Biology

14 pages, 272 KB

Open AccessReview

Cytoskeletal Dynamics and Molecular Motor Dysfunction in Psychiatric Disorders: Insights from Schizophrenia and Autism Spectrum Disorder

by Kenyu Nakamura, Asumi Kubo, Sae Sanaka, Sara Kamiya, Kentaro Itagaki and Tetsuya Sasaki

Biology 2026, 15(7), 550; https://doi.org/10.3390/biology15070550 (registering DOI) - 30 Mar 2026

Abstract

Elucidating the pathophysiological mechanisms of mental disorders remains a critical challenge in psychiatric research. Recent studies have highlighted the potential involvement of cytoskeletal and molecular motor abnormalities in the development of mental disorders such as schizophrenia and autism spectrum disorder (ASD). Although schizophrenia [...] Read more.

Elucidating the pathophysiological mechanisms of mental disorders remains a critical challenge in psychiatric research. Recent studies have highlighted the potential involvement of cytoskeletal and molecular motor abnormalities in the development of mental disorders such as schizophrenia and autism spectrum disorder (ASD). Although schizophrenia and ASD differ clinically, both disorders are increasingly regarded as neurodevelopmental conditions and share vulnerabilities in synapse formation and neural circuit maturation. This review synthesizes the latest findings on the relationship between cytoskeletal and molecular motor abnormalities and mental disorders. The cytoskeleton, composed of microtubules, actin filaments, and intermediate filaments, along with molecular motors such as kinesins, dyneins, and myosins, plays crucial roles in neurodevelopment, synapse formation, and neurotransmission. In schizophrenia, decreased expression of the microtubule-associated protein MAP2 and abnormalities in the DISC1 gene have been reported, potentially leading to dendritic morphological abnormalities and neurodevelopmental disorders. Additionally, abnormalities in molecular motors such as KIF17 and KIF1A have been implicated in schizophrenia pathophysiology. Myosin Id has been identified as a risk gene for ASD. Furthermore, abnormalities in actin-related proteins such as SHANK3 and CYFIP1 have been shown to cause synaptic dysfunction. These findings suggest that mental disorders arise from complex pathologies involving multiple cytoskeletal and molecular motor-related protein abnormalities. Future research should focus on elucidating the functions of individual proteins and adopting a comprehensive approach that includes glial cells. Advances in this field may deepen our understanding of the pathophysiological mechanisms of mental disorders and potentially lead to the development of novel therapeutic strategies. Full article

(This article belongs to the Special Issue Biological Foundations of Psychiatric Disorders)

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Graphical abstract

20 pages, 5303 KB

Open AccessArticle

Impact of Human Activities and Climate Change on Chinese Forest Musk Deer (Moschus berezovskii)

by Du Xu, An-Bang Cui, Xu-Lu Ming, Yu-Lu Fei, Xue-Rui Yang and Wen-Bo Li

Biology 2026, 15(7), 549; https://doi.org/10.3390/biology15070549 (registering DOI) - 30 Mar 2026

Abstract

Human activities and climate change are influencing the survival and distribution of species, threatening the current distribution pattern of biodiversity and potentially leading to the “sixth mass extinction.” The forest musk deer (Moschus berezovskii) is among the most numerous and widely [...] Read more.

Human activities and climate change are influencing the survival and distribution of species, threatening the current distribution pattern of biodiversity and potentially leading to the “sixth mass extinction.” The forest musk deer (Moschus berezovskii) is among the most numerous and widely distributed musk deer species in China. However, its habitat is severely threatened by human activities and climate change. Due to the lack of field surveys and research data, it is difficult to assess the threats posed by human activities and climate change effectively. In this study, we integrate the new records of forest musk deer with climate and human activity data, and apply the MaxEnt species distribution model to evaluate the impact of human activities and climate change on the forest musk deer under current conditions and future scenarios (SSP1-2.6 and SSP5-8.5 for the 2030s, 2050s, and 2070s). Our results showed that the forest musk deer prefer areas with high vegetation cover (NDVI > 0.7), low GDP, and low levels of human activity disturbance. The areas of high-suitability habitats are 90.10 × 10⁴ km², 72.85 × 10⁴ km², and 30.43 × 10⁴ km², respectively. The optimal climatic conditions are an annual precipitation (BIO12) of 750–1500 mm and a seasonal temperature variation (BIO4) of 500–600. Their occurrence probability is highest at elevations between 1500 and 3000 m. Under the current climate conditions, the area of high-suitability habitats is estimated at 5.54 × 10⁴ km², primarily distributed across central–northern Sichuan, northwestern Guangxi, and southern Gansu. Under the future climate scenarios, low and medium-suitability habitats are projected to shrink to varying degrees, whereas the high-suitability area is expected to expand, particularly under the SSP5-8.5-2030s scenario where it is projected to increase by 2.88 × 10⁴ km². The centroid of suitable habitat is projected to shift toward higher-elevation areas in northwestern China, with regional hotspots emerging in southwestern regions such as central–northern Sichuan and northwestern Guangxi. These elevational and distributional shifts highlight the vulnerability of current habitats and the importance of adaptive conservation strategies to strengthen species protection, including continuously advancing forest protection programs, mitigating the impact of human activities in high-altitude areas, and strengthening the protection of key areas in the southwestern region. Full article

(This article belongs to the Section Conservation Biology and Biodiversity)

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18 pages, 2567 KB

Open AccessArticle

Laryngeal Transcriptomic Insights into Echolocation Call Frequency Divergence in Closely Related Rhinolophus Species

by Guiyin Miao, Jinhua Cong, Jinhong Lei, Sirui Quan, Jiqian Li, Yannan Li, Kangkang Zhang and Tong Liu

Biology 2026, 15(7), 548; https://doi.org/10.3390/biology15070548 (registering DOI) - 30 Mar 2026

Abstract

Acoustic divergence is widely recognized as a key driver of speciation and niche differentiation in vocal animals. In echolocating horseshoe bats (Rhinolophus), the larynx is specialized for producing high-duty-cycle signals used in foraging, navigation, and species recognition. While the ecological role [...] Read more.

