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Genome mining of alkaliphilic cyanobacterial consortia: identification of biosynthetic gene clusters in Sodalinema and associated heterotrophs.

Alkaline soda lakes are high-pH environments that host specialized microbial communities with potential for biotechnology and natural product discovery. We characterized three Sodalinema-dominated cyanobacterial consortia enriched from Canadian soda lakes over 510 days. Using hybrid metagenomic sequencing and metatranscriptomics across pH, alkalinity, and temperature gradients, we reconstructed high-quality metagenome-assembled genomes and assessed functional activity. All consortia converged toward cyanobacteria dominance and exhibited temperature optima between 21°C and 30°C. Phylogenetic analysis placed Sodalinema genomes within a distinct clade affiliated with Candidatus Sodalinema alkaliphilum. Genomic analysis indicated complete biosynthetic pathways for vitamin B5, vitamin B7, and the molybdenum cofactor, but incomplete pathways for vitamins B1, B9, and B12, consistent with patterns observed in Sodalinema yuhuli. Metatranscriptomic profiles showed increased expression of genes involved in phycocyanin and carotenoid biosynthesis at pH 10.2 relative to pH 8.5. Biosynthetic gene cluster analysis revealed that most secondary metabolic potential resided in heterotrophic community members. Roseinatronobacter encoded pathways for N-acyl homoserine lactones, osmoprotectants, betalactones, and prodigiosin, while Alkalimonas, Wenzhouxiangella, and members of the Kiloniellales encoded clusters for lanthipeptides, cyclodipeptides, hydrogen cyanide, and pyrroloquinoline quinone. These findings indicate functional partitioning within the consortia and highlight the contribution of heterotrophs to secondary metabolism.IMPORTANCEAlkaline soda lakes contain microbial communities adapted to high pH that remain underexplored for biotechnology. This study focuses on Sodalinema, a filamentous cyanobacterium that dominates enriched consortia from Canadian soda lakes, and its associated heterotrophic partners. We show that while Sodalinema drives primary productivity, heterotrophic bacteria encode most of the pathways for antimicrobial and signaling compounds. These interactions may support community stability and defense against competing microorganisms. By linking genomic potential with gene expression, this work identifies alkaline cyanobacterial consortia as a source of bioactive compounds and provides a framework for exploring extremophilic microbial communities for natural product discovery.

Sodalinema

Uncovering ShuangZi Powder's Anti-Ovarian Cancer Mechanism: A Systems Biology and Experimental Approach.

INTRODUCTION: This study investigated the anti-ovarian cancer (OC) effects of Shuangzi Powder (SZP) and its regulatory impact on the tumor microenvironment. METHOD: This study employed systems biology approaches, integrating molecular docking and experimental validation, to explore the pharmacological mechanisms of SZP in OC treatment. To identify potential bioactive compounds and target genes of SZP, network pharmacology, protein- protein interaction network analysis,.Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted. RESULTS: Among the 11 bioactive ingredients identified in SZP, 1,767 potential therapeutic targets were predicted, while 2,637 differentially expressed genes were found to be associated with OC. KEGG pathway analysis revealed significant enrichment in pathways related to cancer, apoptosis, the PI3K-Akt signaling pathway, and the PD-L1/PD-1 checkpoint pathway. Treatment of A2780 cells with β,β-Dimethylacrylshikonin (DMAS) inhibited cell viability, migration, and invasion. Moreover, DMAS downregulated the expression of cell cycle- and apoptosis-related genes (CCNB1, CHEK1, CCNE1, and PARP1) and upregulated the immune checkpoint gene PD-L1. DISCUSSION: These findings indicate that multiple components, targets, and pathways are involved in OC treatment by SZP. CONCLUSION: DMAS, one of the bioactive ingredients of SZP, was predicted and preliminarily validated to exert inhibitory effects on OC cells, mainly through the regulation of the cell cycle, apoptosis, and immune response, as demonstrated by molecular docking and experimental analyses.

