bluuebunny/crossref_metadata_2025 huggingface dataset:
Internet of Things with Deep Learning Techniques for Pandemic Detection: A Comprehensive Review of Current Trends and Open Issues
Authors: Ajagbe Sunday Adeola , Mudali Pragasen , Adigun Matthew Olusegun
Published: July 2024

Technological advancements for diverse aspects of life have been made possible by the swift development and application of Internet of Things (IoT) based technologies. IoT technologies are primarily intended to streamline various processes, guarantee system (technology or process) efficiency, and ultimately enhance the quality of life. An effective method for pandemic detection is the combination of deep learning (DL) techniques with the IoT. IoT proved beneficial in many healthcare domains, especially during the last worldwide health crisis: the COVID-19 pandemic. Using studies published between 2019 and 2024, this review seeks to examine the various ways that IoT-DL models contribute to pandemic detection. We obtained the titles, keywords, and abstracts of the chosen papers by using the Scopus and Web of Science (WoS) databases. This study offers a comprehensive review of the literature and unresolved problems in applying IoT and DL to pandemic detection in 19 papers that were eligible to be read from start to finish out of 2878 papers that were initially accessed. To provide practitioners, policymakers, and researchers with useful information, we examine a range of previous study goals, approaches used, and the contributions made in those studies. Furthermore, by considering the numerous contributions of IoT technologies and DL as they help in pandemic preparedness and control, we provide a structured overview of the current scientific trends and open issues in this field. This review provides a thorough overview of the state-of-the-art routing approaches currently in use, as well as their limits and potential future developments, making it an invaluable resource for DL researchers and practitioners and it is a useful tool for multidisciplinary research.
Environmental Assessment of Energy System Upgrades in Public Buildings
Authors: Bodziacki Stanisław , Malinowski Mateusz , Famielec Stanisław , Krakowiak-Bal Anna , Basak Zuzanna , Łukasiewicz Maria , Wolny-Koładka Katarzyna , Atılgan Atılgan , Artun Ozan
Published: July 2024

The use of fossil fuel-based energy systems that provide heat and electricity to a building has adverse environmental impacts. These impacts can be mitigated, to a certain extent, through the incorporation of renewable energy sources (RES). The primary objective of this study was to conduct an environmental assessment of the performance of energy systems in existing public facilities located in Poland. Based on the findings, we proposed and implemented changes to these systems and validated the environmental impact of the RES systems used. SimaPro 8.1 software and the Ecoinvent 3.0 database were employed for the analysis, which entailed an environmental assessment of six public facilities located in Poland. The installation of RES resulted in an average 27% reduction in electricity consumption from the national electricity grid. This reduction was observed to be the least in the hospital and the most in the religious building. This was reflected in the environmental assessment of heating systems. The implementation of RES reduced the environmental impact of the religious building by an average of 20%. Concurrently, the CO2 emissions decreased by 35%, SO2 by 44%, and PM10 by 42%. Significant investments and the installation of advanced RES will not prevent the occurrence of unintentional environmental consequences unless the demand for electricity and thermal energy is reduced. The use of RES in the analyzed buildings and the associated avoided emissions do not entirely offset the negative emissions resulting from the utilization of other (conventional) energy sources in the analyzed energy systems of public buildings. Consequently, the analyzed facilities collectively exert a detrimental impact on the environment.
Frequency Modulation Control of Grid-Forming Converter Based on LADRC-MI
Authors: Liu Zejian , Li Fengneng , Yang Ping , Lin Xu , Zhang Guozun
Published: July 2024

The increasing proportion of new energy in the power system leads to a decrease in system inertia and weakens the frequency stability of the system. The use of grid-forming (GFM) control for inverters is an effective method to improve frequency stability in new energy generation systems. Due to uncertain disturbances in microgrids, it can cause changes in system frequency. A control strategy for linear active disturbance rejection control combined with model information (LADRC-MI) is proposed in this manuscript. In this method, the inertia level and damping of the system are improved by using virtual synchronous generator (VSG)-based GFM control. Then, the obtained part of the model information is written into the coefficient matrix of the linear extended state observer. The LADRC-MI is constructed to improve the immunity of the controller. Finally, the effectiveness of the strategy in improving the immunity and frequency stability of the converter is analyzed and verified.
Numerical Simulation of the Transport and Sealing Law of Temporary Plugging Particles in Complex Fractures of Carbonate-Type Thermal Storage
Authors: Tian Anle , Fu Guoqiang , Tang Jinyu , Wang Dezhao
Published: July 2024

