bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate-Change-Driven Shifts in Aegilops tauschii Species Distribution: Implications for Food Security and Ecological Conservation
Authors: Mahmoodi Shirin , Jaffar Aghaei Mohammad , Ahmadi Kourosh , Naghibi Amir
Published: April 2024

Climate change has diverse effects on the planet’s environment, including changes and shifts in the distribution and abundance of species. In this paper, we present a robust prediction ensemble algorithm for the current and future species distribution of Aegilops tauschii. Four modeling approaches were trained using various environmental variables (bioclimatic and soil variables) to accurately predict the species distribution for future scenarios. The results showed that GBM and RF demonstrated the most accurate predictions with an Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of 0.80 and 0.83, respectively. The results of variable importance depicted that the temperature seasonality (bio4) was the most important and effective factor in determining the habitat suitability of Ae. tauschii, followed closely by the precipitation seasonality (bioclimate 15) and the mean temperature of the warmest quarter (bio10). Then, the distribution maps of Ae. tauschii were produced under climate change scenarios for 2050 and 2070. The results showed that Ae. tauschii will lose some of its suitable habitats under climate change and that this loss will be more severe in the east part of the study area. The results of the present study have important implications for ecological conservation as they can assist in identifying critical habitats and inform conservation planning efforts. Our model provides a valuable tool for understanding the potential future distribution of Ae. tauschii and highlights the need for continuous monitoring and protection of this species.
Unselective Measurement of Tumor-to-Stroma Proportion in Colon Cancer at the Invasion Front—An Elusive Prognostic Factor: Original Patient Data and Review of the Literature
Authors: Fekete Zsolt , Ignat Patricia , Resiga Amelia Cristina , Todor Nicolae , Muntean Alina-Simona , Resiga Liliana , Curcean Sebastian , Lazar Gabriel , Gherman Alexandra , Eniu Dan
Published: April 2024

The tumor-to-stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study, we proposed confirming or dismissing the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma < 10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients, had stroma-rich tumors, 4% had stroma-poor tumors and 89.2% had tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease-specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation between stroma proportion and tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma–tumor interaction has to be further elucidated.
Multi-Modality Imaging in Vasculitis
Authors: Allam Mohamed N. , Baba Ali Nima , Mahmoud Ahmed K. , Scalia Isabel G. , Farina Juan M. , Abbas Mohammed Tiseer , Pereyra Milagros , Kamel Moaz A. , Awad Kamal A. , Wang Yuxiang , Barry Timothy , Huang Steve S. , Nguyen Ba D. , Yang Ming , Jokerst Clinton E. , Martinez Felipe , Ayoub Chadi , Arsanjani Reza
Published: April 2024

Systemic vasculitides are a rare and complex group of diseases that can affect multiple organ systems. Clinically, presentation may be vague and non-specific and as such, diagnosis and subsequent management are challenging. These entities are typically classified by the size of vessel involved, including large-vessel vasculitis (giant cell arteritis, Takayasu’s arteritis, and clinically isolated aortitis), medium-vessel vasculitis (including polyarteritis nodosa and Kawasaki disease), and small-vessel vasculitis (granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis). There are also other systemic vasculitides that do not fit in to these categories, such as Behcet’s disease, Cogan syndrome, and IgG4-related disease. Advances in medical imaging modalities have revolutionized the approach to diagnosis of these diseases. Specifically, color Doppler ultrasound, computed tomography and angiography, magnetic resonance imaging, positron emission tomography, or invasive catheterization as indicated have become fundamental in the work up of any patient with suspected systemic or localized vasculitis. This review presents the key diagnostic imaging modalities and their clinical utility in the evaluation of systemic vasculitis.
The Role of Large Language Models (LLMs) in Providing Triage for Maxillofacial Trauma Cases: A Preliminary Study
Authors: Frosolini Andrea , Catarzi Lisa , Benedetti Simone , Latini Linda , Chisci Glauco , Franz Leonardo , Gennaro Paolo , Gabriele Guido
Published: April 2024

Background: In the evolving field of maxillofacial surgery, integrating advanced technologies like Large Language Models (LLMs) into medical practices, especially for trauma triage, presents a promising yet largely unexplored potential. This study aimed to evaluate the feasibility of using LLMs for triaging complex maxillofacial trauma cases by comparing their performance against the expertise of a tertiary referral center. Methods: Utilizing a comprehensive review of patient records in a tertiary referral center over a year-long period, standardized prompts detailing patient demographics, injury characteristics, and medical histories were created. These prompts were used to assess the triage suggestions of ChatGPT 4.0 and Google GEMINI against the center’s recommendations, supplemented by evaluating the AI’s performance using the QAMAI and AIPI questionnaires. Results: The results in 10 cases of major maxillofacial trauma indicated moderate agreement rates between LLM recommendations and the referral center, with some variances in the suggestion of appropriate examinations (70% ChatGPT and 50% GEMINI) and treatment plans (60% ChatGPT and 45% GEMINI). Notably, the study found no statistically significant differences in several areas of the questionnaires, except in the diagnosis accuracy (GEMINI: 3.30, ChatGPT: 2.30; p = 0.032) and relevance of the recommendations (GEMINI: 2.90, ChatGPT: 3.50; p = 0.021). A Spearman correlation analysis highlighted significant correlations within the two questionnaires, specifically between the QAMAI total score and AIPI treatment scores (rho = 0.767, p = 0.010). Conclusions: This exploratory investigation underscores the potential of LLMs in enhancing clinical decision making for maxillofacial trauma cases, indicating a need for further research to refine their application in healthcare settings.
Breaking Borders with Joint Energy and Transmission Right Auctions—Assessing the Required Changes for Empowering Long-Term Markets in Europe
Authors: Huang Diyun , Deconinck Geert
Published: April 2024

