Viruses. 2025 Feb 28;17(3):355. doi: 10.3390/v17030355.

ABSTRACT

Viruses are ubiquitous across all kingdoms of cellular life, posing a significant threat to human health, and analyzing viral communities is challenging due to their genetic diversity and lack of a single, universally conserved marker gene. To address this challenge, we developed the AliMarko pipeline, a tool designed to streamline virus identification in metagenomic data. Our pipeline uses a dual approach, combining mapping reads with reference genomes and a de novo assembly-based approach involving an HMM-based homology search and phylogenetic analysis, to enable comprehensive detection of viral sequences, including low-coverage and divergent sequences. We applied our pipeline to total RNA sequencing of bat feces and identified a range of viruses, quickly validating viral sequences and assessing their phylogenetic relationships. We hope that the AliMarko pipeline will be a useful resource for the scientific community, facilitating the interpretation of viral communities and advancing our understanding of viral diversity and its impact on human health.

PMID:40143285 | DOI:10.3390/v17030355

Pharmaceutics. 2025 Feb 24;17(3):296. doi: 10.3390/pharmaceutics17030296.

ABSTRACT

Melanoma, a highly aggressive form of skin cancer, poses a major therapeutic challenge due to its metastatic potential, resistance to conventional therapies, and the complexity of the tumor microenvironment (TME). Materials science and nanotechnology advances have led to using nanocarriers such as liposomes, dendrimers, polymeric nanoparticles, and metallic nanoparticles as transformative solutions for precision melanoma therapy. This review summarizes findings from Web of Science, PubMed, EMBASE, Scopus, and Google Scholar and highlights the role of nanotechnology in overcoming melanoma treatment barriers. Nanoparticles facilitate passive and active targeting through mechanisms such as the enhanced permeability and retention (EPR) effect and functionalization with tumor-specific ligands, thereby improving the accuracy of drug delivery and reducing systemic toxicity. Stimuli-responsive systems and multi-stage targeting further improve therapeutic precision and overcome challenges such as poor tumor penetration and drug resistance. Emerging therapeutic platforms combine diagnostic imaging with therapeutic delivery, paving the way for personalized medicine. However, there are still issues with scalability, biocompatibility, and regulatory compliance. This comprehensive review highlights the potential of integrating nanotechnology with advances in genetics and proteomics, scalable, and patient-specific therapies. These interdisciplinary innovations promise to redefine the treatment of melanoma and provide safer, more effective, and more accessible treatments. Continued research is essential to bridge the gap between evidence-based scientific advances and clinical applications.

PMID:40142960 | DOI:10.3390/pharmaceutics17030296

J Clin Med. 2025 Mar 17;14(6):2040. doi: 10.3390/jcm14062040.

ABSTRACT

Oncologists increasingly recognize the microbiome as an important facilitator of health as well as a contributor to disease, including, specifically, cancer. Our knowledge of the etiologies, mechanisms, and modulation of microbiome states that ameliorate or promote cancer continues to evolve. The progressive refinement and adoption of "omic" technologies (genomics, transcriptomics, proteomics, and metabolomics) and utilization of advanced computational methods accelerate this evolution. The academic cancer center network, with its immediate access to extensive, multidisciplinary expertise and scientific resources, has the potential to catalyze microbiome research. Here, we review our current understanding of the role of the gut microbiome in cancer prevention, predisposition, and response to therapy. We underscore the promise of operationalizing the academic cancer center network to uncover the structure and function of the gut microbiome; we highlight the unique microbiome-related expert resources available at the City of Hope of Comprehensive Cancer Center as an example of the potential of team science to achieve novel scientific and clinical discovery.

PMID:40142848 | DOI:10.3390/jcm14062040

Int J Mol Sci. 2025 Mar 20;26(6):2823. doi: 10.3390/ijms26062823.

