Biology

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, 2468 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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28 pages, 1077 KB

Open AccessReview

Genetic Variants from Large Cohorts and Familial Studies Implicate Common Mechanisms in Schizophrenia

by Ambreen Kanwal, José V. Pardo and Sadaf Naz

Biology 2026, 15(7), 531; https://doi.org/10.3390/biology15070531 - 26 Mar 2026

Abstract

Schizophrenia has an estimated population prevalence of 1%, but the etiology of this devastating psychiatric condition remains largely uncharacterized. A pronounced genetic component underlies schizophrenia, with heritability estimates ranging from 60% to 80%. Until now, genome-wide association studies have successfully identified 287 distinct [...] Read more.

Schizophrenia has an estimated population prevalence of 1%, but the etiology of this devastating psychiatric condition remains largely uncharacterized. A pronounced genetic component underlies schizophrenia, with heritability estimates ranging from 60% to 80%. Until now, genome-wide association studies have successfully identified 287 distinct genetic loci associated with schizophrenia, but these primarily involve common variants that have minimal individual risk. The recent advent of exome sequencing and genome sequencing has identified ultra-rare sequence variants associated with schizophrenia in familial cases as well as in large cohorts. These studies have implicated multiple gene variants that individually have a large effect size in contributing to schizophrenia. A comparison indicates that these genes exhibit high expression levels in the central nervous system and their protein products participate in many converging pathways encompassing synaptic transmission, glutamatergic neurotransmission, chromatin modification processes, transcriptional regulation, and ubiquitin–proteasome degradation. Although model systems have been established for some genes, most remain to be further studied to identify how gene dysfunction correlates with disease. Full article

(This article belongs to the Special Issue Neurogenetics of Behaviour—2nd Edition)

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14 pages, 239 KB

Open AccessReview

Evolution of Methods for the Quantitative Assessment of Inbreeding in Livestock

by Lyubov Getmantseva, Siroj Bakoev, Maria Kolosova, Alexandr Usatov, Kharon Amerkhanov and Olga Lukonina

Biology 2026, 15(7), 530; https://doi.org/10.3390/biology15070530 - 26 Mar 2026

Abstract

Inbreeding is a quantitative measure of autozygosity that underlies the assessment of genetic risks and the management of genetic progress in livestock populations. The development of methods for its estimation reflects a transition from probabilistic pedigree-based models to the direct analysis of genome [...] Read more.

Inbreeding is a quantitative measure of autozygosity that underlies the assessment of genetic risks and the management of genetic progress in livestock populations. The development of methods for its estimation reflects a transition from probabilistic pedigree-based models to the direct analysis of genome structure. This review systematizes the evolution of approaches to inbreeding assessment—from the classical inbreeding coefficient F based on identity by descent (IBD) to marker-based, segment-based runs of homozygosity (ROH) and probabilistic homozygous-by-descent (HBD) models. It is shown that the coefficients F_ped, F_GRM, F_ROH, and F_HBD capture related but distinct aspects of autozygosity and are therefore not fully interchangeable. Particular attention is paid to the transition from integral indicators to spatially and temporally stratified analyses of autozygosity, enabling the differentiation between ancient and recent inbreeding. Methodological assumptions, limitations, and the sensitivity of various approaches to marker density, detection parameters, and population demographic structure are discussed. A comparative analysis of methods for calculating F_ROH and segment-based autozygosity is presented. The necessity of a comprehensive assessment of inbreeding and the standardization of analytical protocols for its application in modern breeding programs is substantiated. Full article

(This article belongs to the Section Zoology)

15 pages, 4025 KB

Open AccessArticle

Toxicity Effects and Mechanism of Chemical Stress on Pomacea canaliculata

by Huayang Zhou, Meiling Zou, Zhixiong Zhou and Chuanren Li

Biology 2026, 15(7), 529; https://doi.org/10.3390/biology15070529 - 26 Mar 2026

Abstract

Pomacea canaliculata, as a significant invasive alien species, poses severe threats to agricultural development. Currently, chemical applications demonstrate notable efficacy in controlling this pest. However, metaldehyde exhibits overly singular toxicity towards P. canaliculata; niclosamide sulfate is not a molluscicide; and fentin [...] Read more.