Geothermal energy plays a crucial role in the large-scale deep decarbonisation process and the transition of energy structure in our country. Due to the complex reservoir environment of geothermal energy, characterised by low porosity and permeability, conventional fracturing methods struggle to create a complex network of fractures. Temporary plugging and diverting fracturing technology (TPDF) is a key technology to improve the efficiency of geothermal reservoir extraction. However, there is still a lack of knowledge about the migration and sealing law of temporary plugging agents in complex fractures. Therefore, in this study, two multiphase flow models of temporary plugging particle transport at the fracture slit and inside the complex fracture were established by using a Computational Fluid Dynamics (CFD)-Discrete Element Method (DEM) algorithm. The influence of fracturing fluid concentration, temperature, the concentration of temporary plugging particles, and particle size combinations on migration blocking in fractures was investigated. The simulation results indicate the following: High-viscosity fracturing fluid may cause plugging particles to adhere to each other to form clusters of plugging particles, reducing dispersion during transport and slowing down the velocity of the plugging particles. A particle concentration that is too high does not have a better temporary plugging effect. The use of different combinations of particle sizes is significantly better than using a single particle size, which is a key factor for the success of fracture plugging. The research findings are of great theoretical and practical significance for scaled-up, vibration-controlled fracturing technology in geothermal reservoirs.
Modern Lacustrine Phytoliths and their Relationships with Vegetation and Climate in Western Yunnan, SW China
Authors: Xu Yanyan , Shen Caiming , Wang Min , Meng Hongwei , Sun Qifa , Huang Linpei , Sun Huiling
Published: July 2024

As a plant kingdom and a biodiversity hotspot, Yunnan is a key region for our understanding of modern and past global changes in biodiversity and environment. As proxies of vegetation and climate, phytoliths have become increasingly important in ecological and paleoecological studies. In this study, phytolith analysis was carried out on samples of surface sediments from 70 lakes in western Yunnan, southwest China. These lakes are surrounded by modern vegetation types including broadleaved and coniferous forests, scrubs, grasslands, meadows, and alpine vegetation. The results of this study show that modern lacustrine phytoliths in western Yunnan are dominated by herbaceous phytoliths, among which Poaceae types are the most abundant. The 70 phytolith samples used can be divided into 4 groups, reflecting the major vegetation types from which samples were collected. The principal component analysis (PCA) and redundancy analysis (RDA) of the phytolith and climatic data of the 70 lacustrine phytolith samples showed that temperature and precipitation are the climatic parameters controlling the spatial distribution of phytolith assemblages in western Yunnan. Phytolith–MAT (mean annual temperature) and phytolith–MAP (mean annual precipitation) transfer functions were developed using weighted averaging partial least squares (WA-PLS), and both the MAT and MAP functions showed good performances (MAT: R2 = 0.67, RMSEP = 0.96 °C, MAP: R2 = 0.64, RMSEP = 140.4 mm). Our results also reveal that phytolith analysis is a useful technique offering reliable vegetation interpretation and climate reconstruction; thus, this study provides a basis for the vegetational and climatic interpretation of fossil lacustrine phytolith records in western Yunnan.
Autumn Frost Hardiness in Six Tree Species Subjected to Different Winter Storage Methods and Planting Dates in Iceland
Authors: Jonsdottir Rakel J. , Sturludóttir Erla , Fløistad Inger Sundheim , Skulason Brynjar
Published: July 2024

Winter storage of seedlings in freezers reduces the amount of heat sum available for growth in the following growing season compared to seedlings stored outdoors. To test the effects of a reduced growing period on the autumn frost hardiness of the six species most used in Icelandic afforestation, seedlings were stored outdoors or in a freezer during winter. In spring, the seedlings were planted on 24 May, 7 June, 21 June, and 5 July, and the frost hardiness of all treatments was tested on 12 and 26 September. In general, the probability of freezing damage increased with a later planting date, with outdoor-stored seedlings having the lowest probability of damage. The timing of frost events was of great importance; the later the freezing date, the less damage was observed. Growth cessation occurred at different times for each species, and they responded differently to the reduced heat sum. Lodgepole pine and birch accumulated the most frost hardiness in September. Sitka spruce had less autumn frost hardiness than Lutz spruce. Hybrid larch accumulated less frost hardiness than Russian larch and was most sensitive to the reduced heat sum. The results can be used to determine which species should be prioritised in frozen storage with regard to Iceland‘s short growing season.
Prioritizing Management Strategies for Laurel Harvesting to Enhance Forest-Based Bioeconomy: A Hybrid Framework
Authors: Güngör Ersin
Published: July 2024

Laurel (Laurus nobilis L.) is a valuable non-wood forest product (NWFP) in the global export market, with Turkey being the largest supplier. Laurel harvesting is crucial for achieving long-term goals in the NWFP industry. This study assessed the effectiveness of a hybrid framework for prioritizing management strategies for laurel harvesting to boost the forest-based bioeconomy in Turkey. The existing literature highlights the use of multi-criteria decision-making methods when dealing with multiple conflicting criteria. This study proposes a systematic and comprehensive framework to analyze the current situation and develop effective laurel harvesting strategies. An integrated SWOT-fuzzy Pivot Pairwise Relative Criteria Importance Assessment (F-PIPRECIA) and TOWS Matrix approach was used. Data from ten decision makers evaluated four separate SWOT criteria against thirty-two sub-criteria. The most critical strategy identified was Maxi S2 × Maxi O1 (0.0803). Sensitivity analyses validated the results. This study found that the most effective strategies in Turkey include improving environmental and forest planning tools through circular management methods, promoting investment in forest infrastructure, supporting training and entrepreneurship programs in laurel harvesting, and strengthening innovative forest-based value chains. The hybrid framework aims for sustainable laurel resource management while maximizing economic returns. Implementing this methodology will help conserve biodiversity and enhance local communities’ well-being.
Pomegranate Wine Production and Quality: A Comprehensive Review
Authors: Ezeora Kasiemobi Chiagozie , Setati Mathabatha Evodia , Fawole Olaniyi Amos , Opara Umezuruike Linus
Published: July 2024

