MDPI - Publisher of Open Access Journals

30 pages, 1148 KiB

Open AccessReview

Chromosomal Instability and Clonal Heterogeneity in Breast Cancer: From Mechanisms to Clinical Applications

by María Paula Meléndez-Flórez, Oscar Ortega-Recalde, Nelson Rangel and Milena Rondón-Lagos

Cancers 2025, 17(7), 1222; https://doi.org/10.3390/cancers17071222 (registering DOI) - 4 Apr 2025

Background: Chromosomal instability (CIN) and clonal heterogeneity (CH) are
fundamental hallmarks of breast cancer that drive tumor evolution, disease progression,
and therapeutic resistance. Understanding the mechanisms underlying these phenomena
is essential for improving cancer diagnosis, prognosis, and treatment strategies. Methods:
In this review, [...] Read more.

Background: Chromosomal instability (CIN) and clonal heterogeneity (CH) are
fundamental hallmarks of breast cancer that drive tumor evolution, disease progression,
and therapeutic resistance. Understanding the mechanisms underlying these phenomena
is essential for improving cancer diagnosis, prognosis, and treatment strategies. Methods:
In this review, we provide a comprehensive overview of the biological processes
contributing to CIN and CH, highlighting their molecular determinants and clinical
relevance. Results: We discuss the latest advances in detection methods, including singlecell
sequencing and other high-resolution techniques, which have enhanced our ability to
characterize intratumoral heterogeneity. Additionally, we explore how CIN and CH
influence treatment responses, their potential as therapeutic targets, and their role in
shaping the tumor immune microenvironment, which has implications for
immunotherapy effectiveness. Conclusions: By integrating recent findings, this review
underscores the impact of CIN and CH on breast cancer progression and their
translational implications for precision medicine. Full article

(This article belongs to the Special Issue The Role of Chromosomal Instability in Cancer: 2nd Edition)

20 pages, 7325 KiB

Open AccessArticle

Trends in Extreme Precipitation and Associated Natural Disasters in China, 1961–2021

by Xinlei Han, Qixiang Chen and Disong Fu

Climate 2025, 13(4), 74; https://doi.org/10.3390/cli13040074 (registering DOI) - 4 Apr 2025

Abstract

Natural disaster events caused by extreme precipitation have far-reaching and widespread impacts on society, the economy, and ecosystems. However, understanding the long-term trends of extreme precipitation indices and their spatiotemporal correlations with disaster events remains limited. This is especially true given the diverse [...] Read more.

Natural disaster events caused by extreme precipitation have far-reaching and widespread impacts on society, the economy, and ecosystems. However, understanding the long-term trends of extreme precipitation indices and their spatiotemporal correlations with disaster events remains limited. This is especially true given the diverse factors influencing their relationship in China, which makes their spatial linkage highly complex. This study aims to detect recent spatial trends in extreme precipitation indices in China and link them with related natural disaster events, as well as with the spatial evolution of land use and land cover and Gross Domestic Product (GDP). Daily precipitation data from 1274 rain gauge stations spanning the period from 1961 to 2021 were used to analyze the spatial distribution characteristics of extreme precipitation index climate trends in China. The results revealed a significant increasing trend of the intensity of extreme precipitation in eastern China, but a decreasing trend of amount, frequency, and duration of extreme precipitation in southwest China, accompanied by a significant increase in consecutive dry days. Natural disaster records related to extreme precipitation trends indicated a significant increase at an annual rate of 1.3 times in the frequency of flood, storm, drought, and landslide occurrences nationwide, with substantial regional dependence in disaster types. Furthermore, the spatial evolution of land use and GDP levels showed a close association with the spatial distribution of natural disaster events induced by extreme precipitation. Although the number of deaths caused by extreme precipitation-related disasters in China is decreasing (by 51 people per year), the economic losses are increasing annually at an annual rate of USD 530,991, particularly due to floods and storms. This study holds the potential to inform decision-making processes, facilitate the implementation of mitigation and adaptation measures, and contribute to reducing the impacts of natural disasters across diverse regions worldwide. Full article

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13 pages, 817 KiB

Open AccessArticle

Creative Cognitive Reappraisal Promotes Estimation Strategy Execution in Individuals with Trait Anxiety

by Huan Song, Chenghui Tan, Chuanlin Zhu, Dianzhi Liu and Wenbo Peng

Brain Sci. 2025, 15(4), 378; https://doi.org/10.3390/brainsci15040378 (registering DOI) - 4 Apr 2025

Abstract

Objectives: This study aimed to investigate the impact of the creative cognitive reappraisal on the estimation strategies execution in college students with trait anxiety. Methods: Using the Trait Anxiety Scale, 47 participants with high (HTA) and low trait anxiety (LTA) were selected from [...] Read more.

Objectives: This study aimed to investigate the impact of the creative cognitive reappraisal on the estimation strategies execution in college students with trait anxiety. Methods: Using the Trait Anxiety Scale, 47 participants with high (HTA) and low trait anxiety (LTA) were selected from a total of 803 college students. These participants then completed a two-digit multiplication estimation task after using cognitive reappraisal to regulate negative emotions. Results: The results showed that for individuals with low trait anxiety, both standard cognitive reappraisal and creative cognitive reappraisal effectively improved their negative emotional experiences, with creative cognitive reappraisal demonstrating a superior regulatory effect. For individuals with high trait anxiety, creative cognitive reappraisal was effective in regulating negative emotions, whereas the effect of standard cognitive reappraisal on emotion regulation was not significant. Conclusions: Both standard cognitive reappraisal and creative cognitive reappraisal can enhance the speed of estimation strategy execution in college students with trait anxiety after regulating negative emotions, with creative cognitive reappraisal showing a more pronounced facilitative effect. Full article

(This article belongs to the Section Cognitive, Social and Affective Neuroscience)

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19 pages, 3752 KiB

Open AccessReview

Artificial Intelligence Driving Innovation in Textile Defect Detection

by Ahmet Ozek, Mine Seckin, Pinar Demircioglu and Ismail Bogrekci

Textiles 2025, 5(2), 12; https://doi.org/10.3390/textiles5020012 (registering DOI) - 4 Apr 2025

Abstract

The cornerstone of textile manufacturing lies in quality control, with the early detection of defects being crucial to ensuring product quality and sustaining a competitive edge. Traditional inspection methods, which predominantly depend on manual processes, are limited by human error and scalability challenges. [...] Read more.

