Sci Adv. 2025 Mar 28;11(13):eadt9287. doi: 10.1126/sciadv.adt9287. Epub 2025 Mar 28.

ABSTRACT

Photorespiration causes a substantial decrease in crop yield because of mitochondrial decarboxylation. Alternative pathways (APs) have been designed to relocate the decarboxylation step or even fix additional carbon. To improve the success of transferring those engineered APs from model species to crops, we must understand how they will interact with metabolism and how plant physiology affects their performance. Here, we used multiple mathematical modeling techniques to analyze and compare existing AP designs. We show that carbon-fixing APs are the most promising candidates to replace native photorespiration in major crop species. Our results demonstrate the different metabolic routes that APs use to increase yield and which plant physiology can profit the most from them. We anticipate our results to guide the design of new APs and to help improve existing ones.

PMID:40153498 | DOI:10.1126/sciadv.adt9287

Bull Math Biol. 2025 Mar 28;87(5):60. doi: 10.1007/s11538-025-01439-9.

ABSTRACT

A framework for parameter estimation and uncertainty quantification is crucial for understanding the mechanisms of biological interactions within complex systems and exploring their dynamic behaviors beyond what can be experimentally observed. Despite recent advances, challenges remain in achieving the high accuracy of parameter estimation and uncertainty quantification at moderate computational costs. To tackle these challenges, we developed a novel approach that integrates the quantile method with Physics-Informed Neural Networks (PINNs). This method utilizes a network architecture with multiple parallel outputs, each corresponding to a distinct quantile, facilitating a comprehensive characterization of parameter estimation and its associated uncertainty. The effectiveness of the proposed approach was validated across three study cases, where it was compared to the Monte Carlo dropout (MCD) and the Bayesian methods. Furthermore, a larger-scale model was employed to further demonstrate the excellent performance of the proposed approach. Our approach exhibited significantly superior efficacy in parameter estimation and uncertainty quantification. This highlights its great promise to broaden the scope of applications in system biology modeling.

PMID:40153179 | DOI:10.1007/s11538-025-01439-9

Plant Cell Environ. 2025 Mar 28. doi: 10.1111/pce.15464. Online ahead of print.

ABSTRACT

Plant stem cells, residing in the shoot and root apical meristems, are fundamental for continuous growth and organ formation throughout the plant life cycle. Their regulation is driven by the convergence of endogenous developmental cues and exogenous environmental signals, making them pivotal to overall plant growth and development. Auxin, a key phytohormone, serves as a major internal signal, orchestrating stem cell initiation, maintenance, differentiation, and environmental adaptation through intricate biosynthesis, transport, and signaling networks. This review summarizes recent progress in understanding the cellular and molecular mechanisms by which auxin guides stem cell functions in both the shoot and root apical meristems. Through these insights, we explore how plants utilize auxin-driven pathways to optimize growth in ever-changing environments.

PMID:40152539 | DOI:10.1111/pce.15464

J Immunol. 2025 Mar 27:vkaf026. doi: 10.1093/jimmun/vkaf026. Online ahead of print.

ABSTRACT

Increased myeloid lineage production, termed myeloid skewing, leading to decreased tumor immunity, is a hallmark of aberrant hematopoiesis associated with cancer. It is believed that myeloid skewing may occur at the hematopoietic stem and progenitor cells (HSPCs) level to elicit hematopoietic changes. However, our understanding of the underlying molecular mechanisms remains incomplete. Here, we characterize the transcriptional and chromatin accessibility landscapes of bone marrow and splenic hematopoietic progenitors in the MMTV-PyMT mouse model of breast cancer using single-cell ATAC + RNA sequencing. We show that HSPCs in the bone marrow (BM) of the tumor-bearing mice show a modest upregulation of the myeloid-bias transcriptional signature without significant chromatin accessibility changes. By contrast, dendritic cell (DC) progenitors exhibit the most prominent transcriptional and chromatin changes, showing a signature of STAT3, CEBP, and non-DC myeloid gene activation. Compared to BM, splenic HSPCs exhibit a Notch signaling signature associated with erythroid commitment rather than further upregulation of the myeloid-bias signature. In addition, we also identify a cluster of splenic HSPCs in tumor-bearing animals with a transcriptional signature of mobilization. Our paired chromatin data suggest that AP-1 factors play a crucial role in driving this HSPC mobilization signature. Overall, we provide a comprehensive dataset for understanding the hematopoietic consequences of cancer.