ABSTRACT

This study investigates the proteomic dynamics in tomato cultivars with differing resistance to potato cyst nematodes (PCNs). Cyst-forming nematodes, significant agricultural pests, induce complex molecular responses in host plants, forming syncytia in roots for their nutrition. This research employs mass spectrometry to analyze the proteomes of infected and uninfected roots from susceptible (Moneymaker) and resistant (LA1792 and L10) tomato lines. Over 2800 high-confidence protein hits were identified, revealing significant differences in abundance between susceptible and resistant lines. Notably, resistant lines exhibited a higher number of newly expressed proteins compared to susceptible lines; however, the proportion of induced and suppressed proteins was strongly genotype-dependent. Gene ontology (GO) analysis highlighted that nematode infection in susceptible line significantly regulates many defense-related proteins, particularly those involved in oxidative stress, with a similar number being upregulated and downregulated. Some GO terms enriched among nematode-regulated proteins also indicate the involvement of programmed cell death (PCD)-related processes. The susceptible line exhibited a prevalence of downregulated proteins, among which defense associated GO terms were significantly overrepresented. Four proteins (APY2, NIA2, GABA-T, and AATP1) potentially crucial for nematode parasitism were identified and their Arabidopsis orthologs were studied. Mutant Arabidopsis lines showed altered nematode resistance, supporting the involvement of these proteins in plant defense. This study highlights the complexity of host-nematode interactions and emphasizes the importance of proteomic analyses in identifying key factors and understanding plant defense mechanisms.

PMID:40141466 | DOI:10.3390/ijms26062823

Int J Mol Sci. 2025 Mar 11;26(6):2483. doi: 10.3390/ijms26062483.

ABSTRACT

Clinacanthus nutans is a valuable traditional medicinal plant that contains enriched active compounds such as triterpenoids and flavonoids. Understanding the accuulation process of these secondary metabolites in C. nutans requires exploring gene expression regulation under abiotic stresses and hormonal stimuli. qRT-PCR is a powerful method for gene expression analysis, with the selection of suitable reference genes being paramount. However, reports on stably expressed reference genes in C. nutans and even across the entire family Acanthaceae are limited. In this study, we evaluated the expression stability of 12 candidate reference genes (CnUBQ, CnRPL, CnRPS, CnPTB1, CnTIP41, CnACT, CnUBC, CnGAPDH, Cn18S, CnCYP, CnEF1α, and CnTUB) in C. nutans across different tissues and under abiotic stresses and MeJA treatment using three programs (geNorm, NormFinder, and BestKeeper). The integrated ranking results indicated that CnUBC, CnRPL, and CnCYP were the most stably expressed genes across different tissues. Under abiotic stress conditions, CnUBC, CnRPL, and CnEF1α were the most stable, while under MeJA treatment, CnRPL, CnEF1α, and CnGAPDH exhibited the highest stability. Additionally, CnRPL, CnUBC, and CnEF1α were the most stable reference genes across all tested samples, whereas CnGAPDH was the least stable. CnRPL, consistently ranking among the top three most stable genes, may therefore serve as an ideal reference gene for qRT-PCR analysis in C. nutans. To further validate the selected reference genes, we assessed the expression of two key biosynthetic genes, CnPAL and CnHMGR. The results confirmed that using the most stable reference genes yielded expression patterns consistent with biological expectations, while using unstable reference genes led to significant deviations. These findings offer valuable insights for accurately quantifying target genes via qRT-PCR in C. nutans, facilitating investigations into the mechanisms underlying active compound accumulation.

PMID:40141128 | DOI:10.3390/ijms26062483

Nat Microbiol. 2025 Mar 26. doi: 10.1038/s41564-025-01959-z. Online ahead of print.

ABSTRACT

Aging is accompanied by considerable changes in the gut microbiome, yet the molecular mechanisms driving aging and the role of the microbiome remain unclear. Here we combined metagenomics, transcriptomics and metabolomics from aging mice with metabolic modelling to characterize host-microbiome interactions during aging. Reconstructing integrated metabolic models of host and 181 mouse gut microorganisms, we show a complex dependency of host metabolism on known and previously undescribed microbial interactions. We observed a pronounced reduction in metabolic activity within the aging microbiome accompanied by reduced beneficial interactions between bacterial species. These changes coincided with increased systemic inflammation and the downregulation of essential host pathways, particularly in nucleotide metabolism, predicted to rely on the microbiota and critical for preserving intestinal barrier function, cellular replication and homeostasis. Our results elucidate microbiome-host interactions that potentially influence host aging processes. These pathways could serve as future targets for the development of microbiome-based anti-aging therapies.

PMID:40140706 | DOI:10.1038/s41564-025-01959-z

Nature. 2025 Mar 26. doi: 10.1038/s41586-025-08795-5. Online ahead of print.

