bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficiency Optimization in Parallel LLC Resonant Inverters with Current-Controlled Variable-Inductor and Phase Shift for Induction Heating
Authors: Bellido Juan L. , Esteve Vicente , Jordán José
Published: July 2024

This paper presents a comprehensive analysis of a novel control approach to improve the efficiency of parallel LLC resonant inverters using a combination of a current controlled variable inductor (VI) and phase shift (PS). The proposed control aims to reduce the Root Mean Square (RMS) current, thereby reducing conduction and switching losses, and improving power transfer efficiency, while considering zero-voltage-switching (ZVS) operation, output power variations and load changes. Furthermore, a design methodology for the variable inductor is proposed, and design considerations relevant to this application are discussed. The effectiveness of the proposed approach is evaluated through mathematical modeling and experimental results. The mathematical modeling results show that the proposed approach, utilizing SiC MOSFETs, maintains a maximum efficiency of 98.5% for a 20 kW inverter over a wider range of output power, which is a significant improvement over existing approaches. The experimental results also confirm the effectiveness of the proposed control in improving the efficiency of parallel LLC resonant inverters.
Demonstration Project: 1.86 MWH Battery Energy Storage System and 540 KVA Inverter Integration
Authors: Gullu Sahin , Djaho Amour-che , Mensah Adje , Batarseh Issa
Published: July 2024

This research focused on the implementation of state-of-the-art system integration, involving a three-phase 540 KVA bidirectional inverter and a lithium-ion battery energy storage system with a capacity of 1.86 MWh, at the Florida Solar Energy Center (FSEC). The system was firstly put into use at the FSEC for load shifting. The second step was to add photovoltaic (PV) panels for peak shaving. The third step was to take the FSEC completely off-grid. The goal of this research was to provide a case study by implementing a power management algorithm, estimating the PV panel size, and presenting the test results and an analysis. Based on the power management algorithm, load shifting was achieved by using 180 kWh energy storage. To acquire peak shaving and the uniformity of power consumption, an 80 kW PV farm was sufficient. The optimal PV panel size was 500 kW for the off-grid scenario.
Using Knowledge Graphs to Analyze the Characteristics and Trends of Forest Carbon Storage Research at the Global Scale
Authors: Li Jie , Wang Jinliang , He Suling , Liu Chenli , Liu Lanfang
Published: July 2024

Research on forest carbon storage (FCS) is crucial for the sustainable development of human society given the context of global climate change. Previous FCS studies formed the science base of the FCS field but lacked a macrolevel knowledge summary. This study combined the scientometric mapping tool VOSviewer and multiple statistical models to conduct a comprehensive knowledge graph mining and analysis of global FCS papers (covering 101 countries, 1712 institutions, 5435 authors, and 276 journals) in the Web of Science database as of 2022, focusing on revealing the macro spatiotemporal pattern, multidimensional research status, and topic evolution process of FCS research at the global scale, so as to grasp the status of global FCS research more clearly and comprehensively, thereby facilitating the future decision-making and practice of researchers. The results showed the following: (1) In the past three decades, the number of FCS papers indicated an increasing trend, with a growth rate of 4.66/yr, particularly significant after 2010. These papers were mainly from Europe, the Americas, and Asia, while there was a huge gap between Africa, Oceania, and the above regions. (2) For the research status at the national, institutional, scholar, and journal levels, the USA, with 331 FCS papers and 18,653 total citations, was the most active and influential country in global FCS research; the United States Forest Service topped the influential ranking with 4115 citations; Grant M. Domke and Jerome Chave were the most active and influential FCS researchers globally, respectively. China’s activity (237 papers) and influence (5403 citations) ranked second, and the Chinese Academy of Sciences was the most active research institution in the world. Currently, FCS research is published in a growing number of journals, among which Forest Ecology and Management ranked first in the number of papers (154 papers) and citations (6374 citations). (3) In recent years, the keyword frequency of monitoring methods, driving factors, and reasonable management for FCS has increased rapidly, and many new related keywords have emerged, which means that researchers are not only focusing on the estimation and monitoring of FCS but also increasingly concerned about its driving mechanism and sustainable development.
Comparative Cytological and Gene Expression Analysis Reveals That a Common Wild Rice Inbred Line Showed Stronger Drought Tolerance Compared with the Cultivar Rice
Authors: Huang Zijuan , Huang Peishan , Chen Shihui , Hu Mengzhu , Yu Hang , Guo Haibin , Shahid Muhammad Qasim , Liu Xiangdong , Wu Jinwen
Published: July 2024

Common wild rice (Oryza rufipogon Griff.) is an important germplasm resource containing valuable genes. Our previous analysis reported a stable wild rice inbred line, Huaye3, which derives from the common wild rice of Guangdong Province. However, there was no information about its drought tolerance ability. Here, we assessed the germination characteristics and seedling growth between the Dawennuo and Huaye3 under five concentrations of PEG6000 treatment (0, 5%, 10%, 15%, and 20%). Huaye3 showed a stronger drought tolerance ability, and its seed germination rate still reached more than 52.50% compared with Dawennuo, which was only 25.83% under the 20% PEG6000 treatment. Cytological observations between the Dawennuo and Huaye3 indicated the root tip elongation zone and buds of Huaye3 were less affected by the PEG6000 treatment, resulting in a lower percentage of abnormalities of cortical cells, stele, and shrinkage of epidermal cells. Using the re-sequencing analysis, we detected 13,909 genes that existed in the genetic variation compared with Dawennuo. Of these genes, 39 were annotated as drought stress-related genes and their variance existed in the CDS region. Our study proved the strong drought stress tolerance ability of Huaye3, which provides the theoretical basis for the drought resistance germplasm selection in rice.
Anti-Neuroinflammatory Effects of a Novel Bile Acid Derivative
Authors: Bjedov Srđan , Stegnjaić Goran , Stanisavljević Suzana , Lazarević Milica , Pilipović Ivan , Sakač Marija , Miljković Đorđe
Published: July 2024