The cornerstone of textile manufacturing lies in quality control, with the early detection of defects being crucial to ensuring product quality and sustaining a competitive edge. Traditional inspection methods, which predominantly depend on manual processes, are limited by human error and scalability challenges. Recent advancements in artificial intelligence (AI)—encompassing computer vision, image processing, and machine learning—have transformed defect detection, delivering improved accuracy, speed, and reliability. This article critically examines the evolution of defect detection methods in the textile industry, transitioning from traditional manual inspections to AI-driven automated systems. It delves into the types of defects occurring at various production stages, assesses the strengths and weaknesses of conventional and automated approaches, and underscores the pivotal role of deep learning models, especially Convolutional Neural Networks (CNNs), in achieving high precision in defect identification. Additionally, the integration of cutting-edge technologies, such as high-resolution cameras and real-time monitoring systems, into quality control processes is explored, highlighting their contributions to sustainability and cost-effectiveness. By addressing the challenges and opportunities these advancements present, this study serves as a comprehensive resource for researchers and industry professionals seeking to harness AI in optimizing textile production and quality assurance amidst the ongoing digital transformation. Full article

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16 pages, 4912 KiB

Open AccessArticle

Characterization of Laser-Ablated Bound Metal Deposition (laBMD)

by Alexander Watson, Masoud Rais-Rohani, John Belding, Jasper McGill and Brett D. Ellis

J. Manuf. Mater. Process. 2025, 9(4), 119; https://doi.org/10.3390/jmmp9040119 (registering DOI) - 4 Apr 2025

Abstract

Additive manufacturing of metals is limited by a fundamental tradeoff between deposition rates and manufacturability of fine-scale features. To overcome this problem, a laser-ablated bound metal deposition (laBMD) process is demonstrated in which 3D-printed green-state bound metal deposition (BMD) parts are post-processed via [...] Read more.

Additive manufacturing of metals is limited by a fundamental tradeoff between deposition rates and manufacturability of fine-scale features. To overcome this problem, a laser-ablated bound metal deposition (laBMD) process is demonstrated in which 3D-printed green-state bound metal deposition (BMD) parts are post-processed via laser ablation prior to conventional BMD debinding and sintering. The laBMD process is experimentally characterized via a full-factorial design of experiments to determine the effect of five factors—number of laser passes (one pass, three passes), laser power (25%, 75%), scanning speed (50%, 100%), direction of laser travel (perpendicular, parallel), and laser resolution (600 dpi, 1200 dpi)—on as-sintered ablated depth, surface roughness, width, and angle between ablated and non-ablated regions. The as-sintered ablation depth/pass ranged from 3 to 122 µm/pass, the ablated surface roughness ranged from 3 to 79 µm, the angle between ablated and non-ablated regions ranged from 1° to 68°, and ablated bottom widths ranged from 729 to 1254 µm. This study provides novel insights into as-manufactured ablated geometries and surface finishes produced via laser ablation of polymer–metallic composites. The ability to inexpensively and accurately manufacture fine-scale features with tailorable geometric tolerances and surface finishes is important to a variety of applications, such as manufacturing molds for microfluidic devices. Full article

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28 pages, 320 KiB

Open AccessArticle

Situating Place and Wellbeing Within Heritage Interactions for Older Adults

by Jessica Bowden, Ryan Woolrych and Craig J. Kennedy

Heritage 2025, 8(4), 131; https://doi.org/10.3390/heritage8040131 (registering DOI) - 4 Apr 2025

Abstract

As the global population ages, more older adults are engaging with the historic environment than ever before. However, the needs of this population may not always be met by local and national heritage sites and organizations. Here, eight professionals working in the UK [...] Read more.

As the global population ages, more older adults are engaging with the historic environment than ever before. However, the needs of this population may not always be met by local and national heritage sites and organizations. Here, eight professionals working in the UK heritage, health and well-being and aging sectors were interviewed to gather their views on how older adults interact with the historic environment. Three key themes emerged from these interviews: barriers to accessing the historic environment; positive well-being implications of engaging with the historic environment; and the need to develop a wider knowledge base. Barriers to accessing the historic environment include physiological barriers, such as mobility issues, psychological barriers, and financial barriers. Positive well-being derived from engaging with the historic environment are explored in two key themes: communal well-being, and personal well-being. Attention is drawn to activities developed by heritage organizations to engage with older adults, and how these can be better coordinated and implemented to maximize the benefits the historic environment can offer, and minimize the barriers. Full article

(This article belongs to the Section Cultural Heritage)

23 pages, 3022 KiB

Open AccessArticle

Induction of Antifungal Tolerance Reveals Genetic and Phenotypic Changes in Candida glabrata

by Christy Chedraoui, Nour Fattouh, Setrida El Hachem, Maria Younes and Roy A. Khalaf

J. Fungi 2025, 11(4), 284; https://doi.org/10.3390/jof11040284 (registering DOI) - 4 Apr 2025

Abstract

Candida glabrata is an opportunistic, pathogenic fungus that is increasingly isolated from hospitalized patients. The incidence of drug tolerance, heteroresistance, and resistance is on the rise due to an overuse of antifungal drugs. The aim of this study was to expose a sensitive [...] Read more.