The establishment of a long-term, cross-border market in which forward market coupling and bilateral contracts are developed in an integrated approach is instrumental for the European internal electricity market. We propose the joint energy and transmission right auction (JETRA) mechanism, developed by O’Neill et al., as a solution for long-term cross-border markets in Europe. The main contribution of this research lies in its examination of the underlying market structures for effective JETRA implementation. We compare the institutional setting, market rules, and grid modeling under nodal and zonal pricing systems, adapting JETRA to the flow-based market coupling (FBMC) mechanism that is currently implemented in the European day-ahead market. This adaptation reveals the inherent limitations of FBMC in supporting JETRA, in particular in the long-term auction. We also identify constraints posed by existing European market rules, particularly those that affect the application of multi-settlement rules and the effective timeframe of hedging instruments. In conclusion, our research suggests that transitioning from zonal to nodal pricing is essential for JETRA’s effective implementation. Furthermore, a comprehensive market reform is required to seamlessly integrate long- and short-term markets.
Optimizing the Installation of a Centralized Green Hydrogen Production Facility in the Island of Crete, Greece
Authors: Ahmed Arif , Pompodakis Evangelos E. , Katsigiannis Yiannis , Karapidakis Emmanuel S.
Published: April 2024

The European Union is committed to a 55% reduction in greenhouse gas emissions by 2030, as outlined in the Green Deal and Climate Law initiatives. In response to geopolitical events, the RePowerEU initiative aims to enhance energy self-sufficiency, reduce reliance on Russian natural gas, and promote hydrogen utilization. Hydrogen valleys, localized ecosystems integrating various hydrogen supply chain elements, play a key role in this transition, particularly benefiting isolated regions like islands. This manuscript focuses on optimizing a Centralized Green Hydrogen Production Facility (CGHPF) on the island of Crete. A mixed-integer linear programming framework is proposed to optimize the CGHPF, considering factors such as land area, wind and solar potential, costs, and efficiency. Additionally, an in-depth sensitivity analysis is conducted to explore the impact of key factors on the economic feasibility of hydrogen investments. The findings suggest that hydrogen can be sold in Crete at prices as low as 3.5 EUR/kg. Specifically, it was found in the base scenario that, selling hydrogen at 3.5 EUR/kg, the net profit of the investment could be as high as EUR 6.19 million, while the capacity of the solar and wind installation supplying the grid hydrogen facility would be 23.51 MW and 52.97 MW, respectively. It is noted that the high profitability is justified by the extraordinary renewable potential of Crete. Finally, based on our study, a policy recommendation to allow a maximum of 20% direct penetration of renewable sources of green hydrogen facilities into the grid is suggested to encourage and accelerate green hydrogen expansion.
Electromobility Stage in the Energy Transition Policy—Economic Dimension Analysis of Charging Costs of Electric Vehicles
Authors: Lewicki Wojciech , Niekurzak Mariusz , Sendek-Matysiak Ewelina
Published: April 2024

The available literature emphasizes that by 2040, electric vehicles may constitute up to 50% of the fleet of all passenger vehicles. This process will be one of the elements of the energy transformation and, at the same time, consistent with the idea of sustainable transport. As part of this research, the actual energy consumption and the range of electric vehicles were determined. This research was carried out using a selected group of electric cars from the most popular segments of passenger cars. The calculations were based on three charging scenarios: a home electrical network, a public alternating current (AC) charging station that allows charging with single-phase alternating current or alternating current, and a public direct current (DC) charging station that allows charging with direct current. The obtained results were compared with the results of cars with internal combustion and diesel engines after driving a 100-kilometer section of the route. In a broader scope, this research addresses the entities responsible for the energy transformation and the electromobility development strategy. In a narrower sense, vehicle users are considering the purchase of this type of vehicle for political, economic and technological reasons.
Reasonable Energy-Abandonment Operation of a Combined Power Generation System with an Ultra-High Proportion of Renewable Energy
Authors: Zhang Hao , Yang Jingyue , Li Chenxi , Guo Pengcheng , Liu Jun , Jin Ruibao , Hu Jing , Gan Fengyuan , Cao Fei
Published: April 2024