In the search for novel potent immunomodulatory nuclear factor-erythroid 2 related factor 2 (Nrf2) activators, a derivative of cholic bile acid, SB140, was synthesized. The synthesis of SB140 aimed to increase the electrophilic functionality of the compound, enhancing its ability to activate Nrf2. Effects of SB140 on microglial cells, myeloid-derived cells (MDC), and T cells were explored in the context of (central nervous system) CNS autoimmunity. SB140 potently activated Nrf2 signaling in MDC and microglia. It was efficient in reducing the ability of microglial cells to produce inflammatory nitric oxide, interleukin (IL)-6, and tumor necrosis factor (TNF). Also, SB140 reduced the proliferation of encephalitogenic T cells and the production of their effector cytokines: IL-17 and interferon (IFN)-γ. On the contrary, the effects of SB140 on anti-inflammatory IL-10 production in microglial and encephalitogenic T cells were limited or absent. These results show that SB140 is a potent Nrf2 activator, as well as an immunomodulatory compound. Thus, further research on the application of SB140 in the treatment of neuroinflammatory diseases is warranted. Animal models of multiple sclerosis and other inflammatory neurological disorders will be a suitable choice for such studies.
Pilot Study for Isolation of Stromal Vascular Fraction with Collagenase Using an Automated Processing System
Authors: Zinger Gershon , Gronovich Yoav , Lotan Adi Maisel , Sharon-Gabbay Racheli
Published: July 2024

There are many potential therapeutic applications for autologous adipose-derived stromal cells. These cells are found in a heterogeneous population isolated from adipose tissue called the stromal vascular fraction (SVF). Closed automated systems are available to release cells from the adherent stroma. Here, we test one system to evaluate the heterogeneous output for yield, purity, cellular characterization, and stemness criteria. The SVF was isolated from three donors using the Automated Cell Station (ACS) from BSL Co., Ltd., Busan, Republic of Korea. The SVF cellular output was characterized for cell yield and viability, immunophenotyping analysis, pluripotent differentiation potential, adhesion to plastic, and colony-forming units. Additionally, the SVF was tested for endotoxin and collagenase residuals. The SVF yield from the ACS system was an average volume of 7.9 ± 0.5 mL containing an average of 19 × 106 nucleated cells with 85 ± 12% viability. Flow cytometry identified a variety of cells, including ASCs (23%), macrophages (24%), endothelial cells (5%), pericytes (4%), and transitional cells (0.5%). The final concentrated product contained cells capable of differentiating into adipogenic, chondrogenic, and osteogenic phenotypes. Furthermore, tests for SVF sterility and purity showed no evidence of endotoxin or collagenase residuals. The ACS system can efficiently process cells from adipose tissue within the timeframe of a single surgical procedure. The cellular characterization indicated that this system can yield a sterile and concentrated SVF output, providing a valuable source of ASCs within the heterogeneous cell population.
Special Issue “Antimicrobial Biomaterials: Recent Progress”
Authors: Felgueiras Helena P.
Published: July 2024

Biomaterials have demonstrated their ability to serve as effective drug delivery platforms, enabling targeted and localized administration of therapeutic agents [...]
The Effects of Different Doses of Canthaxanthin in the Diet of Laying Hens on Egg Quality, Physical Characteristics, Metabolic Mechanism, and Offspring Health
Authors: Zhang Junnan , Mao Zhiqiong , Zheng Jiangxia , Sun Congjiao , Xu Guiyun
Published: July 2024

Currently, there is a dearth of in-depth analysis and research on the impact of canthaxanthin on the production performance, egg quality, physical characteristics, and offspring health of laying hens. Furthermore, the metabolic mechanism of cantharidin in the body remains unclear. Therefore, to solve the above issues in detail, our study was conducted with a control group (C group), a low-dose canthaxanthin group (L group), and a high-dose canthaxanthin group (H group), each fed for a period of 40 days. Production performance was monitored during the experiment, in which L and H groups showed a significant increase in ADFI. Eggs were collected for quality analysis, revealing no significant differences in qualities except for yolk color (YC). The YC of the C group almost did not change, ranging from 6.08 to 6.20; however, the trend in YC change in other groups showed an initial intense increase, followed by a decrease, and eventually reached dynamic equilibrium. By detecting the content of canthaxanthin in the yolk, the YC change trend was found to be correlated with canthaxanthin levels in the yolk. The content of unsaturated fatty acid increased slightly in L and H groups. Following the incubation period, the physical characteristics and blood biochemical indices of chicks were evaluated. It was observed that the shank color of chicks in the L and H groups was significantly higher than that in the C group at birth. However, by the 35th day, there were no significant differences in shank color among the three groups. Further investigation into the metabolic mechanism involving canthaxanthin revealed that the substance underwent incomplete metabolism upon entering the body, resulting in its accumulation as well as metabolic by-product accumulation in the yolk. In summary, this study highlighted the importance of understanding canthaxanthin’s role in production performance, egg quality, and offspring health, providing valuable insights for breeders to optimize feeding strategies.
May I Help You with Your Coat? HIV-1 Capsid Uncoating and Reverse Transcription
Authors: Arribas Laura , Menéndez-Arias Luis , Betancor Gilberto
Published: July 2024