ABSTRACT

Regulatory T (Treg) cells, which specifically express the master transcription factor FOXP3, have a pivotal role in maintaining immunological tolerance and homeostasis and have the potential to revolutionize cell therapies for autoimmune diseases1-3. Although stimulation of naive CD4+ T cells in the presence of TGFβ and IL-2 can induce FOXP3+ Treg cells in vitro (iTreg cells), the resulting cells are often unstable and have thus far hampered translational efforts4-6. A systematic approach towards understanding the regulatory networks that dictate Treg differentiation could lead to more effective iTreg cell-based therapies. Here we performed a genome-wide CRISPR loss-of-function screen to catalogue gene regulatory determinants of FOXP3 induction in primary human T cells and characterized their effects at single-cell resolution using Perturb-icCITE-seq. We identify the RBPJ-NCOR repressor complex as a novel, context-specific negative regulator of FOXP3 expression. RBPJ-targeted knockout enhanced iTreg differentiation and function, independent of canonical Notch signalling. Repeated cytokine and T cell receptor signalling stimulation in vitro revealed that RBPJ-deficient iTreg cells exhibit increased phenotypic stability compared with control cells through DNA demethylation of the FOXP3 enhancer CNS2, reinforcing FOXP3 expression. Conversely, overexpression of RBPJ potently suppressed FOXP3 induction through direct modulation of FOXP3 histone acetylation by HDAC3. Finally, RBPJ-ablated human iTreg cells more effectively suppressed xenogeneic graft-versus-host disease than control iTreg cells in a humanized mouse model. Together, our findings reveal novel regulators of FOXP3 and point towards new avenues to improve the efficacy of adoptive cell therapy for autoimmune disease.

PMID:40140585 | DOI:10.1038/s41586-025-08795-5

Nature. 2025 Mar 26. doi: 10.1038/s41586-025-08676-x. Online ahead of print.

ABSTRACT

Meningomyelocele (also known as spina bifida) is considered to be a genetically complex disease resulting from a failure of the neural tube to close. Individuals with meningomyelocele display neuromotor disability and frequent hydrocephalus, requiring ventricular shunting. A few genes have been proposed to contribute to disease susceptibility, but beyond that it remains unexplained1. We postulated that de novo mutations under purifying selection contribute to the risk of developing meningomyelocele2. Here we recruited a cohort of 851 meningomyelocele trios who required shunting at birth and 732 control trios, and found that de novo likely gene disruption or damaging missense mutations occurred in approximately 22.3% of subjects, with 28% of such variants estimated to contribute to disease risk. The 187 genes with damaging de novo mutations collectively define networks including actin cytoskeleton and microtubule-based processes, Netrin-1 signalling and chromatin-modifying enzymes. Gene validation demonstrated partial or complete loss of function, impaired signalling and defective closure of the neural tube in Xenopus embryos. Our results indicate that de novo mutations make key contributions to meningomyelocele risk, and highlight critical pathways required for neural tube closure in human embryogenesis.

PMID:40140573 | DOI:10.1038/s41586-025-08676-x

Cell Death Differ. 2025 Mar 27. doi: 10.1038/s41418-025-01479-7. Online ahead of print.

ABSTRACT

Lysine acetyltransferase 2 A (KAT2A) plays a pivotal role in epigenetic gene regulation across various types of cancer. In colorectal cancer (CRC), increased KAT2A expression is associated with a more aggressive phenotype. Our study aims to elucidate the molecular underpinnings of KAT2A dependency in CRC and assess the consequences of KAT2A depletion. We conducted a comprehensive analysis by integrating CRISPR-Cas9 screening data with genomics, transcriptomics, and global acetylation patterns in CRC cell lines to pinpoint molecular markers indicative of KAT2A dependency. Additionally, we characterized the phenotypic effect of a CRISPR-interference-mediated KAT2A knockdown in CRC cell lines and patient-derived 3D spheroid cultures. Moreover, we assessed the effect of KAT2A depletion within a patient-derived xenograft mouse model in vivo. Our findings reveal that KAT2A dependency is closely associated with microsatellite stability, lower mutational burden, and increased molecular differentiation signatures in CRC, independent of the KAT2A expression levels. KAT2A-dependent CRC cells display higher gene expression levels and enriched H3K27ac marks at gene loci linked to enterocytic differentiation. Furthermore, loss of KAT2A leads to decreased cell growth and viability in vitro and in vivo, downregulation of proliferation- and stem cell-associated genes, and induction of differentiation markers. Altogether, our data show that a specific subset of CRCs with a more differentiated phenotype relies on KAT2A. For these CRC cases, KAT2A might represent a promising novel therapeutic target.