With large-scale grid-connected renewable energy, new power systems require more flexible and reliable energy storage power sources. Pumped storage stations play an important role in peak shaving, valley filling, and promoting renewable energy consumption. This paper presents the reasonable energy-abandonment operation of a combined power generation system (CPGS), in which a pumped storage station is the core control power, with an ultra-high proportion of renewable energy. Firstly, based on the seasonal characteristics of wind, solar, and load demand, typical days are selected through improved clustering analysis algorithms. Then, a daily optimal scheduling model for combined power generation systems (CPGS) is developed with the goals of economy, low-carbon, and stable operation. Finally, the correlation between the energy-abandonment rate and pumped storage station peak shaving and system optimization operation indicators is obtained by a reasonable energy-abandonment calculation method considering source-grid-load coordination. Taking the operation data of an energy base in the western region of China as an example, when the penetration rate of renewable energy is 60–70% in the future, the operating cost on the power side is greatly affected by the construction of the source side. When the system operates at a planned reasonable energy-abandonment rate of 2%, electricity regulation, load tracking, and daily operating costs all show better performance.
Anaerobic Digestion as a Possible Method of Managing Waste from Mushroom Production with Sewage Sludge as Co-Substrate
Authors: Bernat Katarzyna , Le Thi Cam Tu , Kulikowska Dorota , Thapa Ram
Published: April 2024

The mushroom agroindustry generates a huge amount of waste from mushroom production (WMP). The composition of WMP is not standardized but differs mainly in terms of organic matter (OM) content and OM biodegradability. This makes WMP management, including anaerobic digestion (AD), a significant challenge. A potential solution could be co-digestion of WMP with municipal sewage sludge (SS), especially SS generated in small rural wastewater treatment plants (WWTPs). Therefore, this study investigated mesophilic methane production (MP) from WMP, SS, and mixtures of SS and WMP at ratios of 70:30, 50:50, and 30:70 (w/w OM). Even though the maximum cumulative MP from WMP was relatively low (approx. 60 NL/kg OM), co-digesting WMP with SS increased both MP and the methane content of the biogas: with 30%, 50%, and 70% shares of SS, MP increased almost 2, 2.5, and 3.3 times, and the methane content increased to 61%, 62%, and 64%, respectively. As the SS content was increased, the kinetic coefficients of MP and OM removal decreased (from 0.211 to 0.146 d−1 and from 0.215 to 0.152 d−1), whereas the initial rate of MP and of OM removal increased (from 12.5 to 36.8 NL/(kg OM·d) and from 0.51 kg OM/(m3·d) to 0.59 kg OM/(m3·d), respectively). The effectiveness of OM removal (EOMrem) was lowest with WMP only, at 46.6%. When the SS content of the mixtures was increased to 30%, 50%, and 70%, EOMrem also increased to 55.3%, 60.1%, and 64.9%, respectively. The relationship between maximal MP and the overall OM removed was such that both increased simultaneously. The higher values of EOMrem and, consequently, the lower final contents of OM with more effective MP indicate that the organics were degraded more efficiently. These results suggest that co-digestion may be a profitable solution for simultaneously utilizing both of these waste products, increasing the efficiency of biogas production to such an extent that it would be profitable to conduct AD on mushroom farms. This is a flexible approach that allows varying proportions of WMP and SS to be used, depending on the availability of both substrates and the energy needs of the mushroom farm. However, it should be borne in mind that a higher share of WMP results in lower gas productivity.
Numerical Analysis of Bearing Capacity in Deep Excavation Support Structures: A Comparative Study of Nailing Systems and Helical Anchors
Authors: Taghavi Seyyed Alireza , Jalali Farhad Mahmoudi , Moezzi Reza , Khaksar Reza Yeganeh , Wacławek Stanisław , Gheibi Mohammad , Annuk Andres
Published: April 2024

The increasing demand for deep excavations in construction projects emphasizes the necessity of robust support structures to ensure safety and stability. Support structures are critical in stabilizing excavation pits, with a primary focus on enhancing their bearing capacity. This paper employs finite element modeling techniques to conduct a numerical analysis of nails and helical anchors’ bearing capacity. To reinforce the stability of pit walls, selecting an appropriate method for guard structure construction is imperative. The chosen method should efficiently redistribute forces induced by soil mass weight, displacements, and potential loads in the pit vicinity to the ground. Various techniques, including trusses, piles, cross-bracing systems, nailing, and anchorage systems, are utilized for this purpose. The study evaluates numerical models for two guard structure configurations: nailing systems and helical anchorage. It examines the impact of parameters such as displacement, helical helix count, helix diameter variations, and the integration of nailing systems with helices. Comparative analyses are conducted, including displacement comparisons between different nailing systems and helical anchor systems, along with laboratory-sampled data. The research yields significant insights, with a notable finding highlighting the superior performance of helical bracings compared to nailing systems. The conclusions drawn from this study provide specific outcomes that contribute valuable knowledge to the field of deep excavation support structures, guiding future design and implementation practices.
Study on Flowability Enhancement and Performance Testing of Ultrafine Dry Powder Fire Extinguishing Agents Based on Application Requirements
Authors: Lu Guangbin , Zhao Junchao , Zhou Yanting , Fu Yangyang , Lu Song , Zhang Heping
Published: April 2024