Acoustic divergence is widely recognized as a key driver of speciation and niche differentiation in vocal animals. In echolocating horseshoe bats (Rhinolophus), the larynx is specialized for producing high-duty-cycle signals used in foraging, navigation, and species recognition. While the ecological role of echolocation is established, the molecular mechanisms regulating laryngeal frequency remain unclear. We compared the laryngeal transcriptomes of three closely related, sympatric Rhinolophus species with distinct resting frequencies (RFs): R. episcopus (~46 kHz), R. siamensis (~66 kHz), and R. osgoodi (~85 kHz). This comparison identified 511 differentially expressed genes. High-frequency species upregulated genes involved in cytoskeletal dynamics and muscle contraction, such as cell adhesion molecules and motor proteins, while low-frequency species upregulated genes related to cellular homeostasis and metabolic maintenance. Weighted gene co-expression network analysis revealed two RF-correlated modules: a high-frequency module enriched in aerobic respiration and carbon metabolism and a low-frequency module enriched in lipid metabolism. Protein–protein interaction analysis identified ACTC1, vital for muscle contraction, as a hub gene. Evolutionary analysis showed that ACTC1 is highly conserved, with no significant positive selection, indicating that transcriptional regulation, rather than coding-sequence divergence, is the primary driver of the observed functional differences. These findings suggest that RF variation likely results from transcriptional remodeling in laryngeal superfast muscles. This study provides the first transcriptomic evidence linking laryngeal gene expression with acoustic divergence and offers new insights into the genetic basis of bat echolocation. Full article

(This article belongs to the Special Issue Advances in Biological Research of Chiroptera)

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18 pages, 2073 KB

Open AccessArticle

Epigenetic Landscape of the Citrus Greek National Germplasm Collection and Its Association with Genetic and Fitness-Related Data

by Fani G. Lyrou, Vasiliki Maria Kotina, Andreas G. Doulis, Nikolaos Tourvas, Vasileios Ziogas, Ioannis Ganopoulos and Filippos A. Aravanopoulos

Biology 2026, 15(7), 546; https://doi.org/10.3390/biology15070546 (registering DOI) - 29 Mar 2026

Abstract

Epigenetic diversity contributes to phenotypic plasticity and environmental responsiveness in Citrus spp. In this work, genome-wide DNA methylation was analyzed in 49 accessions representing six Citrus species, hybrids, varieties, and cultivars from the Greek National Germplasm Collection. Substantial variation in global DNA methylation [...] Read more.

Epigenetic diversity contributes to phenotypic plasticity and environmental responsiveness in Citrus spp. In this work, genome-wide DNA methylation was analyzed in 49 accessions representing six Citrus species, hybrids, varieties, and cultivars from the Greek National Germplasm Collection. Substantial variation in global DNA methylation was detected, while the epigenetic diversity indices did not differ significantly among taxa. The highest values were observed in Citrus × aurantium var. sinensis (orange) varieties (P_epi = 77.33%, Na = 1.55, h = 0.14, I_epi = 0.24), whereas the lowest were recorded in Citrus × aurantifolia (lime) (P_epi = 18.67%, Na = 0.37, h = 0.09, I_epi = 0.13), reflecting potential methylation restructuring impacted by hybridization and selection. Epigenetic and genetic diversity were significantly different. Principal coordinate analyses (PCoA) of epigenetic data revealed limited concordance to taxonomy, except for unmethylated loci, the latter exhibiting similar data to genetic (SSR) results in which groups reflected the taxonomic genealogy. Epigenetic and genetic distances were uncoupled, and associations between epigenetic diversity (P_epi, h, I_epi) and traits directly or indirectly related to fitness (fruit weight, dry matter content, ascorbic acid concentration), were weak. These findings indicate that epigenetic diversity represents an independent layer of variation in Citrus germplasm with potential relevance for breeding, conservation and environmental resilience. Full article

(This article belongs to the Section Plant Science)

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19 pages, 1337 KB

Open AccessArticle

In Silico-Identified Peptides of Five Borrelia burgdorferi Proteins Binding with High Affinity to Human Leukocyte Antigen (HLA) Class II Alleles

by Apostolos P. Georgopoulos, Lisa M. James and Matthew Sanders

Biology 2026, 15(7), 547; https://doi.org/10.3390/biology15070547 (registering DOI) - 28 Mar 2026

Abstract

To date, Lyme vaccine development has largely overlooked the vaccinee’s human leukocyte antigen (HLA) genetic makeup on which antibody production critically depends. Here, we evaluated in silico the predicted binding affinities of 192 HLA-II alleles with all 15-mer peptide sequences of five Borrelia [...] Read more.