Candida glabrata is an opportunistic, pathogenic fungus that is increasingly isolated from hospitalized patients. The incidence of drug tolerance, heteroresistance, and resistance is on the rise due to an overuse of antifungal drugs. The aim of this study was to expose a sensitive C. glabrata strain to sequentially increasing concentrations of two antifungal drugs, fluconazole, an azole that targets ergosterol biosynthesis, or caspofungin, an echinocandin that targets cell wall glucan synthesis. Analysis of the drug-exposed isolates showed development of antifungal tolerance, chromosomal abnormalities, decreased adhesion, attenuated virulence, and an increase in efflux pump activity. Furthermore, whole genome sequencing of all isolates exposed to different concentrations of fluconazole or caspofungin was performed to determine mutations in key genes that could correlate with the observed phenotypes. Mutations were found in genes implicated in adhesion, such as in the AWP, PWP, and EPA family of genes. Isolates exposed to higher drug concentrations displayed more mutations than those at lower concentrations. Full article

(This article belongs to the Section Fungal Genomics, Genetics and Molecular Biology)

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21 pages, 6826 KiB

Open AccessArticle

A Mixed FEM for Studying Jointed Concrete Pavement Blowups

by Daniele Baraldi

Infrastructures 2025, 10(4), 86; https://doi.org/10.3390/infrastructures10040086 (registering DOI) - 4 Apr 2025

Abstract

This work aims to study the compressive buckling and consequent blowup of jointed concrete pavements due to thermal rise. For this purpose, a simple and effective mixed FEM, originally introduced for performing static and buckling analyses of beams on elastic supports, is extended [...] Read more.

This work aims to study the compressive buckling and consequent blowup of jointed concrete pavements due to thermal rise. For this purpose, a simple and effective mixed FEM, originally introduced for performing static and buckling analyses of beams on elastic supports, is extended for performing a preliminary study of jointed concrete pavements. An elastic Euler–Bernoulli beam in frictionless and bilateral contact with an elastic support is considered. Three different elastic support models are assumed, namely a Winkler support, an elastic half-space (3D), and half-plane (2D). The transversal pavement joint or crack is modeled employing a hinge at the beam midpoint with nil rotational stiffness. Numerical tests are performed by determining critical loads and the corresponding modal shapes, with particular attention to the first minimum critical load related to pavement blowup. From a theoretical point of view, the results show that minimum critical loads converge to existing results in the case of Winkler support, whereas new results are obtained in the case of the 2D and 3D support types. Associated modal shapes have maximum upward displacements at the beam midpoint. The second and subsequent critical loads, together with the corresponding sinusoidal modal shapes, converge to existing results. From a practical point of view, minimum critical loads represent a lower bound for estimating axial forces due to thermal variation causing jointed pavement blowup. Full article

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17 pages, 2772 KiB

Open AccessArticle

Trace Metal and Phosphorus Enrichments in Cyanobacteria Cells and Cyanobacterial Precipitated Minerals

by Hanna Leapaldt, Miquela Ingalls, Georgia Soares and Christopher H. House

Minerals 2025, 15(4), 378; https://doi.org/10.3390/min15040378 (registering DOI) - 4 Apr 2025

Abstract

The enrichment of trace metals and other life-essential elements, like phosphorus, in carbonates may be a signature of microbial life. Enrichments of such elements in microbial carbonate facies in the rock record have been attributed to life in previous studies, but the biologic [...] Read more.

The enrichment of trace metals and other life-essential elements, like phosphorus, in carbonates may be a signature of microbial life. Enrichments of such elements in microbial carbonate facies in the rock record have been attributed to life in previous studies, but the biologic origin of these enrichments is contentious. We experimentally tested the hypothesis that enrichments of life-important trace elements occur in both cells and carbonate minerals that form as a result of cellular photosynthesis for the cyanobacteria Synechococcus PCC 8806. We grew Synechococcus PCC 8806 and measured the trace element concentrations of the cells and the minerals that precipitate with the cells, and we compared the results to abiotically precipitated mineral material from the same growth medium conditions. We found that for all the tested trace elements (B, P, K, Mn, Fe, Co, Cu, and Zn, chosen for their requirements in the growth medium of Synechococcus PCC 8806 and known uses in cellular machinery), nearly all the sample types were enriched relative to the medium concentrations. The dominant pattern for most elements was that cells were the most enriched, followed by biotic minerals, and then abiotic minerals. However, this pattern was complicated by varying concentrations of Mg in the mineral samples because the data were normalized to Mg (Mg was the dominant cation in the solution next to Na). Nonetheless, however the data are normalized, Fe was the most enriched element in the cells and both the biotic and abiotic minerals relative to the medium concentrations. Fe had the largest enrichment factor (E.F.) for all the sample types, with an E.F. of approximately 2800 in the biotic minerals, 1620 in the cells, and 230 in the abiotic minerals. Fe was followed by Zn (E.F. of ~329 in cells, 198 in biotic minerals, and 78 in abiotic minerals), Cu (E.F. of ~424 in cells, 171 in biotic minerals, and 50 in abiotic minerals), Mn (E.F. of ~200 in cells, 95 in biotic minerals, and 53 in abiotic minerals), and P (E.F. of ~149 in cells, 37 in biotic minerals, and 6 in abiotic minerals), suggesting that these elements can be useful as biosignatures when used in combination with other evidence. Full article

(This article belongs to the Special Issue Life and Carbonate: Biotic and Abiotic Fingerprints in Past and Recent Carbonate Sediments)

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25 pages, 14510 KiB

Open AccessArticle

Dynamic Analysis of Subsea Sediment Engineering Properties Based on Long-Term In Situ Observations in the Offshore Area of Qingdao

by Zhiwen Sun, Yanlong Li, Nengyou Wu, Zhihan Fan, Kai Li, Zhongqiang Sun, Xiaoshuai Song, Liang Xue and Yonggang Jia

J. Mar. Sci. Eng. 2025, 13(4), 723; https://doi.org/10.3390/jmse13040723 (registering DOI) - 4 Apr 2025

Abstract

The drastic changes in the marine environment can induce the instability of seabed sediments, threatening the safety of marine engineering facilities such as offshore oil platforms, oil pipelines, and submarine optical cables. Due to the lack of long-term in situ observation equipment for [...] Read more.

