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PubMed2026

Comparative Transcriptomics Reveals Shared Downstream Pathways in Craniofacial Pathology.

Treacher Collins syndrome and Nager syndrome are craniofacial developmental disorders caused by defects in ribosome biogenesis and RNA splicing, respectively, yet they exhibit overlapping abnormalities affecting neural crest cell-derived craniofacial structures. To investigate shared downstream pathogenic mechanisms, we performed a comparative transcriptomic analysis of zebrafish polr1c and sf3b4 mutant models from our previous studies. Comparative analysis identified 17 shared differentially expressed genes (DEGs) between polr1c and sf3b4 mutants, with the majority of shared genes dysregulated in the same direction, indicating a coordinated rather than random transcriptional response. Gene ontology analysis identified ATP-dependent protein folding chaperone activity as the only shared molecular function, driven in part by upregulation of hsp90aa1.2, indicating a common proteostasis response. Because chaperone activity is linked to extracellular matrix (ECM) protein processing, we cross-referenced DEGs from both mutants against the curated zebrafish matrisome. Three of the 17 shared DEGs (serpinh1b, il11a, and lepa) were matrisome-associated and upregulated in both mutants. Serpinh1b, a collagen-specific chaperone, was strongly expressed in craniofacial cartilage and mesenchymal populations during pharyngeal arch development and exhibited nearly identical fold changes in both mutants. Il11a is of particular interest because its receptor, IL11RA, is known to be associated with human craniosynostosis, suggesting potential relevance to craniofacial development. Together, it is possible to hypothesize that shared chaperone-associated transcriptional changes, together with altered ECM-related gene expression, may contribute to polr1c- and sf3b4-associated craniofacial disorders, warranting further functional validation.

Extracellular Matrix↗

PubMed2026

In Vivo Genome Editing Approach to Disrupt Hydroxyacid Oxidase 1 for the Treatment of Primary Hyperoxaluria Type 1.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that leads to kidney and liver failure. PH1 is caused by a mutation in the alanine glyoxylate aminotransferase (AGXT) gene, which encodes a key metabolic enzyme that converts glyoxylate to glycine in the liver. Inability to metabolize glyoxylate leads to oxalate overproduction, yielding insoluble calcium oxalate crystals; accumulation of these crystals leads to progressive organ failure. Here, we used a novel, minimally disruptive genome-editing approach to disrupt the mechanism of action of hydroxyacid oxidase 1 (HAO1), an upstream enzyme in the glyoxylate metabolic pathway. Successful gene editing and disruption of the HAO1 gene is expected to increase levels of glycolate, a harmless intermediate of the glycine metabolic pathway, thereby preventing the formation of calcium oxalate crystals. We intravenously administered an adeno-associated virus (AAV) vector expressing the M1HAO1 meganuclease to both wild-type and Agxt-/- mice, a mouse model of PH1. We observed >30% editing of HAO1 in Agxt-/- mice, correlating with a dose-dependent increase in serum glycolate levels. At the highest dose tested, urine glycolate levels increased by 79%, with a concomitant 75% decrease in urine oxalate levels. We also evaluated in vivo targeting in rhesus macaques injected with AAV expressing two different versions of the HAO1 meganuclease. Dose-dependent editing of hepatic DNA and RNA was achieved, and serum glycolate levels changed in a manner consistent with successful liver editing; additionally, the treatment was well tolerated. Our results indicate that AAV-delivered meganucleases can effectively target HAO1 in mice and nonhuman primates to achieve high levels of HAO1 gene editing. Moreover, increased glycolate levels in serum indicate that this intervention significantly impacts the HAO1-mediated glycolate-to-glyoxylate pathway. These data suggest that this approach may represent an effective treatment for PH1.

Hyperoxaluria, Primary↗

PubMed2026

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↗

PubMed2026

Bacteroides cellulosilyticus-derived 2-hydroxyphenylacetic acid rectifies hepatic lipid homeostasis in MASLD by targeting the PPARγ-CD36 axis.

