Cell Metab. 2025 Mar 25:S1550-4131(25)00104-4. doi: 10.1016/j.cmet.2025.03.001. Online ahead of print.

ABSTRACT

Aging affects reproductive capabilities in males through physiological and behavioral alterations, including endocrine changes and decreased libido. In this study, we investigated the influence of intermittent fasting (IF) on these aging-related declines, using male C57BL/6J mice. Our findings revealed that IF significantly preserved reproductive success in aged mice, not by improving traditional reproductive metrics such as sperm quality or endocrine functions but by enhancing mating behavior. This behavioral improvement was attributed to IF's ability to counter age-dependent increases in serotonergic inhibition, primarily through the decreased supply of the serotonin precursor tryptophan from the periphery to the brain. Our research underscores the potential of dietary interventions like IF in mitigating age-associated declines in male reproductive health and suggests a novel approach to managing conditions related to reduced sexual desire, highlighting the complex interplay between diet, metabolism, and reproductive behavior.

PMID:40157367 | DOI:10.1016/j.cmet.2025.03.001

Sci Total Environ. 2025 Mar 28;974:179243. doi: 10.1016/j.scitotenv.2025.179243. Online ahead of print.

ABSTRACT

Deforestation is one of the main drivers of environmental degradation around the world. Slash-and-burn is a common practice, performed in tropical forests to create new agricultural lands for local communities. In Madagascar, this practice affects many natural areas that host lemur habitats. Reforestation within nature reserves including fast-growing native species is desirable, for example in this area using native bamboo with the aim of restoring the habitat increased plantation success. In this context, the extensive detection of forest disturbances can effectively support restoration actions, providing an overall framework to address priorities and maximizing ecological benefits. In this work and with respect to a study area located around the Maromizaha New Protected Area (Madagascar), an analysis was conducted based on a time series of NDVI maps from Landsat missions (GSD = 30 m). The period between 1991 and 2022 was investigated to detect the location and moment of forest disturbances with the additional aim of quantifying the level of damage and of the recovery process at every disturbed location. It is worth noting that the Maromizaha New Protected Area currently hosts 12 species of endangered lemurs, highlighting its pivotal role as a critical conservation and restoration priority due to the ecological significance of preserving habitat integrity to sustain these threatened species. Detection was operated at pixel level by analyzing the local temporal profile of Normalized Difference Vegetation Index - NDVI (yearly step). Time of the eventual detected disturbance was found within the profile looking for the first derivative minimum. Significance of NDVI change was evaluated testing the Chebyshev condition and the following parameters mapped: i) year of disturbance; ii) significance of NDVI change; iii) level of damage; (iv) year of vegetation recovery; (v) rate of recovery. Accordingly, the level of the damage and the rate of recovery were used to estimate resistance and resilience indices of lemurs' habitat (inherently forested areas). Finally, temporal trends of both forest loss and recovery were analyzed to investigate potential impacts onto local lemur populations and, more in general, to the entire Reserve.

PMID:40157089 | DOI:10.1016/j.scitotenv.2025.179243

Curr Opin Biotechnol. 2025 Mar 28;93:103297. doi: 10.1016/j.copbio.2025.103297. Online ahead of print.

ABSTRACT

Oleaginous yeast are remarkably versatile organisms, distinguished by their natural capacities to accumulate high levels of neutral lipids and broad substrate range. With recent growing interests in engineering non-model organisms as superior biomanufacturing platforms, oleaginous yeasts have emerged as promising chassis for oleochemicals, terpenoids, organic acids, and other valuable products. Advancement in systems biology along with genetic tool development have significantly expanded our understanding of the metabolism in these species and enabled engineering efforts to produce biofuels and bioproducts from diverse feedstocks. This review examines the latest technical advances in oleaginous yeast research toward sustainable biomanufacturing. We cover recent developments in systems biology-enabled metabolism understanding, genetic tools, feedstock utilization, and strain engineering approaches for the production of various valuable chemicals.