To date, Lyme vaccine development has largely overlooked the vaccinee’s human leukocyte antigen (HLA) genetic makeup on which antibody production critically depends. Here, we evaluated in silico the predicted binding affinities of 192 HLA-II alleles with all 15-mer peptide sequences of five Borrelia burgdorferi proteins to identify peptides with strong binding affinity, as they would be the best candidates for antibody production in response to vaccination. We found the following: (a) 226 of the 1067 peptides tested (21.2%) were found to bind strongly to HLA-II molecules; (b) decorin-binding protein A had the greatest number of strongly binding peptides; and (c) 69 HLA-II alleles (primarily of the DRB1 gene) bound with strong affinity to peptides from Borrelia burgdorferi proteins. Finally, we tested for possible susceptibility to autoimmunity by any one of the 226 peptides above by searching for their occurrence in ~84,000 proteins of the human proteome and found overlap with only two 8-mer peptide sequences (embedded within the 226 15-mer peptides), neither of which was characterized by strong binding to HLA-I, suggesting a reduced likelihood of autoimmunity. These findings emphasize the importance of a personalized vaccine approach based on the vaccinee’s human leukocyte antigen genetic makeup and offer specific vaccine-candidate peptides that are predicted to maximize vaccine effectiveness and safety. The results of this computational study provide novel directions for future development of Lyme vaccines. Full article

(This article belongs to the Special Issue Human Leukocyte Antigen (HLA)—Antigen Interactions in Vaccine Development)

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18 pages, 2681 KB

Open AccessArticle

Identification of a Novel Disulfidptosis-Related Five-Gene Signature for Prognostic Prediction and Immune Characterization in Esophageal Cancer

by Yiru Chen, Xuefeng Li, Hui Jiang, Xiaohui Liu, Nan Ma and Xuemei Wang

Biology 2026, 15(7), 545; https://doi.org/10.3390/biology15070545 (registering DOI) - 28 Mar 2026

Abstract

Esophageal cancer is a highly aggressive malignancy with a poor prognosis. More precise prognostic biomarkers are therefore needed. Disulfidptosis is a recently identified form of regulated cell death driven by disulfide stress. It has been implicated in tumor progression. However, its prognostic role [...] Read more.

Esophageal cancer is a highly aggressive malignancy with a poor prognosis. More precise prognostic biomarkers are therefore needed. Disulfidptosis is a recently identified form of regulated cell death driven by disulfide stress. It has been implicated in tumor progression. However, its prognostic role in esophageal cancer remains largely unexplored. This study aimed to develop a disulfidptosis-related gene signature for risk stratification and outcome prediction in esophageal cancer patients. Based on 23 disulfidptosis-related genes, consensus clustering was performed to identify molecular subtypes. Differentially expressed genes (DEGs) between subtypes were subjected to functional enrichment, immune microenvironment, and drug sensitivity analyses. Univariate and multivariate Cox regression were used to construct a prognostic risk model, which was evaluated using time-dependent receiver operating characteristic (ROC) curve and Kaplan–Meier analysis. A clinical nomogram integrating the risk score and clinicopathological factors was developed and validated. Two distinct disulfidptosis-related subtypes were identified, showing significant differences in gene expression, immune infiltration, and stromal scores. A total of 1080 DEGs were enriched in pathways related to epidermal differentiation, NRF2 signaling, and glucocorticoid receptor activity. A five-gene prognostic signature was established and effectively stratified patients into high- and low-risk groups. The risk model exhibited strong discrimination for 1-, 3-, and 5-year overall survival outcomes. The predictive accuracy was further maximized through an integrated clinical nomogram, which achieved an outstanding area under the curve (AUC) of 0.94 for 5-year survival predictions. Drug sensitivity analysis revealed subtype-specific therapeutic vulnerabilities, supporting potential precision treatment strategies. This study proposes a novel disulfidptosis-related five-gene signature and nomogram that robustly predict prognosis in esophageal cancer. The findings highlight the clinical relevance of disulfidptosis in tumor biology and offer a potential tool for risk stratification and personalized therapeutic decision-making. Full article

(This article belongs to the Special Issue Current Advances in Cancer Genomics)

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15 pages, 1425 KB

Open AccessArticle

Characterization of the Complete Mitochondrial Genome of Nibea chui: Resolving a Taxonomic Controversy and New Phylogenetic Insights into Sciaenidae

by Chuanhao Chen, Ang Li and Shufang Liu

Biology 2026, 15(7), 544; https://doi.org/10.3390/biology15070544 (registering DOI) - 28 Mar 2026

Abstract

N. chui is an economically important marine fish species distributed along the coastal waters of China, renowned for its delicate flesh texture and high-quality dried swim bladder. However, its scientific name and taxonomic relationship with N. coibor have long remained controversial, hindering accurate [...] Read more.