The drastic changes in the marine environment can induce the instability of seabed sediments, threatening the safety of marine engineering facilities such as offshore oil platforms, oil pipelines, and submarine optical cables. Due to the lack of long-term in situ observation equipment for the engineering properties of seabed sediments, most existing studies have focused on phenomena such as the erosion suspension of the seabed boundary layer and wave-induced liquefaction, leading to insufficient understanding of the dynamic processes affecting the seabed environment. In this study, a long-term in situ observation system for subsea engineering geological environments was developed and deployed for 36 days of continuous monitoring in the offshore area of Qingdao. It was found that wave action significantly altered sediment mechanical properties, with a 5% sound velocity increase correlating to 39% lower compression, 7% higher cohesion, 11% greater internal friction angle, and 50% reduced excess pore water pressure at 1.0–1.8 m depth. suggesting sustained 2.2 m wave loads of expelled pore water, driving dynamic mechanical property variations in seabed sediments. This long-term in situ observation lays the foundation for the monitoring and early warning of marine engineering geological disasters. Full article

(This article belongs to the Special Issue Advances in Marine Gas Hydrate Exploration and Discovery—2nd Edition)

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21 pages, 10060 KiB

Open AccessArticle

The Effects of the Natriuretic Peptide System on Alveolar Epithelium in Heart Failure

by Yara Knany, Safa Kinaneh, Emad E. Khoury, Yaniv Zohar, Zaid Abassi and Zaher S. Azzam

Int. J. Mol. Sci. 2025, 26(7), 3374; https://doi.org/10.3390/ijms26073374 (registering DOI) - 4 Apr 2025

Abstract

Alveolar active sodium transport is essential for clearing edema from airspaces, in a process known as alveolar fluid clearance (AFC). Although it has been reported that atrial natriuretic peptide (ANP) attenuates AFC, little is known about the underlying molecular effects of natriuretic peptides [...] Read more.

Alveolar active sodium transport is essential for clearing edema from airspaces, in a process known as alveolar fluid clearance (AFC). Although it has been reported that atrial natriuretic peptide (ANP) attenuates AFC, little is known about the underlying molecular effects of natriuretic peptides (NPs). Therefore, we examined the contribution of NPs to AFC and their effects as mediators of active sodium transport. By using the isolated liquid-filled lungs model, we investigated the effects of NPs on AFC. The expression of NPs, Na⁺, K⁺-ATPase, and Na⁺ channels was assessed in alveolar epithelial cells. Congestive heart failure (CHF) was induced by using the aortocaval fistula model. ANP and brain NP (BNP) significantly reduced AFC rate from 0.49 ± 0.02 mL/h in sham rats to 0.26 ± 0.013 and 0.19 ± 0.005 in ANP and BNP-treated groups, respectively. These effects were mediated by downregulating the active Na⁺ transport components in the alveolar epithelium while enhancing the ubiquitination and degradation of αENaC in the lungs, as reflected by increased levels of Nedd4-2. In addition, AFC was reduced in compensated CHF rats treated with ANP, while in decompensated CHF, ANP partially restored AFC. In conclusion, NPs regulate AFC in health and CHF. This research could help optimize pharmacological treatments for severe CHF. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms in Lung Health and Disease)

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20 pages, 2480 KiB

Open AccessArticle

Real-World Data Confirm That the Integration of Deuterium Depletion into Conventional Cancer Therapy Multiplies the Survival Probability of Patients

by Gábor Somlyai, András Papp, Ildikó Somlyai, Beáta Zs Kovács and Mária Debrődi

Biomedicines 2025, 13(4), 876; https://doi.org/10.3390/biomedicines13040876 (registering DOI) - 4 Apr 2025

Abstract

Background: Over thirty years of basic research has demonstrated that the deuterium-to-hydrogen ratio plays a pivotal role in regulating metabolism and cell growth via a sub-molecular regulatory system that orchestrates the intricate complexity of life in eukaryotic organisms. Deuterium depletion, achieved through [...] Read more.

Background: Over thirty years of basic research has demonstrated that the deuterium-to-hydrogen ratio plays a pivotal role in regulating metabolism and cell growth via a sub-molecular regulatory system that orchestrates the intricate complexity of life in eukaryotic organisms. Deuterium depletion, achieved through deuterium-depleted water (DDW), has shown anticancer effects in vitro, in vivo, and in Phase 2 prospective and retrospective clinical studies. Methods: In this population-based observational study, 2649 cancer patients undergoing conventional therapy and consuming DDW were included between October 1992 and October 2024. With various cancer types and stages and conventional therapies received, they are representing a broad spectrum of the Hungarian cancer population. Survival was selected as the primary endpoint, and the median survival time (MST) of these patients and various subgroups was calculated and compared to the overall Hungarian cancer population’s MST of 2.4 years. Results: For the entire study population, MST from diagnosis was 12.4 years (95% CI: 9.8–14.9), and from the initiation of DDW treatment, 7.6 years (95% CI: 5.9–9.3). Conclusions: Utilizing DDW enables targeted intervention in the sub-molecular regulatory system, paving the way for innovative therapeutic applications and a more profound understanding of cellular processes. Integrating deuterium depletion into conventional cancer therapies has the potential to significantly enhance survival rates and reduce cancer-related mortality by 75–80%. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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27 pages, 7357 KiB

Open AccessArticle

Target Enclosing Control of Symmetric Unmanned Aerial Vehicle Swarms Based on Crowd Entropy

by Juan Dong, Yunping Liu, Liang Xu, Tianyu Niu, Zhiliang Deng and Hui Zhu

Symmetry 2025, 17(4), 552; https://doi.org/10.3390/sym17040552 (registering DOI) - 4 Apr 2025

Abstract

Drone swarms often need to fly cooperatively in complex spaces filled with multiple obstacles. In such scenarios, they must meet the requirements of both external obstacle avoidance and internal collision avoidance while maintaining a certain topological configuration among individuals. This easily leads to [...] Read more.

Drone swarms often need to fly cooperatively in complex spaces filled with multiple obstacles. In such scenarios, they must meet the requirements of both external obstacle avoidance and internal collision avoidance while maintaining a certain topological configuration among individuals. This easily leads to problems such as congestion, oscillation, and poor stability, including being out of control. Thus, it is essential to measure system-wide stability, regulate the autonomous cooperative evolution of swarms, and enhance their adaptation to environmental changes. To solve this problem, using the symmetric unmanned aerial vehicle (UAV) swarm as the research object, a group entropy measurement theory for the stability of drone swarms is proposed. We introduce an entropy-based metric for group motion consistency. This metric serves as a fitness index for individual collaboration, enabling adaptive adjustment of drone swarm coherence under multi-obstacle conditions. Finally, simulation experiments are conducted to verify the effectiveness of the established theory and algorithm. Full article

(This article belongs to the Section Engineering and Materials)

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13 pages, 2343 KiB

Open AccessArticle

The Elevation and Impact of Peripheral Bile Acids in Chronic Lymphocytic Leukemia

by Audrey L. Smith, Abigail Ridout, Sydney A. Skupa, Rolando Martinez-Rico, Erin M. Drengler, Eslam Mohamed, Christopher R. D’Angelo and Dalia El-Gamal

Biomedicines 2025, 13(4), 874; https://doi.org/10.3390/biomedicines13040874 (registering DOI) - 4 Apr 2025

Abstract

Background: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the Western world. Targeted therapies have made CLL manageable for many patients, but the ongoing threat of disease relapse or transformation beckons a deeper understanding of CLL pathogenesis, and thus, [...] Read more.

