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20 pages, 7700 KiB  
Article
Influence of Pregnancy on Whole-Transcriptome Sequencing in the Mammary Gland of Kazakh Mares
by Zhenyu Zhang, Zhixin Lu, Xinkui Yao, Linling Li, Jun Meng, Jianwen Wang, Yaqi Zeng and Wanlu Ren
Animals 2025, 15(14), 2056; https://doi.org/10.3390/ani15142056 - 11 Jul 2025
Abstract
Kazakh mares have drawn significant attention for their outstanding lactation traits. Lactation, a complex physiological activity, is modulated by multiple factors. This study utilized high-throughput sequencing to conduct whole-transcriptome sequencing analysis on the mammary gland tissue of eight Kazakh mares, of which four [...] Read more.
Kazakh mares have drawn significant attention for their outstanding lactation traits. Lactation, a complex physiological activity, is modulated by multiple factors. This study utilized high-throughput sequencing to conduct whole-transcriptome sequencing analysis on the mammary gland tissue of eight Kazakh mares, of which four were pregnant and four were non-pregnant, to systematically reveal the molecular regulatory mechanisms. The results showed differential expression in 2136 mRNAs, 180 lncRNAs, 104 miRNAs, and 1162 circRNAs. Gene ontology functional annotation indicates that these differentially expressed genes are involved in multiple key biological processes, such as the cellular process (BP), metabolic process, and biological regulation. Kyoto Encyclopedia of Genes and Genomes analysis suggests that the differentially expressed genes are significantly enriched in essential pathways such as cytokine–cytokine receptor interaction, the chemokine signaling pathway, and the PI3K-Akt signaling pathway. Additionally, this study constructed a competing endogenous RNA (ceRNA) regulatory network based on the differentially expressed genes (|log2FC| > 1, FDR < 0.05), offering a novel perspective for revealing the functional regulation of the mammary gland. This study compared genomic differences in mammary gland tissue of pregnant and non-pregnant Kazakh mares and identified candidate genes that are closely related to lactation regulation. It found that various genes, such as PIK3CG, IL7R, and SOD2, play central regulatory roles in activating mammary gland functions. These findings provide theoretical support for explaining the molecular mechanisms underlying the mammary gland development of Kazakh mares. Full article
(This article belongs to the Section Equids)
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18 pages, 3194 KiB  
Article
Identification and Characterization of the Complete Genome of the TGF-β Gene Family in Tupaia belangeri: Expression and Function of Adipose Tissue Under Cold Acclimation Conditions
by Lijie Du, Wanlong Zhu and Lin Zhang
Int. J. Mol. Sci. 2025, 26(14), 6681; https://doi.org/10.3390/ijms26146681 - 11 Jul 2025
Abstract
The transforming growth factor beta (TGF-β) gene family is widely distributed across the animal kingdom, playing a crucial role in various cellular processes and maintaining overall health and homeostasis. The present study identified 34 TGF-β family genes based on the [...] Read more.
The transforming growth factor beta (TGF-β) gene family is widely distributed across the animal kingdom, playing a crucial role in various cellular processes and maintaining overall health and homeostasis. The present study identified 34 TGF-β family genes based on the genome sequence in Tupaia belangeri, which were classified into the TGF-β, bone morphogenetic protein (BMP), growth differentiation factor (GDF), glial cell-derived neurotrophic factor (GDNF), and Activin/Inhibin subfamilies. A phylogenetic analysis revealed the evolutionary relationships among members of the TGF-β family in T. belangeri and their homologous genes in Homo sapiens, Mus musculus, and Pan troglodytes, indicating a high degree of conservation throughout evolution. A chromosomal distribution and collinearity analysis demonstrated the localization of these genes within the genome of T. belangeri and their collinearity with genes from other species. A gene structure and motif analysis further illustrated the conservation and diversity among TGF-β family members. A protein interaction network analysis highlighted the central roles of TGFB1, TGFB3, BMP7, and BMP2 in signal transduction. A functional enrichment analysis underscored the significance of the TGF-β signaling pathway