The human immunodeficiency virus type 1 (HIV-1) capsid is a protein core formed by multiple copies of the viral capsid (CA) protein. Inside the capsid, HIV-1 harbours all the viral components required for replication, including the genomic RNA and viral enzymes reverse transcriptase (RT) and integrase (IN). Upon infection, the RT transforms the genomic RNA into a double-stranded DNA molecule that is subsequently integrated into the host chromosome by IN. For this to happen, the viral capsid must open and release the viral DNA, in a process known as uncoating. Capsid plays a key role during the initial stages of HIV-1 replication; therefore, its stability is intimately related to infection efficiency, and untimely uncoating results in reverse transcription defects. How and where uncoating takes place and its relationship with reverse transcription is not fully understood, but the recent development of novel biochemical and cellular approaches has provided unprecedented detail on these processes. In this review, we present the latest findings on the intricate link between capsid stability, reverse transcription and uncoating, the different models proposed over the years for capsid uncoating, and the role played by other cellular factors on these processes.
Editorial of Special Issue “The Role of Vitamin D in Human Health and Diseases 3.0”
Authors: Silvagno Francesca , Bergandi Loredana
Published: July 2024

After the successful collection of studies published in the past two Special Issues on the role of vitamin D in health and disease, this Special Issue, titled “The Role of Vitamin D in Human Health and Diseases 3 [...]
Transcriptome Analysis Reveals the Role of Sucrose in the Production of Latilactobacillus sakei L3 Exopolysaccharide
Authors: Wang Binbin , Wu Baomei , Xu Min , Zuo Kaiyue , Han Ye , Zhou Zhijiang
Published: July 2024

Latilactobacillus (L.) sakei is a species of lactic acid bacteria (LAB) mostly studied according to its application in food fermentation. Previously, L. sakei L3 was isolated by our laboratory and possessed the capability of high exopolysaccharide (EPS) yield during sucrose-added fermentation. However, the understanding of sucrose promoting EPS production is still limited. Here, we analyzed the growth characteristics of L. sakei L3 and alterations of its transcriptional profiles during sucrose-added fermentation. The results showed that L. sakei L3 could survive between pH 4.0 and pH 9.0, tolerant to NaCl (<10%, w/v) and urea (<6%, w/v). Meanwhile, transcriptomic analysis showed that a total of 426 differentially expressed genes and eight non-coding RNAs were identified. Genes associated with sucrose metabolism were significantly induced, so L. sakei L3 increased the utilization of sucrose to produce EPS, while genes related to uridine monophosphate (UMP), fatty acids and folate synthetic pathways were significantly inhibited, indicating that L. sakei L3 decreased self-growth, substance and energy metabolism to satisfy EPS production. Overall, transcriptome analysis provided valuable insights into the mechanisms by which L. sakei L3 utilizes sucrose for EPS biosynthesis. The study provided a theoretical foundation for the further application of functional EPS in the food industry.
Narrative Review of the Current and Future Perspectives of Phycobiliproteins’ Applications in the Food Industry: From Natural Colors to Alternative Proteins
Authors: Minić Simeon , Gligorijević Nikola , Veličković Luka , Nikolić Milan
Published: July 2024

Vivid-colored phycobiliproteins (PBPs) have emerging potential as food colors and alternative proteins in the food industry. However, enhancing their application potential requires increasing stability, cost-effective purification processes, and consumer acceptance. This narrative review aimed to highlight information regarding the critical aspects of PBP research that is needed to improve their food industry potential, such as stability, food fortification, development of new PBP-based food products, and cost-effective production. The main results of the literature review show that polysaccharide and protein-based encapsulations significantly improve PBPs’ stability. Additionally, while many studies have investigated the ability of PBPs to enhance the techno-functional properties, like viscosity, emulsifying and stabilizing activity, texture, rheology, etc., of widely used food products, highly concentrated PBP food products are still rare. Therefore, much effort should be invested in improving the stability, yield, and sensory characteristics of the PBP-fortified food due to the resulting unpleasant sensory characteristics. Considering that most studies focus on the C-phycocyanin from Spirulina, future studies should concentrate on less explored PBPs from red macroalgae due to their much higher production potential, a critical factor for positioning PBPs as alternative proteins.
Exercise Rescues Obesogenic-Related Genes in the Female Hypothalamic Arcuate Nucleus: A Potential Role of miR-211 Modulation
Authors: Rapps Kayla , Marco Asaf , Pe’er-Nissan Hilla , Kisliouk Tatiana , Stemp Gabrielle , Yadid Gal , Weller Aron , Meiri Noam
Published: July 2024