PMID:40157044 | DOI:10.1016/j.copbio.2025.103297

Br J Surg. 2025 Mar 28;112(4):znaf051. doi: 10.1093/bjs/znaf051.

NO ABSTRACT

PMID:40156895 | DOI:10.1093/bjs/znaf051

Nat Rev Genet. 2025 Mar 28. doi: 10.1038/s41576-025-00828-z. Online ahead of print.

ABSTRACT

Transcriptome sequencing revolutionized the analysis of gene expression, providing an unbiased approach to gene detection and quantification that enabled the discovery of novel isoforms, alternative splicing events and fusion transcripts. However, although short-read sequencing technologies have surpassed the limited dynamic range of previous technologies such as microarrays, they have limitations, for example, in resolving full-length transcripts and complex isoforms. Over the past 5 years, long-read sequencing technologies have matured considerably, with improvements in instrumentation and analytical methods, enabling their application to RNA sequencing (RNA-seq). Benchmarking studies are beginning to identify the strengths and limitations of long-read RNA-seq, although there remains a need for comprehensive resources to guide newcomers through the intricacies of this approach. In this Review, we provide a comprehensive overview of the long-read RNA-seq workflow, from library preparation and sequencing challenges to core data processing, downstream analyses and emerging developments. We present an extensive inventory of experimental and analytical methods and discuss current challenges and prospects.

PMID:40155769 | DOI:10.1038/s41576-025-00828-z

Nat Commun. 2025 Mar 28;16(1):3042. doi: 10.1038/s41467-025-58073-1.

ABSTRACT

Mycobacteria harbor a proteasome that was acquired by Actinobacteria through horizontal gene transfer and that supports the persistence of the human pathogen Mycobacterium tuberculosis within host macrophages. The core particle of the proteasome (20S CP) associates with ring-shaped activator complexes to degrade protein substrates. One of these is the bacterial proteasome activator Bpa that stimulates the ATP-independent proteasomal degradation of the heat shock repressor HspR. In this study, we determine the cryogenic electron microscopy 3D reconstruction of the complex between Bpa and its natural substrate HspR at 4.1 Å global resolution. The resulting maps allow us to identify regions of Bpa that interact with HspR. Using structure-guided site-directed mutagenesis and in vitro biochemical assays, we confirm the importance of the identified residues for Bpa-mediated substrate recruitment and subsequent proteasomal degradation. Additionally, we show that the dodecameric Bpa ring associates asymmetrically with the heptameric α-rings of the 20S CP, adopting a conformation resembling a hinged lid, while still engaging all seven docking sites on the proteasome.

PMID:40155375 | DOI:10.1038/s41467-025-58073-1

Cancer Cell. 2025 Mar 20:S1535-6108(25)00108-4. doi: 10.1016/j.ccell.2025.03.007. Online ahead of print.

ABSTRACT

Myeloid cancers such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) remain resistant to standard of care (SOC) and targeted therapies. In this study, we demonstrate that responsiveness to therapy is associated with activation of β-catenin-JAG1 in osteoblastic cells of patients treated with all-trans-retinoic acid (ATRA). ATRA suppresses β-catenin activity in patients and leukemic mice. Consequently, it inhibits the growth and survival of MDS/AML cells from patients with active β-catenin-JAG1 signaling and promotes their differentiation. This occurs independently of cytogenetics and mutational profile. ATRA also improves disease outcome in mice with no evidence of relapse and a superior safety profile to SOC. A human anti-JAG1 antibody improves efficacy in leukemic mice and patient-derived MDS/AML cells. β-catenin activation provides an explanation for the differential response to ATRA and a mechanistic biomarker for ATRA repurposing in myeloid malignancies, potentially evading relapse and extending across a broad range of cancers.

PMID:40154481 | DOI:10.1016/j.ccell.2025.03.007

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