in the biological processes of T. belangeri, particularly in cell proliferation, differentiation, and apoptosis. We assessed the impact of cold acclimation treatment on the expression of TGF-β family proteins in the adipose tissue (white adipose tissue [WAT] and brown adipose tissue [BAT]) of T. belangeri using ELISA technology, finding that protein expression levels in the experimental group were significantly higher than those of in the control group. These results suggested that cold acclimation may enhance the adaptability of T. belangeri to cold environments by modulating the expression of TGF-β family genes. This study offers new insights into the role of the TGF-β family in the cold acclimation adaptation of T. belangeri, providing a scientific foundation for future genetic improvements and strategies for cold acclimation. Full article
(This article belongs to the Section Molecular Biology)
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12 pages, 2220 KiB  
Article
The Effects of Tree Species on Soil Organic Carbon Mineralization in Reservoir Water-Level Drawdown Zones
by Jiayi Zhang, Fang Wang, Jia Yang, Yanting Zhang, Li Qiu, Ziting Chen, Xi Wang, Tianya Zhang, Songzhe Li, Jiacheng Tong, Shunbao Lu and Yanjie Zhang
Forests 2025, 16(7), 1145; https://doi.org/10.3390/f16071145 - 11 Jul 2025
Abstract
Soil organic carbon (SOC) mineralization is the conversion of SOC to inorganic forms of carbon (C) by microbial decomposition and conversion. It plays an important role in global C cycling. Currently, most of the studies investigating the effects of different tree species on [...] Read more.
Soil organic carbon (SOC) mineralization is the conversion of SOC to inorganic forms of carbon (C) by microbial decomposition and conversion. It plays an important role in global C cycling. Currently, most of the studies investigating the effects of different tree species on SOC mineralization focus on forest ecosystems, and few have focused on reservoir water-level drawdown zones. In this study, we used an indoor incubation method to investigate SOC mineralization in the plantation soils of Glyptostrobus pensilis, Taxodium Zhongshanshan, Taxodium distichum and CK (unplanted plantation) in the reservoir water-level drawdown zones. We aimed to explore the effects of different tree species on the process of SOC mineralization in the reservoir water-level drawdown zones by considering both the biological and chemical processes of the soil. The results showed that the rates of SOC mineralization in the G. pensilis and T. Zhongshanshan plantations were 47% and 37%, respectively, higher than those in CK (p < 0.05), whereas the rate of SOC mineralization in T. distichum soils did not differ from that in CK. The structural equation model’s results showed microbial biomass carbon (MBC) is a key driver of SOC mineralization, while SOC and dissolved organic carbon (DOC) concentrations are also important factors that affect SOC mineralization and follow MBC. Compared to soil biochemical properties, the bacterial community composition has relatively little effect on SOC mineralization. Planted forests can, to a degree, change the biochemical properties of the soil in the reservoir water-level drawdown zones, effectively improving soil pH, and significantly increasing the amount of potential soil C mineralization, the content of SOC and the diversity of the soil bacteria (p < 0.05). Full article
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22 pages, 853 KiB  
Article
Intelligent Multi-Modeling Reveals Biological Mechanisms and Adaptive Phenotypes in Hair Sheep Lambs from a Semi-Arid Region
by Robson Mateus Freitas Silveira, Fábio Augusto Ribeiro, João Pedro dos Santos, Luiz Paulo Fávero, Luis Orlindo Tedeschi, Anderson Antonio Carvalho Alves, Danilo Augusto Sarti, Anaclaudia Alves Primo, Hélio Henrique Araújo Costa, Neila Lidiany Ribeiro, Amanda Felipe Reitenbach, Fabianno Cavalcante de Carvalho and Aline Vieira Landim
Genes 2025, 16(7), 812; https://doi.org/10.3390/genes16070812 - 11 Jul 2025
Abstract
Background: Heat stress challenges small ruminants in semi-arid regions, requiring integrative multi-modeling approaches to identify adaptive thermotolerance traits. This study aimed to identify phenotypic biomarkers and explore the relationships between thermoregulatory responses and hematological, behavioral, morphometric, carcass, and meat traits in lambs. Methods: [...] Read more.