N. chui is an economically important marine fish species distributed along the coastal waters of China, renowned for its delicate flesh texture and high-quality dried swim bladder. However, its scientific name and taxonomic relationship with N. coibor have long remained controversial, hindering accurate resource assessment and germplasm management. To address this issue, we sequenced and annotated the first complete mitochondrial genome of N. chui (GenBank accession: PZ024444). The circular mitogenome is 16,504 bp in length and contains 37 typical genes, with gene arrangement, nucleotide composition (A + T content: 52.07%), and codon usage patterns consistent with general teleost characteristics. Phylogenetic analyses based on 13 concatenated protein-coding genes revealed that N. chui and N. coibor form a maximally supported monophyletic clade (bootstrap support = 100%), with a pairwise genetic distance of 0. These mitochondrial results strongly suggest that the two nominal taxa are very closely related and may represent the same species. However, formal taxonomic synonymy cannot be established on mitochondrial evidence alone and requires further evaluation through examination of type material and comparative morphological study. Gene-specific selection pressure analyses showed that most mitochondrial protein-coding genes were subject to purifying selection, with ATP8 exhibiting the highest mean ω among genes with ω < 1, whereas ND5 and ND6 showed elevated ω values that warrant cautious interpretation. This study provides essential mitochondrial genomic resources for future research on species delimitation, phylogeny, and conservation of this important sciaenid fish. Full article

(This article belongs to the Section Biochemistry and Molecular Biology)

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27 pages, 10362 KB

Open AccessArticle

Decoding the Clinical and Therapeutic Significance of MEAK7 in Triple-Negative Breast Cancer Through Integrative Bioinformatics

by Durmus Ayan, Meltem Uyaner Kan, Ergul Bayram and Sibel Soylemez

Biology 2026, 15(7), 543; https://doi.org/10.3390/biology15070543 (registering DOI) - 28 Mar 2026

Abstract

Triple-negative breast cancer (TNBC) represents a clinically challenging breast cancer (BC) subtype, characterized by aggressive behavior, high recurrence risk, and limited therapeutic options. MEAK7 has been identified as an alternative mTORC1 signaling pathway regulator; however, its role in BC and TNBC remains uninvestigated. [...] Read more.

Triple-negative breast cancer (TNBC) represents a clinically challenging breast cancer (BC) subtype, characterized by aggressive behavior, high recurrence risk, and limited therapeutic options. MEAK7 has been identified as an alternative mTORC1 signaling pathway regulator; however, its role in BC and TNBC remains uninvestigated. This study aims to assess MEAK7 expression, prognostic significance, and therapeutic potential. We employed public datasets, including TCGA, bc-GenExMiner v5.2, GEPIA3, DOSurvive platforms, Kaplan–Meier Plotter, UALCAN, TIMER2.0, STRING, ENCORI, HPA, miRDB, TargetScan, and CRISPRdb. MEAK7 expression was significantly elevated in BC tissues versus normal breast tissue. MEAK7 expression was pronounced in TNBC and basal-like subtypes, with hypomethylation of its promoter region in TNBC. Elevated MEAK7 expression correlated with reduced disease-free survival (DFS) in TNBC and basal-like. Multivariate Cox regression identified MEAK7 as a significant prognostic factor for overall survival, independent of age and tumor stage. MEAK7 showed CRISPR-targetable gRNA profiles with high on-target efficiency and minimal off-target effects. Analyses revealed negative correlation with tumor-suppressive RNAs (miR-149-3p, miR-135a-5p, and LINC00993) and positive correlation with aggressive regulators (miR-135b-5p and HIF1A-AS2). This study represents one of the initial comprehensive and multi-platform bioinformatic analyses demonstrating that MEAK7 exhibits elevated expression in breast cancer, particularly within the aggressive TNBC. The findings indicate that MEAK7 may serve as a promising prognostic biomarker in TNBC biology and suggest its viability as a molecular candidate for future investigation in targeted therapeutic strategies. Full article

(This article belongs to the Special Issue Breast Cancer: Molecular and Cellular Mechanism and Biomarkers)

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15 pages, 2506 KB

Open AccessArticle

Evidence for the Link Between KK-42 and the DH-PBAN Gene in Two Silkmoth Species, with Impacts on Developmental Traits

by Haixu Bian, Yufeng Lin, Yuping Li, Jingchen Sun and Yanqun Liu

Biology 2026, 15(7), 542; https://doi.org/10.3390/biology15070542 (registering DOI) - 28 Mar 2026

Abstract

Diapause hormone (DH) is an important endocrine substance capable of influencing diapause in Lepidoptera moths that is encoded by the neuropeptide hormone DH-PBAN gene. Imidazole derivative KK-42 is a synthetic insect growth regulator that can affect diapause in Lepidoptera moths, and appears to [...] Read more.

Diapause hormone (DH) is an important endocrine substance capable of influencing diapause in Lepidoptera moths that is encoded by the neuropeptide hormone DH-PBAN gene. Imidazole derivative KK-42 is a synthetic insect growth regulator that can affect diapause in Lepidoptera moths, and appears to have an opposite physiological function to DH. To test the hypothesis that KK-42 may be operating through DH to affect diapause, here, we used two Lepidoptera species Bombyx mori L. and Antheraea pernyi that enter egg and pupal diapause, respectively, through examining whether KK-42 can influence DH-PBAN and some associated mRNA expression. We found that the protein sequences of DH-PBAN in insects were highly variable, although the PRXamide C-terminus was conserved. We also found that KK-42 induced significant up-regulation and prolonged expression duration of DH-PBAN in both A. pernyi and B. mori pupae, as well as in trimolter larvae of B. mori that were induced by the application of KK-42 from the normal tetramolter larvae. In addition, KK-42 can significantly upregulate glutamic acid decarboxylase (GAD) expression in B. mori in transcriptome data. Our findings suggested that KK-42 influences diapause by upregulating GAD expression, promoting DH accumulation to prolong the secretion time of DH-PBAN. Full article

24 pages, 3786 KB

Open AccessReview

When Infection Meets Inflammation: Listeria monocytogenes and Host Signaling Pathways

by Yanyan Jia, Ke Yang, Rongxian Guo, Ke Ding, Shaohui Wang and Songbiao Chen

Biology 2026, 15(7), 541; https://doi.org/10.3390/biology15070541 - 27 Mar 2026

Abstract

Listeria monocytogenes (L. monocytogenes) is a significant zoonotic pathogen responsible for listeriosis, a foodborne infection with high mortality. The inflammasome, an innate immune complex, plays a critical role in controlling pathogenic infections through its rapid inflammatory output. During L. monocytogenes infection, [...] Read more.