PMID:40152115 | DOI:10.1093/jimmun/vkaf026

Medeni Med J. 2025 Mar 28;40(1):1-11. doi: 10.4274/MMJ.galenos.2025.34783.

ABSTRACT

OBJECTIVE: Cancer is a disease characterized by an unregulated division of abnormal cells in the body. The discovery of oncogenes and tumor suppressor genes has paved the way for the targeted use of individual biomarkers and proteins in cancer therapy. The signaling pathways in cells are closely linked, and research into these connections would lead to more precise personalized treatments for cancer. An imbalance in the complement system is associated with the development and progression of cancer. Comparable variations in gene expression and common complement biomarkers in different cancer types are poorly understood. This study aims to gain insights into biomarkers linking the complement system to carcinogenesis.

METHODS: Clinical and transcriptome data from the cancer genome atlas were used to analyze differentially expressed genes involved in the complement system in different cancer types. Various bioinformatics and machine learning techniques were used to suggest complement pathway-related carcinogenesis biomarkers.

RESULTS: This study provides a comprehensive elucidation of component 7 (C7), complement factor-D (CFD), interleukin-11 (IL11), apolipoprotein C1 (APOC1), and integrin binding sialic acid protein (IBSP) proteins as common biomarkers associated with the complement system in cancer and highlights the diagnostic and prognostic potential of these biomarkers.

CONCLUSIONS: These biomarkers would pave the way for targeted cancer treatments in the context of precision medicine.

PMID:40152065 | DOI:10.4274/MMJ.galenos.2025.34783

Environ Microbiol. 2025 Apr;27(4):e70084. doi: 10.1111/1462-2920.70084.

ABSTRACT

Rice synthesises diterpenoid phytoalexins (DPs) which are known to operate in defence against foliar microbial pathogens and the root-knot nematode Meloidogyne graminicola. Here, we examined the role of DPs in shaping rice-associated root microbiomes in nematode-infested field soil. Further, we assessed how DPs affect interactions between the root microbiomes and M. graminicola. We used 16S and ITS2 rRNA gene amplicon analysis to characterise the root- and rhizosphere-associated microbiomes of DP knock-out rice mutants and their wild-type parental line, at an early (17 days) and late (28 days) stage of plant development in field soil. Disruption of DP synthesis resulted in distinct changes in the composition and structure of microbial communities both relative to the parental/wild-type line but also between individual mutants, indicating specificity in DP-microbe interactions. Moreover, the abundance of nematode-suppressive microbial taxa, including Streptomyces, Stenotrophomonas and Enterobacter was negatively correlated with that of Meloidogyne. Differential enrichment of microbial taxa in the roots of rice DP knock-out mutants versus wild-type suggests that DPs modulate specific taxa in the rice root microbiome. These findings indicate a role for DPs in plant-microbiome assembly and nematode interactions, further underscoring the potential of leveraging phytoalexins for sustainable management of crop diseases.

PMID:40151894 | DOI:10.1111/1462-2920.70084

Theor Biol Forum. 2024 Jul 1;117(1-2):61-68. doi: 10.19272/202411402005.

ABSTRACT

This review explores the critical role of information in biological regulation, extending beyond traditional concepts of homeostasis and homeorhesis. Information, recognized as a fundamental entity alongside matter and energy, governs the dynamic and adaptive processes of living systems. By proposing the concept of «homeoinformation », this paper highlights the continuous processing and integration of information as the foundation for stability and adaptation in life. This perspective offers a more comprehensive framework for understanding the complexity of biological systems and opens new avenues for research into the intricate dynamics of life.

PMID:40151861 | DOI:10.19272/202411402005

Theor Biol Forum. 2024 Jul 1;117(1-2):25-32. doi: 10.19272/202411402003.

ABSTRACT

Inheritance is a fundamental process that shapes the diversity of life on Earth. While DNA is commonly considered the primary carrier of genetic information, recent advances in molecular biology have shown that other forms of information, such as epigenetic modifications and non-coding RNAs, play important roles in inheritance. Here, we propose a theoretical framework that unifies the diverse sources of inheritance under the common concept of information. we argue that information, in its broadest sense, is the basis of inheritance.

