Anal Chem. 2025 Apr 18. doi: 10.1021/acs.analchem.4c05407. Online ahead of print.

ABSTRACT

Liquid biopsy is an appealing approach for early diagnosis and assessment of treatment efficacy in cancer. Typically, liquid biopsy involves the detection of endogenous biomarkers, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), and proteins. The levels of these endogenous biomarkers are higher in cancer patients compared to those in healthy individuals. However, the clinical application of liquid biopsy using endogenous biomarker analysis faces challenges due to its low abundance and poor stability in circulation. Recently, a promising strategy involving the engineering of exogenous probes has been developed to overcome these limitations. These exogenous probes are activated within the tumor microenvironment, generating distinct exogenous markers that can be easily distinguished from background biological signals. Alternatively, these exogenous probes can be labeled with intrinsic endogenous biomarkers in vivo and detected in vitro after metabolic processes. In this review, we primarily focus on microfluidic-based liquid biopsy techniques that allow for the transition from analyzing existing endogenous biomarkers to emerging exogenous ones. First, we introduce common endogenous biomarkers, as well as synthetic exogenous ones. Next, we discuss recent advancements in microfluidic-based liquid biopsy techniques for analyzing both existing endogenous and emerging exogenous biomarkers. Lastly, we provide insights into future directions for liquid biopsy on microfluidic systems.

PMID:40247704 | DOI:10.1021/acs.analchem.4c05407

Phys Rev E. 2025 Mar;111(3-2):035401. doi: 10.1103/PhysRevE.111.035401.

ABSTRACT

Glassy soft matter is often continuously polydisperse, in which the sizes or various properties of the constituent particles are distributed continuously. However, most of the microscopic theories of the glass transition focus on the monodisperse particles. Here, we developed a replica theory for the dynamic glass transition of continuously polydisperse hard spheres. We focused on the limit of infinite spatial dimension, where replica theory becomes exact. In theory, the cage size A, which plays the role of an order parameter, appears to depend on the particle size σ, and thus, the effective free energy, the so-called Franz-Parisi potential, is a functional of A(σ). We applied this theory to two fundamental systems: a nearly monodisperse system and an exponential distribution system. We found that dynamic decoupling occurs in both cases; the critical particle size σ^{*} emerges, and larger particles with σ≥σ^{*} vitrify, while smaller particles σ<σ^{*} remain mobile. Moreover, the cage size A(σ) exhibits a critical behavior at σ≃σ^{*}, originating from spinodal instability of σ^{*}-sized particles. We discuss the implications of these results for finite dimensional systems.

PMID:40247574 | DOI:10.1103/PhysRevE.111.035401

Nat Plants. 2025 Apr 17. doi: 10.1038/s41477-025-01986-y. Online ahead of print.

ABSTRACT

Molecular and physiological changes across crop developmental stages shape the plant phenome and render its prediction from genetic markers challenging. Here we present dynamicGP, an efficient computational approach that combines genomic prediction with dynamic mode decomposition to characterize the temporal changes and to predict genotype-specific dynamics for multiple morphometric, geometric and colourimetric traits scored by high-throughput phenotyping. Using genetic markers and data from high-throughput phenotyping of a maize multiparent advanced generation inter-cross population and an Arabidopsis thaliana diversity panel, we show that dynamicGP outperforms a baseline genomic prediction approach for the multiple traits. We demonstrate that the developmental dynamics of traits whose heritability varies less over time can be predicted with higher accuracy. The approach paves the way for interrogating and integrating the dynamical interactions between genotype and environment over plant development to improve the prediction accuracy of agronomically relevant traits.

PMID:40247143 | DOI:10.1038/s41477-025-01986-y

Nat Genet. 2025 Apr 17. doi: 10.1038/s41588-025-02157-7. Online ahead of print.