Listeria monocytogenes (L. monocytogenes) is a significant zoonotic pathogen responsible for listeriosis, a foodborne infection with high mortality. The inflammasome, an innate immune complex, plays a critical role in controlling pathogenic infections through its rapid inflammatory output. During L. monocytogenes infection, pore-forming toxins such as listeriolysin-O and flagellin are quickly recognized by pattern recognition receptors (PRRs), triggering inflammatory responses and activating the host’s anti-infection immunity. However, excessive or chronic inflammasome activation and subsequent interleukin-1β (IL-1β) release are implicated in the pathogenesis of L. monocytogenes. Although inflammasome activation is an effective defense against L. monocytogenes, the bacterium has evolved multiple mechanisms to inhibit this immune pathway. Hence, research on inflammasomes activation is crucial for better understanding the pathogenic mechanism of L. monocytogenes. In this review, we highlight recent advances in the understanding of the molecular mechanisms of inflammasome activation by L. monocytogenes infection. We then discuss advances in the role of the inflammasome pathway in the pathogenesis of L. monocytogenes, along with an overview of the applications of inflammasome inhibitors. Extensive studies into the mechanisms by which L. monocytogenes activates the inflammasome could lead to the discovery of novel therapeutic targets and strategies to fight L. monocytogenes infections. Full article

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14 pages, 6994 KB

Open AccessArticle

Enzymatic Degradation of Polyethylene Terephthalate Model Substrates by Esterase E4

by Shuyan Duan, Huifang Yang, Rumeng Sun, Jiankang Ma and Kun Wang

Biology 2026, 15(7), 540; https://doi.org/10.3390/biology15070540 - 27 Mar 2026

Abstract

As the demand for polyethylene terephthalate (PET) continues to rise, significant environmental pollution caused by challenges in PET degradation has garnered global attention. Given the crucial role of esterases in depolymerizing PET into reusable monomers, such enzymes capable of degrading plastics have attracted [...] Read more.

As the demand for polyethylene terephthalate (PET) continues to rise, significant environmental pollution caused by challenges in PET degradation has garnered global attention. Given the crucial role of esterases in depolymerizing PET into reusable monomers, such enzymes capable of degrading plastics have attracted considerable interest. In this study, we used the previously reported ultra-efficient mutant of the PET-degrading enzyme Ideonella sakaiensis PETase, known as FASTase, as a positive control. We investigated the PET-degrading activity of esterase E4, derived from Altererythrobacter indicus. The results demonstrated that E4 exhibits degradative activity toward the PET substrate bis(2-hydroxyethyl) terephthalate, the PET model substrate bis(benzyloxyethyl) terephthalate, and PET nanoparticles. Notably, E4 retains its degradation activity under high-temperature and high-salt conditions and can enhance the enzymatic activity of FASTase when acting synergistically. Given the low structural and sequence similarity between E4 and IsPETase, our research broadens the scope for screening PET-degrading enzymes. Full article

(This article belongs to the Section Biochemistry and Molecular Biology)

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18 pages, 4940 KB

Open AccessArticle

FGF23 Controls Myocardial Fibrosis Progression via Promoting Cardiac Fibroblast Proliferation and Activation in Mice

by Leyi Shen, Mingqi Hu, Mei Xue and Santie Li

Biology 2026, 15(7), 539; https://doi.org/10.3390/biology15070539 - 27 Mar 2026

Abstract

Heart failure (HF) is the leading cause of morbidity and mortality worldwide, while myocardial fibrosis acts as a pivotal hallmark, which exacerbates ventricular dysfunction and remodeling in HF. In this study, we found FGF23, a critical endocrine regulator, which regulates phosphate and vitamin [...] Read more.

Heart failure (HF) is the leading cause of morbidity and mortality worldwide, while myocardial fibrosis acts as a pivotal hallmark, which exacerbates ventricular dysfunction and remodeling in HF. In this study, we found FGF23, a critical endocrine regulator, which regulates phosphate and vitamin D metabolism, was significantly upregulated in fibrotic mouse hearts after transverse aortic constriction (TAC). By using the FGF23 monoclonal antibody, we found that inhibition of FGF23 alleviated TAC-induced cardiac fibrosis, while injection of recombinant FGF23 (rFGF23) protein exacerbated tissue fibrosis in mouse hearts after TAC. RNA sequencing indicated that FGF23 may promote cardiac fibroblast proliferation and activation in stressed mouse hearts. In human primary cardiac fibroblasts, rFGF23 treatment further upregulated the expression of Ki67, Cyclin D1, Cyclin E1, PCNA, α-SMA, and collagen 1A1 after TGF-β stimulation. Further results indicated that FGF23 promoted cardiac fibroblast proliferation and activation through FGFR4 and activated the downstream MAPK/ERK signaling. This study suggests a role of FGF23 in the regulation of myocardial fibrosis, which shows the potential of targeting FGF23 in the treatment of HF and cardiac fibrosis. Full article

(This article belongs to the Special Issue Advances in Cardiac and Vascular Biology: From Mechanisms to Pathophysiology)