PMID:40140561 | DOI:10.1038/s41418-025-01479-7

Nat Plants. 2025 Mar 26. doi: 10.1038/s41477-025-01938-6. Online ahead of print.

ABSTRACT

During secondary growth, the vascular cambium produces conductive xylem and phloem cells, while the phellogen (cork cambium) deposits phellem (cork) as the outermost protective barrier. Although most of the secondary tissues are made up of parenchyma cells, which are also produced by both cambia, their diversity and function are poorly understood. Here we combined single-cell RNA sequencing analysis with lineage tracing to recreate developmental trajectories of the cell types in the Arabidopsis root undergoing secondary growth. By analysing 93 reporter lines, we were able to identify 20 different cell types or cell states, many of which have not been described before. We additionally observed distinct transcriptome signatures of parenchyma cells depending on their maturation state and proximity to the conductive cell types. Our data show that both xylem and phloem parenchyma tissues are required for normal formation of conductive tissue cell types. Furthermore, we show that mature phloem parenchyma gradually obtains periderm identity, and this transformation can be accelerated by jasmonate treatment or wounding. Our study thus reveals the diversity of parenchyma cells and their capacity to undergo considerable identity changes during secondary growth.

PMID:40140531 | DOI:10.1038/s41477-025-01938-6

Nat Plants. 2025 Mar 26. doi: 10.1038/s41477-025-01944-8. Online ahead of print.

ABSTRACT

Differential growth between tissues generates mechanical conflicts influencing organogenesis in plants. Here we use the anther, the male floral reproductive organ, as a model system to understand how cell dynamics and tissue-scale mechanics control 3D morphogenesis of a complex shape. Combining deep live-cell imaging, growth analysis, osmotic treatments, genetics and mechanical modelling, we show that localized expansion of internal cells actively drives anther lobe outgrowth, while the epidermis stretches in response. At later stages, mechanical load is transferred to the sub-epidermal layer (endothecium), contributing to proper organ shape. We propose the concept of 'inflation potential', encapsulating mechanical and anatomical features causing differential growth. Our data emphasize the active mechanical role of inner tissue in controlling both organ shape acquisition and cell dynamics in outer layers.

PMID:40140530 | DOI:10.1038/s41477-025-01944-8

Transl Psychiatry. 2025 Mar 26;15(1):97. doi: 10.1038/s41398-025-03321-7.

ABSTRACT

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by early molecular events that influence disease progression. Still, the molecular mechanisms caused by different mutations of AD are not understood. We have performed a multidisciplinary study to investigate and compare the early stages of the pathology in two transgenic AD mouse models: P301S and 5xFAD. Using SNOTRAP-based mass spectrometry, we assessed changes in S-nitrosylation, a nitric oxide-mediated post-translational modification, of proteins in both models during their juvenile age. The increased levels of 3-nitrotyrosine confirmed nitrosative stress in the mutant mice. Systems biology analysis revealed shared processes between the models, particularly in the γ-aminobutyric acid (GABA)ergic and glutamatergic neurotransmission processes. In the P301S model, we identified 273 S-nitrosylated (SNOed) proteins in the cortex, with 244 proteins uniquely SNOed in the diseased mice. In the 5xFAD model, 309 SNOed proteins were identified. We have found altered proteins expression of different glutamate/GABA-related markers in the cortex and hippocampus of both AD mouse models. Additionally, the phosphorylation levels of the mTOR signaling components revealed hyperactivation of this pathway in P301S mice. Conversely, 5xFAD mice showed no significant changes in mTOR signaling except for elevated phosphorylation of the ribosomal protein S6 in the cortex. Our findings revealed key molecular mechanisms in the two AD mouse models during their early stages. These mechanisms could serve as potential biomarkers and therapeutic targets for early-stage AD.

PMID:40140365 | DOI:10.1038/s41398-025-03321-7

Environ Sci Pollut Res Int. 2025 Mar 26. doi: 10.1007/s11356-025-36286-7. Online ahead of print.