Background: Heat stress challenges small ruminants in semi-arid regions, requiring integrative multi-modeling approaches to identify adaptive thermotolerance traits. This study aimed to identify phenotypic biomarkers and explore the relationships between thermoregulatory responses and hematological, behavioral, morphometric, carcass, and meat traits in lambs. Methods: Twenty 4-month-old non-castrated male lambs, with an average body weight of 19.0 ± 5.11 kg, were evaluated under natural heat stress. Results: Thermoregulatory variables were significantly associated with non-carcass components (p = 0.002), carcass performance (p = 0.027), commercial meat cuts (p = 0.032), and morphometric measures (p = 0.029), with a trend for behavioral responses (p = 0.078). The main phenotypic traits related to thermoregulation included idleness duration, cold carcass weight, blood, liver, spleen, shank, chest circumference, and body length. Exploratory factor analysis reduced the significant indicators to seven latent domains: carcass traits, commercial meat cuts, non-carcass components, idleness and feeding behavior, and morphometric and thermoregulatory responses. Bayesian network modeling revealed interdependencies, showing carcass traits influenced by morphometric and thermoregulatory responses and non-carcass traits linked to ingestive behavior. Thermoregulatory variables were not associated with meat quality or hematological traits. Conclusions: These findings highlight the complex biological relationships underlying heat adaptation and emphasize the potential of combining phenomic data with computational tools to support genomic selection for climate-resilient and welfare-oriented breeding programs. Full article
(This article belongs to the Section Animal Genetics and Genomics)
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18 pages, 1777 KiB  
Review
Biochar in Agriculture: A Review on Sources, Production, and Composites Related to Soil Fertility, Crop Productivity, and Environmental Sustainability
by Md. Muzammal Hoque, Biplob Kumar Saha, Antonio Scopa and Marios Drosos
C 2025, 11(3), 50; https://doi.org/10.3390/c11030050 - 11 Jul 2025
Abstract
Due to soil nutrient depletion and rising food demand from an increasing global population, it is essential to find sustainable ways to boost crop yields, improve soil health, and address the environmental issues induced by agriculture. The most appropriate approach is to consider [...] Read more.
Due to soil nutrient depletion and rising food demand from an increasing global population, it is essential to find sustainable ways to boost crop yields, improve soil health, and address the environmental issues induced by agriculture. The most appropriate approach is to consider sustainable amendments, such as biochar and its derivatives, which are vital constituents of soil health due to their affordability, low reactivity, large surface area, and reduced carbon footprint. In this context, biochar and its derivatives in farming systems focus on improving soil structure, nutrient holding capacity, microbial activities, and the perpetuation of soil fertility. Despite its benefits, biochar, if it is used in high concentration, can sometimes become highly toxic, causing soil erosion due to reducing surface area, increasing pH levels, and altering soil properties. This review highlights the production methods and sources of feedstocks, emphasizing their important contribution to the soil’s physicochemical and biological properties. Furthermore, it critically evaluates the environmental applications and their impacts, providing data built upon the literature on contaminant removal from soil, economic factors, heavy metal immobilization, carbon sequestration, and climate resilience. This review emphasizes the main challenges and future prospects for biochar use in comparison to modified biochar (MB) to propose the best practices for sustainable farming systems. Full article
(This article belongs to the Special Issue Carbons for Health and Environmental Protection (2nd Edition))
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12 pages, 270 KiB  
Perspective
Biological Age, Aging Clocks, and the Interplay with Lymphoid Neoplasms: Mechanisms and Clinical Frontiers
by Xiaocan Wu, Hanna Liu and Kejun Ying
Lymphatics 2025, 3(3), 19; https://doi.org/10.3390/lymphatics3030019 - 11 Jul 2025
Abstract
Lymphoid neoplasms (LN), a diverse group of malignancies arising from lymphocytes, exhibit a striking increase in incidence with chronological age, suggesting a deep connection with the aging process. While chronological age remains a primary risk factor, the concept of biological age, reflecting an [...] Read more.