Food and beverages with healthy and functional properties, especially those that prevent chronic diseases, are receiving considerable interest among consumers and researchers. Among the products with enhanced properties, fermented beverages from non-grape wines have a high potential for growth. Pomegranate (Punica granatum L.) is a super fruit known for its richness in bioactive compounds that have been reported to have several therapeutic properties against non-communicable diseases. Diverse products can be obtained from the valorization of pomegranate fruit, including wines, supplements, dried arils, juices, vinegar, and syrup. There is no literature evidence of the optimization of the fermentation processes of pomegranate juice that explores the relationships between multiple factors and their interactions. This review provides an overview of the composition of pomegranate fruit and the related health benefits for human health. It also discusses the ways in which pomegranate wine fermentation is impacted by pre-fermentation and fermentation factors. Additionally, it highlights the different subjective and objective techniques for analyzing pomegranate wine quality and the advancement of technologies such as sensors to replace traditional methods of sensory evaluation. It provides comprehensive insights into how different fermentation factors interact and can improve the bioprocess, leading to the production of high-quality wine.
Functional Study on the BMP Signaling Pathway in the Molting of Scylla paramamosain
Authors: Zhong Botao , Yu Huaihua , Han Shengming , Song Weiwei , Ren Zhiming , Wang Chunlin , Mu Changkao
Published: July 2024

In this study, we added LDN-193189 2HCL to inhibit the BMP signaling pathway in Scylla paramamosain and then explored the function of this pathway in molting through the changes in the growth performance and molt-related gene expression. The study findings indicated that the expression of ACVR1, BMPRIB, and Smad1 in Scylla paramamosain was suppressed when the LDN-193189 2HCL concentration in the culture water was 2 µm/L. Subsequently, following a 30-day experiment, there was a significant reduction in the molting frequency, growth rate, and body size of the S. paramamosain larvae. An analysis of the BMP pathway gene expression during the molting phase revealed that the BMP2, BMPR2, and Smad1 genes displayed cyclic expression patterns, while ACVR1, BMP7, and BMPRIB maintained consistent expression levels throughout the molting cycle. Additionally, the expression levels of BMP2, BMPR2, and Smad1 in the inhibition group were significantly lower compared to those in the control group. Furthermore, the inhibition of the BMP pathway led to an increase in the expression of MIH during the intermolt period and a decrease in the expression of EcR during the premolt period. These findings demonstrate that the BMP signaling pathway affects the molting of Scylla paramamosain juvenile crabs by influencing the expression of the critical genes MIH and ECR during molting, offering valuable data for functional research on the BMP signaling pathway in crustaceans.
Valorization of Saithe (Pollachius virens) Residuals into Protein Hydrolysates—Silaging as Preservation Technology
Authors: Meidell Line Skontorp , Slizyte Rasa , Mozuraityte Revilija , Carvajal Ana Karina , Rustad Turid , Falch Eva
Published: July 2024

Silaging can be used as preservation technology to valorize currently discarded raw material into protein hydrolysate on board deep-sea vessels. The aim of this study was to investigate the effect of sorting and raw material freshness on the quality and yield of protein hydrolysates obtained through silaging of saithe (Pollachius virens) viscera. Additionally, the effect of using acid-containing antioxidants was tested. Out sorting of the liver prior to silaging resulted in slightly higher hydrolysate yields. The hydrolysates with the highest protein contents were obtained from silages made from fresh raw materials (day 0), and the content decreased significantly after longer storage of the raw material (2–3 days at 4 °C). Storage of the raw material for 1 day did not affect the quality. However, a significantly higher degree of hydrolysis (DH), content of free amino acids (FAA), and total volatile basic nitrogen (TVB-N) were obtained when raw materials were stored for 3 days. The FAA composition was influenced by the raw material’s freshness, with increases in free glutamic acid and lysine and a decrease in free glutamine after longer storage. None of the studied parameters were significantly affected by out sorting of liver or the addition of antioxidants. Overall, the results indicate that the whole fraction of the viscera can be utilized without reducing the quality of the hydrolysate and that the raw material should be stored for a maximum of 1 day prior to preservation to optimize the quality.
Anabolic Androgenic Steroids and Hepatocellular Adenoma and Carcinoma: Molecular Mechanisms and Clinical Implications
Authors: Ielasi Luca , Fulco Enrico , Reggidori Nicola , Domenicali Marco , Foschi Francesco Giuseppe
Published: July 2024

Anabolic androgenic steroids (AAS) are a class of hormones that are used for hormonal replacement therapy in cases of male hypogonadism and for a few other medical conditions, mainly anemias, as well as for the female-to-male transition process. At the same time, AAS are widely abused for their muscle-building and strength-increasing properties. Among their side effects, androgens can exert a toxic effect on the liver, causing hepatotoxicity, but they can also induce hepatocyte proliferation and malignant transformation. Hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) are two primary liver lesions that have been described as potentially related to AAS. This review provides an up-to-date analysis of how androgens can induce liver carcinogenesis and a comprehensive overview on the available data in the literature about AAS and primary liver tumors.
Attributions and Relationship Satisfaction in an Arab American Population
Authors: Leonard Michelle , Rehman Aamina , Whayeb Zeena , Giraud Charles , Mejia-Hans Brianna , Abraham Christen
Published: July 2024