ABSTRACT

Circular RNA (circRNA) represents a type of RNA molecule characterized by a closed-loop structure that is distinct from linear RNA counterparts. Recent studies have revealed the emerging role of these circular transcripts in gene regulation and disease pathogenesis. However, their low expression levels and high sequence similarity to linear RNAs present substantial challenges for circRNA detection and characterization. Recent advances in long-read and single-cell RNA sequencing technologies, coupled with sophisticated deep learning-based algorithms, have revolutionized the investigation of circRNAs at unprecedented resolution and scale. This Review summarizes recent breakthroughs in circRNA discovery, characterization and functional analysis algorithms. We also discuss the challenges associated with integrating large-scale circRNA sequencing data and explore the potential future development of artificial intelligence (AI)-driven algorithms to unlock the full potential of circRNA research in biomedical applications.

PMID:40247051 | DOI:10.1038/s41588-025-02157-7

NPJ Syst Biol Appl. 2025 Apr 17;11(1):37. doi: 10.1038/s41540-025-00509-x.

ABSTRACT

MIRO1 is a mitochondrial outer membrane protein important for mitochondrial distribution, dynamics and bioenergetics. Over the last decade, evidence has pointed to a link between MIRO1 and Parkinson's disease (PD) pathogenesis. Moreover, a heterozygous MIRO1 mutation (p.R272Q) was identified in a PD patient, from which an iPSC-derived midbrain organoid model was derived, showing MIRO1 mutant-dependent selective loss of dopaminergic neurons. Herein, we use patient-specific iPSC-derived midbrain organoids carrying the MIRO1 p.R272Q mutation to further explore the cellular and molecular mechanisms involved in dopaminergic neuron degeneration. Using single-cell RNA sequencing (scRNAseq) analysis and metabolic modeling we show that the MIRO1 p.R272Q mutation affects the dopaminergic neuron developmental path leading to metabolic deficits and disrupted neuron-astrocyte metabolic crosstalk, which might represent an important pathogenic mechanism leading to their loss.

PMID:40246848 | DOI:10.1038/s41540-025-00509-x

J Proteomics. 2025 Apr 15:105442. doi: 10.1016/j.jprot.2025.105442. Online ahead of print.

ABSTRACT

This white paper presents a comprehensive biobanking framework developed at the European Cancer Moonshot Lund Center that merges rigorous sample handling, advanced automation, and multi-omic analyses to accelerate precision oncology. Tumor and blood-based workflows, supported by automated fractionation systems and standardized protocols, ensure the collection of high-quality biospecimens suitable for proteomic, genomic, and metabolic studies. A robust informatics infrastructure, integrating LIMS, barcoding, and REDCap, supports end-to-end traceability and realtime data synchronization, thereby enriching each sample with critical clinical metadata. Proteogenomic integration lies at the core of this initiative, uncovering tumor- and blood-based molecular profiles that inform cancer heterogeneity, metastasis, and therapeutic resistance. Machine learning and AI-driven models further enhance these datasets by stratifying patient populations, predicting therapeutic responses, and expediting the discovery of actionable targets and companion biomarkers. This synergy between technology, automation, and high-dimensional data analytics enables individualized treatment strategies in melanoma, lung, and other cancer types. Aligned with international programs such as the Cancer Moonshot and the ICPC, the Lund Center's approach fosters open collaboration and data sharing on a global scale. This scalable, patient-centric biobanking paradigm provides an adaptable model for institutions aiming to unify clinical, molecular, and computational resources for transformative cancer research.

PMID:40246065 | DOI:10.1016/j.jprot.2025.105442

Cell Stem Cell. 2025 Apr 11:S1934-5909(25)00102-X. doi: 10.1016/j.stem.2025.03.012. Online ahead of print.

ABSTRACT

Considerable phenotypic variation under identical culture conditions limits the potential of stem-cell-based embryo models (SEMs) in basic and applied research. The biological processes causing this seemingly stochastic variation remain unclear. Here, we investigated the roots of phenotypic variation by parallel recording of transcriptomic states and morphological history in individual structures modeling embryonic trunk formation. Machine learning and integration of time-resolved single-cell RNA sequencing with imaging-based phenotypic profiling identified early features predictive of phenotypic end states. Leveraging this predictive power revealed that early imbalance of oxidative phosphorylation and glycolysis results in aberrant morphology and a neural lineage bias, which we confirmed by metabolic measurements. Accordingly, metabolic interventions improved phenotypic end states. Collectively, our work establishes divergent metabolic states as drivers of phenotypic variation and offers a broadly applicable framework to chart and predict phenotypic variation in organoids and SEMs. The strategy can be used to identify and control underlying biological processes, ultimately increasing reproducibility.