Obesity is a major public health concern that is associated with negative health outcomes. Exercise and dietary restriction are commonly recommended to prevent or combat obesity. This study investigates how voluntary exercise mitigates abnormal gene expression in the hypothalamic arcuate nucleus (ARC) of diet-induced obese (DIO) rats. Using a transcriptomic approach, novel genes in the ARC affected by voluntary wheel running were assessed alongside physiology, pharmacology, and bioinformatics analysis to evaluate the role of miR-211 in reversing obesity. Exercise curbed weight gain and fat mass, and restored ARC gene expression. High-fat diet (HFD) consumption can dysregulate satiety/hunger mechanisms in the ARC. Transcriptional clusters revealed that running altered gene expression patterns, including inflammation and cellular structure genes. To uncover regulatory mechanisms governing gene expression in DIO attenuation, we explored miR-211, which is implicated in systemic inflammation. Exercise ameliorated DIO overexpression of miR-211, demonstrating its pivotal role in regulating inflammation in the ARC. Further, in vivo central administration of miR-211-mimic affected the expression of immunity and cell cycle-related genes. By cross-referencing exercise-affected and miR-211-regulated genes, potential candidates for obesity reduction through exercise were identified. This research suggests that exercise may rescue obesity through gene expression changes mediated partially through miR-211.
IL-8 Induces Neutrophil Extracellular Trap Formation in Severe Thermal Injury
Authors: Asiri Ali , Hazeldine Jon , Moiemen Naiem , Harrison Paul
Published: July 2024

Neutrophil extracellular traps (NETs) have a dual role in the innate immune response to thermal injuries. NETs provide an early line of defence against infection. However, excessive NETosis can mediate the pathogenesis of immunothrombosis, disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) in sepsis. Recent studies suggest that high interleukin-8 (IL-8) levels in intensive care unit (ICU) patients significantly contribute to excessive NET generation. This study aimed to determine whether IL-8 also mediates NET generation in patients with severe thermal injuries. IL-8 levels were measured in serum samples from thermally injured patients with ≥15% of the total body surface area (TBSA) and healthy controls (HC). Ex vivo NET generation was also investigated by treating isolated neutrophils with serum from thermal injured patients or normal serum with and without IL-8 and anti-IL-8 antibodies. IL-8 levels were significantly increased compared to HC on days 3 and 5 (p < 0.05) following thermal injury. IL-8 levels were also significantly increased at day 5 in septic versus non-septic patients (p < 0.001). IL-8 levels were also increased in patients who developed sepsis compared to HC at days 3, 5 and 7 (p < 0.001), day 10 (p < 0.05) and days 12 and 14 (p < 0.01). Serum containing either low, medium or high levels of IL-8 was shown to induce ex vivo NETosis in an IL-8-dependent manner. Furthermore, the inhibition of DNase activity in serum increased the NET-inducing activity of IL-8 in vitro by preventing NET degradation. IL-8 is a major contributor to NET formation in severe thermal injury and is increased in patients who develop sepsis. We confirmed that DNase is an important regulator of NET degradation but also a potential confounder within assays that measure serum-induced ex vivo NETosis.
Treatment of Allergies to Fur Animals
Authors: Rosada Tomasz , Bartuzi Zbigniew , Grześk-Kaczyńska Magdalena , Rydzyńska Magdalena , Ukleja-Sokołowska Natalia
Published: July 2024

Allergy to fur animals is becoming an increasingly common clinical problem in everyday medical practice. Depending on the route of exposure to the allergen, patients present with many, often non-specific symptoms. The most common illnesses among people with allergies to the above-mentioned allergens are as follows: allergic rhinitis, allergic conjunctivitis, atopic bronchial asthma, food allergy, allergic contact dermatitis, and sometimes anaphylactic shock. In recent years, there has been a change in the holistic approach to the treatment of allergy patients. The method of treatment should be tailored to a specific patient, taking into account his or her predispositions, economic possibilities, and therapeutic goals. The article describes the main methods of treating allergies, focusing primarily on allergies to fur animals. Allergy treatment always requires great care, and qualification for specific types of therapy should be preceded by a thorough and accurate diagnosis.
Mass Spectrometry-Based Proteomic Analysis of Potential Host Proteins Interacting with N in PRRSV-Infected PAMs
Authors: Zhao Shijie , Li Fahao , Li Wen , Wang Mengxiang , Wang Yueshuai , Zhang Yina , Xia Pingan , Chen Jing
Published: July 2024

One of the most significant diseases in the swine business, porcine reproductive and respiratory syndrome virus (PRRSV) causes respiratory problems in piglets and reproductive failure in sows. The PRRSV nucleocapsid (N) protein is essential for the virus’ assembly, replication, and immune evasion. Stages in the viral replication cycle can be impacted by interactions between the PRRSV nucleocapsid protein and the host protein components. Therefore, it is of great significance to explore the interaction between the PRRSV nucleocapsid protein and the host. Nevertheless, no information has been published on the network of interactions between the nucleocapsid protein and the host proteins in primary porcine alveolar macrophages (PAMs). In this study, 349 host proteins interacting with nucleocapsid protein were screened in the PRRSV-infected PAMs through a liquid chromatography–tandem mass spectrometry (LC–MS/MS)-based proteomics approach. Bioinformatics analysis, which included gene ontology annotation, Kyoto Encyclopedia of Genes and Genomes database enrichment, and a protein–protein interaction (PPI) network, revealed that the host proteins interacting with PRRSV-N may be involved in protein binding, DNA transcription, metabolism, and innate immune responses. This study confirmed the interaction between the nucleocapsid protein and the natural immune-related proteins. Ultimately, our findings suggest that the nucleocapsid protein plays a pivotal role in facilitating immune evasion during a PRRSV infection. This study contributes to enhancing our understanding of the role played by the nucleocapsid protein in viral pathogenesis and virus–host interaction, thereby offering novel insights for the prevention and control of PRRS as well as the development of vaccines.
TGC-ARG: Anticipating Antibiotic Resistance via Transformer-Based Modeling and Contrastive Learning
Authors: Dong Yihan , Quan Hanming , Ma Chenxi , Shan Linchao , Deng Lei
Published: July 2024