There has been a lack of research on the Arab American population despite a noted increase in divorce and marital discord among Arabs and Arab American couples. Moreover, knowledge is limited on ways to enhance existing couple-based treatments to become more sensitive toward the unique intersection that Arab American couples are faced with. One consideration when improving treatment is to examine and better understand the negative attributions Arab American spouses make about each other’s behavior, as they can be detrimental to the satisfaction of the relationship. In this study, a sample of 142 married Arab Americans were asked to complete the Relationship Attribution Measure, Patient Health Questionnaire, and the Dyadic Adjustment Scale (DAS). A large portion of the participants fell within the distressed range of the DAS. Attributions, especially motivations and blame, were significant predictors of relationship satisfaction. Both causal and responsibility attributions were associated with depression, while only responsibility attributions were associated with anxiety. Results are discussed in terms of how future research and couple-based interventions can integrate cultural considerations within this group.
Ubiquitination-Related Gene Signature, Nomogram and Immune Features for Prognostic Prediction in Patients with Head and Neck Squamous Cell Carcinoma
Authors: Yang Huiwen , Zhou Liuqing , Shi Mengwen , Yu Jintao , Xie Yi , Sun Yu
Published: July 2024

The objective of this research was to create a prognostic model focused on genes related to ubiquitination (UbRGs) for evaluating their clinical significance in head and neck squamous cell carcinoma (HNSCC) patients. The transcriptome expression data of UbRGs were obtained from The Cancer Genome Atlas (TCGA) database, and weighted gene co-expression network analysis (WGCNA) was used to identify specific UbRGs within survival-related hub modules. A multi-gene signature was formulated using LASSO Cox regression analysis. Furthermore, various analyses, including time-related receiver operating characteristics (ROCs), Kaplan–Meier, Cox regression, nomogram prediction, gene set enrichment, co-expression, immune, tumor mutation burden (TMB), and drug sensitivity, were conducted. Ultimately, a prognostic signature consisting of 11 gene pairs for HNSCC was established. The Kaplan–Meier curves indicated significantly improved overall survival (OS) in the low-risk group compared to the high-risk group (p < 0.001), suggesting its potential as an independent and dependable prognostic factor. Additionally, a nomogram with AUC values of 0.744, 0.852, and 0.861 at 1-, 3-, and 5-year intervals was developed. Infiltration of M2 macrophages was higher in the high-risk group, and the TMB was notably elevated compared to the low-risk group. Several chemotherapy drugs targeting UbRGs were recommended for low-risk and high-risk patients, respectively. The prognostic signature derived from UbRGs can effectively predict prognosis and provide new personalized therapeutic targets for HNSCC.
A Parametric Study of the Dynamic Soil–Structure Interaction for Shear Vulnerable Structures with Nonlinear Finite Element Modelling
Authors: Savvides Ambrosios-Antonios
Published: July 2024

In precedent years mostly, though rarely nowadays, shear deformable structures were constructed across the globe. Also, the soil is deformed as a shear cantilever, which means that the shear forces and stresses are more prominent than the respective normal forces and stresses; thus, the dynamic soil–structure interaction of shear deformable bodies is an important aspect to be researched. In this article, the dynamic soil–structure interaction of shear deformable structures is investigated through nonlinear finite element modelling. The goal of this work is to enlighten the qualitative response of both soil and structures, as well as the differences between the sole structure and the soil–structure system. The Athens 1999 earthquake accelerogram is used, which is considered as a palm load (which means a load that is not periodic like the Ricker wavelets), in order to enlighten the importance of the investigation of palm loading. It is demonstrated that the total displacements of the soil–structure system are larger than the case of the sole structure, as expected when taking into account the dynamic soil–structure interaction. However, the residual displacements of the top are larger when a moderate soil thickness is assumed. Moreover, the output acceleration functions over time, comparing the same buildings as the sole building and as the soil-building system, have the same time function, but they are amplified with a constant value. As a consequence, the critical time of the maximum energy flux that is transmitted to the building is not dependent on the dynamic soil–structure interaction.
Body Dysmorphic Disorder in Aesthetic and Reconstructive Plastic Surgery—A Systematic Review and Meta-Analysis
Authors: Kaleeny Joseph D. , Janis Jeffrey E.
Published: July 2024