Ovarian Neoplasms

Integrated Network Pharmacology and Molecular Docking Analysis of Sishen Decoction Identifies Potential Targets and Pathways in Gout.

Gout is a disease characterized by hyperuricemia and the deposition of urate crystals in joints and soft tissues, leading to recurrent acute arthritis. Its increasing prevalence imposes substantial clinical and socioeconomic burdens. Sishen Decoction (SSD) has been used in the treatment of gout, but its potential molecular mechanisms remain unclear. This study applied an integrated network pharmacology and molecular docking approach to identify potential targets and signaling pathways associated with SSD in gout. Active compounds and corresponding targets of SSD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), while gout-related targets were collected from the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. Overlapping targets were identified and used to construct a drug-component-target-disease network. A protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed, followed by molecular docking using the docking server analysis module. A total of 37 bioactive compounds were associated with 116 overlapping gout-related targets. The top hub targets included TP53, IL6, IL1B, TNF, AKT1, EGFR, CASP3, JUN, BCL2, and MMP9. GO analysis suggested that these targets are involved in gene expression regulation and signal transduction. KEGG enrichment analysis indicated significant associations with the mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), interleukin-17 (IL-17), and tumor necrosis factor (TNF) signaling pathways. Molecular docking predicted favorable interactions between key compounds and hub targets, with all binding energies of ≤-5 kcal/mol. These computational findings provide potential mechanistic hypotheses for the action of SSD in gout and may support future experimental validation.

Molecular Docking Simulation

Genomic and biosynthetic landscape of high-temperature Daqu microbiome.

As the core starter for Chinese Baijiu, high-temperature Daqu is produced through open solid-state fermentation with recurrent inoculation by mature Daqu, forming a rich yet largely untapped reservoir of genomes and bioactive compounds. This study constructs the High-temperature Daqu Fermentation Microbiome catalog using 463 metagenomes spanning the full fermentation cycle. The catalog comprises 4,264 metagenome-assembled genomes that are dereplicated into 252 representative genome-based species, 82 % of which are absent from current global food microbiome databases. It further contains 14.3 million non-redundant genes, of which 17.3 % are novel, and 17,031 biosynthetic gene clusters, of which 62.63 % are novel, thereby substantially expanding the known genomic and biosynthetic space of food microbiomes. Genome-resolved analyses revealed a U-shaped ecological trajectory, shifting from early Bacillus velezensis-enriched assemblages to transient dominance of lactic acid bacteria during peak thermogenesis, before returning in late fermentation to thermotolerant, spore-forming Bacillota and Actinomycetota. In parallel, biosynthetic potential was further organized into four recurrent, stage-enriched profiles, from RiPP-rich thermogenic states to mature-state assemblages enriched in PKS-, NRPS-, and terpene-related capacities, with Bacillus, Kroppenstedtia, and Saccharopolyspora constituting the principal biosynthetic reservoir. Together, this work uncovers a largely unexplored genomic and biosynthetic reservoir in high-temperature Daqu fermentation, providing a target resource for mining thermotolerant industrial enzymes, flavor-related genes, and bioactive metabolites with biotechnological potential.

Microbiota

New microbial secondary metabolites under preclinical development for cancer treatment.