PMID:40245869 | DOI:10.1016/j.stem.2025.03.012

Cell. 2025 Apr 14:S0092-8674(25)00352-6. doi: 10.1016/j.cell.2025.03.034. Online ahead of print.

ABSTRACT

Regulatory DNA provides a platform for transcription factor binding to encode cell-type-specific patterns of gene expression. However, the effects and programmability of regulatory DNA sequences remain difficult to map or predict. Here, we develop variant effects from flow-sorting experiments with CRISPR targeting screens (Variant-EFFECTS) to introduce hundreds of designed edits to endogenous regulatory DNA and quantify their effects on gene expression. We systematically dissect and reprogram 3 regulatory elements for 2 genes in 2 cell types. These data reveal endogenous binding sites with effects specific to genomic context, transcription factor motifs with cell-type-specific activities, and limitations of computational models for predicting the effect sizes of variants. We identify small edits that can tune gene expression over a large dynamic range, suggesting new possibilities for prime-editing-based therapeutics targeting regulatory DNA. Variant-EFFECTS provides a generalizable tool to dissect regulatory DNA and to identify genome editing reagents that tune gene expression in an endogenous context.

PMID:40245860 | DOI:10.1016/j.cell.2025.03.034

Plant Physiol Biochem. 2025 Apr 1;224:109868. doi: 10.1016/j.plaphy.2025.109868. Online ahead of print.

ABSTRACT

Stress-associated proteins (SAPs), characterized by zinc finger domains, play a crucial role in regulating plant responses to various stresses. These proteins modulate stress-related gene expression and are integral to enhancing plant immunity, development, cell proliferation, and hormone regulation. In this study, we conducted a genome-wide analysis of the SAP gene family in Suaeda glauca (S. glauca), identifying 15 SAP genes encoding A20/AN1 zinc finger proteins. Functional analyses of three candidate genes under salinity stress were performed, examining phenotypic and physiological responses to better understand their role in stress tolerance. Sequence alignment, conserved domain analysis, and gene structure analysis revealed high conservation among S. glauca SAPs. Phylogenetic analysis identified two major groups within the gene family, providing insights into their evolutionary relationships. Transcription profiling analysis demonstrated significant expression of most SAP genes in response to salt stress, with qPCR validation confirming the upregulation of specific genes. Notably, transgenic Arabidopsis lines heterologously overexpressing the candidate genes SgSAP4, SgSAP5, and SgSAP7 demonstrated enhanced tolerance to salinity stress. This was evident from improved seed germination, root elongation, and reduced levels of stress markers, including malondialdehyde and free proline, compared to wild-type plants. These findings highlight the potential of these SAP genes in breeding programs aimed at improving salinity tolerance in crops.

PMID:40245556 | DOI:10.1016/j.plaphy.2025.109868

Phys Chem Chem Phys. 2025 Apr 17. doi: 10.1039/d5cp00024f. Online ahead of print.

ABSTRACT

Fentanyl is a synthetic opioid with higher potency compared to morphine and heroin, making it an essential drug for pain management and also an abused drug. Beyond fentanyl, derivatives, such as o-fluoro fentanyl and furanyl fentanyl, also possess similar potency and present a significant risk of misuse, but without medical utility. A major challenge for law enforcement is detecting fentanyl and its analogues in their degraded forms. While the degradation fragments of fentanyl are well-known, those of its analogues are not as well studied. Here, we investigated the thermal degradation pathways of fentanyl analogues using extensive ab initio molecular dynamics simulations combined with enhanced sampling techniques, including multiple walker metadynamics and umbrella sampling. We calculated the free energy profiles for each bond previously identified as a potential degradation site to map out the thermodynamic driving forces. Additionally, we estimated the forward attempt rate of each bond degradation reaction to gain insights into the kinetics of those degradation processes. Our results show that, despite high similarity in structure, the bond breaking pathways differ for the analogues compared with fentanyl. We also observed that traditional force fields with fixed charges are insufficient for studies of fentanyl and its analogues due to polarizability of the electronic structure. Distribution Statement A. Approved for Public Release. Distribution Unlimited.