In various domains, including everyday activities, agricultural practices, and medical treatments, the escalating challenge of antibiotic resistance poses a significant concern. Traditional approaches to studying antibiotic resistance genes (ARGs) often require substantial time and effort and are limited in accuracy. Moreover, the decentralized nature of existing data repositories complicates comprehensive analysis of antibiotic resistance gene sequences. In this study, we introduce a novel computational framework named TGC-ARG designed to predict potential ARGs. This framework takes protein sequences as input, utilizes SCRATCH-1D for protein secondary structure prediction, and employs feature extraction techniques to derive distinctive features from both sequence and structural data. Subsequently, a Siamese network is employed to foster a contrastive learning environment, enhancing the model’s ability to effectively represent the data. Finally, a multi-layer perceptron (MLP) integrates and processes sequence embeddings alongside predicted secondary structure embeddings to forecast ARG presence. To evaluate our approach, we curated a pioneering open dataset termed ARSS (Antibiotic Resistance Sequence Statistics). Comprehensive comparative experiments demonstrate that our method surpasses current state-of-the-art methodologies. Additionally, through detailed case studies, we illustrate the efficacy of our approach in predicting potential ARGs.
Piezo1 Activation Drives Enhanced Collagen Synthesis in Aged Animal Skin Induced by Poly L-Lactic Acid Fillers
Authors: Byun Kyung-A , Lee Je Hyuk , Lee So Young , Oh Seyeon , Batsukh Sosorburam , Cheon Gwahn-woo , Lee Dongun , Hong Jeong Hee , Son Kuk Hui , Byun Kyunghee
Published: July 2024

Poly L-lactic acid (PLLA) fillers stimulate collagen synthesis by activating various immune cells and fibroblasts. Piezo1, an ion channel, responds to mechanical stimuli, including changes in extracellular matrix stiffness, by mediating Ca2+ influx. Given that elevated intracellular Ca2+ levels trigger signaling pathways associated with fibroblast proliferation, Piezo1 is a pivotal regulator of collagen synthesis and tissue fibrosis. The aim of the present study was to investigate the impact of PLLA on dermal collagen synthesis by activating Piezo1 in both an H2O2-induced cellular senescence model in vitro and aged animal skin in vivo. PLLA elevated intracellular Ca2+ levels in senescent fibroblasts, which was attenuated by the Piezo1 inhibitor GsMTx4. Furthermore, PLLA treatment increased the expression of phosphorylated ERK1/2 to total ERK1/2 (pERK1/2/ERK1/2) and phosphorylated AKT to total AKT (pAKT/AKT), indicating enhanced pathway activation. This was accompanied by upregulation of cell cycle-regulating proteins (CDK4 and cyclin D1), promoting the proliferation of senescent fibroblasts. Additionally, PLLA promoted the expression of phosphorylated mTOR/S6K1/4EBP1, TGF-β, and Collagen I/III in senescent fibroblasts, with GsMTx4 treatment mitigating these effects. In aged skin, PLLA treatment similarly upregulated the expression of pERK1/2/ERK1/2, pAKT/AKT, CDK4, cyclin D1, mTOR/S6K1/4EBP1, TGF-β, and Collagen I/III. In summary, our findings suggest Piezo1′s involvement in PLLA-induced collagen synthesis, mediated by heightened activation of cell proliferation signaling pathways such as pERK1/2/ERK1/2, pAKT/AKT, and phosphorylated mTOR/S6K1/4EBP1, underscoring the therapeutic potential of PLLA in tissue regeneration.
A Novel Class I HDAC Inhibitor, AW01178, Inhibits Epithelial–Mesenchymal Transition and Metastasis of Breast Cancer
Authors: Liu Xiangxiang , Chen Yawen , Li Yang , Shen Ying , Dong Shasha , Tan Jiang
Published: July 2024