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38 pages, 1700 KB

Open AccessReview

Long Non-Coding RNA–Derived Peptides as a Novel Source of Tumor Neoantigens: Expanding the Immunopeptidome Beyond Canonical Coding Regions

by Ismael López-Calvo, Inés Bao-Camacho, Samuel Martín-Revuelta, Cora Rey-Souto, Anahir Franco-Gacio, José Manuel Pérez-Martínez, Iván Sandino-Somoza, Álvaro Mourenza, Esther Rodríguez-Belmonte, Mónica Lamas-Maceiras, M Esperanza Cerdán, Aida Barreiro-Alonso and Ángel Vizoso-Vázquez

Biology 2026, 15(7), 538; https://doi.org/10.3390/biology15070538 - 27 Mar 2026

Abstract

Cancer immunotherapy has transformed the clinical management of several malignancies; however, its efficacy remains limited in tumors with low mutational burden and restricted availability of classical mutation-derived neoantigens. In this context, increasing evidence indicates that the tumor immunopeptidome extends far beyond canonical protein-coding [...] Read more.

Cancer immunotherapy has transformed the clinical management of several malignancies; however, its efficacy remains limited in tumors with low mutational burden and restricted availability of classical mutation-derived neoantigens. In this context, increasing evidence indicates that the tumor immunopeptidome extends far beyond canonical protein-coding regions, incorporating peptides derived from non-coding transcripts through non-canonical translation mechanisms. Long non-coding RNAs (lncRNAs), traditionally regarded as transcriptional or post-transcriptional regulators, have recently emerged as an unexpected source of small open reading frame-encoded peptides (lncPEPs). A subset of these peptides is processed and presented by major histocompatibility complex class I molecules, generating tumor-specific neoantigens capable of eliciting CD8⁺ T cell responses. Owing to the high tissue and context specificity of lncRNA expression, lncRNA-derived neoantigens offer unique advantages over mutation-based targets, including increased tumor selectivity and potential recurrence across patient subsets. In this review, we synthesize current knowledge on the biogenesis, detection, and immunogenic potential of lncRNA-derived peptides, highlighting experimental and computational strategies for their identification within the cancer immunopeptidome. We discuss the challenges associated with their validation and clinical translation, as well as their relevance for the development of vaccines and adoptive T cell–based therapies. Finally, we illustrate these concepts using epithelial ovarian cancer as a representative model of low-mutational-burden tumors, where lncRNA-derived neoantigens may help overcome current limitations of immunotherapy and enable patient stratification for personalized treatment approaches. Full article

(This article belongs to the Section Immunology)

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23 pages, 2362 KB

Open AccessReview

Asparagus Decline and Replant Problem: Autotoxicity, Autotoxic Substances, and Their Biological Functions

by Hisashi Kato-Noguchi and Midori Kato

Biology 2026, 15(7), 537; https://doi.org/10.3390/biology15070537 - 27 Mar 2026

Abstract

The cultivation of asparagus (Asparagus officinalis L.) is plagued by two serious issues: “asparagus decline” and “asparagus replant problem”. The average lifespan of an asparagus plant is 15 to 20 years. However, its productivity decreases after a few years (asparagus decline). Even [...] Read more.

The cultivation of asparagus (Asparagus officinalis L.) is plagued by two serious issues: “asparagus decline” and “asparagus replant problem”. The average lifespan of an asparagus plant is 15 to 20 years. However, its productivity decreases after a few years (asparagus decline). Even when these asparagus plants are replaced with new ones, the new plants remain unproductive (asparagus replant problem). The main causes of these problems are a Fusarium infection and asparagus autotoxicity. Several reviews have been conducted on Fusarium. Despite the accumulation of evidence on asparagus autotoxicity in the literature over the past four decades, no review has focused specifically on asparagus autotoxicity. It has been reported that asparagus growth is inhibited by asparagus root residues, leachates, root exudates, and rhizosphere soils. Several phenylpropanoids, including trans-cinnamic acid, p-coumaric acid, caffeic acid, and ferulic acid, have been identified as asparagus autotoxic substances in these root residues, root exudates, rhizosphere soils, growth media, and/or plant tissues. Tryptophan, 3,4-methylenedioxycinnamic acid, and iso-agatharesinol were also identified as asparagus autotoxic substances. These substances may cause autotoxicity by disrupting phytohormone levels, cellular metabolism, impairing membrane function, and by inducing oxidative stress. Although cinnamic, p-coumaric, caffeic, and ferulic acids have been reported to act as antibiotics, these compounds have also been shown to weaken the defense mechanisms of asparagus against pathogen infection, and enhance the Fusarium pathogenicity. The presence of these autotoxic substances, coupled with a Fusarium infection, may create a vicious cycle that worsens “asparagus decline” and “asparagus replant problem”. This is the first review to focus on the asparagus autotoxicity. Full article

(This article belongs to the Section Plant Science)

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21 pages, 4652 KB

Open AccessArticle

Soil and Foliar Applications of Silicon Mitigate Biotic Stress in Cape Gooseberry Plants Caused by Fusarium Vascular Wilt

by David Sebastián Chitiva-Sánchez, Ana María Pérez-Rincón, Cristhian Camilo Chávez-Arias, Hermann Restrepo-Díaz and Sandra Gómez-Caro

Biology 2026, 15(7), 536; https://doi.org/10.3390/biology15070536 - 27 Mar 2026

Abstract

Vascular wilt caused by Fusarium oxysporum f. sp. physali (Foph) severely limits cape gooseberry (Physalis peruviana L.) production in Andean regions, where management options are restricted and largely dependent on fungicides. Silicon (Si) has been proposed as a sustainable strategy to enhance [...] Read more.