PMID:40245086 | DOI:10.1039/d5cp00024f

Cell Rep. 2025 Apr 16;44(5):115591. doi: 10.1016/j.celrep.2025.115591. Online ahead of print.

ABSTRACT

We present an isotope-based metabolic flux analysis (MFA) approach to simultaneously quantify metabolic fluxes in the liver, heart, and skeletal muscle of individual mice. The platform was scaled to examine metabolic flux adaptations in age-matched cohorts of mice exhibiting varying levels of chronic obesity. We found that severe obesity increases hepatic gluconeogenesis and citric acid cycle flux, accompanied by elevated glucose oxidation in the heart that compensates for impaired fatty acid oxidation. In contrast, skeletal muscle fluxes exhibit an overall reduction in substrate oxidation. These findings demonstrate the dichotomy in fuel utilization between cardiac and skeletal muscle during worsening metabolic disease and demonstrate the divergent effects of obesity on metabolic fluxes in different organs. This multi-tissue MFA technology can be extended to address important questions about in vivo regulation of metabolism and its dysregulation in disease, which cannot be fully answered through studies of single organs or isolated cells/tissues.

PMID:40244853 | DOI:10.1016/j.celrep.2025.115591

J Toxicol Environ Health A. 2025 Apr 17:1-12. doi: 10.1080/15287394.2025.2491556. Online ahead of print.

ABSTRACT

Myricetin (ME) is a major constituent of various foods and beverages consumed by humans, including vegetables, teas and fruits, and is primarily recognized for its iron-chelating, antioxidant, anti-inflammatory and anti-cancer properties. This study evaluated the cytostatic, genotoxic, and chemopreventive effects of ME in CHO-K1 cells using the Cytokinesis-Block Micronucleus (CBMN) assay and explored molecular interactions through in silico systems biology analysis. CHO-K1 cells were exposed to ME (2.5-40 µM). Cytostasis was assessed by the Cytokinesis-Block Proliferation Index (CBPI), and chromosomal instability was measured by the frequency of micronuclei (MNi), nucleoplasmic bridges (NPBs), and nuclear buds (NBUDs). ME at 40 µM significantly reduced CBPI, while concentrations of 20 and 40 µM increased chromosomal instability (p < 0.05). For chemoprevention, ME (2.5-10 µM) was administered in pre-, co-, and post-treatment with bleomycin (BLM). ME significantly reduced BLM-induced MNi and NPBs in all protocols (p < 0.05). In silico analysis revealed strong interactions between ME and key proteins related to DNA damage response, apoptosis, and bleomycin detoxification. Notably, the in silico analysis revealed a strong association between ME and bleomycin hydrolase (BLMH) and the interaction of ME with proteins related to DNA damage response and apoptosis regulation. Overall, ME exhibited genotoxicity at high concentrations but demonstrated a significant chemopreventive effect at lower, nontoxic doses. These findings provide insights into the dual biological activity of ME and support its potential use as a protective agent against genotoxic damage.

PMID:40244708 | DOI:10.1080/15287394.2025.2491556

Int J Mol Sci. 2025 Apr 7;26(7):3447. doi: 10.3390/ijms26073447.