Background: Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the Western world. Targeted therapies have made CLL manageable for many patients, but the ongoing threat of disease relapse or transformation beckons a deeper understanding of CLL pathogenesis, and thus, its durable eradication. This study identifies bile acids (BAs) as elevated in the peripheral blood of CLL patients and a murine model of CLL, in comparison to healthy controls. Elevated BA concentrations have been associated with intestinal malignancies and immunomodulation; however, their role in CLL is relatively unknown. Methods: Metabolomic analysis was performed on murine and human plasma. Flow cytometry analysis of CLL patient B-cells and healthy donor T-cells were utilized to evaluate the immunomodulatory impact of differentially abundant BAs. Results: Herein, BAs were found to be differentially abundant in CLL. Elevated BAs demonstrated minimal impact on CLL cell proliferation or CLL-associated T-cell function. Conclusions: Future studies are needed to determine the mechanistic influence of BAs on CLL pathogenesis. Full article

(This article belongs to the Section Cell Biology and Pathology)

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27 pages, 2344 KiB

Open AccessArticle

Decision-Making on Key Factors Driving the Demand for Electric Vehicles

by Ondrej Stopka, Vladimír Ľupták, Anna Borucka, Mária Stopková, Branislav Šarkan and Tomáš Kalina

Appl. Sci. 2025, 15(7), 3982; https://doi.org/10.3390/app15073982 (registering DOI) - 4 Apr 2025

Abstract

The article presents a research study dealing with the issue of identifying the crucial criteria driving the demand for electric vehicles and decision-making on the ideal electric vehicle choice for the company under investigation. Specifically, the research aimed to identify key factors influencing [...] Read more.

The article presents a research study dealing with the issue of identifying the crucial criteria driving the demand for electric vehicles and decision-making on the ideal electric vehicle choice for the company under investigation. Specifically, the research aimed to identify key factors influencing the decision-making process to purchase electric vans and to propose adequate recommendations when applying adequate multi-criteria decision-making methods, namely, ELECTRE I and PROMETHEE II, in the Czech and Slovak market conditions. The present survey identified six key criteria: mileage, load-carrying capacity, recharging speed, purchase price, load-bearing capacity, and electricity consumption. Based on the expert team preferences, the criteria weights were calculated, followed by data normalization and the application of both methods to evaluate individual vehicle models. Using the ELECTRE I method, the options were classified as either preferred (dominant) or unpreferred (undominant), while the PROMETHEE II ranked them from the best to the worst, preserving viable alternatives should the preferred model be unavailable. The study concludes by emphasizing the relevance of these methods in optimizing the selection of sustainable transport solutions and their broader applicability in the decision-making process on transport and mobility. Full article

(This article belongs to the Special Issue A New Approach to Renewable Energy Sources to Increase the Efficiency of Electric Vehicles)

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20 pages, 3206 KiB

Open AccessReview

Modeling Necroptotic and Pyroptotic Signaling in Saccharomyces cerevisiae

by Óscar Barbero-Úriz, Marta Valenti, María Molina, Teresa Fernández-Acero and Víctor J. Cid

Biomolecules 2025, 15(4), 530; https://doi.org/10.3390/biom15040530 (registering DOI) - 4 Apr 2025

Abstract

The yeast Saccharomyces cerevisiae is the paradigm of a eukaryotic model organism. In virtue of a substantial degree of functional conservation, it has been extensively exploited to understand multiple aspects of the genetic, molecular, and cellular biology of human disease. Many aspects of [...] Read more.

The yeast Saccharomyces cerevisiae is the paradigm of a eukaryotic model organism. In virtue of a substantial degree of functional conservation, it has been extensively exploited to understand multiple aspects of the genetic, molecular, and cellular biology of human disease. Many aspects of cell signaling in cancer, aging, or metabolic diseases have been tackled in yeast. Here, we review the strategies undertaken throughout the years for the development of humanized yeast models to study regulated cell death (RCD) pathways in general, and specifically, those related to innate immunity and inflammation, with an emphasis on pyroptosis and necroptosis. Such pathways involve the assembly of distinct modular signaling complexes such as the inflammasome and the necrosome. Like other supramolecular organizing centers (SMOCs), such intricate molecular arrangements trigger the activity of enzymes, like caspases or protein kinases, culminating in the activation of lytic pore-forming final effectors, respectively, Gasdermin D (GSDMD) in pyroptosis and MLKL in necroptosis. Even though pathways related to those governing innate immunity and inflammation in mammals are missing in fungi, the heterologous expression of their components in the S. cerevisiae model provides a “cellular test tube” to readily study their properties and interactions, thus constituting a valuable tool for finding novel therapies. Full article

(This article belongs to the Section Cellular Biochemistry)

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26 pages, 482 KiB

Open AccessArticle

Computational Construction of Sequential Efficient Designs for the Second-Order Model

by Norah Alshammari, Stelios Georgiou and Stella Stylianou

Mathematics 2025, 13(7), 1190; https://doi.org/10.3390/math13071190 (registering DOI) - 4 Apr 2025

Abstract

Sequential experimental designs enhance data collection efficiency by reducing resource usage and accelerating experimental objectives. This paper presents a model-driven approach to sequential Latin hypercube designs (SLHDs) tailored for second-order models. Unlike traditional model-free SLHDs, our method optimizes a conditional A-criterion to improve [...] Read more.