Epithelial–mesenchymal transition (EMT) refers to the transformation of polar epithelial cells into motile mesenchymal cells under specific physiological or pathological conditions, thus promoting the metastasis of cancer cells. Epithelial cadherin (E-cadherin) is a protein that plays an important role in the acquisition of tumor cell motility and serves as a key EMT epithelial marker. In the present study, AW01178, a small-molecule compound with potential therapeutic efficacy, was identified via in-cell Western high-throughput screening technology using E-cadherin as the target. The compound induced the upregulation of E-cadherin at both mRNA and protein levels and inhibited the EMT of breast cancer cells in vitro as well as metastasis in vivo. Mechanistically, AW01178 is a novel benzacetamide histone deacetylase inhibitor (HDACi) mainly targeting class I histone deacetylases. AW01178 promoted the transcription and expression of E-cadherin through enhancing the acetylation level of histone H3 in the E-cadherin promoter region, thereby inhibiting the metastasis of breast cancer cells. The collective findings support the potential utility of the novel HDACi compound identified in this study, AW01178, as a therapeutic drug for breast cancer and highlight its value for the future development of HDACi structures as anticancer drugs.
Exosomes Derived from Hypertrophic Scar Fibroblasts Suppress Melanogenesis in Normal Human Epidermal Melanocytes
Authors: Cui Hui Song , Joo So Young , Cho Yoon Soo , Lee You Ra , Ro Yu Mi , Kwak In Suk , Hur Gi Yeun , Seo Cheong Hoon
Published: July 2024

Post-burn hypertrophic scars often exhibit abnormal pigmentation. Exosomes play important roles in maintaining normal physiological homeostasis and in the pathological development of diseases. This study investigated the effects of the exosomes derived from hypertrophic scar fibroblasts (HTSFs) on melanocytes, which are pigment-producing cells. Normal fibroblasts (NFs) and HTSFs were isolated and cultured from normal skin and hypertrophic scar (HTS) tissue. Both the NF- and HTSF-exosomes were isolated from a cell culture medium and purified using a column-based technique. The normal human epidermal melanocytes were treated with both exosomes at a concentration of 100 μg/mL at different times. The cell proliferation, melanin content in the medium, apoptotic factors, transcription factors, melanin synthesis enzymes, signaling, signal transduction pathways, and activators of transcription factors (STAT) 1, 3, 5, and 6 were investigated. Compared with the Dulbecco’s phosphate-buffered saline (DPBS)-treated controls and NF-exosomes, the HTSF-exosomes decreased the melanocyte proliferation and melanin secretion. The molecular patterns of apoptosis, proliferation, melanin synthesis, Smad and non-Smad signaling, and STATs were altered by the treatment with the HTSF-exosomes. No significant differences were observed between the DPBS-treated control and NF-exosome-treated cells. HTSF-derived exosomes may play a role in the pathological epidermal hypopigmentation observed in patients with HTS.
Creation of an Isogenic Human iPSC-Based RGC Model of Dominant Optic Atrophy Harboring the Pathogenic Variant c.1861C>T (p.Gln621Ter) in the OPA1 Gene
Authors: García-López Marta , Jiménez-Vicente Lydia , González-Jabardo Raquel , Dorado Helena , Gómez-Manjón Irene , Martín Miguel Ángel , Ayuso Carmen , Arenas Joaquín , Gallardo María Esther
Published: July 2024

Autosomal dominant optic atrophy (ADOA) is a rare progressive disease mainly caused by mutations in OPA1, a nuclear gene encoding for a mitochondrial protein that plays an essential role in mitochondrial dynamics, cell survival, oxidative phosphorylation, and mtDNA maintenance. ADOA is characterized by the degeneration of retinal ganglion cells (RGCs). This causes visual loss, which can lead to legal blindness in many cases. Nowadays, there is no effective treatment for ADOA. In this article, we have established an isogenic human RGC model for ADOA using iPSC technology and the genome editing tool CRISPR/Cas9 from a previously generated iPSC line of an ADOA plus patient harboring the pathogenic variant NM_015560.3: c.1861C>T (p.Gln621Ter) in heterozygosis in OPA1. To this end, a protocol based on supplementing the iPSC culture media with several small molecules and defined factors trying to mimic embryonic development has been employed. Subsequently, the created model was validated, confirming the presence of a defect of intergenomic communication, impaired mitochondrial respiration, and an increase in apoptosis and ROS generation. Finally, we propose the analysis of OPA1 expression by qPCR as an easy read-out method to carry out future drug screening studies using the created RGC model. In summary, this model provides a useful platform for further investigation of the underlying pathophysiological mechanisms of ADOA plus and for testing compounds with potential pharmacological action.
Sickle Cell Disease and Gut Health: The Influence of Intestinal Parasites and the Microbiome on Angolan Children
Authors: Delgadinho Mariana , Ginete Catarina , Santos Brígida , de Vasconcelos Jocelyne Neto , Arez Ana Paula , Brito Miguel
Published: July 2024

Parasitic infections are a common problem in developing countries and can intensify morbidity in patients with sickle cell disease (SCD), increasing the severity of anemia and the need for transfusions. It has been demonstrated that both helminths and protozoa can affect gut microbiome composition. On the other hand, the presence of specific bacterial communities can also influence parasite establishment. Considering this, our aim was to associate the presence of intestinal parasites with the results of hematological analyses and microbiome composition evaluations in a population of Angolan children with and without SCD. A total of 113 stool samples were collected, and gut microbiome analysis was performed using 16S sequencing and real-time PCR to detect eight different intestinal parasites. In our population, more than half of children (55%) had at least one parasitic infection, and of these, 43% were co-infected. Giardia intestinalis and Ascaris lumbricoides were more frequently found in children from the rural area of Bengo. Moreover, SCD children with ascariasis exhibited higher values of leukocytes and neutrophils, whereas the total hemoglobin levels were lower. In regards to the gut microbiome, the presence of intestinal parasites lowered the prevalence of some beneficial bacteria, namely: Lactobacillus, Bifidobacterium, Cuneatibacter, Bacteroides uniformis, Roseburia, and Shuttleworthia. This study presents the prevalence of several intestinal parasites in a high-risk transmission area with scarce information and opens new perspectives for understanding the interaction between parasites, the microbiome, and SCD.
Self-Assembling Nanoparticle Hemagglutinin Influenza Vaccines Induce High Antibody Response
Authors: Ren Hongying , Zhang Bin , Zhang Xinwei , Wang Tiantian , Hou Xvchen , Lan Xianyong , Pan Chuanying , Wu Jun , Liu Bo
Published: July 2024