Flowability greatly affects the application of ultrafine dry powder fire extinguishing systems, while hydrophobicity and acute inhalation toxicity are concerns for fire extinguishing agents. In the present study, we examined the impact of hydrophobic fumed silica on the hydrophobicity and flow properties of ammonium dihydrogen phosphate as the base. Our findings revealed that incorporating 6 wt.% of hydrophobic fumed silica resulted in optimal flowability, accompanied by a hydrophobicity angle of 126.48°. The excessive inclusion of hydrophobic fumed silica impeded powder flow within the ammonium dihydrogen phosphate particles. Furthermore, the investigations indicated that the incorporation of a small quantity of bentonite (0.5 wt.%) amongst the three functional additives—bentonite, magnesium stearate, and perlite—offered further enhancements in powder flowability. In fire extinguishing experiments’ total flooding conditions (1 m3), the designed UDPA exhibited a minimum required extinguishing concentration of merely 41.5 g/m3, which is better than the publicly reported value. Moreover, observations on the well-being of mice subjected to nearly three times the extinguishing concentration at 60 s, 10 min, and 3 days, respectively, demonstrated the absence of acute inhalation toxicity associated with the designed UDPA. Collectively, the developed ultrafine dry powder fire extinguishing agent displayed promising performance and possesses broad applicability.
Age Gelation in Direct Steam Infusion Ultra-High-Temperature Milk: Different Heat Treatments Produce Different Gels
Authors: Wu Peipei , Guo Mengyuan , Wang Pengjie , Wang Yi , Fan Ke , Zhou Hui , Qian Wentao , Li Hongliang , Wang Menghui , Wei Xiaojun , Ren Fazheng , Luo Jie
Published: April 2024

To investigate the gelation process of direct ultra-high-temperature (UHT) milk, a pilot-scale steam infusion heat treatment was used to process milk samples over a wide temperature of 142–157 °C for 0.116–6 s, followed by storage at 4 °C, 25 °C, and 37 °C. The results of the physicochemical properties of milk showed that the particle sizes and plasmin activities of all milk samples increased during storage at 25 °C, but age gelation only occurred in three treated samples, 147 °C/6 s, 142 °C/6 s, and 142 °C/3 s, which all had lower plasmin activities. Furthermore, the properties of formed gels were further compared and analyzed by the measures of structure and intermolecular interaction. The results showed that the gel formed in the 147 °C/6 s-treated milk with a higher C* value had a denser network structure and higher gel strength, while the 142 °C/6 s-treated milk had the highest porosity. Furthermore, disulfide bonds were the largest contributor to the gel structure, and there were significant differences in disulfide bonds, hydrophobic interaction forces, hydrogen bonds, and electrostatic force among the gels. Our results showed that the occurrence of gel was not related to the thermal load, and the different direct UHT treatments produced different age gels in the milk.
Evaluation of Blue Honeysuckle Berries (Lonicera caerulea L.) Dried at Different Temperatures: Basic Quality, Sensory Attributes, Bioactive Compounds, and In Vitro Antioxidant Activity
Authors: Yu Min , Wang Beibei , Huang Zhiqiang , Lv Jinjiao , Teng Yunfei , Li Tianbo , Zhang Yu , Dong Kun , Qin Dong , Huo Junwei , Zhu Chenqiao
Published: April 2024

This study aims to comprehensively investigate the effects of hot-air dehydration on the quality of blue honeysuckle berries (Lonicera caerulea L.). The results demonstrated that drying with hot air at 40–65 °C for 7–72 h resulted in blue honeysuckle berries with a moisture content of 0.21–1.10 g H2O/g dry weight. Generally, low to medium temperatures (40–55 °C) showed a better effect on the quality than high temperatures (60–65 °C). Specifically, drying at 40 °C exclusively resulted in better retention of cuticular wax, the best sensory appearance, and the highest total phenolic content. Drying at 45 °C and 50 °C resulted in the highest antioxidant capacity and the optimal sensory flavor. Drying at 55 °C led to the highest soluble solid/acid ratio, ascorbic acid concentration, total flavonoid, and total anthocyanin. The work introduces an innovative raw berry product and provides a comprehensive practical and theoretical framework for convective dehydration of blue honeysuckle berries.
Exploration and Improvement of Acid Hydrolysis Conditions for Inulin-Type Fructans Monosaccharide Composition Analysis: Monosaccharide Recovery and By-Product Identification
Authors: Zong Xinyan , Lei Ningyu , Yin Junyi , He Weiwei , Nie Shaoping , Xie Mingyong
Published: April 2024

Acid hydrolysis serves as the primary method for determining the monosaccharide composition of polysaccharides. However, inappropriate acid hydrolysis conditions may catalyze the breakdown of monosaccharides such as fructans (Fru), generating non-sugar by-products that affect the accuracy of monosaccharide composition analysis. In this study, we determined the monosaccharide recovery rate and non-sugar by-product formation of inulin-type fructan (ITF) and Fru under varied acid hydrolysis conditions using HPAEC-PAD and UPLC-Triple-TOF/MS, respectively. The results revealed significant variations in the recovery rate of Fru within ITF under different hydrolysis conditions, while glucose remained relatively stable. Optimal hydrolysis conditions for achieving a relatively high monosaccharide recovery rate for ITF entailed 80 °C, 2 h, and 1 M sulfuric acid. Furthermore, we validated the stability of Fru during acid hydrolysis. The results indicated that Fru experienced significant degradation with an increasing temperature and acid concentration, with a pronounced decrease observed when the temperature exceeds 100 °C or the H2SO4 concentration surpasses 2 M. Finally, three common by-products associated with Fru degradation, namely 5-hydroxymethyl-2-furaldehyde, 5-methyl-2-furaldehyde, and furfural, were identified in both Fru and ITF hydrolysis processes. These findings revealed that the degradation of Fru under acidic conditions was a vital factor leading to inaccuracies in determining the Fru content during ITF monosaccharide analysis.
Research Progress and Applications of Bovine Genome in the Tribe Bovini
Authors: Du Xingjie , Sun Yu , Fu Tong , Gao Tengyun , Zhang Tianliu
Published: April 2024