Lymphoid neoplasms (LN), a diverse group of malignancies arising from lymphocytes, exhibit a striking increase in incidence with chronological age, suggesting a deep connection with the aging process. While chronological age remains a primary risk factor, the concept of biological age, reflecting an individual’s physiological state and susceptibility to age-related diseases, offers a more nuanced understanding of this relationship. Aging clocks, particularly epigenetic clocks based on DNA methylation, provide quantitative measures of biological age and have revealed associations between accelerated aging and increased cancer risk, including LN. Immunosenescence, the age-related decline in immune function characterized by thymic involution, altered lymphocyte populations, and chronic inflammation (inflammaging), appears to be a key mechanistic link between aging and LN development, potentially providing a more accurate predictor of cancer risk than mutation accumulation alone. Accelerated biological aging, measured by various clocks, correlates with LN risk and progression (e.g., in chronic lymphocytic leukemia), and may influence treatment tolerance and outcomes, particularly in older adults who are often burdened by frailty and comorbidities like sarcopenia. Integrating biological age assessments into clinical practice holds promise for refining diagnosis, prognosis, and personalizing treatment strategies (including guiding intensity and considering anti-aging interventions), and improving outcomes for patients with LN. This review synthesizes the current understanding of the intricate relationship between LN, immunosenescence, biological age, and aging clocks, highlighting clinical implications and key future research directions aimed at translating these insights into better patient care. Full article
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11 pages, 505 KiB  
Article
The Role of Musculoskeletal Ultrasound in Biologic Drug Tapering and Relapse Monitoring: Findings from a One-Year Prospective Study in a Cohort of Rheumatoid Arthritis Patients in Sustained Clinical Remission
by Zguro Batalov, Tanya Sapundzhieva, Konstantin Batalov, Rositsa Karalilova and Anastas Batalov
Diagnostics 2025, 15(14), 1753; https://doi.org/10.3390/diagnostics15141753 - 10 Jul 2025
Abstract
Objectives: To assess the role of musculoskeletal ultrasound (MSUS) in selecting patients with rheumatoid arthritis (RA) in sustained clinical remission, suitable for tapering of biologic therapy (BT), and monitoring for a subclinical relapse. Methods: In this prospective study, seventy-eight patients with RA in [...] Read more.
Objectives: To assess the role of musculoskeletal ultrasound (MSUS) in selecting patients with rheumatoid arthritis (RA) in sustained clinical remission, suitable for tapering of biologic therapy (BT), and monitoring for a subclinical relapse. Methods: In this prospective study, seventy-eight patients with RA in sustained Disease Activity for twenty-eight joints (DAS28) clinical remission underwent ultrasound (US) examination of twenty-two joints (bilaterally wrists and metacarpophalangeal and proximal interphalangeal joints). US assessment was performed on gray scale ultrasound (GSUS) and power Doppler US (PDUS) to select patients in imaging remission, defined as a total PD score of synovitis = 0. Group 1 consisted of patients in clinical and imaging remission, in which tapering of BT was done through spacing of the Tumour Necrosis Factor Alpha (TNF-α) blocker. Group 2 consisted of patients only in clinical remission (PDUS > 0), who continued standard therapy. Clinical and US assessment was done at months 6 and 12, and the rate of a clinical (defined as DAS28 ≥ 2.6) and an US relapse (PDUS score ≥ 1) was recorded. Results: Thirty-eight patients were in clinical and US remission (group 1) and forty patients only in clinical remission (group 2). At month 6, 26% of patients in group 1 and 10% in group 2 experienced a clinical and an US relapse, whereas 20% and 15% of them, respectively, only an US relapse. At month 12, 26% of patients in group 1 and 20% of patients in group 2 experienced a clinical and an US relapse, whereas 35% and 22% of them, respectively, only an US relapse. Conclusions: Real-world data show that MSUS is a useful tool to identify RA patients in sustained clinical remission appropriate for BT tapering. US monitoring could predict a clinical relapse and the need to re-escalate treatment in patients with subclinical US relapse during BT tapering. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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16 pages, 2888 KiB  
Article
Vitamin K Epoxide Reductase Complex (VKORC1) Electrochemical Genosensors: Towards the Identification of 1639 G>A Genetic Polymorphism
by Tiago Barbosa, Stephanie L. Morais, Renato Carvalho, Júlia M. C. S. Magalhães, Valentina F. Domingues, Cristina Delerue-Matos, Hygor Ferreira-Fernandes, Giovanny R. Pinto, Marlene Santos and Maria Fátima Barroso
Chemosensors 2025, 13(7), 248; https://doi.org/10.3390/chemosensors13070248 - 10 Jul 2025
Abstract
Anticoagulants, including warfarin, are often administered to patients who are exhibiting early symptoms of thromboembolic episodes or who have already experienced such episodes. However, warfarin has a limited therapeutic index and might cause bleeding and other clinical problems. Warfarin inhibits the vitamin K [...] Read more.