Vascular wilt caused by Fusarium oxysporum f. sp. physali (Foph) severely limits cape gooseberry (Physalis peruviana L.) production in Andean regions, where management options are restricted and largely dependent on fungicides. Silicon (Si) has been proposed as a sustainable strategy to enhance tolerance to vascular pathogens; however, its role in the cape gooseberry–Foph pathosystem remains unknown. This study evaluated the effects of soil and foliar Si applications on disease development and physiological responses in cape gooseberry plants under greenhouse conditions. Three soil doses and three foliar doses were tested, including inoculated and non-inoculated controls without treatment. Si significantly reduced disease progression, decreasing the area under the disease progress curve (AUDPC) and disease severity index, with efficacy values of up to 69% in inoculated plants, particularly at 8 g kg⁻¹ soil application. Si also reduced vascular browning and mitigated pathogen-induced physiological impairment by maintaining higher stomatal conductance, relative chlorophyll content, maximum quantum efficiency of photosystem II, and plant growth. These findings indicate that Si, especially when soil-applied, enhances physiological tolerance to Foph and represents a promising complementary tool for its integrated management. Full article

(This article belongs to the Special Issue Plant Mineral Nutrition: Enhancing Plant Resilience)

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20 pages, 2808 KB

Open AccessArticle

CRISPR/Cas9-Mediated Polyketide Synthase Replacement for High-Yield Biosynthesis and Biological Activity of Milbemycin D

by Shenchen Tao, Huan Qi, Xian Luo, Jingyi Shen, Yunfei He, Jun Huang, Ruijun Wang, Shaoyong Zhang, Yongsheng Gao, Jidong Wang and Liqin Zhang

Biology 2026, 15(7), 535; https://doi.org/10.3390/biology15070535 - 27 Mar 2026

Abstract

Milbemycin D is a promising 16-membered macrolide insecticide with reported superior efficacy, but its commercial development has been hindered by extremely low natural yields. This study aimed to construct a high-yielding microbial platform for milbemycin D production using combinatorial biosynthesis and advanced genome [...] Read more.

Milbemycin D is a promising 16-membered macrolide insecticide with reported superior efficacy, but its commercial development has been hindered by extremely low natural yields. This study aimed to construct a high-yielding microbial platform for milbemycin D production using combinatorial biosynthesis and advanced genome editing. An optimized CRISPR/Cas9-AcrIIA4 system was employed to seamlessly replace the aveA3 polyketide synthase (PKS) gene in the ivermectin B1b-producing strain Streptomyces avermitilis HU501 with the heterologous milA3 PKS from S. bingchenggensis. The engineered strain was validated genetically and metabolically, followed by high-throughput screening and fermentation optimization in various media. The biosynthesized compound was structurally confirmed by spectroscopy. Bioactivity was evaluated against Bursaphelenchus xylophilus, Hyphantria cunea, and Plutella xylostella. The engineered strain S. avermitilis HU501-M successfully shifted its major product to milbemycin D, reaching a final titer of 679.03 mg/L. Bioassays revealed that milbemycin D exhibited significantly enhanced potency, with LC₅₀ values 8–24% lower than those of milbemycin A3/A4. This work demonstrates an efficient CRISPR/Cas9-mediated PKS replacement strategy to achieve the high-yield production of milbemycin D, offering a promising microbial source and a generalizable framework for engineering complex polyketide pathways. This proof-of-concept establishes a foundation for future process development toward potential commercial application. Full article

(This article belongs to the Topic Research on Natural Bioactive Product-Based Pesticidal Agents—2nd Edition)

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18 pages, 7148 KB

Open AccessArticle

Genome-Wide Identification and Characterization of the JMJ Histone Demethylase Gene Family in Maize (Zea mays L.) and Its Potential Role Under Drought Stress

by Li Gao, Hui Tian, Xiangli Bai, Aokun Shi and Mian Wang

Biology 2026, 15(7), 534; https://doi.org/10.3390/biology15070534 - 27 Mar 2026

Abstract

Drought stress is a major abiotic factor limiting maize yield and stability. Although Jumonji C (JMJ) histone demethylases are known to regulate plant growth, development, and stress responses, their systematic characterization in maize has remained limited. Here, 27 ZmJMJ genes were identified in [...] Read more.

Drought stress is a major abiotic factor limiting maize yield and stability. Although Jumonji C (JMJ) histone demethylases are known to regulate plant growth, development, and stress responses, their systematic characterization in maize has remained limited. Here, 27 ZmJMJ genes were identified in the maize genome through BLAST and conserved-domain analyses and classified into five subfamilies: JMJD6, KDM3/JHDM2, KDM4/JHDM3, KDM5/JARID1, and JmjC domain-only. Members within the same subfamily showed similar physicochemical properties, domain composition, and motif distribution, whereas clear divergence was observed among subfamilies. Chromosomal mapping revealed that ZmJMJ genes were unevenly distributed across nine chromosomes, with two interchromosomal homologous gene pairs, suggesting roles for segmental and/or whole-genome duplication in family expansion. Promoter analysis indicated widespread enrichment of elements related to light responsiveness, growth and development, and hormone and stress responses. Expression profiling showed that most ZmJMJ genes were highly expressed in leaves, while several displayed tissue specificity. Under drought stress, ZmJMJ17a, ZmJMJ17b, ZmJMJ28, and ZmJMJ32 were significantly induced, highlighting them as promising candidates for functional studies and molecular breeding for drought tolerance in maize. This study provides a foundation for elucidating the evolution and functions of the ZmJMJ family and identifies candidate genes for drought-related functional validation and molecular breeding. Full article