Various bovine species have been domesticated and bred for thousands of years, and they provide adequate animal-derived products, including meat, milk, and leather, to meet human requirements. Despite the review studies on economic traits in cattle, the genetic basis of traits has only been partially explained by phenotype and pedigree breeding methods, due to the complexity of genomic regulation during animal development and growth. With the advent of next-generation sequencing technology, genomics projects, such as the 1000 Bull Genomes Project, Functional Annotation of Animal Genomes project, and Bovine Pangenome Consortium, have advanced bovine genomic research. These large-scale genomics projects gave us a comprehensive concept, technology, and public resources. In this review, we summarize the genomics research progress of the main bovine species during the past decade, including cattle (Bos taurus), yak (Bos grunniens), water buffalo (Bubalus bubalis), zebu (Bos indicus), and gayal (Bos frontalis). We mainly discuss the development of genome sequencing and functional annotation, focusing on how genomic analysis reveals genetic variation and its impact on phenotypes in several bovine species.
Stable Dual miR-143 and miR-506 Upregulation Inhibits Proliferation and Cell Cycle Progression
Authors: Shrestha Archana , Lahooti Behnaz , Hossian A. K. M. Nawshad , Madadi Mahboubeh , Mikelis Constantinos M. , Mattheolabakis George
Published: April 2024

The mainstays of lung cancer pathogenesis are cell cycle progression dysregulation, impaired apoptosis, and unregulated cell proliferation. While individual microRNA (miR) targeting or delivering is a promising approach that has been extensively studied, combination of miR targeting can enhance therapeutic efficacy and overcome limitations present in individual miR regulations. We previously reported on the use of a miR-143 and miR-506 combination via transient transfections against lung cancer. In this study, we evaluated the effect of miR-143 and miR-506 under stable deregulations in A549 lung cancer cells. We used lentiviral transductions to either up- or downregulate the two miRs individually or in combination. The cells were sorted and analyzed for miR deregulation via qPCR. We determined the miR deregulations’ effects on the cell cycle, cell proliferation, cancer cell morphology, and cell motility. Compared to the individual miR deregulations, the combined miR upregulation demonstrated a miR-expression-dependent G2 cell cycle arrest and a significant increase in the cell doubling time, whereas the miR-143/506 dual downregulation demonstrated increased cellular motility. Furthermore, the individual miR-143 and miR-506 up- and downregulations exhibited cellular responses lacking an apparent miR-expression-dependent response in the respective analyses. Our work here indicates that, unlike the individual miR upregulations, the combinatorial miR treatment remained advantageous, even under prolonged miR upregulation. Finally, our findings demonstrate potential advantages of miR combinations vs. individual miR treatments.
Targeting Colorectal Cancer: Unravelling the Transcriptomic Impact of Cisplatin and High-THC Cannabis Extract
Authors: Cherkasova Viktoriia , Ilnytskyy Yaroslav , Kovalchuk Olga , Kovalchuk Igor
Published: April 2024

Cisplatin and other platinum-derived chemotherapy drugs have been used for the treatment of cancer for a long time and are often combined with other medications. Unfortunately, tumours often develop resistance to cisplatin, forcing scientists to look for alternatives or synergistic combinations with other drugs. In this work, we attempted to find a potential synergistic effect between cisplatin and cannabinoid delta-9-THC, as well as the high-THC Cannabis sativa extract, for the treatment of HT-29, HCT-116, and LS-174T colorectal cancer cell lines. However, we found that combinations of the high-THC cannabis extract with cisplatin worked antagonistically on the tested colorectal cancer cell lines. To elucidate the mechanisms of drug interactions and the distinct impacts of individual treatments, we conducted a comprehensive transcriptomic analysis of affected pathways within the colorectal cancer cell line HT-29. Our primary objective was to gain a deeper understanding of the underlying molecular mechanisms associated with each treatment modality and their potential interactions. Our findings revealed an antagonistic interaction between cisplatin and high-THC cannabis extract, which could be linked to alterations in gene transcription associated with cell death (BCL2, BAD, caspase 10), DNA repair pathways (Rad52), and cancer pathways related to drug resistance.
Molecular Basis of Neuronal and Microglial States in the Aging Brain and Impact on Cerebral Blood Vessels
Authors: Maeda Chihiro , Tsuruta Fuminori
Published: April 2024

Brain aging causes a wide variety of changes at the molecular and cellular levels, leading to the decline of cognitive functions and increased vulnerability to neurodegenerative disorders. The research aimed at understanding the aging of the brain has made much progress in recent decades. Technological innovations such as single-cell RNA-sequencing (scRNA-seq), proteomic analyses, and spatial transcriptomic analyses have facilitated the research on the dynamic changes occurring within neurons, glia, and other cells along with their impacts on intercellular communication during aging. In this review, we introduce recent trends of how neurons and glia change during aging and discuss the impact on the brain microenvironment such as the blood-brain barrier (BBB).
The Microglial Transcriptome of Age-Associated Deep Subcortical White Matter Lesions Suggests a Neuroprotective Response to Blood–Brain Barrier Dysfunction
Authors: Almansouri Taghreed , Waller Rachel , Wharton Stephen B. , Heath Paul R. , Matthews Fiona E. , Brayne Carol , van Eeden Fredericus , Simpson Julie E.
Published: April 2024