The gut microbiota plays an important role in the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD), but the specific molecular mechanisms involved have not been fully elucidated. In this study, human cohort studies were performed to identify that the relative abundance of Bacteroides cellulosilyticus (B. cellulosilyticus) was significantly decreased in patients with MASLD. Through the integration of metagenomic and metabolomic analyses, it was confirmed that B. cellulosilyticus and its metabolite 2-hydroxyphenylacetic acid (2HPAA) are key factors regulating the occurrence and development of MASLD. Single-cell sequencing and lipidomic analyses revealed that 2HPAA can enter the liver through the enterohepatic circulation to exert regulatory effects. Specifically, 2HPAA inhibits the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway, thereby suppressing the expression of the fatty acid transporter CD36. Meanwhile, 2HPAA regulates lipid metabolism in hepatocytes by significantly enhancing palmitate conversion efficiency and inhibiting CD36 palmitoylation. This dual regulatory effect on CD36 expression and palmitoylation can reduce lipid accumulation in hepatocytes and ultimately alleviate MASLD progression. These findings reveal the mechanism by which B. cellulosilyticus and 2HPAA alleviate MASLD by targeting the PPARγ-CD36 pathway. This work provides a new perspective for the study of gut microbiota-host interactions in regulating liver diseases.

PPAR gamma↗

PubMed2026

Exploring the mechanism of aroma production in fermented cherry juice by L. brevis LD1.0600 using flavomics and whole genome analysis.

This study focused on L.brevis LD1.0600 with excellent fermentation traits: it analyzed genome-wide key regulatory genes for micro-metabolites, combined with fermented cherry juice flavor metabolomics data, and used machine learning to explore correlations between gene regulation, metabolite production, and flavor formation. The SVM model screened and verified fermented cherry juice VOCs; through OAV and flavor wheel analysis, LD1.0600 emerged as the top-performing strain, with a sweet, fruity dominant aroma. Key aroma-active components (OAV > 100) included 2-methoxy-4-vinylphenol, benzaldehyde, 2-methyl-butanoic acid and hexanoic acid, and 2-methoxy-4-vinylphenol and hexanoic acid elevated by LD1.0600-regulated genes (Chrom1-001884, Chrom1-000925, fabF and Chrom1-000199). At the same time, through research, a "strain screening-SVM screening of DVCs-OAV screening of key aroma components-whole genome sequencing of flavor regulatory genes" system was established. This system can not only be applied to the screen fermentation strains, but also can be extended to the application of other fermentation products.

Fermentation↗

PubMed2026

Introgression shapes the genomic conflict landscape of Malus, providing evidence for a reticulate backbone in a woody crop lineage.

Phylogenomic discordance is widespread across plants, but its evolutionary significance is often obscured when conflict is treated primarily as analytical noise rather than as evidence of underlying processes. In woody lineages in particular, incomplete lineage sorting, introgression, and genome duplication can interact over long timescales to produce complex genomic histories that are not adequately summarized by a strictly bifurcating tree. Here, we use Malus as a model woody genus to investigate how these processes structure conflict across a genus-scale, accession-based phylogenomic framework. Using broad taxon sampling, hundreds of nuclear loci, plastid genomes, and genome-wide SNP summaries, we reconstruct a robust nuclear backbone for sampled Malus lineages and evaluate where discordance is concentrated and which processes best explain it. Nuclear analyses resolve eight major clades, whereas conflict is non-random and localized to recurrent hotspots rather than evenly distributed across the tree. Cytonuclear discordance is similarly concentrated, especially around Clade H, represented by sampled accessions of M. tschonoskii, where localized plastid-nuclear disagreement is consistent with candidate plastid capture or organellar introgression. Multiple complementary analyses further indicate that the strongest conflict is not explained by ILS alone, but instead reflects lineage-structured introgression, while polyploid complexes represent additional localized sources of evolutionary complexity. Together, these results provide evidence for a reticulate genomic backbone in Malus and show how integrating nuclear, plastid, and genome-wide conflict analyses can help distinguish background discordance from process-specific signals in woody plant radiations. Several lineage-level reticulation hypotheses identified here should now be tested with broader population-level sampling and curated reference accessions.