(1) Background: Body dysmorphic disorder (BDD) presents significant challenges in aesthetic and reconstructive plastic surgery, impacting patient outcomes and well-being. Understanding its prevalence and associated factors is crucial for effective patient care. (2) Methods: A systematic review of national and international databases on body dysmorphic disorder, plastic surgery, cosmetic surgery, reconstructive surgery, and prevalence yielded 999 studies between 1878 and April 2024. Inclusion criteria focused on studies reporting prevalence while excluding those with small sample sizes (<20 participants), unclear diagnostic criteria for BDD, and non-English accessibility. (3) Results: A meta-analysis using a random effects model was conducted on 65 studies involving 17,107 patients to estimate the prevalence of BDD. The overall estimated prevalence of BDD was 18.6%; 10,776 (62.9%) were females, with a mean age of 35.5 ± 11.7 years. Subgroup meta-analysis found significant variability in effect sizes across countries and types of specialty, of which Brazil showed the highest proportion and dermatology exhibited the smallest. Meta-regression analysis found no significant relationship between the year of publication and prevalence rates. (4) Conclusions: Our findings update the current literature on BDD prevalence in aesthetic and reconstructive plastic surgery. We emphasize the importance of proactive screening and multidisciplinary care approaches to address the complex challenges posed by patients with BDD. Further research is needed to explore evolving trends in BDD prevalence and factors influencing its expression across different cultural contexts.
Mortality among HIV-Positive and HIV-Negative People Who Inject Drugs in Mizoram, Northeast India: A Repeated Cross-Sectional Study (2007–2021)
Authors: Pachuau Lucy Ngaihbanglovi , Tannous Caterina , Chawngthu Richard Lalramhluna , Agho Kingsley Emwinyore
Published: July 2024

Background: HIV and drug overdose continue to be the leading causes of death among people who inject drugs (PWID). Mizoram, a small state in the northeast of India, has the highest prevalence of HIV in India and a high HIV prevalence among PWID. Objective: To estimate the mortality among HIV-positive and HIV-negative PWID and to describe its associated factors. Methods: Cross-sectional datasets from the 2007–2021 Mizoram State AIDS Control Society (MSACS) data comprising 14626 PWID were analyzed. Logistic regression analysis was conducted to examine the factors associated with mortality among HIV-negative and HIV-positive PWID after adjusting for potential confounding factors. Results: Mortality among HIV-negative PWID declined by 59% between 2007 and 2021. The mortality rate among HIV-positive PWID also declined by 41% between 2007 and 2021. The multiple logistic regression analysis revealed that being divorced/separated/widowed (AOR = 1.41, 95% CI 1.03–1.94) remained positively associated with mortality among HIV-positive PWID. Mortality among HIV-negative PWID remained positively associated with ages of 24–34 years (AOR = 1.54, 95% CI 1.29–1.84) and above 35 years (AOR = 2.08, 95% CI 1.52–2.86), being divorced/separated/widowed (AOR = 1.28, 95% CI 1.02–1.61), and the sharing of needles/syringes (AOR = 1.28, 95% CI 1.34–2.00). Mortality among HIV-negative PWID was negatively associated with being married (AOR = 0.72, 95% CI 0.57–0.90), being employed (AOR = 0.77, 95% CI 0.64–0.94), and having a monthly income. Conclusions: The mortality rate among HIV-negative and HIV-positive PWID declined significantly between 2007 and 2021 in Mizoram. To further reduce mortality among PWID, interventions should target those sharing needles/syringes, those above 24 years of age, and unmarried participants.
The Hidden Hunger among Nepalese Non-Pregnant Women Aged 15–49 Years: The Role of Individual, Household, and Community-Level Factors
Authors: Agho Kingsley Emwinyore , Chitekwe Stanley , Sahiledengle Biniyam , Pachuau Lucy Ngaihbanglovi , Rijal Sanjay , Paudyal Naveen , Sahani Sanjeev Kumar , Renzaho Andre
Published: July 2024

Micronutrient deficiencies remain a public health burden among non-pregnant women in developing countries, including Nepal. Hence, this study examined micronutrient deficiencies among non-pregnant Nepalese women aged 15–49 using the 2016 Nepal National Micronutrient Status Survey (NNMSS). Data for 2143 non-pregnant women was extracted from the 2016 NNMSS. The study analysed the levels of ferritin, soluble transferrin receptor (sTfR), red blood cell (RBC) folate, and zinc of the participants. Multivariable logistic analysis was carried out to assess factors associated with micronutrient deficiencies. The prevalence of ferritin, sTfR, folate, and zinc was observed to be 19%, 13%, 16%, and 21%, respectively. Non-pregnant women from the Janajati region were significantly less prone to high levels of ferritin [adjusted odds ratio (AOR): 0.45; 95% confidence interval (CI): 0.25, 0.80], and those who had body mass index (BMI) of 25 kg/m2 or higher had significantly elevated ferritin levels [AOR: 2.69; 95% CI: 1.01, 7.17]. Non-pregnant women aged 35–49 years were significantly less predisposed to folate deficiency [AOR: 0.58; 95% CI: 0.40, 0.83], and the odds of zinc deficiency were significantly lower among non-pregnant women from wealthier households [AOR: 0.48; 95% CI: 0.31, 0.76]. This study provides further insight into screening high-risk subgroups and instituting public health interventions to address the prevailing micronutrient deficiencies among non-pregnant Nepalese women.
Role of Ciminalum-4-thiazolidinone Hybrids in Molecular NF-κB Dependent Pathways
Authors: Szlachcikowska Dominika , Tabęcka-Łonczyńska Anna , Holota Serhii , Roman Olexandra , Shepeta Yulia , Lesyk Roman , Szychowski Konrad A.
Published: July 2024