Sequential experimental designs enhance data collection efficiency by reducing resource usage and accelerating experimental objectives. This paper presents a model-driven approach to sequential Latin hypercube designs (SLHDs) tailored for second-order models. Unlike traditional model-free SLHDs, our method optimizes a conditional A-criterion to improve efficiency, particularly in higher dimensions. By relaxing the restriction of non-replicated points within equally spaced intervals, our approach maintains space-filling properties while allowing greater flexibility for model-specific optimization. Using Sobol sequences, the algorithm iteratively selects good points, enhancing conditional A-efficiency compared to distance minimization methods. Additional criteria, such as D-efficiency, further validate the generated design matrices, ensuring robust performance. The proposed approach demonstrates superior results, with detailed tables and graphs illustrating its advantages across applications in engineering, pharmacology, and manufacturing. Full article

(This article belongs to the Special Issue Advances in Computational Statistics, Design of Experiments, and Its Applications)

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21 pages, 14258 KiB

Open AccessArticle

Biomass, Phyto-Ash, and Biochar from Beech Wood as Functional Additives for Natural Rubber-Based Elastomer Composites

by Justyna Miedzianowska-Masłowska, Marcin Masłowski and Krzysztof Strzelec

Materials 2025, 18(7), 1659; https://doi.org/10.3390/ma18071659 (registering DOI) - 4 Apr 2025

Abstract

The growing interest in renewable resource-based materials has driven efforts to develop elastomeric biocomposites using biomass, phyto-ash, and biochar as fillers. These bio-additives, derived from beech wood through various processing methods, were incorporated into natural rubber (NR) at varying weight ratios. The primary [...] Read more.

The growing interest in renewable resource-based materials has driven efforts to develop elastomeric biocomposites using biomass, phyto-ash, and biochar as fillers. These bio-additives, derived from beech wood through various processing methods, were incorporated into natural rubber (NR) at varying weight ratios. The primary objective of this study was to assess how the type and content of each bio-filler influence the structural, processing, and performance properties of the biocomposites. Mechanical properties, including tensile strength and hardness, were evaluated, while crosslink density of the vulcanizates was determined using equilibrium swelling in solvents. Additionally, the composites underwent thermogravimetric analysis (TGA) to determine the decomposition temperature of individual components within the polymer matrix. Bio-fillers influenced rheological and mechanical properties, with phyto-ash reducing viscosity and cross-linking density, and biochar and biomass increasing stiffness and maximum torque. Biochar extended curing time due to the absorption of curing agents, whereas phyto-ash accelerated vulcanization. Mechanical tests showed that all bio-filled composites were stiffer than the reference, with biochar and biomass (30 phr) exhibiting the highest hardness (45.8 °ShA and 49.1 °ShA, respectively) and cross-link density (2.68 × 10⁻⁵ mol/cm³ and 2.77 × 10⁻⁵ mol/cm³, respectively), contributing to improved tensile strength, in particular in the case of biochar, where the TS was 17.6 MPa. The study also examined the effects of thermal-oxidative aging on the samples, providing insights into the changes in the mechanical properties of the biocomposites under simulated aging conditions. Full article

(This article belongs to the Special Issue Advances in Bio-Polymer and Polymer Composites)

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15 pages, 1291 KiB

Open AccessArticle

Optimizing Silage Efficiency: The Role of Ryegrass Varieties, Harvest Time, and Additives in Enhancing Perennial Ryegrass (Lolium perenne) Fermentation

by Tianyi Guo, Tong Niu, Katrin Kuka and Nils Tippkötter

Fermentation 2025, 11(4), 192; https://doi.org/10.3390/fermentation11040192 (registering DOI) - 4 Apr 2025

Abstract

The increasing demand for bio-based chemicals and sustainable materials has placed biomass-derived lactic acid in the spotlight as a key building block for biodegradable polylactic acid (PLA). Perennial ryegrass (Lolium perenne) is a promising feedstock due to its high dry matter [...] Read more.

The increasing demand for bio-based chemicals and sustainable materials has placed biomass-derived lactic acid in the spotlight as a key building block for biodegradable polylactic acid (PLA). Perennial ryegrass (Lolium perenne) is a promising feedstock due to its high dry matter (DM) yield, adaptability, and widespread agricultural use. This study investigates an integrated lactic acid–silage cascade process, focusing on how pH regulation, harvest timing, and biomass characteristics influence lactic acid production while maintaining agronomic efficiency. The results highlighted the crucial role of pH management and silage duration in optimizing lactic acid production. A silage period of 21 days was found to be optimal, as peak lactic acid yields were consistently observed at this stage. Maintaining a pH range of 4.5 to 6 proved essential for stabilizing fermentation, with citrate buffering at pH 6 leading to the highest lactic acid yields and minimizing undesirable by-products. Harvest timing also significantly affected lactic acid yield per hectare. While later harvesting increased total DM yield, it led to a decline in lactic acid concentration per kg DM. Tetraploid ryegrass (Explosion) maintained stable lactic acid yields due to higher biomass accumulation, whereas diploid varieties (Honroso) experienced a net reduction. From an agronomic perspective, optimizing harvest timing and variety selection is key to balancing biomass yield and fermentation efficiency. While tetraploid varieties offer greater flexibility, diploid varieties require precise harvest timing to avoid losses. These findings contribute to sustainable forage management, improving lactic acid production, silage efficiency, and agricultural resource use. Full article

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18 pages, 793 KiB

Open AccessReview

Main Methods of Regionalization of Minimum Flows, Advantages and Disadvantages and Their Limitations: A Review

by Walter Vaca, Joel Vasco and Raviel Basso

Water 2025, 17(7), 1079; https://doi.org/10.3390/w17071079 (registering DOI) - 4 Apr 2025

Abstract

Estimating surface runoff in ungauged basins is important for planning and managing water resources, as well as for developing civil and environmental projects. Within the estimation of surface runoff are the minimum flows, which are important for assessing water availability and the possibility [...] Read more.

