential.
Identification of Sympetrum depressiusculum Sélys, 1841 in South Korea (Odonata: Libellulidae) According to Morphology and Genetic Markers
Authors: Pyo Jee-Young , Kim Sung-Soo , Park Jeong Sun , Kim Jong-Moon , Song Yang-Keun , Kim Iksoo
Published: August 2023

In South Korea, both Sympetrum depressiusculum Sélys, 1841 (Odonata: Libellulidae), which is distributed throughout Europe and from Russia to the Korean Peninsula, and Sympetrum frequens Sélys, 1883, which is endemic to Japan, are recorded. However, the identity of South Korean populations and the validity of listing the two species have not yet been settled. In this study, we collected seventy-four individuals of Sympetrum species from South Korea (five localities), Russia, The Netherlands, and Japan. These samples were examined for morphology and sequenced for partial COI, 16S rRNA, and a nuclear internal spacer (ITS) region, after which these molecular data were combined with available public data from Russia, Japan, and The Netherlands. Major morphological characters that have been used to distinguish the two species and phylogenetic, network, and structure analyses all consistently suggest that South Korean populations form a single species. Consequently, it could be valid to treat South Korean populations as one species, S. depressiusculum, by applying the senior name. Nevertheless, the validity of maintaining each as an independent species in other countries may need additional study considering that our samples were focused more on South Korea and limited for Europe, Russia, and Japan.
Insights into Brochosome Distribution, Synthesis, and Novel Rapid-Release Mechanism in Maiestas dorsalis (Hemiptera: Cicadellidae)
Authors: Wu Wei , Lei Jia-Ning , Mao Qianzhuo , Tian Yan-Zhen , Shan Hong-Wei , Chen Jian-Ping
Published: August 2023

The leafhopper family Cicadellidae, comprising over 22,000 species, exhibits a unique behavior of anointing their bodies with excretions containing brochosomes. Brochosomes are synthesized in the distal segment of the Malpighian tubules and serve various functions, including hydrophobic protection and defense against pathogens and predators. In this study, we investigated the distribution, synthesis, and release mechanisms of brochosomes in the rice pest leafhopper Maiestas dorsalis. Using SEM and TEM, we observed brochosomes’ consistent coverage on the integument throughout the insect’s life cycle. Moreover, we identified four distinct developmental stages of brochosome synthesis within the distal segment of the Malpighian tubules, originating from the Golgi region. Most importantly, our research revealed a novel and highly efficient release mechanism involving the fusion of brochosome-containing vesicles, leading to a rapid and substantial release of brochosomes into the tubule lumen after molting. These findings shed light on the intricate processes of brochosome synthesis and release in leafhoppers, offering valuable insights into their functional significance and ecological role in these fascinating insects.
Sequential and Simultaneous Interactions of Plant Allelochemical Flavone, Bt Toxin Vip3A, and Insecticide Emamectin Benzoate in Spodoptera frugiperda
Authors: Huang Kaiyuan , He Haibo , Wang Shan , Zhang Min , Chen Xuewei , Deng Zhongyuan , Ni Xinzhi , Li Xianchun
Published: August 2023

Target pests of genetically engineered crops producing both defensive allelochemicals and Bacillus thuringiensis (Bt) toxins often sequentially or simultaneously uptake allelochemicals, Bt toxins, and/or insecticides. How the three types of toxins interact to kill pests remains underexplored. Here we investigated the interactions of Bt toxin Vip3A, plant allelochemical flavone, and insecticide emamectin benzoate in Spodoptera frugiperda. Simultaneous administration of flavone LC25 + Vip3A LC25, emamectin benzoate LC25 + Vip3A LC25, and flavone LC15 + emamectin benzoate LC15 + Vip3A LC15 but not flavone LC25 + emamectin LC25 yielded a mortality significantly higher than their expected additive mortality (EAM). One-day pre-exposure to one toxin at LC5 followed by six-day exposure to the same toxin at LC5 plus another toxin at LC50 showed that the mortality of flavone LC5 + Vip3A LC50, emamectin benzoate LC5 + Vip3A LC50, and Vip3A LC5 + emamectin benzoate LC50 were significantly higher than their EAM, while that of flavone LC5 + emamectin benzoate LC50 was significantly lower than their EAM. No significant difference existed among the mortalities of Vip3A LC5 + flavone LC50, emamectin benzoate LC5 + flavone LC50, and their EAMs. The results suggest that the interactions of the three toxins are largely synergistic (inductive) or additive, depending on their combinations and doses.
Microbiome and MicroRNA or Long Non-Coding RNA—Two Modern Approaches to Understanding Pancreatic Ductal Adenocarcinoma
Authors: Izdebska Wiktoria Maria , Daniluk Jaroslaw , Niklinski Jacek
Published: August 2023