A range of hybrid molecules incorporating the ciminalum moiety in the thiazolidinone ring demonstrate significant anticancer and antimicrobial properties. Therefore, the aim of our study was to evaluate the properties and mechanism of action of two 4-thiazolidinone-based derivatives, i.e., 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (Les-45) and 5-[2-chloro-3-(4-nitrophenyl)-2-propenylidene]-2-(3-hydroxyphenylamino)thiazol-4(5H)-one (Les-247). In our study, we analyzed the impact of Les-45 and Les-247 on metabolic activity, caspase-3 activity, and the expression of genes and proteins related to inflammatory and antioxidant defenses and cytoskeleton rearrangement in healthy human fibroblasts (BJ) and a human lung carcinoma cell line (A549). The cells were exposed to increasing concentrations (1 nM to 100 μM) of the studied compounds for 24 h and 48 h. A decrease in the metabolic activity in the BJ and A549 cell lines was induced by both compounds at a concentration range from 10 to 100 µM. Both compounds decreased the mRNA expression of NRF2 (nuclear factor erythroid 2-related factor 2) and β-actin in the BJ cells. Interestingly, a significant decrease in the level of NF-κB gene and protein expression was detected in the BJ cell line, suggesting a direct impact of the studied compounds on the inhibition of inflammation. However, more studies are needed due to the ability of Les-45 and Les-247 to interfere with the tubulin/actin cytoskeleton, i.e., a critical system existing in eukaryotic cells.
hTERT Epigenetics Provides New Perspectives for Diagnosis and Evidence-Based Guidance of Chemotherapy in Cancer
Authors: Santourlidis Simeon , Araúzo-Bravo Marcos J. , Brodell Robert T. , Hassan Mohamed , Bendhack Marcelo L.
Published: July 2024

Strong epigenetic pan-cancer biomarkers are required to meet several current, urgent clinical needs and to further improve the present chemotherapeutic standard. We have concentrated on the investigation of epigenetic alteration of the hTERT gene, which is frequently epigenetically dysregulated in a number of cancers in specific developmental stages. Distinct DNA methylation profiles were identified in our data on early urothelial cancer. An efficient EpihTERT assay could be developed utilizing suitable combinations with sequence-dependent thermodynamic parameters to distinguish between differentially methylated states. We infer from this data set, the epigenetic context, and the related literature that a CpG-rich, 2800 bp region, a prominent CpG island, surrounding the transcription start of the hTERT gene is the crucial epigenetic zone for the development of a potent biomarker. In order to accurately describe this region, we have named it “Acheron” (Ἀχέρων). In Greek mythology, this is the river of woe and misery and the path to the underworld. Exploitation of the DNA methylation profiles focused on this region, e.g., idiolocal normalized Methylation Specific PCR (IDLN-MSP), opens up a wide range of new possibilities for diagnosis, determination of prognosis, follow-up, and detection of residual disease. It may also have broad implications for the choice of chemotherapy.
Differential Immune Checkpoint Protein Expression in HNSCC: The Role of HGF/MET Signaling
Authors: Boschert Verena , Boenke Johannes , Böhm Ann-Kathrin , Teusch Jonas , Steinacker Valentin , Straub Anton , Hartmann Stefan
Published: July 2024

Although inhibitors targeting the PD1/PD-L1 immune checkpoint are showing comparably good outcomes, a significant percentage of head and neck squamous cell carcinoma (HNSCC) patients do not respond to treatment. Apart from using different treatment strategies, another possibility would be to target other immune checkpoints operating in these non-responding tumors. To obtain an overview of which checkpoint ligands are expressed on HNSCC tumor cells and if these ligands are affected by HGF/MET signaling, we used mRNA sequencing and antibody-based techniques for identifying checkpoint ligands in six HNSCC tumor cell lines. Furthermore, we compared our results to mRNA sequencing data. From the checkpoint ligands we investigated, VISTA was expressed the highest at the RNA level and was also the most ubiquitously expressed. PD-L2 and B7-H3 were expressed comparably lower and were not present in all cell lines to the same extent. B7-H4, however, was only detectable in the Detroit 562 cell line. Concerning the effect of HGF on the ligand levels, PD-L2 expression was enhanced with HGF stimulation, whereas other checkpoint ligand levels decreased with stimulation. B7-H4 levels in the Detroit 562 cell line drastically decreased with HGF stimulation. This is of interest because both the checkpoint ligand and the growth factor are reported to be connected to epithelial–mesenchymal transition in the literature.
The Antimicrobial Activity of Human Defensins at Physiological Non-Permeabilizing Concentrations Is Caused by the Inhibition of the Plasma Membrane H+-ATPases
Authors: Andrés María T. , Fierro Patricia , Antuña Victoria , Fierro José F.
Published: July 2024