PMID:40151859 | DOI:10.19272/202411402003

J Tradit Chin Med. 2025 Apr;45(2):376-384. doi: 10.19852/j.cnki.jtcm.2025.02.012.

ABSTRACT

OBJECTIVE: To investigate the mechanism underlying the effect of the Huanglian decoction (, HLD) on morphine tolerance (MT), using network pharmacology, and to verify these mechanisms in vitro and in vivo.

METHODS: Available biological data on each drug in the HLD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The target proteins of MT were retrieved from the GeneCards, PharmGkb, Therapeutic Target Database, DrugBank, and Online Mendelian Inheritance in Man databases. Information regarding MT and the drug targets was compared to obtain overlapping elements. This information was imported into the Search Tool for the Retrieval of Interacting Genes/Proteins platform to obtain a protein-protein interaction network diagram. Then, a "component-target" network diagram was constructed using screened drug components and target information, viaCytoscape (Institute for Systems Biology, Seattle, WA, USA). The database for annotation, visualization, and integrated discovery was used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways analyses. Pathway information predicted by network pharmacology was verified using animal studies and cell experiments.

RESULTS: Network pharmacology analysis identified 22 active compounds of HLD and revealed that HLD partially ameliorated MT by modulating inflammatory, apoptosis, and nuclear factor kappa B (NF-κB) signaling pathways. Berberine (BBR), one of the main components of HLD, inhibited the development of MT in mice. BBR reduced cell viability while increasing B-cell lymphoma 2 (Bcl-2) protein expression and decreasing CD86, NF-κB, Bax, and Caspase-3 protein expression in brain vascular 2 (BV2) mcroglia cells treated with morphine. Additionally, BBR contributed to a reduction in pro-inflammatory cytokine release and apoptotic cell number.

CONCLUSIONS: BBR, a key component of HLD, effectively suppressed microglial activation and neuro-inflammation by regulating the NF-κB and apoptosis signaling pathways, thereby delaying MT. This study offers a novel approach to enhance the clinical analgesic efficacy of morphine.

PMID:40151124 | DOI:10.19852/j.cnki.jtcm.2025.02.012

Biomolecules. 2025 Mar 4;15(3):370. doi: 10.3390/biom15030370.

ABSTRACT

In the heart, Connexin 43 (Cx43) is involved in intercellular communication through gap junctions and exosomes. In addition, Cx43-formed hemichannels at the plasma membrane are important for ion homeostasis and cellular volume regulation. Through its localization within nuclei and mitochondria, Cx43 influences the function of the respective organelles. Several cardiovascular diseases such as heart failure, ischemia/reperfusion injury, hypertrophic cardiomyopathy and arrhythmias are characterized by Cx43 downregulation and a dysregulated Cx43 function. Accordingly, a putative therapeutic approach of these diseases would include the induction of Cx43 expression in the damaged heart, albeit such induction may have both beneficial and detrimental effects. In this review we discuss the consequences of increasing cardiac Cx43 expression, and discuss this manipulation as a strategy for the treatment of cardiovascular diseases.

PMID:40149906 | DOI:10.3390/biom15030370

Biomedicines. 2025 Mar 3;13(3):612. doi: 10.3390/biomedicines13030612.