ABSTRACT

Nanotechnology has been utilized in diverse domains, encompassing sustainable agriculture. However, the ecotoxicity and environmental safety of nanoparticles need to be evaluated before their large-scale use. This study synthesizes and characterizes magnesium (Mg) and zinc (Zn) co-doped aluminum (Al) oxide (MgZnAl2O4) NPs and elucidates its potential growth-promoting or genotoxic performance on barley (Hordeum vulgare L.). XRD, EDX, TEM, SEM, and XPS were used to characterize the MgZnAl2O4 NPs. After characterization, the seedlings were grown in a hydroponic solution containing 0, 50, 100, 200, and 400 mg L-1 NPs for 3 weeks. The germination, growth indices, photosynthetic parameters, and nutrient absorption properties were determined. Confocal microscopy, TEM, and SEM were utilized to follow the path and reveal the structural and morphological effects of NPs. The potential genotoxic effect was evaluated using the RAPD-PCR method. Elemental composition analysis of plant parts confirmed that synthesized MgZnAl2O4 NPs, sized at 21.8 nm, were up-taken by the plant roots, leading to increased Mg, Zn, and Al contents of leaves. In addition, compared with the untreated control, the abundance of Ca, K, B, Fe, Mn, and Cu were increased by the NPs treatment. In addition, physiological indices like germination rate (~ 11%), root and leaf growth (15-29%), chlorophyll, and carotenoids (~ 39%) pigments were significantly raised by the NPs inclusion. It can be concluded that low concentrations (< 200 mg L-1) of MgZnAl2O4 NPs enhance growth parameters effectively and are safe for plant growth. On the other hand, a phytotoxic and genotoxic impact was observed at high concentrations (100-400 mg L-1). However, considerable amounts of NPs were found to be adsorbed on roots, disrupting root morphology and cell membrane integrity, thus nutrient trafficking and transport. Therefore, it is recommended that MgZnAl2O4 NPs can be used in barley breeding programs at low concentrations. Adding micro- or macroelements required by plants to the NP composition is a promising way to compensate for plant nutrition. However, the negative effects of MgZnAl2O4 NPs on the environment and other living beings due to their genotoxic effects at high doses must be carefully considered.

PMID:40140202 | DOI:10.1007/s11356-025-36286-7

Cell Mol Gastroenterol Hepatol. 2025 Mar 24:101505. doi: 10.1016/j.jcmgh.2025.101505. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: The incidence of Barrett esophagus (BE) and Gastroesophageal Adenocarcinoma (GEAC) correlates with obesity and a diet rich in fat. Bile acids (BA) support fat digestion and undergo microbial metabolism in the gut. The farnesoid X receptor (FXR) is an important modulator of the BA homeostasis. When activated, FXR can inhibit cancer-related processes and thus, it is an appealing therapeutic target. Here, we assess the effect of diet on the microbiota-BA axis and evaluate the role of FXR in disease progression.

METHODS: L2-IL1B mice (mouse model of BE and GEAC) under different diets, and L2-IL1B-FXR KO-mice were characterized. L2-IL1B-derived organoids were exposed to different BAs and to the FXR agonist obeticholic acid, OCA. The BA profile in serum and stool of healthy controls, BE- and GEAC-patients was assessed.

RESULTS: Here we show that high fat diet accelerated tumorigenesis in L2-IL1B mice while increasing BA levels and altering the composition of the gut microbiota. While upregulated in BE, expression of FXR was downregulated in GEAC in mice and humans. In L2-IL1B mice, FXR knockout enhanced the dysplastic phenotype and increased Lgr5 progenitor cell numbers. Treatment of murine BE organoids and L2-IL1B mice with OCA notably ameliorated the phenotype.

CONCLUSION: GEAC carcinogenesis appears to be partially driven via loss or inhibition of FXR on progenitor cells at the gastroesophageal junction. Considering that the resulting aggravation in the phenotype could be reversed with OCA treatment, we suggest that FXR agonists have great potential as a preventive strategy against GEAC progression.

PMID:40139565 | DOI:10.1016/j.jcmgh.2025.101505

Stem Cells Transl Med. 2025 Mar 18;14(3):szae099. doi: 10.1093/stcltm/szae099.