Malus↗

PubMed2026

Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.

BACKGROUND: Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation. METHODS: We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking. RESULTS: In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing. CONCLUSIONS: Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.

Animals↗

PubMed2026

Immunohistochemical evaluation of Ki-67 and GLI1 in sporadic and nevoid basal cell carcinoma syndrome-associated odontogenic keratocysts.

INTRODUCTION: Odontogenic keratocyst (OKC) is a developmental odontogenic cyst that may occur sporadically (OKCsp) or in association with nevoid basal cell carcinoma syndrome (NBCCS) (OKC-sy). NBCCS is an autosomal dominant disorder characterised by morphological abnormalities and an increased predisposition to several neoplasms, including basal cell carcinomas. Mutations in the tumour suppressor gene PTCH1 have been reported in patients with OKC and NBCCS. PTCH1 participates in a signalling cascade that culminates in the translocation of GLI transcription factors to the nucleus, thereby activating target genes involved in cell proliferation. Aberrant GLI1 expression has been associated with increased proliferation in lung adenocarcinoma and other cancers. OBJECTIVE: To compare GLI1 and Ki-67 protein expression in OKCs associated with NBCCS versus sporadic OKCs. MATERIALS AND METHODS: We included 13 OKCsp and 9 OKCsy from a children's hospital and university ... Immunohistochemistry was performed using anti-GLI1 and anti-Ki-67 to assess GLI1 expression and cell proliferation. RESULTS: No significant differences were observed in GLI1 or Ki-67 expression in the epithelial component of OKCsy versus OKCsp. A positive correlation between GLI1 and Ki-67 expression was detected in the total sample (r = 0.71, p < 0.05). CONCLUSION: The positive correlation between GLI1 and Ki-67 expression in OKCs suggests an association between SHH pathway activity and cell proliferation in both sporadic and syndromic lesions.

GLI1↗

PubMed2026

The science of Arabic coffee (Qahwa): from phytochemistry and nutritional profile to health benefits and safety evaluation.

Arabic coffee (Qahwa), a traditional beverage widely consumed in the Middle East, has attracted increasing scientific attention due to its distinctive phytochemical composition and associated health effects. This review provides an integrated analysis of Qahwa's nutritional profile, focusing on its key bioactive constituents, including chlorogenic acids, caffeine, diterpenes (cafestol and kahweol), and phenolic compounds. These constituents contribute to a range of biological activities, notably antioxidant, anti-inflammatory, hepatoprotective, and metabolic regulatory effects. The influence of technological variables, including roasting degree, brewing method, and bean origin, on the chemical composition and functional properties is critically examined. Safety concerns, particularly acrylamide formation and mycotoxin contamination, are also discussed. Although emerging data support Qahwa's potential as a functional beverage, further research is required to clarify dose-response relationships, synergistic interactions, and long-term health outcomes. This work highlights Qahwa as a promising candidate for food and nutraceutical applications, warranting standardized compositional profiling and toxicological evaluation.

Humans↗

PubMed2026

Biomass burning contributions to Mexico City's atmospheric CO2 estimated using a multi-isotope approach.

Fossil fuel combustion dominates anthropogenic emissions worldwide; however, special attention should be addressed to biomass burning, since it is an increasingly important contributor under warmer, drier fire-weather conditions exacerbated by climate change. These emissions could impact the atmospheric composition of heavily urbanized environments. To assess the influence of biomass burning, along with fossil fuels combustion and soil and plant respiration on Mexico City's atmospheric composition, we conducted a year-long (December 2023-December 2024) isotopic monitoring of atmospheric CO2, combining radiocarbon (Δ14C), CO2 stable isotopes (δ13C, δ18O), and CO/CO2 ratios. Once defined the isotopic signatures and the characteristic CO/CO2 that describe the sources, we performed Monte Carlo simulations under two tracer modalities (Δ14C + CO/CO2 and Δ14C + CO2 stable isotopes) for source apportionment. Results show that during the dry season, particularly in March-April, atmospheric Δ14C values approached and overlapped background levels despite Mexico City's fossil-fuel dominance, indicating enhanced non-fossil inputs. Moreover, backward HYSPLIT trajectories supported that these elevated Δ14C values coincided with regional wildfire activity. Monte Carlo results attributed up to ∼34 %-60 % of local CO2 to biomass burning in April, followed by March with contributions of ∼31 %-49 %. Since these biomass burning figures contrast with the official emissions inventory of Mexico City metropolitan area, which assigns <1 % of total CO2 emissions to biomass burning, this study could exhibit the emissions inventory underestimation of this source, and thus, the need to reassess and incorporate top-down isotopic constraints in fire-affected urban regions.