As a highly pathogenic avian virus, H5 influenza poses a serious threat to livestock, the poultry industry, and public health security. Hemagglutinin (HA) is both the dominant epitope and the main target of influenza-neutralizing antibodies. Here, we designed a nanoparticle hemagglutinin influenza vaccine to improve the immunogenicity of the influenza vaccine. In this study, HA5 subtype influenza virus was used as the candidate antigen and was combined with the artificially designed double-branch scaffold protein I53_dn5 A and B. A structurally correct and bioactive trimer HA5-I53_dn5B/Y98F was obtained through secretion and purification using an insect baculovirus expression system; I53_dn5A was obtained by purification using a prokaryotic expression system. HA5-I53_dn5B/Y98F and I53_dn5A self-assembled into spherical nanoparticles (HA5-I53_dn5) in vitro with a diameter of about 45 nm. Immunization and serum test results showed that both HA5-I53_dn5B/Y98F and HA5-I53_dn5 could induce HA5-specific antibodies; however, the immunogenicity of HA5-I53_dn5 was better than that of HA5-I53_dn5B/Y98F. Groups treated with HA5-I53_dn5B and HA5-I53_dn5 nanoparticles produced IgG antibody titers that were not statistically different from those of the nanoparticle-containing adjuvant group. This production of trimerized HA5-I53_dn5B and HA5-I53_dn5 nanoparticles using baculovirus expression provides a reference for the development of novel, safe, and efficient influenza vaccines.
Genetic and Epigenetic Biomarkers Linking Alzheimer’s Disease and Age-Related Macular Degeneration
Authors: Kaštelan Snježana , Nikuševa-Martić Tamara , Pašalić Daria , Antunica Antonela Gverović , Zimak Danijela Mrazovac
Published: July 2024

Alzheimer’s disease (AD) represents a prominent neurodegenerative disorder (NDD), accounting for the majority of dementia cases worldwide. In addition to memory deficits, individuals with AD also experience alterations in the visual system. As the retina is an extension of the central nervous system (CNS), the loss in retinal ganglion cells manifests clinically as decreased visual acuity, narrowed visual field, and reduced contrast sensitivity. Among the extensively studied retinal disorders, age-related macular degeneration (AMD) shares numerous aging processes and risk factors with NDDs such as cognitive impairment that occurs in AD. Histopathological investigations have revealed similarities in pathological deposits found in the retina and brain of patients with AD and AMD. Cellular aging processes demonstrate similar associations with organelles and signaling pathways in retinal and brain tissues. Despite these similarities, there are distinct genetic backgrounds underlying these diseases. This review comprehensively explores the genetic similarities and differences between AMD and AD. The purpose of this review is to discuss the parallels and differences between AMD and AD in terms of pathophysiology, genetics, and epigenetics.
Endothelial Protection by Sodium-Glucose Cotransporter 2 Inhibitors: A Literature Review of In Vitro and In Vivo Studies
Authors: Mylonas Nikolaos , Nikolaou Panagiota Efstathia , Karakasis Paschalis , Stachteas Panagiotis , Fragakis Nikolaos , Andreadou Ioanna
Published: July 2024

Endothelial dysfunction often precedes the development of cardiovascular diseases, including heart failure. The cardioprotective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) could be explained by their favorable impact on the endothelium. In this review, we summarize the current knowledge on the direct in vitro effects of SGLT2is on endothelial cells, as well as the systematic observations in preclinical models. Four putative mechanisms are explored: oxidative stress, nitric oxide (NO)-mediated pathways, inflammation, and endothelial cell survival and proliferation. Both in vitro and in vivo studies suggest that SGLT2is share a class effect on attenuating reactive oxygen species (ROS) and on enhancing the NO bioavailability by increasing endothelial nitric oxide synthase activity and by reducing NO scavenging by ROS. Moreover, SGLT2is significantly suppress inflammation by preventing endothelial expression of adhesion receptors and pro-inflammatory chemokines in vivo, indicating another class effect for endothelial protection. However, in vitro studies have not consistently shown regulation of adhesion molecule expression by SGLT2is. While SGLT2is improve endothelial cell survival under cell death-inducing stimuli, their impact on angiogenesis remains uncertain. Further experimental studies are required to accurately determine the interplay among these mechanisms in various cardiovascular complications, including heart failure and acute myocardial infarction.
Exploring the Link between Oxidative Stress, Selenium Levels, and Obesity in Youth
Authors: Bizerea-Moga Teofana Otilia , Pitulice Laura , Bizerea-Spiridon Otilia , Moga Tudor Voicu
Published: July 2024