Limitless numbers of various genetic structures have been formed in chromosomes and plasmids and numerous bioactive compounds are produced by microorganisms. Therefore, it may be said that compounds useful in treatment of cancer will be found more and more in microbial secondary metabolites and more effective antitumor antibiotics and their derivatives, or more effective products producing immune resistance to cancer, will be discovered. In these studies, as discussed in this paper, the most urgent problem is to establish a rational screening principle or system to select compounds worth clinical examination. This is particularly important in the analog area. Bleomycin is an analog of phleomycin chosen because of lower renal toxicity. It has become an antitumor agent of significant value. Macromycin is a new structure which has been found to bind with animal cells and inhibit growth. Neothramycin is a new benzodiazepine antibiotic which has lower toxicity than other structures studied in this class and is active against L1210, Yoshida sarcoma, and Sarcoma 180. Aclacinomycin A is an analog of adriamycin chosen for clinical study based on its low cardiac toxicity and high distribution in mouse lung and spleen. Coriolins are another new structural class. Diketocoriolin B has activity in L1210 leukemia and has been shown to inhibit Na-K-ATPase. Bestatin is a compound which inhibits aminopeptidase B and leucine aminopeptidase has been shown to increase delayed hypersensitivity. Bestatin also increases the effects of other antitumor agents such as adriamycin, and bleomycin.

Animals

Heterologous expression of DobHLH25 from Dendrobium officinale enhances drought tolerance in Arabidopsis.

Drought stress severely constrains the growth, yield, and accumulation of bioactive compounds in Dendrobium officinale (D. officinale), a valuable medicinal orchid, and this challenge is exacerbated under simulated wild cultivation where plants are inevitably exposed to recurring water deficits. Basic helix-loop-helix (bHLH) transcription factors are well-established regulators of plant abiotic stress responses. However, the molecular mechanisms by which bHLH transcription factors respond to drought stress in this species remain largely unknown. In this study, a bHLH transcription factor gene, DobHLH25, was cloned from D. officinale. Phylogenetic analysis revealed that DobHLH25 shares the highest sequence identity with its ortholog in Dendrobium nobile. Additionally, subcellular localization analysis indicated that DobHLH25 is targeted to the nucleus and possesses a functional transcriptional activation domain. Expression pattern analysis showed that DobHLH25 is most abundantly expressed in old leaves, and its expression in roots, stems, and leaves is induced by polyethylene glycol treatments. Heterologous expression of DobHLH25 in Arabidopsis thaliana resulted in higher seed germination rates and longer root lengths under mannitol-induced osmotic stress compared to wild-type plants. Under drought stress, DobHLH25 heterologous expression lines exhibited higher survival rates, reduced leaf water loss, lower malondialdehyde accumulation, and increased proline content. Moreover, the activities of antioxidant enzymes such as superoxide dismutase and peroxidase were significantly enhanced, and the expression levels of multiple drought-responsive genes were markedly upregulated. Collectively, these findings suggest a correlation between DobHLH25 expression and plant drought tolerance, as evidenced by reduced oxidative damage, increased osmolyte accumulation, enhanced antioxidant enzyme activities, and upregulation of drought-responsive genes. Together, these results suggest that DobHLH25 plays a positive role in drought tolerance, and provides a basis for future dissection of its regulatory network in D. officinale.

Drought Resistance

Coating materials enhance urochordate primary cell culture adherence.

Marine invertebrate cell cultures are a potential source for diverse biotechnological applications, given the wide range of bioactive compounds they synthesize and accumulate. Yet, the number of established marine invertebrate cell culture systems remains limited compared with those of insects and vertebrates, particularly with respect to adherent cell cultures. Here we studied the in vitro adherence of circulating blood cells from the colonial ascidian Botryllus schlosseri. Two experimental approaches were employed, seeding blood cells either alone (setup 1) or in combination with tissue fragments (setup 2), using three basal media (DMEM, DMEM/F-12, RPMI) on culture plates coated with either Poly-L/D-lysine, gelatin, collagen, or laminin. Each experiment lasted for up to 3 d. Setup 1 results reveal that Botryllus cells remain viable and can adhere to coated surfaces in all tested media. Collagen- and laminin-coated plates supported longer-term cultures, whereas Poly-D (or L)-lysine coatings were more suitable for short-term studies. Among the basal media, RPMI and DMEM/F12 most effectively supported cell attachment. Setup 2 plates consistently showed higher cell adherence compared to setup 1, suggesting that tissue-derived factors may enhance attachment. Overall, circulating Botryllus cells demonstrate the capacity for substrate adhesion in vitro, offering a foundation for the development of adherent cell cultures.