Human defensins are cysteine-rich peptides (Cys-rich peptides) of the innate immune system. Defensins contain an ancestral structural motif (i.e., γ-core motif) associated with the antimicrobial activity of natural Cys-rich peptides. In this study, low concentrations of human α- and β-defensins showed microbicidal activity that was not associated with cell membrane permeabilization. The cell death pathway was similar to that previously described for human lactoferrin, also an immunoprotein containing a γ-core motif. The common features were (1) cell death not related to plasma membrane (PM) disruption, (2) the inhibition of microbicidal activity via extracellular potassium, (3) the influence of cellular respiration on microbicidal activity, and (4) the influence of intracellular pH on bactericidal activity. In addition, in yeast, we also observed (1) partial K+-efflux mediated via Tok1p K+-channels, (2) the essential role of mitochondrial ATP synthase in cell death, (3) the increment of intracellular ATP, (4) plasma membrane depolarization, and (5) the inhibition of external acidification mediated via PM Pma1p H+-ATPase. Similar features were also observed with BM2, an antifungal peptide that inhibits Pma1p H+-ATPase, showing that the above coincident characteristics were a consequence of PM H+-ATPase inhibition. These findings suggest, for the first time, that human defensins inhibit PM H+-ATPases at physiological concentrations, and that the subsequent cytosolic acidification is responsible for the in vitro microbicidal activity. This mechanism of action is shared with human lactoferrin and probably other antimicrobial peptides containing γ-core motifs.
Emerging Synthetic Bioluminescent Reactions for Non-Invasive Imaging of Freely Moving Animals
Authors: Kuchimaru Takahiro
Published: July 2024

Bioluminescence imaging (BLI) is an indispensable technique for visualizing the dynamics of diverse biological processes in mammalian animal models, including cancer, viral infections, and immune responses. However, a critical scientific challenge remains: non-invasively visualizing homeostatic and disease mechanisms in freely moving animals to understand the molecular basis of exercises, social behavior, and other phenomena. Classical BLI relies on prolonged camera exposure to accumulate the limited number of photons that traveled from deep tissues in anesthetized or constrained animals. Recent advancements in synthetic bioluminescence reactions, utilizing artificial luciferin–luciferase pairs, have considerably increased the number of detectable photons from deep tissues, facilitating high-speed BLI to capture moving objects. In this review, I provide an overview of emerging synthetic bioluminescence reactions that enable the non-invasive imaging of freely moving animals. This approach holds the potential to uncover unique physiological processes that are inaccessible with current methodologies.
Structural Studies of the Taurine Transporter: A Potential Biological Target from the GABA Transporter Subfamily in Cancer Therapy
Authors: Stary Dorota , Bajda Marek
Published: July 2024

The taurine transporter (TauT, SLC6A6) is a member of the solute carrier 6 (SLC6) family, which plays multiple physiological roles. The SLC6 family is divided into four subfamilies: GABA (γ-aminobutyric acid), monoamine, glycine and neutral amino acid transporters. Proteins from the GABA group, including the taurine transporter, are primarily considered therapeutic targets for treating central nervous system disorders. However, recent studies have suggested that inhibitors of SLC6A6 could also serve as anticancer agents. Overexpression of TauT has been associated with the progression of colon and gastric cancer. The pool of known ligands of this transporter is limited and the exact spatial structure of taurine transporter remains unsolved. Understanding its structure could aid in the development of novel inhibitors. Therefore, we utilized homology modelling techniques to create models of TauT. Docking studies and molecular dynamics simulations were conducted to describe protein–ligand interactions. We compared the obtained information for TauT with literature data on other members of the GABA transporter group. Our in silico analysis allowed us to characterize the transporter structure and point out amino acids crucial for ligand binding: Glu406, Gly62 and Tyr138. The significance of selected residues was confirmed through structural studies of mutants. These results will aid in the development of novel taurine transporter inhibitors, which can be explored as anticancer agents.
Identification of SIBO Subtypes along with Nutritional Status and Diet as Key Elements of SIBO Therapy
Authors: Wielgosz-Grochowska Justyna Paulina , Domanski Nicole , Drywień Małgorzata Ewa
Published: July 2024

Small intestinal bacterial overgrowth (SIBO) is a pathology of the small intestine and may predispose individuals to various nutritional deficiencies. Little is known about whether specific subtypes of SIBO, such as the hydrogen-dominant (H+), methane-dominant (M+), or hydrogen/methane–dominant (H+/M+), impact nutritional status and dietary intake in SIBO patients. The aim of this study was to investigate possible correlations between biochemical parameters, dietary nutrient intake, and distinct SIBO subtypes. This observational study included 67 patients who were newly diagnosed with SIBO. Biochemical parameters and diet were studied utilizing laboratory tests and food records, respectively. The H+/M+ group was associated with low serum vitamin D (p < 0.001), low serum ferritin (p = 0.001) and low fiber intake (p = 0.001). The M+ group was correlated with high serum folic acid (p = 0.002) and low intakes of fiber (p = 0.001) and lactose (p = 0.002). The H+ group was associated with low lactose intake (p = 0.027). These results suggest that the subtype of SIBO may have varying effects on dietary intake, leading to a range of biochemical deficiencies. Conversely, specific dietary patterns may predispose one to the development of a SIBO subtype. The assessment of nutritional status and diet, along with the diagnosis of SIBO subtypes, are believed to be key components of SIBO therapy.
Complex Role of Regulatory T Cells (Tregs) in the Tumor Microenvironment: Their Molecular Mechanisms and Bidirectional Effects on Cancer Progression
Authors: Wang Yu , Li Jiazhou , Nakahata Shingo , Iha Hidekatsu
Published: July 2024