Pancreatic ductal adenocarcinoma (PDAC) is one of humans’ most common and fatal neoplasms. Nowadays, a number of PDAC studies are being conducted in two different fields: non-coding RNA (especially microRNA and long non-coding RNA) and microbiota. It has been recently discovered that not only does miRNA affect particular bacteria in the gut microbiome that can promote carcinogenesis in the pancreas, but the microbiome also has a visible impact on the miRNA. This suggests that it is possible to use the combined impact of the microbiome and noncoding RNA to suppress the development of PDAC. Nevertheless, insufficient research has focused on bounding both approaches to the diagnosis, treatment, and prevention of pancreatic ductal adenocarcinoma. In this article, we summarize the recent literature on the molecular basis of carcinogenesis in the pancreas, the two-sided impact of particular types of non-coding RNA and the pancreatic cancer microbiome, and possible medical implications of the discovered phenomenon.
Serological Responses and Predictive Factors of Booster COVID-19 Vaccines in Patients with Hematologic Malignancies
Authors: Huang Chien-Tzu , Lee Ching-Ping , Chen Tzu-Yin , Liu Yi-Chang , Cho Shih-Feng , Du Jeng-Shiun , Yu Ming-Lung , Huang Chung-Feng , Wang Sheng-Fan , Hsiao Hui-Hua
Published: August 2023

Patients with hematologic malignancies are reported to have a more severe course of coronavirus disease 2019 (COVID-19) and be less responsive to vaccination. In this prospective study, we aimed to evaluate the serological responses to booster COVID-19 vaccines of Taiwanese patients with hematologic malignancies and identify potential predictive markers for effective neutralizing immunity. This study enrolled 68 patients with hematologic malignancies and 68 age- and gender-matched healthy control subjects who received three doses of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 1 January 2022 to 31 October 2022. The SARS-CoV-2 immunoglobulin G (IgG) spike antibody level was measured with the Abbott assay. The effective neutralization capacity was defined as an anti-spike IgG level of ≥4160 AU/mL. Among the 68 patients with hematologic malignancies, 89.7% achieved seroconversion after booster doses. Seven patients with actively treated lymphoma remained seronegative and had the lowest humoral responses among patients with different types of hematologic malignancies. Despite comparable antibody titers between patients and healthy individuals, rates of effective neutralization (66.2% vs. 86.8%, respectively; p = 0.005) were significantly reduced in patients with hematologic malignancies. In a multivariate analysis, the independent predictors for effective neutralization were a lack of B-cell-targeted agents within six months of vaccination (odds ratio, 15.2; 95% confidence interval, 2.7–84.2; p = 0.002) and higher immunoglobulin levels (odds ratio, 4.4; 95% confidence interval, 1.3–14.7; p = 0.017). In conclusion, the majority of patients with hematologic malignancies achieved seroconversion after booster vaccination. Patients with ongoing B-cell depletion and hypogammaglobinemia were identified as having negative predictive markers for effective neutralization.
Impact of COVID-19 Era on the Anterior Cruciate Ligament Injury Rehabilitation: A Scoping Review
Authors: Marotta Nicola , de Sire Alessandro , Calafiore Dario , Agostini Francesco , Lippi Lorenzo , Curci Claudio , Ferraro Francesco , Bernetti Andrea , Invernizzi Marco , Ammendolia Antonio
Published: August 2023

The surgical intervention rate and the subsequent rehabilitation plan for anterior cruciate ligament (ACL) injury was crucially affected by the COVID-19 pandemic due to the necessity in the face of the emergency. This review aimed to evaluate potential persistent and residual symptoms after COVID-19 disease, including fatigue and neuromuscular disorders. A scoping review design and methodology were used due to the exploratory nature of the research question, according to literature searches on PubMed/Medline, Scopus, Web of Science (WoS), and Physiotherapy Evidence Database (PEDro) electronic databases using the following keywords: “Anterior Cruciate Ligament”, “ACL”, “SARS-CoV-2”, and “COVID-19”. Undertraining and muscular knee imbalance might cause inefficient movement strategies, lack of knee stability, and increasing load with negative implications in ACL injuries. In the post-surgery period, during COVID-19, telerehabilitation approaches appeared to be successfully applied to maintain strength and range of motion in this condition. However, no definitive data are available regarding the most effective interventions. This scoping review showed the influence of the COVID-19 pandemic and associated restrictions on postoperative and rehabilitative care of ACL injuries.
New Effective Intraoperative Techniques for the Prevention of Coronal Imbalance after Circumferential Minimally Invasive Correction Surgery for Adult Spinal Deformity
Authors: Ishihara Masayuki , Taniguchi Shinichirou , Ono Naoto , Adachi Takashi , Tani Yoichi , Paku Masaaki , Kawashima Koki , Ando Muneharu , Saito Takanori
Published: August 2023