Estimating surface runoff in ungauged basins is important for planning and managing water resources, as well as for developing civil and environmental projects. Within the estimation of surface runoff are the minimum flows, which are important for assessing water availability and the possibility of granting water resources. To estimate surface runoff in ungauged basins, regionalization is a technique that has been used and consists of transferring variables, functions and/or parameters from gauged basins to the ungauged basin. This study reviews the minimum flow regionalization methods used in studies published between 2015 and 2023 in the CAPES, Scielo, Scopus and Web of Science databases. The regionalization methods were grouped according to their approach, namely the regionalization of hydrological signatures and the regionalization of hydrological model parameters. Most studies focused on regionalizing hydrological signatures, particularly minimum flows and flow duration curves. For regionalizing hydrological model parameters, common approaches included spatial proximity, physical similarity and regression techniques. Some methods can estimate the flow time series at the location of interest, which can be an advantage for estimating different statistics from the data; other methods focus on estimating a specific flow statistic. Most methods require several gauged basins in their study area to obtain reliable estimates of minimum flows in ungauged basins. The study discusses the advantages, disadvantages and limitations of each method. Full article

(This article belongs to the Special Issue Application of Big Data and Deep Learning in Hydrological Modelling, Flood and Drought Monitoring)

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17 pages, 24696 KiB

Open AccessArticle

Energy Transition and Heritage in Anthropocene Era—Proposal for a Methodological Analysis at Local Scale

by Belén Pérez-Pérez and Eva Chacón-Linares

Urban Sci. 2025, 9(4), 112; https://doi.org/10.3390/urbansci9040112 (registering DOI) - 4 Apr 2025

Abstract

In the Anthropocene era, climate change highlights the need to abandon the centralized energy generation model using large installations located far from consumption centers, and to move towards an urban energy transition based on decentralized self-consumption models—both individual and collective—and local energy communities. [...] Read more.

In the Anthropocene era, climate change highlights the need to abandon the centralized energy generation model using large installations located far from consumption centers, and to move towards an urban energy transition based on decentralized self-consumption models—both individual and collective—and local energy communities. These approaches reduce emissions and external dependency, strengthening resilience, urban sustainability, and promoting energy justice and citizen participation. This work aims to develop a model for integrating photovoltaic solar systems in urban centers of high heritage value, combining the protection of cultural legacy with climate change adaptation strategies. A methodology is designed to integrate solar energy into urban areas while respecting cultural heritage in the most reasonable way possible. The proposed methodology consists of carrying out a characterization of the municipalities under study, considering legal, demographic, energy, and heritage aspects. Next, a territorial zoning is proposed that differentiates between protected and unprotected areas in each municipality. Visibility maps are developed to assess the impact of the installations by sector from the main visual consumption points, facilitating differentiated decisions to protect the most sensitive environments. In addition, specific measures are proposed, such as locating the installations in non-visible areas and using materials and techniques adapted to the construction typology, to preserve areas of higher cultural value and to implement energy communities and collective self-consumption outside culturally protected zones. This methodology is applied to two urban areas in the province of Jaén (South of Andalusia): Alcalá la Real and Cazorla, which, due to their different characteristics, demonstrate its versatility and adaptability. It is concluded that the transition toward decentralized models is an effective way to adapt cities to climate change, reinforcing social cohesion, contributing to the fight against energy vulnerability, and protecting historical heritage. Full article

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13 pages, 785 KiB

Open AccessArticle

Neutrophil Elastase and Elafin in Inflammatory Bowel Diseases: Urinary Biomarkers Reflecting Intestinal Barrier Dysfunction and Proteolytic Activity

by Aleksandra Górecka and Katarzyna Komosinska-Vassev

J. Clin. Med. 2025, 14(7), 2466; https://doi.org/10.3390/jcm14072466 (registering DOI) - 4 Apr 2025

Abstract

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory disorder driven by a complex interplay of immune and proteolytic mechanisms. Neutrophil elastase (NE), released at sites of inflammation, plays a central role by promoting inflammation, [...] Read more.

Background: Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic inflammatory disorder driven by a complex interplay of immune and proteolytic mechanisms. Neutrophil elastase (NE), released at sites of inflammation, plays a central role by promoting inflammation, degrading the extracellular matrix (ECM), and disturbing intestinal barrier integrity via NF-κB activation and E-cadherin degradation. Elafin, an endogenous NE inhibitor, mitigates proteolytic damage, reinforces the intestinal barrier, and exerts anti-inflammatory effects by suppressing NF-κB and reducing pro-inflammatory cytokines. Since the NE/elafin balance is critical in IBD, assessing their ratio may provide a more precise measure of proteolytic dysregulation. This study aimed to evaluate the diagnostic and prognostic utility of urinary NE, elafin, and their ratio in IBD patients. Methods: Urinary concentrations of NE and elafin were measured by immunoassay in 88 subjects including ulcerative colitis and Crohn’s disease patients and healthy individuals. The diagnostic accuracy of these biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Results: Urinary NE levels were significantly elevated in both UC and CD patients compared to controls, with a 17-fold increase in the UC patients and a 28-fold increase in the CD patients (p < 0.0001). Elafin levels were also increased in IBD patients. The NE/elafin ratio was significantly increased in both disease groups, with a 4.5-fold increase in the UC and 5.6-fold increase in the CD patients compared to healthy controls. The ROC curve analysis demonstrated that the NE/elafin ratio is the most effective biomarker for distinguishing CD patients from healthy individuals (AUC = 0.896), with a high sensitivity (92.9%) and specificity (69.7%), making it a strong diagnostic tool. NE also showed an excellent diagnostic performance both in CD (AUC = 0.842) and UC (AUC = 0.880). The elafin urinary profile had a high diagnostic value, with a better accuracy in the UC patients (AUC = 0.772) than the CD patients (AUC = 0.674), though it was inferior to NE and NE/elafin. Conclusions: Our findings indicate that urinary NE, elafin, the and NE/elafin ratio have significant diagnostic value in differentiating IBD patients from healthy controls. The NE/elafin ratio and NE proved to be the most reliable urinary biomarkers in both CD and UC diagnosis, with a high predictive value and strong discriminatory power. Full article

(This article belongs to the Special Issue Inflammatory Bowel Disease (IBD): Clinical Diagnosis and Treatment)

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15 pages, 9347 KiB

Open AccessArticle

Fine-Scale Identification of Agricultural Flooding Disaster Areas Based on Sentinel-1/2: A Case Study of Shengzhou, Zhejiang Province, China

by Jiayun Li, Jiaqi Gao, Haiyan Chen, Xiaoling Shen, Xiaochen Zhu and Yinhu Qiao

Atmosphere 2025, 16(4), 420; https://doi.org/10.3390/atmos16040420 (registering DOI) - 4 Apr 2025

Abstract

Flood disasters are one of the major natural hazards threatening agricultural production. To reduce agricultural disaster losses, accurately identifying agricultural flood-affected areas is crucial. Taking Shengzhou City as a case study, we proposed a refined method for identifying agricultural flood-affected areas by integrating [...] Read more.