Mexico↗

PubMed2026

Transforming Curcuma longa leaf waste into cellulose scaffolds.

The constant dearth of transplantable tissues and organs in India required the development of substitute biomaterials for tissue engineering. Plant-based decellularized scaffolds have become attractive options because of their abundance, ethical acceptability, architectural diversity, and lower risks of zoonotic transmission. Curcuma longa leaves were investigated in this study as a possible source of cellulose-based scaffolding for use in biomedical applications. After cuticle removal, an immersion decellularization technique utilizing sodium dodecyl sulphate (SDS) and triton-X-100 was developed to successfully remove cellular and nuclear material while maintaining leaf parenchyma architecture. Histology, DAPI staining, scanning electron microscopy, and a notable decrease in leftover DNA content all demonstrated efficient decellularization. When contrasted with native leaves, the resultant decellularized C. longa leaf scaffolds showed significant increase in porosity, water vapor transmission rate and swelling percent, and significantly lower contact angle with an optimum surface roughness promoting cell adhesion. Mechanical test manifest higher tensile strength with decreased stiffness. Fourier transform infrared spectra of leaf scaffold reveals persistence of different components except cuticle but the intensity of different peaks was decreased. The leaf scaffolds showed superior hemocompatibility and excellent compatibility with Madin-Darby canine kidney cells (MDCK) which is demonstrated by cell attachment and proliferation. MTT assay of seeded scaffold showed significantly higher metabolically active cell. In vivo subcutaneous implantation of decellularized scaffolds showed host tissue incorporation, accumulation of collagen, and neovascularization. C. longa leaf scaffolds can be utilized as cost effective and sustainable biomaterials for soft tissue engineering and regenerative medicine.

Curcuma↗

PubMed2026

Protein sorting and proteostasis mechanisms in CFTR-related exocrine pancreas dysfunction: A systematic narrative review.

The pancreas consists of exocrine and endocrine compartments. In the exocrine pancreas, cystic fibrosis transmembrane conductance regulator (CFTR) functions mainly in ductal epithelial cells as a chloride and bicarbonate channel. Its activity depends on proper protein folding, trafficking, and localization to the apical membrane. This systematic narrative review aims to synthesize the available evidence on the role of protein sorting machinery in CFTR channelopathies and its contribution to exocrine pancreatic dysfunction. A thorough search was conducted using PRISMA criteria on PubMed, Wiley Online Library, and Scopus for studies published in English between January 2000 and November 2025. Twenty studies that met the inclusion criteria were included in this review. Pathogenic CFTR variants impair protein folding, endoplasmic reticulum (ER) exit, and endosomal recycling, resulting in reduced apical membrane expression and stability. These defects disrupt the localization of associated transporters and secretory proteins, impair ductal bicarbonate secretion, alter zymogen handling, and promote acinar injury, although these claims are supported mainly by indirect experimental models and therefore require clinical confirmation. CFTR channelopathies in the exocrine pancreas encompass both ion transport defects and broader disruptions of protein sorting machinery. CFTR may contribute to the assembly, stabilization, or localization of selected apical transport complexes, and its loss can secondarily alter epithelial organization. Therapeutic approaches targeting both channel correction and intracellular trafficking may improve pancreatic function and mitigate disease progression.

Humans↗

PubMed2026

LINE-1 repeats are a defining feature of the Xce.