This study aimed to devise measures and investigate their effect on coronal imbalance (CI) after circumferential minimally invasive correction surgery (CMIS) with lateral lumbar interbody fusion and percutaneous pedicle screw for adult spinal deformity (ASD). A total of 115 patients with ASD who underwent CMIS from the lower thoracic spine to the ilium were included. Patients were stratified based on the distance between the spinous process of the upper instrumented vertebra and central sacrum vertical line (UIV-CSVL) after the first intraoperative rod application into groups P (UIV-CSVL > 10 mm, n = 50) and G (UIV-CSVL < 10 mm, n = 65). Measures to correct postoperative CI introduced during surgery, preoperative and postoperative UIV-CSVL, and changes in UIV-CSVL after various measures (ΔUIV-CSVL) were investigated in group P. Rod rotation (RR), S2 alar-iliac screw distraction (SD), and kickstand-rod (KR) technique were performed in group P. Group P was further divided into group RR (n = 38), group SD (RR and SD) (n = 7), and group KR (RR and KR) (n = 5); the ΔUIV-CSVLs were 13.9 mm, 20.1 mm, and 24.4 mm in these three groups, respectively. Postoperative C7-CSVL < 10 mm was achieved in all three correction groups. In conclusion, our measures enabled sufficient correction of the UIV-CSVL and are useful for preventing CI after CMIS for ASD.
Rehabilitation in Older Adults Affected by Immobility Syndrome, Aided by Virtual Reality Technology: A Narrative Review
Authors: Zak Marek , Wasik Magdalena , Sikorski Tomasz , Aleksandrowicz Krzysztof , Miszczuk Renata , Courteix Daniel , Dutheil Frederic , Januszko-Szakiel Aneta , Brola Waldemar
Published: August 2023

Individual mobility deficit in older adults induces a variety of medical conditions, diminishing their functional capacity in pursuing activities of daily living. In immobility syndrome patients, such conditions are prone further deterioration through a drastically reduced scope of physical activity, owing mostly to poor self-motivation and the monotonous character of conventional rehabilitation regimens. As evidenced by published research, virtual reality technology solutions in rehabilitation management actually add significantly to patients’ self-motivation, while promoting their active involvement in therapy through visual, auditory, and kinaesthetic stimuli. Effective rehabilitation training aided by virtual reality solutions helps patients acquire specific physical and cognitive skills to be subsequently emulated in the real-world environment. The extra added advantage lies in facilitating such training within patients’ own home environments, combined with online monitoring of their progress, when not personally supervised by a physiotherapist, which also boosts the overall cost effectiveness of the therapeutic management itself. This narrative review appears to be the very first one principally focused on critically comparing individual immobilisation with immobility syndrome, especially through the application of the Authors’ own substantial hands-on therapeutic experience in managing various rehabilitation schemes, specifically aided by diverse virtual reality technology solutions.
Comparative Biocompatibility and Odonto-/Osteogenesis Effects of Hydraulic Calcium Silicate-Based Cements in Simulated Direct and Indirect Approaches for Regenerative Endodontic Treatments: A Systematic Review
Authors: Yousefi-Koma Amir-Ali , Assadian Hadi , Mohaghegh Sadra , Nokhbatolfoghahaei Hanieh
Published: August 2023

Background: Regenerative dentistry is the operation of restoring dental, oral and maxillofacial tissues. Currently, there are no guidelines for the ideal cement/material in regenerative endodontic treatments (RET). Hydraulic calcium silicate-based cements (hCSCs) are currently the material of choice for RET. Objectives: This systematic review was conducted to gather all of the different direct and indirect approaches of using hCSCs in RET in vitro and in vivo, and to ascertain if there are any superiorities to indirect approaches. Methods and Materials: This systematic review was conducted according to the 2020 PRISMA guidelines. The study question according to the PICO format was as follows: Comparison of the biological behavior (O) of stem cells (P) exposed to hCSCs through direct and indirect methods (I) with untreated stem cells (C). An electronic search was executed in Scopus, Google Scholar, and PubMed. Results: A total of 78 studies were included. Studies were published between 2010 and 2022. Twenty-eight commercially available and eighteen modified hCSCs were used. Seven exposure methods (four direct and three indirect contacts) were assessed. ProRoot MTA and Biodentine were the most used hCSCs and had the most desirable results. hCSCs were either freshly mixed or set before application. Most studies allowed hCSCs to set in incubation for 24 h before application, which resulted in the most desirable biological outcomes. Freshly mixed hCSCs had the worst outcomes. Indirect methods had significantly better viability/proliferation and odonto-/osteogenesis outcomes. Conclusion: Biodentine and ProRoot MTA used in indirect exposure methods result in desirable biological outcomes.