Animals

Microalgae-Mediated Synthesis of Gold Nanoparticles from Indonesian Chlorella vulgaris InaCC M205 with Potential Anticancer Properties for Biomedical Application.

Sustainable nanomaterial synthesis has emerged as a critical strategy to reduce the environmental burden associated with conventional chemical synthesis method. Microalgae-derived biomolecules offer a promising platform for the green production of metal nanoparticles due to their rich bioactive compounds capable of acting as natural reducing and stabilizing agents. Here, we report the eco-friendly synthesis of gold nanoparticles (AuNPs) using extract of Indonesian microalga Chlorella vulgaris extract. To optimize the synthesis process, the effects of precursor-to-extract ratio, temperature, and incubation time were evaluated. Optimal synthesis of C5-AuNPs was obtained at 37 °C for 20 h with precursor to extract ratio of 6:4, resulting in moderately stable C5-AuNPs characterized by a surface plasmon resonance (SPR) peak at 541 nm. Furthermore, Fourier-transmission infra-red (FT-IR) analysis revealed the involvement of functional groups of C. vulgaris extract in the interaction with Au+ during the production of C5-AuNPs. Transmission electron microscopy (TEM) demonstrated the formation of uniformly spherical nanoparticles with an average diameter of approximately 8.8 nm. Biological evaluation showed that the synthesized C5-AuNPs exerted pronounced dose-dependent cytotoxicity against MCF-7 breast cancer cells with an IC50 threshold of 21.17 ppm, while no toxicity appears in normal HEK293 cells. Mechanistically, the C5-AuNPs induced early apoptosis and inhibit cell-cycle progression at the stage of G0/G1. Collectively, these findings demonstrate that C. vulgaris-mediated AuNPs represent a promising preliminary in vitro findings for cancer therapy candidate.

Gold

Draft genome sequence data of Streptomyces antibioticus SCBA4 isolated from the Soils of Surigao del Sur, Philippines.

The draft genome of Streptomyces antibioticus SCBA4 isolated from the soils of Surigao del Sur, Philippines is reported here. S. antibioticus is a member of the phylum Actinomycetota, a diverse group of Gram positive, high G+C content bacteria well known for their production of a variety of bioactive compounds. Sequencing using the Illumina NovaSeq 6000 platform yielded a 8,616,999 bp genome across 36 contigs with 7621 coding sequences, 87 tRNA, and 1 tmRNA. Consistent with the members of the same phylum, the GC content was 71.83% and was found to contain putative gene clusters of secondary metabolites such as NRPs, terpenes and polyketides. The genome sequence has been deposited at NCBI under the accession number JBSWZT020000000.

Actinobacteria

Genome sequence data of the chitinase-producing bacterium Paenibacillus mucilaginosus YWY-5.1.

Paenibacillus mucilaginosus is a beneficial bacterium widely applied as a biofertilizer in agriculture. To date, genomic information on this species remains limited; however, no genome assemblies from Vietnam have been reported. This work presented the draft genome of P. mucilaginosus YWY-5.1, a promising strain with strong chitin-degrading capability and agricultural potential, isolated from Yok Don National Park, Vietnam, using Illumina technology. Results showed that the assembled genome comprised 48 contigs with 4,076,146 bp and 73.8% GC-content. Genome annotation identified 3,611 protein-coding genes, 2 rRNA genes, and 53 tRNA genes. A total of 150 carbohydrate-active enzyme-related genes were predicted from the genome; among them, seven putative chitinolytic genes were identified, including 4 genes related to family 18 chitinase, 2 genes to family 20 β-N-acetylglucosaminidase, and one gene to auxiliary activity family 10. In addition, at least 32 genes related to plant growth-promoting functions were identified, including those associated with indole-3-acetic acid production, phosphate and potassium solubilization, siderophore biosynthesis, iron uptake, ACC metabolism, and nitrate transport and reduction. Furthermore, genome mining identified 4 biosynthetic gene clusters probably involved in secondary metabolite production, of which 3 displayed no similarity to previously reported clusters, indicating potential for novel bioactive compounds. These genomic data improved our understanding of the biodegradation capacity and agricultural potential of P. mucilaginosus YWY-5.1 isolated from Vietnam, and provided a valuable genomic resource for future functional and biotechnological investigations toward crop production and related fields.