Anticoagulants, including warfarin, are often administered to patients who are exhibiting early symptoms of thromboembolic episodes or who have already experienced such episodes. However, warfarin has a limited therapeutic index and might cause bleeding and other clinical problems. Warfarin inhibits the vitamin K epoxide reductase complex subunit 1 (VKORC1), an enzyme essential for activating vitamin K, in the coagulation cascade. Genetic factors, such as polymorphisms, can change the natural function of VKORC1, causing variations in the medication reaction among individuals. Hence, before prescribing warfarin, the patient’s genetic profile should also be considered. In this study, an electrochemical genosensor capable of detecting the VKORC1 1639 G>A polymorphism was designed and optimized. This analytical approach detects the electric current obtained during the hybridization reaction between two 52 base pair complementary oligonucleotide sequences. Investigating public bioinformatic platforms, two DNA sequences with the A and G single-nucleotide variants were selected and designed. The experimental protocol of the genosensor implied the formation of a bilayer composed of a thiolate DNA and an alkanethiol immobilized onto gold electrodes, as well as the formation of a DNA duplex using a sandwich-format hybridization reaction through a fluorescein labelled DNA signalling probe and the enzymatic amplification of the electrochemical signal, detected by chronoamperometry. A detection limit of 20 pM and a linear range of 0.05–1.00 nM was obtained. A clear differentiation between A/A, G/A and G/G genotypes in biological samples was successfully identified by his novel device. Full article
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21 pages, 305 KiB  
Review
Physical Activity Monitors in Companion Animal Chronic Pain Research—A Review Focused on Osteoarthritis Pain
by Connor Thonen-Fleck, Kate P. Sharon, Masataka Enomoto, Max LeBouef, David L. Roberts, Margaret E. Gruen and B. Duncan X. Lascelles
Animals 2025, 15(14), 2025; https://doi.org/10.3390/ani15142025 - 10 Jul 2025
Abstract
Accelerometry-based physical activity monitors (PAMs) are a useful tool to collect objective measurements of physical activity and movement. Recently, there has been an increased utilization of PAMs in companion animal chronic pain research. However, a general lack of understanding of PAMs contributes to [...] Read more.
Accelerometry-based physical activity monitors (PAMs) are a useful tool to collect objective measurements of physical activity and movement. Recently, there has been an increased utilization of PAMs in companion animal chronic pain research. However, a general lack of understanding of PAMs contributes to challenges and misconceptions around the interpretation and utility of these data. Commercially available devices differ in how they acquire, process, report, and, in some cases, interpret data. Furthermore, various factors relating to the subject, such as age, body condition, and species, clearly influence PAM data, and on top of this, understanding the biological meaning of PAM data is in its relative infancy. This review examines the principles of PAM technology and the technical and biological considerations when applying PAMs to companion animal chronic pain research, in particular osteoarthritis pain research. It also provides an overview of applications of these devices in veterinary chronic pain research thus far, and the potential of these devices in future studies. Full article
(This article belongs to the Special Issue Advances in Companion Animal Pain Assessment)
29 pages, 1189 KiB  
Review
Decoding Skin Aging: A Review of Mechanisms, Markers, and Modern Therapies
by Jorge Naharro-Rodriguez, Stefano Bacci, Maria Luisa Hernandez-Bule, Alfonso Perez-Gonzalez and Montserrat Fernandez-Guarino
Cosmetics 2025, 12(4), 144; https://doi.org/10.3390/cosmetics12040144 - 10 Jul 2025
Abstract
Skin aging is a multifactorial process driven by both intrinsic mechanisms—such as telomere shortening, oxidative stress, hormonal decline, and impaired autophagy—and extrinsic influences including ultraviolet radiation, pollution, smoking, and diet. Together, these factors lead to the structural and functional deterioration of the skin, [...] Read more.