Age-associated deep-subcortical white matter lesions (DSCLs) are an independent risk factor for dementia, displaying high levels of CD68+ microglia. This study aimed to characterize the transcriptomic profile of microglia in DSCLs and surrounding radiologically normal-appearing white matter (NAWM) compared to non-lesional control white matter. CD68+ microglia were isolated from white matter groups (n = 4 cases per group) from the Cognitive Function and Ageing Study neuropathology cohort using immuno-laser capture microdissection. Microarray gene expression profiling, but not RNA-sequencing, was found to be compatible with immuno-LCM-ed post-mortem material in the CFAS cohort and identified significantly differentially expressed genes (DEGs). Functional grouping and pathway analysis were assessed using the Database for Annotation Visualization and Integrated Discovery (DAVID) software, and immunohistochemistry was performed to validate gene expression changes at the protein level. Transcriptomic profiling of microglia in DSCLs compared to non-lesional control white matter identified 181 significant DEGs (93 upregulated and 88 downregulated). Functional clustering analysis in DAVID revealed dysregulation of haptoglobin–haemoglobin binding (Enrichment score 2.5, p = 0.017), confirmed using CD163 immunostaining, suggesting a neuroprotective microglial response to blood–brain barrier dysfunction in DSCLs. In NAWM versus control white matter, microglia exhibited 347 DEGs (209 upregulated, 138 downregulated), with significant dysregulation of protein de-ubiquitination (Enrichment score 5.14, p < 0.001), implying an inability to maintain protein homeostasis in NAWM that may contribute to lesion spread. These findings enhance understanding of microglial transcriptomic changes in ageing white matter pathology, highlighting a neuroprotective adaptation in DSCLs microglia and a potentially lesion-promoting phenotype in NAWM microglia.
Roles of Erythrocytes in Human Health and Disease 2.0
Authors: Misiti Francesco
Published: April 2024

This Special Issue titled “Roles of Erythrocytes in Human Health and Disease 2 [...]
A Closer Look at Histamine in Drosophila
Authors: Volonté Cinzia , Liguori Francesco , Amadio Susanna
Published: April 2024

The present work intends to provide a closer look at histamine in Drosophila. This choice is motivated firstly because Drosophila has proven over the years to be a very simple, but powerful, model organism abundantly assisting scientists in explaining not only normal functions, but also derangements that occur in higher organisms, not excluding humans. Secondly, because histamine has been demonstrated to be a pleiotropic master molecule in pharmacology and immunology, with increasingly recognized roles also in the nervous system. Indeed, it interacts with various neurotransmitters and controls functions such as learning, memory, circadian rhythm, satiety, energy balance, nociception, and motor circuits, not excluding several pathological conditions. In view of this, our review is focused on the knowledge that the use of Drosophila has added to the already vast histaminergic field. In particular, we have described histamine’s actions on photoreceptors sustaining the visual system and synchronizing circadian rhythms, but also on temperature preference, courtship behavior, and mechanosensory transmission. In addition, we have highlighted the pathophysiological consequences of mutations on genes involved in histamine metabolism and signaling. By promoting critical discussion and further research, our aim is to emphasize and renew the importance of histaminergic research in biomedicine through the exploitation of Drosophila, hopefully extending the scientific debate to the academic, industry, and general public audiences.
Multilevel Regulation of Membrane Proteins in Response to Metal and Metalloid Stress: A Lesson from Yeast
Authors: Zbieralski Kacper , Staszewski Jacek , Konczak Julia , Lazarewicz Natalia , Nowicka-Kazmierczak Malgorzata , Wawrzycka Donata , Maciaszczyk-Dziubinska Ewa
Published: April 2024

In the face of flourishing industrialization and global trade, heavy metal and metalloid contamination of the environment is a growing concern throughout the world. The widespread presence of highly toxic compounds of arsenic, antimony, and cadmium in nature poses a particular threat to human health. Prolonged exposure to these toxins has been associated with severe human diseases, including cancer, diabetes, and neurodegenerative disorders. These toxins are known to induce analogous cellular stresses, such as DNA damage, disturbance of redox homeostasis, and proteotoxicity. To overcome these threats and improve or devise treatment methods, it is crucial to understand the mechanisms of cellular detoxification in metal and metalloid stress. Membrane proteins are key cellular components involved in the uptake, vacuolar/lysosomal sequestration, and efflux of these compounds; thus, deciphering the multilevel regulation of these proteins is of the utmost importance. In this review, we summarize data on the mechanisms of arsenic, antimony, and cadmium detoxification in the context of membrane proteome. We used yeast Saccharomyces cerevisiae as a eukaryotic model to elucidate the complex mechanisms of the production, regulation, and degradation of selected membrane transporters under metal(loid)-induced stress conditions. Additionally, we present data on orthologues membrane proteins involved in metal(loid)-associated diseases in humans.
A Review of Antisynthetase Syndrome-Associated Interstitial Lung Disease
Authors: Patel Puja , Marinock Jenna M. , Ajmeri Aamir , Brent Lawrence H.
Published: April 2024