ABSTRACT

The OsTHION family represents a class of cysteine-rich signal peptides widely recognized for their significant roles in plant disease resistance and immunity. While members of this family are known to be induced under various biotic and abiotic stresses, their responses to environmental stressors beyond disease resistance remain underexplored. This study investigates the evolution, expression patterns, and functional roles of the OsTHION gene family in rice (Oryza sativa) under diverse stress conditions. Using sequence data from the Phytozome database, we identified 44 OsTHION family members and classified them into four groups based on phylogenetic analysis. Cis-acting element analysis revealed that the promoter regions of OsTHION genes are enriched with regulatory elements associated with light response, hormone signaling, plant growth, and stress responses. The OsTHION genes exhibit complex organ-specific expression patterns, with OsTHION30 and OsTHION36 showing ubiquitous expression, while other members are highly expressed in specific tissues or developmental stages. Under drought, salt, and low-temperature stress, OsTHION genes undergo significant expression changes, underscoring their critical role in plant adaptation to environmental challenges. Notably, OsTHION15 was markedly upregulated under drought stress, and the Osthion15 mutant displayed heightened sensitivity to drought and ABA stress, confirming its pivotal role in stress resistance. RNA sequencing analysis identified many differentially expressed genes (DEGs), primarily enriched in pathways related to ribosomal function and plant hormone signaling, suggesting that OsTHION15 may regulate stress responses through multiple mechanisms. In summary, this study advances our understanding of the OsTHION gene family and highlights its intricate involvement in regulating rice growth, development, and environmental stress responses. These findings offer valuable insights and technical support for crop improvement, with potential applications in enhancing environmental adaptability and yield stability in crops.

PMID:40244412 | DOI:10.3390/ijms26073447

Int J Mol Sci. 2025 Apr 7;26(7):3455. doi: 10.3390/ijms26073455.

ABSTRACT

The regulation of downstream responsive genes by transcription factors (TFs) is a critical step in the stress response system of plants. While bZIP transcription factors are known to play important roles in stress reactions, their functional characterization in soybeans remains limited. Here, we identified a soybean bZIP gene, GmbZIP60, which encodes a protein containing a typical bZIP domain with a basic region and a leucine zipper region. Subcellular localization studies confirmed that GmbZIP60 is localized in the nucleus. Expression analysis demonstrated that GmbZIP60 is induced by salt stress, drought stress, and various plant hormone treatments, including abscisic acid (ABA), ethylene (ETH), and methyl jasmonate acid (MeJA). Overexpressing GmbZIP60 (OE-GmbZIP60) in transgenic soybean and rice enhanced tolerance to both salt and drought stresses. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that the expression levels of abiotic stress-responsive genes were significantly higher in transgenic plants than in wild-type (WT) plants under stress conditions. Chromatin immunoprecipitation-qPCR (ChIP-qPCR) analysis further confirmed that GmbZIP60 directly binds to the promoters of abiotic stress-related genes induced by ABA, ETH, JA, and salicylic acid (SA). Overall, these findings revealed GmbZIP60 as a positive regulator of salt and drought stress tolerance.

PMID:40244391 | DOI:10.3390/ijms26073455

Eur J Nucl Med Mol Imaging. 2025 Apr 17. doi: 10.1007/s00259-025-07272-5. Online ahead of print.

ABSTRACT

PURPOSE: Prior studies reveal seasonal variations of mu-opioid receptor (MOR) signaling in both the brain and the brown adipose tissue (BAT). However, the potential seasonality effect on brain-BAT interactions, related to this signaling pathway, remains unknown. Understanding this dynamic seasonal rhythm may provide novel insights into seasonal affective changes and related psychiatric disorders.

METHODS: Nine adult rats (6 males and 3 females) were housed under standard conditions with photoperiodic cycles simulating local seasonal changes. The rats underwent repeated [11C]carfentanil PET imaging to assess MOR availability in the brain and BAT. Partial Least Squares Regression (PLSR) analysis was applied to evaluate the predictability of brain MOR availability on corresponding BAT measures. Latent variables in the PLSR models were eventually categorized by photoperiod.

RESULTS: PLSR models indicated that brain MOR availability considerably accounted for the variance of MOR levels in the BAT (22.82%), comparable to age (23%). Models applying different brain regional measures (striatum, neocortex and thalamus) produced consistent latent variables across models. A shorter photoperiod was associated with increased latent variable (beta = -4.32, 95% CI [-5.30, -3.35]).