Pomacea canaliculata, as a significant invasive alien species, poses severe threats to agricultural development. Currently, chemical applications demonstrate notable efficacy in controlling this pest. However, metaldehyde exhibits overly singular toxicity towards P. canaliculata; niclosamide sulfate is not a molluscicide; and fentin acetate is a fungicide. Currently, these findings fail to elucidate the physiological and biochemical effects of the compounds after they enter the P. canaliculata’s body. In this study, we evaluated the toxicity of metaldehyde (ME), niclosamide sulfate (NS), and fentin acetate (FA) against P. canaliculata and analyzed the morphological and physiological changes in response to chemical stress. The results indicated that three chemicals exhibited potent molluscicidal activity, especially in the NS treatment group. After 12 h exposure to LC₅₀ concentrations (48 h LC₅₀), the surface area of livers was reduced significantly by 12.1%, 13.9%, and 2.8% compared to the control group, while the kidneys expanded significantly by 6.4%, 3.2%, and 16.7%, respectively. The heart showed marked enlargement by 152.1% and 44.2% under niclosamide sulfate and metaldehyde treatments. The pulmonary sac significantly contracted by 23.6% under niclosamide sulfate stress but expanded by 6.1% under fentin acetate exposure. The stomach enlarged significantly after niclosamide sulfate treatment, whereas it shrank by 2.1% and 5.7% under metaldehyde and fentin acetate treatments, respectively. Metabolomic analysis of liver tissues revealed 553, 99, and 585 differential metabolites compared to the control group, respectively. KEGG pathway enrichment analysis showed that the metabolism pathway, lysine degradation, and bile secretion are likely related to the response to chemical stress in P. canaliculata. Further examination showed a significant decrease in total protein content and the activities of malondialdehyde (MDA), acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT) under chemical stress. These findings enhance our understanding of the targeted mechanisms of molluscicides against P. canaliculata. Metaldehyde may exert neurotoxic effects on the P. canaliculata, while niclosamide sulfate may interfere with its respiratory system. Additionally, both chemicals affect metabolic pathways in the snail’s liver, including lipid metabolism and metabolic pathways associated with energy metabolism. These findings provide valuable insights for designing a novel snail control agent and formulating scientific management strategy. Full article

(This article belongs to the Special Issue Metabolic and Stress Responses in Aquatic Animals (2nd Edition))

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23 pages, 1415 KB

Open AccessReview

Inhibin Immunization to Enhance Reproductive Performance in Livestock: A Review

by Abd Ullah, Muhammad Zahoor Khan and Changfa Wang

Biology 2026, 15(7), 528; https://doi.org/10.3390/biology15070528 - 26 Mar 2026

Abstract

Reproductive efficiency substantially determines livestock productivity, and suboptimal fertility continues to limit productivity across species. Inhibin immunization represents a novel strategy to enhance fertility by neutralizing inhibin’s negative feedback on follicle-stimulating hormone (FSH) secretion. This comprehensive review synthesizes evidence from ruminants (cattle, sheep, [...] Read more.

Reproductive efficiency substantially determines livestock productivity, and suboptimal fertility continues to limit productivity across species. Inhibin immunization represents a novel strategy to enhance fertility by neutralizing inhibin’s negative feedback on follicle-stimulating hormone (FSH) secretion. This comprehensive review synthesizes evidence from ruminants (cattle, sheep, goats, camels, and buffalo) and non-ruminants (pigs, donkeys, rabbits, and avian species), evaluating inhibin immunization mechanisms and reproductive outcomes. Immunoneutralization of inhibin consistently elevates FSH, activin A, and estradiol, thereby promoting ovarian follicular recruitment and spermatogenesis. In females, this approach has been widely reported to increase ovulatory activity and improve embryo production and quality. In males, immunization enhances testicular function and semen quality while mitigating seasonal infertility. However, species-specific variations in response and dose-dependent luteal suppression (particularly in pigs) necessitate optimized protocols. While inhibin immunization shows consistent benefits when integrated with multiple ovulation and embryo transfer (MOET) and in vitro fertilization (IVF), standardized protocols and long-term fertility data remain insufficient for commercial implementation. This review identifies critical evidence gaps and safety considerations essential for clinical translation. Full article

(This article belongs to the Special Issue Reproductive Physiology and Pathology in Livestock)

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