Our objective in this review article is to present a clinical case of a patient with antisynthetase syndrome (ASyS) and provide an overview of the pathogenesis, classification criteria, antibody profiles, clinical features, and current knowledge of treatment options, focusing on interstitial lung disease (ILD). ASyS is an uncommon autoimmune disease with a heterogenous clinical presentation characterized by the presence of autoantibodies against an aminoacyl-tRNA synthetase and manifested by myositis, fever, inflammatory arthritis, Raynaud’s phenomenon, mechanics hands, and ILD. ASyS-associated ILD (ASyS-ILD) is the most serious complication of ASyS, which may evolve to rapidly progressive ILD; therefore, it often requires thorough clinical and radiologic evaluation including recognition of a specific clinical phenotype associated with the antisynthetase antibodies (ASAbs) to guide therapeutic interventions.
Genome-Wide Characterization and Functional Validation of the ACS Gene Family in the Chestnut Reveals Its Regulatory Role in Ovule Development
Authors: Cui Yanhong , Ji Xingzhou , Yu Wenjie , Liu Yang , Bai Qian , Su Shuchai
Published: April 2024

Ovule abortion significantly contributes to a reduction in chestnut yield. Therefore, an examination of the mechanisms underlying ovule abortion is crucial for increasing chestnut yield. In our previous study, we conducted a comprehensive multiomic analysis of fertile and abortive ovules and found that ACS genes in chestnuts (CmACS) play a crucial role in ovule development. Therefore, to further study the function of ACS genes, a total of seven CmACS members were identified, their gene structures, conserved structural domains, evolutionary trees, chromosomal localization, and promoter cis-acting elements were analyzed, and their subcellular localization was predicted and verified. The spatiotemporal specificity of the expression of the seven CmACS genes was confirmed via qRT–PCR analysis. Notably, CmACS7 was exclusively expressed in the floral organs, and its expression peaked during fertilization and decreased after fertilization. The ACC levels remained consistently greater in fertile ovules than in abortive ovules. The ACSase activity of CmACS7 was identified using the genetic transformation of chestnut healing tissue. Micro Solanum lycopersicum plants overexpressing CmACS7 had a significantly greater rate of seed failure than did wild-type plants. Our results suggest that ovule fertilization activates CmACS7 and increases ACC levels, whereas an overexpression of CmACS7 leads to an increase in ACC content in the ovule prior to fertilization, which can lead to abortion. In conclusion, the present study demonstrated that chestnut ovule abortion is caused by poor fertilization and not by nutritional competition. Optimization of the pollination and fertilization of female flowers is essential for increasing chestnut yield and reducing ovule abortion.
Special Issue: “Genes and Human Diseases”
Authors: Churnosov Mikhail
Published: April 2024

Studying mechanisms of development and the causes of various human diseases continues to be the focus of attention of various researchers [...]
Integrating Proteomics and Transcriptomics Reveals the Potential Pathways of Hippocampal Neuron Apoptosis in Dravet Syndrome Model Mice
Authors: Kong Xuerui , Dai Gaohe , Zeng Zhong , Zhang Yi , Gu Jiarong , Ma Teng , Wang Nina , Gu Jinhai , Wang Yin
Published: April 2024

An important component contributing to the onset of epilepsy is the death of hippocampal neurons. Several studies have shown that Dravet syndrome model mice: Scn1a KO mice have a high number of apoptotic neurons following seizures, but the precise mechanism underlying this remains unclear. The aim of this research was to elucidate the potential molecular mechanism of neuronal apoptosis in Scn1a KO mice by integrating proteomics and transcriptomics, with the ultimate goal of offering better neuroprotection. We found that apoptotic processes were enriched in both proteomic and transcriptomic GO analyses, and KEGG results also indicated that differential proteins and genes play a role in neurotransmission, the cell cycle, apoptosis, and neuroinflammation. Then, we examined the upstream and downstream KGML interactions of the pathways to determine the relationship between the two omics, and we found that the HIF-1 signaling pathway plays a significant role in the onset and apoptosis of epilepsy. Meanwhile, the expression of the apoptosis-related protein VHL decreased in this pathway, and the expression of p21 was upregulated. Therefore, this study suggests that VHL/HIF-1α/p21 might be involved in the apoptosis of hippocampal neurons in Scn1a KO mice.
VvJAZ13 Positively Regulates Cold Tolerance in Arabidopsis and Grape
Authors: Che Lili , Lu Shixiong , Gou Huimin , Li Min , Guo Lili , Yang Juanbo , Mao Juan
Published: April 2024