CONCLUSION: These findings suggest that shorter photoperiods enhance, while longer photoperiods reduce, the predictability of brain MOR levels on BAT MOR signaling. These data imply that darker seasons may amplify the interaction between brain activity and peripheral physiology associated with MOR signaling. The adaptability of brain-BAT interactions under stress stimuli offers a new avenue for exploring systems biology.

PMID:40244343 | DOI:10.1007/s00259-025-07272-5

Arch Dermatol Res. 2025 Apr 17;317(1):713. doi: 10.1007/s00403-025-04227-6.

ABSTRACT

Dysbiosis, an imbalance in skin microflora, is a key contributor to inflammatory skin conditions, including atopic dermatitis (AD), seborrheic dermatitis (SD), and psoriasis. In AD, Staphylococcus aureus colonization of skin lesions is prevalent approximately 70% of cases, with disease severity positively correlating with bacterial presence. Moreover, methicillin-resistant Staphylococcus aureus (MRSA) is found in 10-30% of AD skin lesions, highlighting the need for novel therapeutic strategies that target both microbial imbalance and inflammation. This study evaluates Ligilactobacillus salivarius Lac45 (LS-Lac45), a breast milk-derived bacterial strain, for its antimicrobial and anti-inflammatory potential in dermatology. We assessed its antimicrobial activity against MRSA using an agar disk-diffusion assay and its anti-inflammatory effects in a peptidoglycan (PGN)-induced inflammation model in HaCaT keratinocytes. To elucidate its mechanisms of action, mass spectrometry was used to analyze protein expression changes in LS-Lac45-treated keratinocytes. Our results demonstrate that live LS-Lac45 effectively inhibits MRSA growth. Additionally, heat-killed LS-Lac45 significantly reduces PGN-induced production of pro-inflammatory cytokines IL-6, IL-8, and TNF-α. Proteomic analysis further identifies LS-Lac45-mediated modulation of immune-related proteins, including heat shock protein 60, metallothionein 2A, and antioxidant-1, suggesting a role in inflammatory regulation. These findings highlight LS-Lac45 as a candidate for managing MRSA-associated inflammatory skin conditions, particularly AD. While this study provides key insights into its antimicrobial and immunomodulatory properties, further research is needed to evaluate its probiotic characteristics and clinical applicability in dermatology.

PMID:40244342 | DOI:10.1007/s00403-025-04227-6

Int J Mol Sci. 2025 Apr 5;26(7):3419. doi: 10.3390/ijms26073419.

ABSTRACT

Recent studies show that patients with Alzheimer's disease (AD) harbor specific methylation marks in the brain that, if accessible, could be used as epigenetic biomarkers. Liquid biopsy enables the study of circulating cell-free DNA (cfDNA) fragments originated from dead cells, including neurons affected by neurodegenerative processes. Here, we isolated and epigenetically characterized plasma cfDNA from 35 patients with AD and 35 cognitively healthy controls by using the Infinium® MethylationEPIC BeadChip array. Bioinformatics analysis was performed to identify differential methylation positions (DMPs) and regions (DMRs), including APOE ε4 genotype stratified analysis. Plasma pTau181 (Simoa) and cerebrospinal fluid (CSF) core biomarkers (Fujirebio) were also measured and correlated with differential methylation marks. Validation was performed with bisulfite pyrosequencing and bisulfite cloning sequencing. Epigenome-wide cfDNA analysis identified 102 DMPs associated with AD status. Most DMPs correlated with clinical cognitive and functional tests including 60% for Mini-Mental State Examination (MMSE) and 80% for Global Deterioration Scale (GDS), and with AD blood and CSF biomarkers. In silico functional analysis connected 30 DMPs to neurological processes, identifying key regulators such as SPTBN4 and APOE genes. Several DMRs were annotated to genes previously reported to harbor epigenetic brain changes in AD (HKR1, ZNF154, HOXA5, TRIM40, ATG16L2, ADAMST2) and were linked to APOE ε4 genotypes. Notably, a DMR in the HKR1 gene, previously shown to be hypermethylated in the AD hippocampus, was validated in cfDNA from an orthogonal perspective. These results support the feasibility of studying cfDNA to identify potential epigenetic biomarkers in AD. Thus, liquid biopsy could improve non-invasive AD diagnosis and aid personalized medicine by detecting epigenetic brain markers in blood.