Regulatory T cells (Tregs) possess unique immunosuppressive activity among CD4-positive T cells. Tregs are ubiquitously present in mammals and function to calm excessive immune responses, thereby suppressing allergies or autoimmune diseases. On the other hand, due to their immunosuppressive function, Tregs are thought to promote cancer progression. The tumor microenvironment (TME) is a multicellular system composed of many cell types, including tumor cells, infiltrating immune cells, and cancer-associated fibroblasts (CAFs). Within this environment, Tregs are recruited by chemokines and metabolic factors and impede effective anti-tumor responses. However, in some cases, their presence can also improve patient’s survival rates. Their functional consequences may vary across tumor types, locations, and stages. An in-depth understanding of the precise roles and mechanisms of actions of Treg is crucial for developing effective treatments, emphasizing the need for further investigation and validation. This review aims to provide a comprehensive overview of the complex and multifaceted roles of Tregs within the TME, elucidating cellular communications, signaling pathways, and their impacts on tumor progression and highlighting their potential anti-tumor mechanisms through interactions with functional molecules.
Exploring Molecular Mechanisms and Biomarkers in COPD: An Overview of Current Advancements and Perspectives
Authors: Li Chin-Ling , Liu Shih-Feng
Published: July 2024

Chronic obstructive pulmonary disease (COPD) plays a significant role in global morbidity and mortality rates, typified by progressive airflow restriction and lingering respiratory symptoms. Recent explorations in molecular biology have illuminated the complex mechanisms underpinning COPD pathogenesis, providing critical insights into disease progression, exacerbations, and potential therapeutic interventions. This review delivers a thorough examination of the latest progress in molecular research related to COPD, involving fundamental molecular pathways, biomarkers, therapeutic targets, and cutting-edge technologies. Key areas of focus include the roles of inflammation, oxidative stress, and protease–antiprotease imbalances, alongside genetic and epigenetic factors contributing to COPD susceptibility and heterogeneity. Additionally, advancements in omics technologies—such as genomics, transcriptomics, proteomics, and metabolomics—offer new avenues for comprehensive molecular profiling, aiding in the discovery of novel biomarkers and therapeutic targets. Comprehending the molecular foundation of COPD carries substantial potential for the creation of tailored treatment strategies and the enhancement of patient outcomes. By integrating molecular insights into clinical practice, there is a promising pathway towards personalized medicine approaches that can improve the diagnosis, treatment, and overall management of COPD, ultimately reducing its global burden.
Lysine Methylation and Histone Modifications during Cold Stress of Insects: Freeze-Tolerant Eurosta solidaginis and Freeze-Avoiding Epiblema scudderiana
Authors: Yu Zhijun , Pei Tingwei , Wang Han , Wang Chunyuan , Liu Jingze , Storey Kenneth B.
Published: July 2024

Overwintering survival by insects, whether of the freeze-tolerant or freeze-avoiding types, is typically associated with a strong suppression of metabolic rate (e.g., entry into diapause) that involves the differential expression of many genes with regulation at the transcriptional, translational or post-translational levels. Epigenetic modifications have been suggested to play a vital role in regulating cold responses of insects. However, knowledge of the roles of epigenetic mechanisms in modulating gene expression for winter survival of the larvae of two goldenrod gall formers, the freeze-tolerant dipteran Eurosta solidaginis and the freeze-avoiding lepidopteran Epiblema scudderiana, remain unknown. The current study evaluates the role of cold-induced lysine methylation and histone modifications, with enzymes of lysine methylation (SETD8, SETD7, SUV39H1, SMYD2 and ASH2L), as well as relative levels of histone H3 acetylation (H3K9ac, H3K18ac, H3K27ac, H3K56ac) and methylation (H3K4me1, H3K9me3, H3K36me2) examined in two insects. Significant (p < 0.05) reductions were observed in most of the targets of histone methylation/acetylation for decreasing temperatures of Ep. scudderiana larvae, whereas selected histone methylation/acetylation targets were conversely elevated (p < 0.05) in E. solidaginis, particularly under conditions of 5 °C for 4 h. Histone H3 expression was found to be variable without statistical differences in larval goldenrod gall moths and gall flies. These results provide basic information on the patterns of epigenetic regulation involved in insect cold hardiness.
An Empowerment-Based Physical Activity Intervention for Older People with Advanced Age-Related Macular Degeneration: An Exploratory Qualitative Case Study Design
Authors: Håman Linn , Källstrand Jeanette , Carlsson Ing-Marie , Ivarsson Andreas , Kristén Lars , Lindgren Eva-Carin
Published: July 2024

Background: Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment and impacts daily life. There are benefits of physical activity for people who are affected with AMD; however, living with AMD is associated with lower levels of physical activity and social isolation. The aim of this study was to explore how older people with AMD in Sweden experienced participation in a 6-month empowerment-based physical activity intervention and how it influenced their physical abilities. Methods: The participants were nine individuals with AMD aged 70–87 years. The intervention comprised physical and social activities in a group twice a week and individual health coaching on three occasions. The study was based on an exploratory qualitative case study design. Results: The findings showed two themes: created meaningfulness in life and creative and playful ways to develop body movements. The findings also showed improved muscle strength after the intervention. Conclusions: The findings showed that participants had increased social connectedness, improved physical self-efficacy and physical ability, as well as improved muscle strength. The empowerment process of the intervention was appreciated by the participants and challenged them to participate in physical activity offered by the municipality for older individuals.