Cold stress adversely impacts grape growth, development, and yield. Therefore, improving the cold tolerance of grape is an urgent task of grape breeding. The Jasmonic acid (JA) pathway responsive gene JAZ plays a key role in plant response to cold stress. However, the role of JAZ in response to low temperatures in grape is unclear. In this study, VvJAZ13 was cloned from the ‘Pinot Noir’ (Vitis vinefera cv. ‘Pinot Noir’) grape, and the potential interacting protein of VvJAZ13 was screened by yeast two-hybrid (Y2H). The function of VvJAZ13 under low temperature stress was verified by genetic transformation. Subcellular localization showed that the gene was mainly expressed in cytoplasm and the nucleus. Y2H indicated that VvF-box, VvTIFY5A, VvTIFY9, Vvbch1, and VvAGD13 may be potential interacting proteins of VvJAZ13. The results of transient transformation of grape leaves showed that VvJAZ13 improved photosynthetic capacity and reduced cell damage by increasing maximum photosynthetic efficiency of photosystem II (Fv/Fm), reducing relative electrolyte leakage (REL) and malondialdehyde (MDA), and increasing proline content in overexpressed lines (OEs), which played an active role in cold resistance. Through the overexpression of VvJAZ13 in Arabidopsis thaliana and grape calli, the results showed that compared with wild type (WT), transgenic lines had higher antioxidant enzyme activity and proline content, lower REL, MDA, and hydrogen peroxide (H2O2) content, and an improved ability of scavenging reactive oxygen species. In addition, the expression levels of CBF1-2 and ICE1 genes related to cold response were up-regulated in transgenic lines. To sum up, VvJAZ13 is actively involved in the cold tolerance of Arabidopsis and grape, and has the potential to be a candidate gene for improving plant cold tolerance.
Olfactory Loss in Rhinosinusitis: Mechanisms of Loss and Recovery
Authors: Dekeyser Agnès , Huart Caroline , Hummel Thomas , Hox Valérie
Published: April 2024

Chronic rhinosinusitis (CRS) is a highly prevalent disease and up to 83% of CRS patients suffer from olfactory dysfunction (OD). Because OD is specifically seen in those CRS patients that present with a type 2 eosinophilic inflammation, it is believed that type 2 inflammatory mediators at the level of the olfactory epithelium are involved in the development of this olfactory loss. However, due to the difficulties in obtaining tissue from the olfactory epithelium, little is known about the true mechanisms of inflammatory OD. Thanks to the COVID-19 pandemic, interest in olfaction has been growing rapidly and several studies have been focusing on disease mechanisms of OD in inflammatory conditions. In this paper, we summarize the most recent data exploring the pathophysiological mechanisms underlying OD in CRS. We also review what is known about the potential capacity of olfactory recovery of the currently available treatments in those patients.
Anti-Neuroinflammatory Effects of a Macrocyclic Peptide-Peptoid Hybrid in Lipopolysaccharide-Stimulated BV2 Microglial Cells
Authors: Sun Lu , Wilke Saliba Soraya , Apweiler Matthias , Akmermer Kamil , Herlan Claudine , Grathwol Christoph , de Oliveira Antônio Carlos Pinheiro , Normann Claus , Jung Nicole , Bräse Stefan , Fiebich Bernd L.
Published: April 2024

Inflammation processes of the central nervous system (CNS) play a vital role in the pathogenesis of several neurological and psychiatric disorders like depression. These processes are characterized by the activation of glia cells, such as microglia. Clinical studies showed a decrease in symptoms associated with the mentioned diseases after the treatment with anti-inflammatory drugs. Therefore, the investigation of novel anti-inflammatory drugs could hold substantial potential in the treatment of disorders with a neuroinflammatory background. In this in vitro study, we report the anti-inflammatory effects of a novel hexacyclic peptide-peptoid hybrid in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. The macrocyclic compound X15856 significantly suppressed Interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), c-c motif chemokine ligand 2 (CCL2), CCL3, C-X-C motif chemokine ligand 2 (CXCL2), and CXCL10 expression and release in LPS-treated BV2 microglial cells. The anti-inflammatory effects of the compound are partially explained by the modulation of the phosphorylation of p38 mitogen-activated protein kinases (MAPK), p42/44 MAPK (ERK 1/2), protein kinase C (PKC), and the nuclear factor (NF)-κB, respectively. Due to its remarkable anti-inflammatory properties, this compound emerges as an encouraging option for additional research and potential utilization in disorders influenced by inflammation, such as depression.
Promising Approaches in Plant-Based Therapies for Thyroid Cancer: An Overview of In Vitro, In Vivo, and Clinical Trial Studies
Authors: Kaczmarzyk Ilona , Nowak-Perlak Martyna , Woźniak Marta
Published: April 2024

Thyroid cancer, particularly undifferentiated tumors, poses a significant challenge due to its limited response to standard therapies. The incidence of thyroid cancer, predominantly differentiated carcinomas, is on the rise globally. Anaplastic thyroid carcinoma (ATC), though rare, is highly aggressive and challenging to treat. Therefore, this study aimed to collect data and explore alternative treatments, focusing on the efficacy of photodynamic therapy (PDT) combined with natural compounds as well as the potential role of phytochemicals, including quercetin, kaempferol, apigenin, genistein, daidzein, naringenin, hesperitin, anthocyanidins, epigallocatechin gallate (EGCG), resveratrol, ellagic acid, ferulic acid, caffeic acid, curcumin, saponins, ursolic acid, indole-3-carbinol (I3C), capsaicin, and piperine in thyroid cancer treatment. PDT, utilizing sensitizers activated by tumor-directed light, demonstrates promising specificity compared to traditional treatments. Combining PDT with natural photosensitizers, such as hypericin and genistein, enhances cytotoxicity against thyroid carcinoma cells. This literature review summarizes the current knowledge on phytochemicals and their anti-proliferative effects in in vitro and in vivo studies, emphasizing their effectiveness and mechanism of action as a novel therapeutic approach for thyroid cancers, especially those refractory to standard treatments.