Skin aging is a multifactorial process driven by both intrinsic mechanisms—such as telomere shortening, oxidative stress, hormonal decline, and impaired autophagy—and extrinsic influences including ultraviolet radiation, pollution, smoking, and diet. Together, these factors lead to the structural and functional deterioration of the skin, manifesting as wrinkles, pigmentation disorders, thinning, and reduced elasticity. This review provides an integrative overview of the biological, molecular, and clinical dimensions of skin aging, emphasizing the interplay between inflammation, extracellular matrix degradation, and senescence-associated signaling pathways. We examine histopathological hallmarks and molecular markers and discuss the influence of genetic and ethnic variations on aging phenotypes. Current therapeutic strategies are explored, ranging from topical agents (e.g., retinoids, antioxidants, niacinamide) to procedural interventions such as lasers, intense pulsed light, photodynamic therapy, microneedling, and injectable biostimulators. Special attention is given to emerging approaches such as microneedle delivery systems, with mention of exosome-based therapies. The review underscores the importance of personalized anti-aging regimens based on biological age, phototype, and lifestyle factors. As the field advances, integrating mechanistic insights with individualized treatment selection will be key to optimizing skin rejuvenation and preserving long-term dermal health. Full article
(This article belongs to the Special Issue Feature Papers in Cosmetics in 2025)
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26 pages, 967 KiB  
Review
Clinicopathological Predictors of Recurrence in Uterine Sarcomas—A Narrative Review
by Emmanuel N. Kontomanolis, Ioakeim Sapantzoglou, Konstantinos Nikolettos, Evangelia Kontogeorgi, Vasiliki Lampraki, Dimitrios Papageorgiou, Paraskevas Perros, Zacharias Fasoulakis, Aristotelis-Marios Koulakmanidis, Maria-Anastasia Daskalaki, Vasilios Pergialiotis, Panagiotis Antsaklis, Marianna Theodora and George Daskalakis
J. Clin. Med. 2025, 14(14), 4883; https://doi.org/10.3390/jcm14144883 - 9 Jul 2025
Abstract
Background: Sarcomas are a rare and biologically diverse group of malignant tumors that originate from mesenchymal tissues. They are characterized by a broad range of histopathological subtypes, varying clinical courses, and differing responses to treatment. This study seeks to clarify the clinicopathological and [...] Read more.
Background: Sarcomas are a rare and biologically diverse group of malignant tumors that originate from mesenchymal tissues. They are characterized by a broad range of histopathological subtypes, varying clinical courses, and differing responses to treatment. This study seeks to clarify the clinicopathological and molecular predictors of recurrence in leiomyosarcomas, carcinosarcomas, and endometrial stromal sarcomas to enhance our understanding, thereby improving clinical knowledge, consultation practices, and the overall benefit for patients. Methods: A literature search was conducted utilizing PubMed/MEDLINE, Embase, Cochrane Library, and Scopus to execute a comprehensive structured narrative review of articles published up to 31 March 2025. Results: We summarize existing evidence on the clinical, histological, and molecular predictors of recurrence and poor prognosis for leiomyosarcomas, carcinosarcomas, and endometrial stromal sarcomas. While the stage, grade, tumor size, and novel molecular biomarkers are crucial high-risk parameters that have been associated with recurrence, existing data demonstrate contradictory results, indicating the need for further research. Conclusions: Recent advancements in next-generation sequencing have facilitated the identification of women at increased risk of recurrence, poor disease-free survival, and overall adverse prognosis. Stratifying this risk requires a comprehensive understanding of the clinical, histological, and molecular risk factors involved. Understanding these underlying factors is essential for effectively addressing the initial consultation, guiding management, and—considering the novel treatment modalities—individualizing the care provided to the affected women. Full article
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20 pages, 8199 KiB  
Article
Piezo-Type Mechanosensitive Ion Channel Component 1 (PIEZO1) as a Potential Prognostic Marker in Renal Clear Cell Carcinoma
by Paulina Antosik, Martyna Szachniewicz, Michał Baran, Klaudia Bonowicz, Dominika Jerka, Ewelina Motylewska, Maciej Kwiatkowski, Maciej Gagat and Dariusz Grzanka
Int. J. Mol. Sci. 2025, 26(14), 6598; https://doi.org/10.3390/ijms26146598 - 9 Jul 2025
Abstract
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer and is often diagnosed at advanced stages. PIEZO1, a mechanosensitive ion channel, has been implicated in cancer progression, but its prognostic relevance in ccRCC remains unclear. This study [...] Read more.
Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of kidney cancer and is often diagnosed at advanced stages. PIEZO1, a mechanosensitive ion channel, has been implicated in cancer progression, but its prognostic relevance in ccRCC remains unclear. This study aimed to evaluate the expression pattern of PIEZO1 in ccRCC and its association with clinicopathological characteristics and patient survival. Immunohistochemical analysis was performed on formalin-fixed, paraffin-embedded tumor tissues from 111 patients with ccRCC, along with 23 matched peritumoral non-cancerous tissues. Protein expression was quantified using the H-score system. Associations with tumor grade, staging, and overall survival (OS) were analyzed. mRNA expression data were retrieved from The Cancer Genome Atlas (TCGA) to validate the protein-level findings. Functional enrichment and pathway analyses were conducted to explore the biological context of PIEZO1-related gene expression. PIEZO1 showed predominantly cytoplasmic localization, with significantly lower expression in tumor tissues compared to adjacent non-malignant tissue (p < 0.0001). High PIEZO1 expression was correlated with higher tumor grade (p = 0.0147) and shorter OS (p = 0.0047). These findings were confirmed at the mRNA level in the TCGA cohort. Multivariate Cox regression analysis identified PIEZO1 as an independent prognostic factor for OS. In conclusion, PIEZO1 may serve as a clinically relevant biomarker in ccRCC. Its overexpression is associated with more aggressive tumor characteristics and poor prognosis, underscoring the need for further investigation into its functional role and potential as a therapeutic target. Full article
(This article belongs to the Section Molecular Oncology)
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11 pages, 349 KiB  
Article
Reliability of the Polish Version of the Kinesiophobia Causes Scale (KCS) Questionnaire in Assessing the Level of Fear of Movement Among People Suffering from Chronic Nonspecific Low Back Pain
by Edward Saulicz, Andrzej Knapik, Aleksandra Saulicz, Damian Sikora and Mariola Saulicz
Diagnostics 2025, 15(14), 1746; https://doi.org/10.3390/diagnostics15141746 - 9 Jul 2025
Abstract
Background: The phenomenon of fear of movement is called kinesiophobia. Kinesiophobia is a significant factor that complicates the treatment process. Fear of movement and physical activity is a risk factor for the transformation of acute pain into chronic pain. Therefore, the assessment of [...] Read more.
Background: The phenomenon of fear of movement is called kinesiophobia. Kinesiophobia is a significant factor that complicates the treatment process. Fear of movement and physical activity is a risk factor for the transformation of acute pain into chronic pain. Therefore, the assessment of the level of kinesiophobia is a prognostic factor for disability and mental stress, thus having a significant impact on the quality of life of people with lower back pain. One of the psychometric diagnostic tools for assessing the level of kinesiophobia is the Kinesiophobia Causes Scale (KCS). The aim of the study was to assess the reliability of the KCS test used in people suffering from chronic nonspecific lower back pain (nsLBP). Methods: The study included a group of 112 people suffering from chronic nsLBP. The subjects completed the same Polish version of the KCS questionnaire 4 weeks apart. Results: Good internal consistency was recorded for both domains—the biological and psychological one—as well as the general KCS index (Cronbach’s alpha index α from 0.8 to 0.9). Reliability was excellent for both domains (95% CI of ICC3.1 biological domain: 0.86–0.93 and for psychological domain: 0.92–0.96) and for the total score of the Kinesiophobia Causes Scale (95% CI of ICC3.1: 0.91–0.93). Conclusions: These results indicate very good measurement reliability of the Polish version of the KCS questionnaire among people suffering from chronic nsLBP. Full article
(This article belongs to the Special Issue Low Back Pain: Diagnosis and Management)
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32 pages, 4717 KiB  
Article
MOGAD: Integrated Multi-Omics and Graph Attention for the Discovery of Alzheimer’s Disease’s Biomarkers
by Zhizhong Zhang, Yuqi Chen, Changliang Wang, Maoni Guo, Lu Cai, Jian He, Yanchun Liang, Garry Wong and Liang Chen
Informatics 2025, 12(3), 68; https://doi.org/10.3390/informatics12030068 - 9 Jul 2025
Abstract
The selection of appropriate biomarkers in clinical practice aids in the early detection, treatment, and prevention of disease while also assisting in the development of targeted therapeutics. Recently, multi-omics data generated from advanced technology platforms has become available for disease studies. Therefore, the [...] Read more.