ABSTRACT

Many electronic cigarettes (ECs) contain high concentrations of menthol. The effect of menthol on human embryos in pregnant women who vape is not well understood. Human embryonic stem cells (hESCs) (an epiblast model) were used to test the hypothesis that 6.4-640 nM and 19.2-192 µM menthol, which activates TRP (transient-receptor-potential) channels, alters calcium homeostasis in embryos and adversely affects processes that are critical to gastrulation. Micromolar concentrations of menthol inhibited mitochondrial reductase activity in hESCs, an effect that was blocked by TRPA1 and TRPM8 inhibitors. Pulsatile exposure to menthol elevated intracellular calcium primarily by activating TRPA1 channels at nanomolar concentrations and TRPM8 channels at µM concentrations. nM menthol significantly inhibited colony growth by activating TRPA1 channels, while both TRPA1 and TRPM8 were activated by µM menthol. Inhibition of colony growth was attributed to cell death induced by menthol activation of TRPA1 and TRPM8 channels. nM menthol altered colony phenotype by increasing the major/minor axis ratio via TRPA1 and TRPM8 channels. Both nM and µM menthol induced alterations in hESC colony motility, an effect that was blocked only by the TRPM8 inhibitor. The menthol-induced increase in intracellular calcium adversely influenced growth, death, and migration, processes that are critical in gastrulation. Menthol concentrations that reach embryos in women who vape are high enough to activate TRPA1 and TRPM8 channels and perturbed calcium homeostasis. Pregnant women who vape likely expose their embryos to menthol concentrations that are harmful. These data could help prevent birth defects or embryo/fetal death.

PMID:40139559 | DOI:10.1093/stcltm/szae099

J Dairy Sci. 2025 Mar 24:S0022-0302(25)00171-7. doi: 10.3168/jds.2024-26011. Online ahead of print.

ABSTRACT

Improving calf health on dairy farms contributes to animal welfare and business productivity gains. In recent years, traditional genetic evaluations have broadened to include cow health traits that have economic importance. Calf health is a new frontier to explore but new traits require sufficient data to be effectively evaluated. Researchers who work in countries without obligatory record keeping systems, commonly promote the need to significantly improve record keeping practices to enable research, benchmarking, and genetic evaluation, as is the case in Australia. The aim of this study was to estimate variance components for novel calf traits using a data set that was co-designed with farmers and included calf identity, calving ease, health records and genotypes. Almost 20,000 calf records from over 50 farms located throughout Australia were collected between 2020 and 2023. In Holstein calves, the mean ± SE prevalence of preweaning mortality (PWM) and scours, were 0.020 ± 0.001 and 0.059 ± 0.002, respectively. A newly defined and subjectively scored trait called Calf Vitality (vitality) was co-developed with farmers, where 21% of calves were classed in the top category of ripper/vigorous, while 54% were good or average, 6% were duds and 19% of scored calves died. Univariate linear models that included a genomic relationship matrix were used to estimate variance components for diseases and vitality, where heritability values were between 1% and 11% in Holsteins depending on the trait. The models included herd-year-season (HYS), sex, parity group and calving ease (Holstein only) as fixed effects and these were found to be significant (P < 0.05 to 0.001) for most breed and trait combinations. The estimated reliability of EBVs ranged between 0.2 and 0.3. In Australia, Holsteins are more numerous than the Jersey breed, and so despite efforts to compile an appropriate data set, the disease prevalence and record numbers were too low to report genetic variance for calf health traits in the Jersey breed. Approximate genetic correlations with other calf health traits such as stillbirth (SB) and PWM were modest but favorable. There were few significant correlations with lactating cow traits (such as survival, somatic cell count and likeability) and national selection indexes that are routinely evaluated in Australia and those that were significant were in a favorable direction.

PMID:40139346 | DOI:10.3168/jds.2024-26011

Food Chem. 2025 Mar 19;480:143966. doi: 10.1016/j.foodchem.2025.143966. Online ahead of print.