Chitinases

Precision UV-B irradiation for flavonoid biofortification in indoor-cultivated Morus nigra: Integrated multi-omics and molecular docking insights.

Precision application of UV irradiation represents an effective strategy for improving the quality of functional food crops under controlled environmental conditions. Morus nigra serves as a significant functional food resource in Xinjiang, with its leaves being rich in diverse bioactive compounds with nutritional and health-promoting properties. In this study, a low-dose UV-B treatment regimen was developed to enhance flavonoids in indoor-cultivated M. nigra without growth penalty. Multi-omics revealed a hormone shift (suppressed auxin vs. activated JA signaling). This triggered transcriptional reprogramming of PAL/4CL and CHS/CYP75B1, redirecting carbon flux towards flavonoid biosynthesis. Transient overexpression of MYB, NAC, and TIFY variants validated this regulatory network. The UV-B-induced NAC upregulated key genes and flavonoids, while different TIFY members showed diverse regulatory effects. Molecular docking predicted that the induced flavonoids had hypoglycemic, antioxidant, and anti-browning potential. This study indicates targeted UV-B as a green biofortification strategy for high-value crops in controlled environments.

Flavonoid biosynthesis

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics

Painting new pathways: Castilleja enters the genomic era.

Castilleja (Orobanchaceae), commonly known as Indian paintbrush, is a genus of approximately 200 hemiparasitic species found primarily across the Americas. Long studied for its taxonomic complexity, vibrant floral displays, and ecological interactions with host plants, Castilleja has recently emerged as a versatile research system spanning parasitic biology, specialized metabolism, conservation genetics, and pharmacology. The availability of whole-genome sequencing is transforming the field, revealing expanded gene families involved in host recognition, enabling genomic species delimitation of cryptic taxa, and providing frameworks for mapping biosynthetic pathways of bioactive compounds, including iridoid glycosides and phenylethanoid glycosides. This review synthesizes advances across these disciplines and highlights how genomics serves as an integrative force connecting taxonomy, ecology, phytochemistry, and parasitic biology in this genus.

Castilleja

Comparative metabolomic and transcriptomic profiling of flavonoid diversity and antioxidant capacity in three Isatis species.

Flavonoids are key bioactive compounds in plants with significant health benefits. This study employs an integrated multi-omics approach to investigate flavonoid diversity and antioxidant capacity across three Isatis species: I. oblongata, I. tinctoria, and I. indigotica. Metabolomic profiling identified 200 flavonoids, with glycosides being the most abundant class. I. tinctoria exhibited the highest total flavonoid content and antioxidant activity, strongly correlated with the accumulation of 53 core differential flavonoid metabolites, most of which were glycosylated derivatives. Transcriptomic analysis revealed coordinated upregulation of phenylpropanoid pathway genes and specific UDP-glycosyltransferases (UGTs) in I. tinctoria, providing a genetic basis for its enhanced glycoside production. The study establishes a clear genotype-metabolite-phenotype linkage, highlighting glycosylation as a key mechanism underlying flavonoid-driven antioxidant superiority in Isatis. Although the current evidence is primarily correlative, the consistent and strong associations across independent transcriptomic, metabolomic, and antioxidant datasets provide a robust foundation for this conclusion. These findings offer new insights into the metabolic evolution and regulatory networks of flavonoids, with implications for breeding and metabolic engineering of high-value medicinal plants.