The selection of appropriate biomarkers in clinical practice aids in the early detection, treatment, and prevention of disease while also assisting in the development of targeted therapeutics. Recently, multi-omics data generated from advanced technology platforms has become available for disease studies. Therefore, the integration of this data with associated clinical data provides a unique opportunity to gain a deeper understanding of disease. However, the effective integration of large-scale multi-omics data remains a major challenge. To address this, we propose a novel deep learning model—the Multi-Omics Graph Attention biomarker Discovery network (MOGAD). MOGAD aims to efficiently classify diseases and discover biomarkers by integrating various omics data such as DNA methylation, gene expression, and miRNA expression. The model consists of three main modules: Multi-head GAT network (MGAT), Multi-Graph Attention Fusion (MGAF), and Attention Fusion (AF), which work together to dynamically model the complex relationships among different omics layers. We incorporate clinical data (e.g., APOE genotype) which enables a systematic investigation of the influence of non-omics factors on disease classification. The experimental results demonstrate that MOGAD achieves a superior performance compared to existing single-omics and multi-omics integration methods in classification tasks for Alzheimer’s disease (AD). In the comparative experiment on the ROSMAP dataset, our model achieved the highest ACC (0.773), F1-score (0.787), and MCC (0.551). The biomarkers identified by MOGAD show strong associations with the underlying pathogenesis of AD. We also apply a Hi-C dataset to validate the biological rationality of the identified biomarkers. Furthermore, the incorporation of clinical data enhances the model’s robustness and uncovers synergistic interactions between omics and non-omics features. Thus, our deep learning model is able to successfully integrate multi-omics data to efficiently classify disease and discover novel biomarkers. Full article
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15 pages, 2330 KiB  
Review
Fungal Melanin in Plant Pathogens: Complex Biosynthesis Pathways and Diverse Biological Functions
by Hui Jia, Ning Liu, Lu Zhang, Pan Li, Yanan Meng, Wei Yuan, Haixiao Li, Dezeng Tantai, Qing Qu, Zhiyan Cao and Jingao Dong
Plants 2025, 14(14), 2121; https://doi.org/10.3390/plants14142121 - 9 Jul 2025
Abstract
Fungal melanin plays a vital role in the survival, reproduction, infection, and environmental adaptation of plant pathogenic fungi. To develop innovative strategies for managing plant fungal diseases, comprehensive investigations into melanin are imperative. Such research is fundamental to elucidating the mechanistic basis of [...] Read more.
Fungal melanin plays a vital role in the survival, reproduction, infection, and environmental adaptation of plant pathogenic fungi. To develop innovative strategies for managing plant fungal diseases, comprehensive investigations into melanin are imperative. Such research is fundamental to elucidating the mechanistic basis of fungal pathogenesis and holds promise for the design of targeted interventions against melanin-mediated virulence determinants. This review systematically elaborates on the classification of fungal melanin in plant pathogens, provides a detailed analysis of the biosynthetic processes of 3,4-dihydroxyphenylalanine (DOPA) and 1,8-dihydroxynaphthalene melanin (DHN melanins), and reveals the catalytic functions and regulatory mechanisms of key enzymes within these pathways. Melanin modulates fungal virulence by influencing appressorial integrity and turgor pressure formation, thereby participating in the host infection process and the formation of overwintering sclerotia. Melanin provides stress resistance by protecting against extreme environmental factors, including UV radiation and high temperatures. It also has the capacity to absorb heavy metals, which increases pathogen survival under adverse conditions. Furthermore, the review also explores the mechanisms of action of melanin inhibitors that target plant pathogenic fungi, providing a theoretical foundation for developing efficient and environmentally friendly antifungal medications. The complex biosynthesis pathways and diverse biological functions of fungal melanin highlight its significant theoretical and practical importance for elucidating pathogenic mechanisms and formulating scientific control strategies. Full article
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