During early development, female mammals inactivate one X chromosome to balance their X-linked gene dosage with males. While allelic choice is random in inbred mouse populations, choice can be significantly skewed in interstrain hybrids. The genetic basis of skewing has long been attributed to the mysterious "X chromosome controlling element(s)" (Xce) with different strengths among species, subspecies, and strains. When two X-chromosomes with different Xce strengths are inherited by offspring, the X chromosome with the stronger Xce will have a higher probability of remaining active. Here, we provide evidence that L1Tf repeats-a subfamily of long interspersed nuclear elements 1-plays a role in determining Xce strength. L1Tf elements form a condensed core within the inactive X (Xi) territory. Mouse strains with varying Xce strengths differ in the L1Tf copy number on the X chromosome, with the strength of the Xce allele being inversely related to L1Tf copy number. L1Tf expression mediates the Xce effect. However, in contrast to a prior report, L1Tf RNA does not coat the Xi. Rather, L1Tf promotes condensation of the Xi core. Intriguingly, L1Tfs recruit and sequester YY1 from active genes, accelerating XCI in cis. Thus, L1Tf copy number, expression, and binding of YY1 are key defining features of the Xce. We propose a model in which the Xce influences the choice of Xist alleles by promoting YY1 binding to the nucleation site for the initiation of Xist spreading.

Animals↗

PubMed2026

LC-IMS-MS profiling of avocado acetogenins reveals tissue-dependent distribution and cultivar-specific metabolic signatures.

This study presents a comprehensive characterisation of acetogenin-related metabolites in avocado using an LC-IMS-MS workflow. A total of 26 metabolites were semi-quantified across peel, pulp and seed tissues from three cultivars (Hass, Bacon and Fuerte). The integration of ion mobility spectrometry enabled the generation of the first experimental database of collision cross section (CCS) values for avocado acetogenins, improving confidence in metabolite annotation. Results revealed a pronounced tissue-dependent distribution, with seeds and pulp as the primary reservoir of several acetogenins, whereas the peel consistently exhibited lower concentrations. In contrast, acetogenin levels remained largely stable throughout ripening. Clear cultivar-dependent differences were observed, with Hass displaying a distinct metabolic profile compared to Bacon and Fuerte. Multivariate analysis confirmed these findings, showing tissue-dependent cultivar differentiation. This study provides new insights into avocado chemical diversity and highlights the potential of avocado by-products as consistent and promising sources of bioactive acetogenins.

Persea↗

PubMed2026

Recovery of polysaccharides from marc and pomace through sequential extractions assisted by ultrasound, enzymes and acid maceration.

This study evaluated the pilot-scale recovery of polysaccharides from Vitis vinifera pomace/marc using sequential extraction strategies combining high-power ultrasound (UAE), enzymes (EAE), and acid maceration (AAE). Laboratory-scale trials identified optimal conditions for enzyme dosage and liquid/solid ratio (L/S). Pilot-scale trials demonstrated that the extraction sequence and the processing byproducts influenced extraction efficiency, total soluble polysaccharide in the extract (TSP), and polysaccharide composition. Post-maceration at pH 3.2, with/without the maximum enzyme dose after UAE in a L/S of 1.3/1, improved structural polysaccharide extraction from Viura pomace, while Tempranillo marc showed better recovery of pectic families and TSP with UAE + EAE. Separating grape pomace extract (UAE) from the post-maceration stage at pH 3.2 produced two extracts: E1, with higher yield (19.9%), enriched in structural polysaccharides and oligosaccharides, and E2, enriched in high and medium molecular weight pectic polysaccharides (58.03%), a low degree of esterification (17.1%) and more complex rhamnogalacturan structures.

Polysaccharides↗

PubMed2026

Pervasive hybridization and introgression in Diervilleae (Caprifoliaceae).