Obesity is a worldwide increasing concern. Although in adults this is easily estimated with the body mass index, in children, who are constantly growing and whose bodies are changing, the reference points to assess weight status are age and gender, and need corroboration with complementary data, making their quantification highly difficult. The present review explores the interaction spectrum of oxidative stress, selenium status, and obesity in children and adolescents. Any factor related to oxidative stress that triggers obesity and, conversely, obesity that induces oxidative stress are part of a vicious circle, a complex chain of mechanisms that derive from each other and reinforce each other with serious health consequences. Selenium and its compounds exhibit key antioxidant activity and also have a significant role in the nutritional evaluation of obese children. The balance of selenium intake, retention, and metabolism emerges as a vital aspect of health, reflecting the complex interactions between diet, oxidative stress, and obesity. Understanding whether selenium status is a contributor to or a consequence of obesity could inform nutritional interventions and public health strategies aimed at preventing and managing obesity from an early age.
Artificial Neural Network Learning, Attention, and Memory
Authors: Manca Vincenzo
Published: July 2024

The learning equations of an ANN are presented, giving an extremely concise derivation based on the principle of backpropagation through the descendent gradient. Then, a dual network is outlined acting between synapses of a basic ANN, which controls the learning process and coordinates the subnetworks selected by attention mechanisms toward purposeful behaviors. Mechanisms of memory and their affinity with comprehension are considered, by emphasizing the common role of abstraction and the interplay between assimilation and accommodation, in the spirit of Piaget’s analysis of psychological acquisition and genetic epistemology. Learning, comprehension, and knowledge are expressed as different levels of organization of informational processes inside cognitive systems. It is argued that formal analyses of cognitive artificial systems could shed new light on typical mechanisms of “natural intelligence” and, in a specular way, that models of natural cognition processes could promote further developments of ANN models. Finally, new possibilities of chatbot interaction are briefly discussed.
Clinical Workflow Algorithm for Preoperative Planning, Reduction and Stabilization of Complex Acetabular Fractures with the Support of Three-Dimensional Technologies
Authors: Solyom Arpad , Moldovan Flaviu , Moldovan Liviu , Strnad Gabriela , Fodor Pal
Published: July 2024

Background: Treatment of pelvic injuries poses serious problems for surgeons due to the difficulties of the associated injuries. The objective of this research is to create a clinical workflow that integrates three-dimensional technologies in preoperative planning and performing surgery for the reduction and stabilization of associated acetabular fractures. Methods: The research methodology consisted of integrating the stages of virtual preoperative planning, physical preoperative planning, and performing the surgical intervention in a newly developed clinical workflow. The proposed model was validated in practice in a pilot surgical intervention. Results: On a complex pelvic injury case of a patient with an associated both-column acetabular fracture (AO/OTA-62C1g), we presented the results obtained in the six stages of the clinical workflow: acquisition of three-dimensional (3D) images, creation of the virtual model of the pelvis, creation of the physical model of the pelvis, preoperative physical simulation, orthopedic surgery, and imaging validation of the intervention. The life-size 3D model was fabricated based on computed tomography imagistics. To create the virtual model, the images were imported into Invesalius (version 3.1.1, CTI, Brazil), after which they were processed with MeshLab (version 2023.12, ISTI—CNR, Italy) and FreeCAD (version 0.21.2, LGPL, FSF, Boston, MA, USA). The physical model was printed in 21 h and 37 min using Ultimaker Cura software (version 5.7.2), on an Ultimaker 2+ printing machine through a Fused Deposition Modeling process. Using the physical model, osteosynthesis plate dimensions and fixation screw trajectories were tested to reduce the risk of neurovascular injury, after which they were adjusted and resterilized, which enhanced preoperative decision-making. Conclusions: The life-size physical model improved anatomical appreciation and preoperative planning, enabling accurate surgical simulation. The tools created demonstrated remarkable accuracy and cost-effectiveness that support the advancement and efficiency of clinical practice.
Analysing the Directional Dependence of Wind and Wave Interactions for Offshore Wind Turbines Using Environmental Contours
Authors: Kaliske Malte , Schmidt Boso
Published: July 2024

The structural design of offshore wind turbines is dominated by environmental conditions such as wind and waves, in addition to deadweight loads and loads from operation. Probabilistic combination approaches exist for the ultimate limit state (ULS) to estimate the simultaneous occurrence of extreme meteorological and oceanographic (metocean) environmental conditions at the site of an offshore wind turbine. The site-specific direction of action of the load parameters is mostly neglected in these approaches; the design of offshore wind turbines in the ULS is usually carried out for the most structurally unfavourable directional superposition of load parameters—which is not based on physical principles and wastes potential material savings. The reasons for different load parameters in different directions of action are the influences of nearby land masses and the topographic shape of the sea floor, atmospheric air circulation, and marine current systems. In this paper, wind and sea state data from the coastDat-2 WAM database are statistically analysed for two sites in the North Sea, common environmental contours are estimated using the example of significant wave height and wind speed, and the site-specific influence of the direction of the load parameters on the environmental contours are investigated. It is shown that, depending on the site under consideration, the direction of action can significantly influence the metocean environmental conditions and that direction-resolved probabilistic combination approaches can contribute to a safe and economic structural design of offshore wind turbines.