Flood disasters are one of the major natural hazards threatening agricultural production. To reduce agricultural disaster losses, accurately identifying agricultural flood-affected areas is crucial. Taking Shengzhou City as a case study, we proposed a refined method for identifying agricultural flood-affected areas by integrating microwave and optical remote sensing data with deep learning techniques, GIS, and the pixel-based direct differencing method. Complementary advantages of microwave and optical remote sensing data can effectively solve the problem of difficulty in accurately detecting floods due to thick clouds before and after flood disasters. Deep learning technology can effectively identify farmland areas, and the pixel direct difference method can accurately analyze agricultural flood disasters. Analyzing three typical rainfall events along with the topographical and geomorphological characteristics of Shengzhou City, the results indicate that agricultural flood disaster areas exhibit significant spatial heterogeneity. The primary influencing factors include rainfall intensity, topography, and drainage infrastructure. The northern, eastern, and southwestern regions of Shengzhou City, particularly the peripheral areas adjacent to mountainous and hilly terrains, contain most of the flood-affected farmland. These areas, characterized by low-lying topography, are highly susceptible to flood disasters. Therefore, optimizing the drainage systems of farmland in low-lying areas near mountainous and hilly regions of Shengzhou City is essential to enhance flood resilience. Full article

(This article belongs to the Section Meteorology)

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30 pages, 7718 KiB

Open AccessReview

Research Progress of the Preparation of Cellulose Ethers and Their Applications: A Short Review

by Meng He, Yanmei Lin, Yujia Huang, Yunhui Fang and Xiaopeng Xiong

Molecules 2025, 30(7), 1610; https://doi.org/10.3390/molecules30071610 (registering DOI) - 4 Apr 2025

Abstract

Cellulose ethers (CEs), synthesized through the etherification of cellulose, have emerged as indispensable “green additives” in our modern industries, earning the moniker of industrial “monosodium glutamate” due to their unparalleled multifunctionality. Unlike traditional petroleum-based modifiers, CEs offer a unique combination of renewability, low [...] Read more.

Cellulose ethers (CEs), synthesized through the etherification of cellulose, have emerged as indispensable “green additives” in our modern industries, earning the moniker of industrial “monosodium glutamate” due to their unparalleled multifunctionality. Unlike traditional petroleum-based modifiers, CEs offer a unique combination of renewability, low toxicity, and tunable properties (e.g., water retention, thickening, and stimuli-responsiveness), making them pivotal for advancing sustainable construction practices. This review presents an overview of the preparation methods of various CEs and the applications of CEs especially in concrete and mortars as well as corresponding mechanisms. We systematically analyze the preparation methodologies (homogeneous vs. heterogeneous processes) and highlight the effect of molecular determinants (degree of substitution, molecular weight, functional groups) on the performances of CEs. CEs can enhance the workability and other properties of concrete and mortars primarily by acting as water-retaining and thickening agents to mitigate rapid water loss, improve hydration efficiency and cohesion. The effects of CEs on the delay of hydration and microstructure of concrete and mortars are also analyzed and highlighted. Beyond construction, we reviewed the current and emerging CE applications in biomedicine, tissue-engineering, petroleum industry and food engineering, highlighting their cross-disciplinary potential. This review provides some insights into the structure–property–application relationships of CEs and their brief historical developments, offering guidance for optimizing their utilizations especially in sustainable construction practices. Full article

(This article belongs to the Special Issue Bio-Based Polymers for Sustainable Future)

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19 pages, 2032 KiB

Open AccessArticle

Diversity of Potential Resistance Mechanisms in Honey Bees (Apis mellifera) Selected for Low Population Growth of the Parasitic Mite, Varroa destructor

by Alvaro De la Mora, Paul H. Goodwin, Nuria Morfin, Tatiana Petukhova and Ernesto Guzman-Novoa

Insects 2025, 16(4), 385; https://doi.org/10.3390/insects16040385 (registering DOI) - 4 Apr 2025

Abstract

Honey bees (Apis mellifera) bred for resistance to the parasitic mite, Varroa destructor, were examined for potential Varroa resistance mechanisms following bidirectional selection for low (resistant) or high (susceptible) Varroa population growth (LVG and HVG, respectively) based on mite fall [...] Read more.

Honey bees (Apis mellifera) bred for resistance to the parasitic mite, Varroa destructor, were examined for potential Varroa resistance mechanisms following bidirectional selection for low (resistant) or high (susceptible) Varroa population growth (LVG and HVG, respectively) based on mite fall in colonies at two different time points. Hygienic and grooming behavior rates in LVG colonies were significantly higher than those in HVG colonies for two out of three generations of selection, indicating that behavioral resistance to the mite increased. For the third generation, grooming start time was significantly shorter, and grooming intensity more frequent in LVG bees than in HVG bees. Cellular immunity was increased as well, based on significantly higher haemocyte concentrations in non-parasitized and Varroa-parasitized LVG bees. Humoral immunity was increased with Varroa-parasitized LVG bees, which had significantly higher expression of the antimicrobial peptide gene, hymenoptaecin 2. In addition, antiviral resistance may be involved as there were significantly lower levels of deformed wing virus (DWV) in Varroa-parasitized LVG bees. While selection for LVG and HVG bees was solely based on Varroa population growth, it appears that behavioral, cellular, and humoral mechanisms were all selected along with this resistance. Thus, LVG resistance appears to be a multi-gene trait, involving multiple resistance mechanisms. Full article

(This article belongs to the Section Insect Physiology, Reproduction and Development)

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