Diervilleae (Caprifoliaceae) is a horticulturally important lineage with striking floral diversity and a long history of interspecific crossing, suggesting reticulate evolution. We integrated nuclear SNPs and whole plastome data to reconstruct a phylogenomic backbone for the tribe and to identify hybrids, cultivated accessions, and introgression among lineages. Nuclear and plastid phylogenies consistently recover Weigela and Diervilla as reciprocally monophyletic and resolve four major lineages within Weigela, providing a reproducible framework for revising sectional limits and species boundaries. Cultivated accessions form a well supported clade sister to W. florida and show predominantly W. florida ancestry while retaining contributions from multiple wild lineages, consistent with recurrent crossing, backcrossing, and selection. Analyses of wild populations reveal recurrent hybrids and enable plausible parental combinations to be inferred. Tests across the genome further indicate strong evidence for historical introgression across Diervilleae, with the strongest signals involving W. middendorffiana, W. maximowiczii, and Diervilla. Fossil evidence, divergence time estimation, and paleodistribution modelling together suggest range expansion during the Miocene and Pliocene followed by climate driven contraction, providing a spatiotemporal context for episodic contact, introgression, and the East Asia-North America disjunction.

Hybridization, Genetic↗

PubMed2026

Predictive evolutionary genomics: principles, validation, and practice.

Climate change and habitat loss are driving rapid evolutionary responses in populations world-wide, which creates an urgent need for evolutionary forecasting in conservation and agriculture. Such forecasting can be categorized into three time scales: trait-based models that use multivariate quantitative genetic equations to project correlated phenotypic responses up to c. 20 generations, allele-based analyses that model allele frequency dynamics up to 100 generations, and composite adaptation scores that aggregate many small effects to yield predictions across longer horizons. However, these approaches have remained largely disconnected. Here, we present a Bayesian framework that integrates these three complementary approaches for evolutionary prediction. Our framework combines genomic, phenotypic, and environmental data to yield probabilistic predictions with explicit uncertainty. We show how predictive evolutionary forecasts can be validated with experimental evolution, field experimentation, historical specimens, and reciprocal transplants. These validated forecasts can help advance conservation and agricultural programmes by helping predict which populations are at risk of future extinction, optimizing breeding programmes for future climates, and planning ecosystem management under environmental change. By supporting a shift towards more predictive approaches in evolutionary biology, this framework may help improve our ability to manage biodiversity and food security in a changing world.

Genomics↗

PubMed2026

Dynamic evolution of chaperone-mediated autophagy is associated with tumor microenvironment remodeling and prognostic stratification in lung adenocarcinoma: insights from single-cell transcriptomics, ensemble machine learning, and experimental validation.

BACKGROUND: Lung adenocarcinoma (LUAD) shows prognostic heterogeneity, and tumor-node-metastasis (TNM) staging is limited for individualized management. Chaperone-mediated autophagy (CMA) maintains proteostasis, but its role during adenocarcinoma in situ (AIS)-minimally invasive adenocarcinoma (MIA)-invasive adenocarcinoma (IAC) progression remains unclear. METHODS: Single-cell RNA sequencing (scRNA-seq) data from GSE189357 and bulk transcriptomes from The Cancer Genome Atlas (TCGA)-LUAD and Gene Expression Omnibus (GEO) cohorts were integrated. CMA activity, cell-cell communication, weighted gene co-expression network analysis (WGCNA), tumor-normal differential expression, machine-learning survival modeling, tumor microenvironment (TME) features, drug sensitivity, and EPC1 function were analyzed. RESULTS: CMA-high tumor epithelial cells increased from AIS (58.1%) to MIA (65.7%) but declined in IAC (44.4%; p < 0.001). CMA-low cells preferentially received fibroblast-derived extracellular matrix cues. A CMA-negatively correlated module identified 69 core genes. Random survival forest (RSF) performed best among 117 machine-learning combinations (mean concordance index > 0.873). High-risk patients had worse survival across cohorts, and the risk score was independently associated with overall survival (hazard ratio = 16.013, 95% confidence interval: 9.579-26.768, p < 0.001). High-risk tumors showed proliferative activation and M0 macrophage enrichment, whereas low-risk tumors showed stronger immune-related signaling. EPC1 overexpression suppressed malignant phenotypes in A549 cells. CONCLUSION: CMA dynamics are associated with stromal and immune remodeling during LUAD progression. A CMA-based model provides robust prognostic stratification and may offer a basis for future TME-guided studies.

Chaperone-mediated autophagy↗