Flavonoids

Chromosome-level genome assembly of Elaeocarpus petiolatus (Elaeocarpaceae).

Elaeocarpus petiolatus is an ecologically and economically important species in tropical and subtropical forests. Despite its significance, the lack of genomic resources has hindered research on the genetic diversity and adaptive traits of E. petiolatus. To address this gap, we present a comprehensive chromosome-level genome assembly of E. petiolatus generated using advanced PacBio high-fidelity (HiFi) long-read sequencing and Hi-C technology. The assembly spans 322.45 Mb, with a scaffold N50 of 20.58 Mb, indicating that 37.11% of the genome is composed of repetitive elements. We identified 25,295 protein-coding genes, of which 96.74% were functionally annotated. This high-quality genome provides a critical resource for understanding the genetic mechanisms underlying environmental adaptability and biosynthesis of bioactive compounds in E. petiolatus, thereby supporting conservation efforts and sustainable forest management. The assembled genome and associated sequencing data are publicly available, facilitating further evolutionary and functional studies on the Elaeocarpaceae family.

Chromosomes, Plant

Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.

Dipeptidyl peptidase-4 (DPP4), a serine protease with both enzymatic and non-enzymatic roles, has emerged as a context-dependent modulator of tumor progression. In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.

Male

Carrot Juice Intake Modulates Oncogenic and Inflammatory Pathways in Advanced Colorectal Adenomas: A Pilot Feasibility Study.

Carrots are a rich dietary source of carotenoids and polyacetylenes, bioactive compounds with demonstrated anti-inflammatory and anticancer properties in experimental models. Epidemiological evidence suggests that carrot consumption is associated with a reduced risk of colorectal cancer; however, clinical data linking carrot intake to molecular changes in premalignant colorectal tissue remain limited. In this pilot intervention study, 20 patients with advanced colorectal adenomas were enrolled. Fifteen participants consumed carrot juice daily for 21 days, while five served as untreated controls. Paired adenoma biopsies were collected before and after the intervention and were analyzed using gene expression microarrays to assess transcriptional responses. Carrot juice intake was well tolerated, with adherence exceeding 95% and no reported adverse events. Transcriptomic analysis revealed modulation of key pathways implicated in colorectal carcinogenesis, including downregulation of the WNT, PI3K-AKT, and MAPK signaling pathways, as well as cyclooxygenase-2-related inflammatory pathways and cytokine signaling. These changes were consistent with reduced oncogenic signaling and attenuation of inflammatory activity within adenoma tissue. In summary, short-term carrot juice consumption was associated with coordinated suppression of molecular pathways involved in colorectal adenoma progression. These findings provide preliminary clinical evidence that a whole-food dietary intervention may influence early carcinogenic processes and support the need for larger controlled studies evaluating clinical outcomes.

Journal Article

Integrative chemical genetics platform identifies condensate modulators linked to neurological disorders.

Dysregulation of biomolecular condensates is implicated across multiple neurological disorders. However, approaches to systematically identify their modulators remain limited. Here, we expand the utility of MLF2 as a versatile condensate biomarker and develop CondenScreen, an integrated high-content screening and bioinformatics pipeline enabling identification of condensate modulators across chemical and genetic space. Screening 1760 bioactive compounds in a cellular DYT1 dystonia model, we validate the platform for condensate-targeted drug discovery, identifying drugs that prevent the accumulation of the MLF2 reporter into nuclear envelope condensates. In parallel, a genome-wide CRISPR/Cas9 screen correlates nuclear condensate abundance with genes implicated in microcephaly and over eight additional neurodevelopmental disorders. Machine learning and confocal imaging resolve distinct condensate phenotypes, with RNF26 deletion provoking nuclear envelope condensates that phenocopy hallmarks of torsin deficiency. Our study provides a scalable platform for identifying modulators of condensates and establishes a correlative connection between nuclear condensate accumulation and genes implicated in neurodevelopmental disorders.

Humans