PMID:40244264 | DOI:10.3390/ijms26073419

Int J Mol Sci. 2025 Apr 1;26(7):3283. doi: 10.3390/ijms26073283.

ABSTRACT

Medical treatment of glioblastoma presents a significant challenge. A conventional medication has limited effectiveness, and a single-target therapy is usually effective only in the early stage of the treatment. Recently, there has been increasing focus on multi-target therapies, but the vast range of possible combinations makes clinical experimentation and implementation difficult. From the perspective of systems biology, this study conducted simulations for multi-target glioblastoma therapy based on dynamic analysis of previously established endogenous networks, validated with glioblastoma single-cell RNA sequencing data. Several potentially effective target combinations were identified. The findings also highlight the necessity of multi-target rather than single-target intervention strategies in cancer treatment, as well as the promise in clinical applications and personalized therapies.

PMID:40244148 | DOI:10.3390/ijms26073283

Int J Mol Sci. 2025 Apr 1;26(7):3266. doi: 10.3390/ijms26073266.

ABSTRACT

Metacestodes of Echinococcus multilocularis are the causative agents of alveolar echinococcosis, a neglected, life-threatening, zoonotic disease. To study these metacestodes in vitro, a model system using a culture medium conditioned by rat hepatoma cells is available. A key question is how the parasite interacts with the host and, in particular, which host-derived compounds are taken up. In this study, we focus on the uptake of host-derived proteins. Studies with artificially labeled proteins suggest that this uptake may occur independently of protein size or charge. Closer investigation using proteomics draws, however, a different picture. Of 1170 host (i.e., rat or bovine) proteins as identified by LC-MS/MS-based proteomics present in the culture medium, only 225 are found in metacestode vesicle tissue or fluid. Moreover, their relative abundances differ. Serum albumin, the most abundant culture medium host protein, is only the third most abundant protein in vesicle fluid, where Alpha-2-HS-glycoprotein becomes the most abundant protein. In vesicle fluid obtained ex vivo from experimentally infected mice, the situation is again different, with histone isoforms as the most abundant proteins. This suggests that while maintaining their internal milieu constant, metacestodes may adjust the spectrum of host proteins taken up. Potential uptake mechanisms and functions are discussed.

PMID:40244114 | DOI:10.3390/ijms26073266

Int J Mol Sci. 2025 Mar 28;26(7):3116. doi: 10.3390/ijms26073116.

ABSTRACT

The utilization of photosynthetic microbes, such as cyanobacteria and microalgae, offers sustainable solutions to addressing global resource shortages and pollution. While these microorganisms have demonstrated significant potential in biomanufacturing, their industrial application is limited by suboptimal photosynthetic efficiency. Synthetic biology integrates molecular biology, systems biology, and engineering principles to provide a powerful tool for elucidating photosynthetic mechanisms and rationally optimizing photosynthetic platforms. This review summarizes recent advancements in regulating photosynthesis in cyanobacteria and microalgae via synthetic biology, focusing on strategies to enhance light energy absorption, optimize electron transport chains, and improve carbon assimilation. Furthermore, we discuss key challenges in translating these genetic modifications to large-scale bioproduction, highlighting specific bottlenecks in strain stability, metabolic burden, and process scalability. Finally, we propose potential solutions, such as AI-assisted metabolic engineering, synthetic microbial consortia, and next-generation photobioreactor designs, to overcome these limitations. Overall, while synthetic biology holds great promise for enhancing photosynthetic efficiency in cyanobacteria and microalgae, further research is needed to refine genetic strategies and develop scalable production systems.

PMID:40243859 | DOI:10.3390/ijms26073116