ABSTRACT

Background: There is an urgent need to identify new biomarkers for early diagnosis and development of therapeutic strategies for diabetes mellitus (DM) patients who have invasive breast cancer (BC). We previously reported the increased activated form of 70 kDa ribosomal protein S6 kinase 1 (phospho-p70S6K1) in a triple-negative BC (TNBC) cell line MDA-MB-231 exposed to glycated albumin (GA) and in invasive ductal carcinoma tissues from T2DM patients, compared to untreated cells and their non-diabetic counterparts, respectively. Objective: We aimed to explore the function of p70S6K1 in GA-promoted TNBC progression. Methods: By employing small interference (si)RNA technology or blocking its kinase activity using its specific pharmacological inhibitor, we monitored cell invasion using Transwell® inserts and the expression levels of activated signaling proteins and cancer-related proteins using Western blot. Results: In silico analysis revealed that high mRNA levels of p70S6K1 were associated with an unfavorable prognosis and progression to advanced stages of TNBC in DM patients. The downregulation/blockade of p70S6K1 inhibited GA-promoted MDA-MB-231 cell invasion and the phosphorylation of protein S6 and ERK1/2, the p70S6K1 downstream effector, and the key oncogenic signaling protein, respectively. The suppression of the expression of GA-upregulated cancer proteins, including enolase-2, capping protein CapG, galectin-3, and cathepsin D, was observed after p70S6K1 downregulation/blockade. Further in silico validation analyses revealed increased gene expression of galectin-3 in DM TNBC patients, resulting in poor overall survival and disease-free survival. Conclusions: Targeting p70S6K1 may present a valuable therapeutic strategy, while galectin-3 could serve as a potential prognostic biomarker for invasive BC progression in DM patients.

PMID:40149589 | DOI:10.3390/biomedicines13030612

Genes (Basel). 2025 Feb 28;16(3):297. doi: 10.3390/genes16030297.

ABSTRACT

This study introduces a novel framework that simultaneously addresses the challenges of performance accuracy and result interpretability in transcriptomic-data-based classification. Background/objectives: In biological data classification, it is challenging to achieve both high performance accuracy and interpretability at the same time. This study presents a framework to address both challenges in transcriptomic-data-based classification. The goal is to select features, models, and a meta-voting classifier that optimizes both classification performance and interpretability. Methods: The framework consists of a four-step feature selection process: (1) the identification of metabolic pathways whose enzyme-gene expressions discriminate samples with different labels, aiding interpretability; (2) the selection of pathways whose expression variance is largely captured by the first principal component of the gene expression matrix; (3) the selection of minimal sets of genes, whose collective discerning power covers 95% of the pathway-based discerning power; and (4) the introduction of adversarial samples to identify and filter genes sensitive to such samples. Additionally, adversarial samples are used to select the optimal classification model, and a meta-voting classifier is constructed based on the optimized model results. Results: The framework applied to two cancer classification problems showed that in the binary classification, the prediction performance was comparable to the full-gene model, with F1-score differences of between -5% and 5%. In the ternary classification, the performance was significantly better, with F1-score differences ranging from -2% to 12%, while also maintaining excellent interpretability of the selected feature genes. Conclusions: This framework effectively integrates feature selection, adversarial sample handling, and model optimization, offering a valuable tool for a wide range of biological data classification problems. Its ability to balance performance accuracy and high interpretability makes it highly applicable in the field of computational biology.

PMID:40149449 | DOI:10.3390/genes16030297

Genes (Basel). 2025 Feb 27;16(3):293. doi: 10.3390/genes16030293.

ABSTRACT

Background/Objectives: microRNAs are small non-coding RNAs that regulate gene expression by inducing mRNA degradation or inhibiting translation. A growing body of evidence suggests that miRNAs may be utilized as anti-cancer therapeutics by targeting expression of key genes involved in cancerous transformation and progression. Renal cell cancer (RCC) is the most common kidney malignancy. The most efficient RCC treatments involve blockers of immune checkpoints, including antibodies targeting PD-L1 (Programmed Death Ligand 1). Interestingly, recent studies revealed the cross-kingdom horizontal transfer of plant miRNAs into mammalian cells, contributing to the modulation of gene expression by food ingestion. Here, we hypothesized that PD-L1 expression may be modulated by miRNAs originating from edible plants. Methods: To verify this hypothesis, we performed bioinformatic analysis to identify mes-miR395e from Manihot esculenta (cassava) as a promising candidate miRNA that could target PD-L1. To verify PD-L1 regulation mediated by the predicted plant miRNA, synthetic mes-miR395 mimics were transfected into cell lines derived from RCC tumors, followed by evaluation of PD-L1 expression using qPCR and Western blot. Results: Transfection of mes-miR395e mimics into RCC-derived cell lines confirmed that this miRNA decreases expression of PD-L1 in RCC cells at both mRNA and protein levels. Conclusions: This preliminary study shows the promise of plant miRNA as potential adjuvants supporting RCC treatment.