(This article belongs to the Section Bioinformatics)

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16 pages, 1749 KB

Open AccessArticle

Integrated Genomic Analysis Unveils MicroRNA Roles in Glioma Development

by Sevan Omer Majed, Gaylany H. Abdullah, Kazhal Muhammad Sulaiman, Shawnim M. Maaruf, Raya Kh. Yashooa, Saman S. Abdulla, Chiara Villa and Suhad A. Mustafa

Biology 2026, 15(7), 533; https://doi.org/10.3390/biology15070533 (registering DOI) - 27 Mar 2026

Abstract

Gliomas are the most common type of primary brain tumors in adults, with a high level of recurrence and mortality. Their complex biology and adaptive resistance mechanisms pose major obstacles to existing treatment strategies. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), are crucial in [...] Read more.

Gliomas are the most common type of primary brain tumors in adults, with a high level of recurrence and mortality. Their complex biology and adaptive resistance mechanisms pose major obstacles to existing treatment strategies. Non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs), are crucial in tumor development and progression. Small RNA sequencing technology was performed in 25 patients with high-grade gliomas (HGGs) to analyze ncRNA expression in gliomas compared to normal adjacent tissues (NATs) aiming to elucidate their possible roles in these malignancies. Samples from patients with gliomas were examined, revealing an overall upregulation of ncRNAs. Specific ncRNA classes, including miRNAs, transfer RNAs (tRNAs), Piwi-interacting RNAs (piRNAs), and small nucleolar RNAs (snoRNAs) showed notable shifts in abundance between tumor and normal samples. Among the upregulated miRNAs, a set of top five, such as miR-21, miR-221, miR-1321, miR-1306-5p, and miR-374a-5p, were validated by real-time quantitative PCR (RT-qPCR) in a cohort of 17 low-grade gliomas (LGGs) and 52 HGGs. These miRNAs are associated with critical oncogenic pathways and correlated with a worse prognosis. This study expanded the understanding of glioma biology and further confirmed the role of ncRNAs in the pathogenesis, supporting their potential use as novel possible biomarkers or therapeutic targets. Moreover, it provided an integrated analysis of multiple ncRNA classes, offering validation across both LGG and HGG, and uniquely incorporating a Kurdish cohort. Full article

(This article belongs to the Section Cancer Biology)

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17 pages, 3154 KB

Open AccessArticle

Unveiling Key Biomarkers of Cardiovascular Risk in Psoriasis Through Explainable Artificial Intelligence

by Hasan Ucuzal and Mehmet Kıvrak

Biology 2026, 15(7), 532; https://doi.org/10.3390/biology15070532 - 26 Mar 2026

Abstract

Psoriasis patients face a significantly elevated risk of cardiovascular diseases (CVD), necessitating early and accurate risk prediction tools. This study developed and validated a machine learning model to predict CVD risk in psoriasis patients using clinical and biochemical data from 2685 individuals. After [...] Read more.

Psoriasis patients face a significantly elevated risk of cardiovascular diseases (CVD), necessitating early and accurate risk prediction tools. This study developed and validated a machine learning model to predict CVD risk in psoriasis patients using clinical and biochemical data from 2685 individuals. After preprocessing and addressing class imbalance with SMOTE-NC, six machine learning models (Logistic Regression as baseline, XGBoost, LightGBM, CatBoost, GradientBoosting, AdaBoost) were evaluated using a completely leak-free nested cross-validation framework (outer k = 10, inner k = 3) with randomized hyperparameter search (n_iter = 50). Feature selection via the Boruta algorithm was performed separately within each training fold to prevent data leakage. The Boruta algorithm identified 21 key predictors, including age, systolic blood pressure (SBP), apolipoprotein B (apoB), fasting blood glucose (FBG), and complement C1q. CatBoost emerged as the top-performing model (OOF ROC-AUC = 0.908, 95% CI [0.892–0.924]; PR-AUC = 0.509, 95% CI [0.448–0.578]; F1 = 0.540; MCC = 0.498; Brier = 0.078), while the Logistic Regression baseline achieved ROC-AUC = 0.909 but was eliminated due to poor calibration (Brier = 0.114 > 0.10). All metrics were evaluated with 95% bootstrap confidence intervals (n = 1000 iterations). Explainable AI techniques (SHAP, LIME, Anchors) revealed that older age, elevated SBP, and metabolic dysregulation (e.g., high apoB, FBG) were the strongest CVD predictors. Local explanations were provided for five representative patients (high-risk, low-risk, and randomly selected), rather than a single instance, to better characterize model stability. Limitations include the single-center, retrospective design and lack of external validation. Future work should incorporate multi-ethnic cohorts and advanced biomarkers (e.g., genetic, imaging data) to enhance generalizability. This study demonstrates the potential of explainable AI to improve CVD risk stratification in psoriasis patients, offering a scalable tool for preventive cardiology. Full article

(This article belongs to the Special Issue Advancing Translational Science Using Bioinformatics and Big Data-Driven Approaches)

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