ABSTRACT

Consumers' interest in healthy and sustainable food of superior organoleptic quality has contributed to an increased market of mildly processed chilled NFC orange juices, preserved by methods such as high pressure processing (HPP) and pulsed electric fields (PEF). To protect consumers from food fraud, analytical methods to differentiate such juices from thermally pasteurized juices are required. To screen for appropriate candidate markers, we applied a complementary non-targeted volatilomics and sensomics approach resulting in a total of 58 candidate markers, among which 20 were quantitated and nine were statistically confirmed. Extension of the quantitations to stored and doubly-treated juices finally resulted in (S)-carvone and vanillin as promising candidate markers. In combination, the two compounds allowed to distinguish the HPP-treated juice from thermally treated juices and even was able to identify an HPP-treated juice that had received an additional thermal pasteurization.

PMID:40138831 | DOI:10.1016/j.foodchem.2025.143966

Sci Adv. 2025 Mar 28;11(13):eads6021. doi: 10.1126/sciadv.ads6021. Epub 2025 Mar 26.

ABSTRACT

Emerging evidence has shown that epigenetic regulation plays a fundamental role in cancer metastasis, the major cause of cancer-related deaths. Here, we conducted an in vivo screen for vulnerabilities of brain metastasis and identified N-acetyltransferase 10 (NAT10) as a driver of brain metastasis. Knockdown of NAT10 restrains cancer cell proliferation and migration in vitro and tumor growth and brain metastasis in vivo. The poorly characterized RNA helicase domain of NAT10 is critical for cell growth in vitro, while both RNA helicase and NAT domains are essential for primary tumor growth and brain metastasis in vivo. Mechanically, NAT10 promotes the expression of 3-phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase 1 (PSAT1), two enzymes for serine biosynthesis implicated in brain metastasis. Silencing PHGDH or PSAT1 in metastatic breast cancer cells inhibits their growth in the serine/glycine-limited condition, phenocopying the effects of NAT10 depletion. These findings establish NAT10 as a key regulator of brain metastasis and nominate NAT10 as a target for treating metastasis.

PMID:40138393 | DOI:10.1126/sciadv.ads6021

STAR Protoc. 2025 Mar 24;6(2):103714. doi: 10.1016/j.xpro.2025.103714. Online ahead of print.

ABSTRACT

A reproducible study system is essential for understanding the role of microbes in human skin health and disease. We present a protocol for constructing a synthetic microbial community (SkinCom) of nine strains dominant to native human skin microbiome. We describe steps for computing growth metrics, constructing communities, and extracting DNA and library preparation for shotgun sequencing. We detail steps for data preprocessing and analysis of community samples. We illustrate SkinCom's application with an epicutaneous murine model and downstream multiomic analysis. For complete details on the use and execution of this protocol, please refer to Lekbua et al.1.

PMID:40138316 | DOI:10.1016/j.xpro.2025.103714

PLoS One. 2025 Mar 26;20(3):e0320377. doi: 10.1371/journal.pone.0320377. eCollection 2025.

ABSTRACT

Decisions where an individual lays their eggs are important, as the choice may affect their offspring's survival and lifetime reproductive success. Information produced by conspecifics can potentially be useful in making decisions as this "social information" may provide an energetically cheaper means of assessing oviposition site suitability rather than acquiring it personally. However, as not all public information may be equally beneficial, cues produced by kin may be especially valuable as they might signal suitable microenvironments, and are associated with other fitness advantages resulting from improved foraging success and/or a decreased risk of competition/cannibalism compared to sites where unrelated conspecifics are located. Using the fruit fly, Drosophila melanogaster, we explored whether public information use is associated with kin-based egg-laying decisions. Kinship is potentially recognized in several ways, including environmentally-associated proxy cues, so we explored whether there were biases in how focal females interacted with cues from conspecifics that differed in both genetic relatedness, and environmental "familiarity." In a series of inter-connected assays, we examined the behaviour of focal females that interacted with a choice of potential egg-laying substrates that differed in the manner of their prior conspecific exposure, and counted the offspring that eclosed from these different substrates. Sites that had exhibited cues produced by conspecific demonstrators were visited more, and yielded more focal offspring compared to unexposed substrates. Furthermore, patterns of bias in offspring production were consistent with ovipositing females exhibiting sensitivity to the kinship status of the prior substrate's occupants. The basis of the kinship categorization by ovipositing females appears to be based on phenotypes that reflect true genetic relatedness, but the nature of the social information can be affected by other factors. These results further highlight the potential usefulness of D. melanogaster as a model to understand the evolution of social behaviour in the expression of decision-making.

PMID:40138267 | DOI:10.1371/journal.pone.0320377