PMID:40149445 | DOI:10.3390/genes16030293

Genes (Basel). 2025 Feb 23;16(3):258. doi: 10.3390/genes16030258.

ABSTRACT

BACKGROUND/OBJECTIVES: Genes with similar expression patterns across multiple samples are considered coexpressed, and they may participate in similar biological processes or pathways. Gene coexpression networks depict the degree of similarity between the expression profiles of all genes in a set of samples. Gene coexpression tools allow for the prediction of functional gene partners or the assignment of roles to genes of unknown function. Weighted Gene Correlation Network Analysis (WGCNA) is an R package that provides a multitude of functions for constructing and analyzing a weighted or unweighted gene coexpression network.

METHODS: Previously preprocessed, high-quality gene expression data of 3500 samples of Affymetrix microarray technology from various tissues of the Arabidopsis thaliana plant model species were used to construct a weighted gene coexpression network, using WGCNA.

RESULTS: The gene dendrogram was used as the basis for the creation of a new Arabidopsis coexpression tool (ACT) version (ACT2.6). The dendrogram contains 21,273 leaves, each one corresponding to a single gene. Genes that are clustered in the same clade are coexpressed. WGCNA grouped the genes into 27 functional modules, all of which were positively or negatively correlated with specific tissues.

DISCUSSION: Genes known to be involved in common metabolic pathways were discovered in the same module. By comparing the current ACT version with the previous one, it was shown that the new version outperforms the old one in discovering the functional connections between gene partners. ACT2.6 is a major upgrade over the previous version and a significant addition to the collection of public gene coexpression tools.

PMID:40149410 | DOI:10.3390/genes16030258

Entropy (Basel). 2025 Mar 7;27(3):280. doi: 10.3390/e27030280.

ABSTRACT

The known laws of nature in the physical sciences are well expressed in the language of mathematics, a fact that caused Eugene Wigner to wonder at the "unreasonable effectiveness" of mathematical concepts to explain physical phenomena. The biological sciences, in contrast, have resisted the formulation of precise mathematical laws that model the complexity of the living world. The limits of mathematics in biology are discussed as stemming from the impossibility of constructing a deterministic "Laplacian" model and the failure of set theory to capture the creative nature of evolutionary processes in the biosphere. Indeed, biology transcends the limits of computation. This leads to a necessity of finding new formalisms to describe biological reality, with or without strictly mathematical approaches. In the former case, mathematical expressions that do not demand numerical equivalence (equations) provide useful information without exact predictions. Examples of approximations without equal signs are given. The ineffectiveness of mathematics in biology is an invitation to expand the limits of science and to see that the creativity of nature transcends mathematical formalism.

PMID:40149204 | DOI:10.3390/e27030280

Mol Neurodegener. 2025 Mar 28;20(1):38. doi: 10.1186/s13024-025-00826-z.

ABSTRACT

Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are overwhelmingly linked to TDP-43 dysfunction. Mutations in TDP-43 are rare, indicating that the progressive accumulation of exogenous factors - such as cellular stressors - converge on TDP-43 to play a key role in disease pathogenesis. Post translational modifications such as SUMOylation play essential roles in response to such exogenous stressors. We therefore set out to understand how SUMOylation may regulate TDP-43 in health and disease. We find that TDP-43 is regulated dynamically via SUMOylation in response to cellular stressors. When this process is blocked in vivo, we note age-dependent TDP-43 pathology and sex-specific behavioral deficits linking TDP-43 SUMOylation with aging and disease. We further find that SUMOylation is correlated with human aging and disease states. Collectively, this work presents TDP-43 SUMOylation as an early physiological response to cellular stress, disruption of which may confer a risk for TDP-43 proteinopathy.

PMID:40149017 | DOI:10.1186/s13024-025-00826-z

New Phytol. 2025 Mar 27. doi: 10.1111/nph.70101. Online ahead of print.

ABSTRACT

Robinia pseudoacacia L. (black locust) is a nitrogen (N)-fixing legume tree with significant ecological and agricultural importance. Unlike well-studied herbaceous legumes, R. pseudoacacia is a perennial woody species, representing an understudied group of legume trees that establish symbiosis with Mesorhizobium. Understanding its genomic and transcriptional responses to nodulation provides key insights into N fixation in long-lived plants and their role in ecosystem N cycling. We assembled a high-quality 699.6-Mb reference genome and performed transcriptomic analyses comparing inoculated and noninoculated plants. Differential expression and co-expression network analyses revealed organ-specific regulatory pathways, identifying key genes associated with symbiosis, nutrient transport, and stress adaptation. Unlike Medicago truncatula, which predominantly responds to nodulation in roots, R. pseudoacacia exhibited stem-centered transcriptional reprogramming, with the majority of differentially expressed genes located in stems rather than in roots. Co-expression network analysis identified gene modules associated with "leghemoglobins", metal detoxification, and systemic nutrient allocation, highlighting a coordinated long-distance response to N fixation. This study establishes R. pseudoacacia as a genomic model for nodulating trees, providing essential resources for evolutionary, ecological, and applied research. These findings have significant implications for reforestation, phytoremediation, forestry, and sustainable N management, particularly in depleted, degraded, and contaminated soil ecosystems.

PMID:40149007 | DOI:10.1111/nph.70101

J Biol Eng. 2025 Mar 27;19(1):25. doi: 10.1186/s13036-025-00493-0.

ABSTRACT

Achieving consistent and predictable gene expression from plasmids remains challenging. While much attention has focused on intra-genetic elements like promoters and ribosomal binding sites, the spatial arrangement of genes within plasmids-referred to as gene syntax-also plays a crucial role in shaping gene expression dynamics. This study addresses the largely overlooked impact of gene syntaxes on gene expression variability and accuracy. Utilizing a dual-fluorescent protein system, we systematically investigated how different gene orientations and orders affect expression profiles including mean levels, relative expression ratios, and cell-to-cell variations. We found that arbitrary gene placement on a plasmid can cause significantly different expression means and ratios. Genes aligned in the same direction as a plasmid's origin of replication (Ori) typically exhibit higher expression levels; adjacent genes in the divergent orientation tend to suppress each other's expression; altering gene order without changing orientation can yield varied expression. Despite unchanged total cell-to-cell variation across different syntaxes, gene syntaxes can also influence intrinsic and extrinsic noise. Interestingly, cell-to-cell variation appears to depend on the reporter proteins, with RFP consistently showing higher variation than GFP. Moreover, the effects of gene syntax can propagate to downstream circuits, strongly affecting the performance of incoherent feedforward loops and contributing to unpredictable outcomes in genetic networks. Our findings reveal that gene syntaxes on plasmids modulate gene expression and circuit behavior, providing valuable insights for the rational design of plasmids and genetic circuits.

PMID:40148941 | DOI:10.1186/s13036-025-00493-0

Plant Cell Environ. 2025 Mar 27. doi: 10.1111/pce.15481. Online ahead of print.

ABSTRACT

Plant reactions to stress vary with development stage and fitness. This study assessed the relationship between light and chilling stress in Arabidopsis acclimation. By analysing the transcriptome and proteome responses of expanding leaves subjected to varying light intensity and cold, 2251 and 2064 early response genes and proteins were identified, respectively. Many of these represent as a yet unknown part of the early response to cold, illustrating a development-dependent response to stress and duality in plant adaptations. While standard light promoted photosynthetic upregulation, plastid maintenance, and increased resilience, low light triggered a unique metabolic shift, prioritizing ribosome biogenesis and lipid metabolism and attenuating the expression of genes associated with plant immunity. The comparison of early response in young leaves with that in expanded ones showed striking differences, suggesting a sacrifice of expanded leaves to support young ones. Validations of selected DEGs in mutant background confirmed a role of HSP90-1, transcription factor FLZ13, and Phospholipase A1 (PLIP) in response to cold, and the PLIP family emerged as crucial in promoting acclimation and freezing stress tolerance. The findings highlight the dynamic mechanisms that enable plants to adapt to challenging environments and pave the way for the development of genetically modified crops with enhanced freezing tolerance.

PMID:40148745 | DOI:10.1111/pce.15481

Nat Rev Genet. 2025 Mar 27. doi: 10.1038/s41576-025-00835-0. Online ahead of print.

NO ABSTRACT

PMID:40148574 | DOI:10.1038/s41576-025-00835-0