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PubMed2026

A Biomimetic Dual-Targeting Nano-APA-Editor Reprograms the 3'UTR Landscape for Tongue Squamous Cell Carcinoma Therapy.

Targeting post-transcriptional dysregulation of tumor suppressors represents a new frontier in cancer therapy. Here, we identify the alternative polyadenylation (APA) regulator NUDT21 as a pivotal therapeutic target in oral squamous cell carcinoma (OSCC). NUDT21 is highly upregulated, correlating strongly with poor survival and advanced clinical stage. We outline a pathogenic mechanism whereby NUDT21 drives this phenotype by forcing a network of tumor suppressor transcripts, notably PTEN, into translationally-repressed, long-3'UTR isoforms. To therapeutically "re-engineer" this APA switch, we design a "Nano-APA-editor." This platform features an HMSN core with an sgRNA-NUDT21 payload and a hierarchical targeting strategy: a cancer-educated dendritic cell (DC) membrane for biomimetic camouflage and homotypic affinity, "gated" by a TA-aptamer for final precision. This system enables potent and selective NUDT21 silencing, driving a shift toward short-3'UTR isoforms. Consequently, the Nano-APA-editor effectively reinstates PTEN and associated suppressors and inhibits multiple malignant phenotypes in vitro. In an orthotopic OSCC model, it demonstrates profound tumor regression, outperforming conventional chemotherapy (PTX) with excellent biocompatibility. In vivo analysis confirmed target engagement (NUDT21-down) and functional restoration (PTEN-, WEE1-, TGF-β-up). This work validates a "post-transcriptional re-engineering" strategy, executed by a logically designed nanoplatform, as a powerful and safe modality for precision gene therapy.

Humans↗
PubMed2026

Chronic psychological stress potentiates IgE class switch recombination via glucocorticoid receptor-mediated epigenetic reprogramming of B cells.

BACKGROUND: Chronic psychological stress is a well-recognized factor in the exacerbation of allergic diseases, with IgE playing a central role in their pathophysiology. However, the exact molecular mechanisms by which stress hormones directly influence IgE production and contribute to allergic responses remain largely uncharacterized. OBJECTIVE: This study aimed to elucidate the direct mechanisms through which chronic psychological stress, via elevated cortisol, regulates IgE class switch recombination (CSR) in B cells and contributes to stress-aggravated allergic inflammation in vivo. METHODS: We employed a chronic restraint stress (CRS) mouse model to investigate the impact of psychological stress on humoral immunity. In vitro experiments utilized primary murine B cells treated with physiological cortisol concentrations (250 nM), incorporating molecular techniques such as CRISPR-Cas9-mediated gene knockdown, chromatin immunoprecipitation (ChIP), whole-genome bisulfite sequencing, and pharmacological inhibitors of epigenetic enzymes. Primary human B cells and the U266 human myeloma cell line were used for translational validation. In vivo validation was performed using an ovalbumin (OVA)-induced allergic airway inflammation model with B cell-specific glucocorticoid receptor (GR) knockout mice. RESULTS: Chronic psychological stress significantly elevated plasma corticosterone and serum IgE levels in mice, with no changes in IgG1 or IgM. In purified in vitro B-cell cultures, cortisol promotes epigenetic remodeling at the Iε promoter region and enhances Iε germline transcript expression in an isotype-specific manner, and this effect was recapitulated in human B cells. GR bound to the Iε promoter's Amp_1 region (-154 to -62 bp), and CRISPR-Cas9-mediated GR knockdown abolished cortisol-induced IgE production. Mechanistically, cortisol increases enrichment of activating histone marks (H3K27ac, H3K4me3) and reduces H3K27me3 at the Iε promoter region, and induces site-specific DNA hypomethylation; inhibition of histone acetyltransferases (HATs) or DNA demethylation attenuated this effect. In vivo, B cell-specific GR knockout completely abrogated stress-induced exacerbation of allergic airway inflammation, including elevated serum IgE, eosinophilic inflammation, and airway hyperresponsiveness (AHR). CONCLUSION: Our findings support a mechanistic model in which chronic psychological stress, through elevated glucocorticoids, acts via GR to promote epigenetic remodeling at the Iε promoter region in B cells to enhance IgE synthesis and exacerbate allergic responses. This study provides a critical molecular link between the neuroendocrine system and adaptive immunity, offering promising therapeutic targets for stress-aggravated IgE-mediated diseases.

Animals↗
PubMed2026

Integrated proteomic and acetylomic analyses reveal the metabolic reprogramming associated with increased tylosin-equivalent concentration in Streptomyces xinghaiensis sf106-B1.

Deciphering the metabolic basis of high-yield antibiotic production in Streptomyces is crucial for strain optimization. Atmospheric and room-temperature plasma (ARTP) mutagenesis of Streptomyces xinghaiensis sf106 generated a mutant with a 30% increase in tylosin-equivalent concentration (μg/mL). 4D-FastDIA quantitative proteomics identified 279 differentially abundant proteins enriched in the Type I polyketide synthase (PKS) pathway, with increased abundance of key macrolide-biosynthesis-related proteins. Lysine-acetylome profiling identified 1152 differentially abundant acetylation sites and revealed altered acetylation of enzymes involved in fatty acid metabolism and the tricarboxylic acid (TCA) cycle, suggesting adjustments in central metabolism associated with acyl-CoA precursor availability and energy generation. Integration of proteomic and acetylomic data suggests coordinated changes in protein abundance and lysine acetylation associated with the increased tylosin-equivalent concentration. These results highlight candidate nodes for rational metabolic engineering of S. xinghaiensis.

Streptomyces↗
PubMed2026

Quantitative proteomic profiling of neural cells-specific metabolic reprogramming in response to mitochondrial dysfunction using iMPAQT2.

Age-related mitochondrial dysfunction is increasingly recognized as a key contributor to neurodegenerative disease pathogenesis. In the central nervous system, neurons, oligodendrocytes, and astrocytes which derived from neural stem cells, fulfill distinct metabolic and functional roles. However, the specific vulnerabilities of these cell types to mitochondrial impairment remain unclear. In this study, we employed the iMPAQT2 proteomics platform to systematically compare the metabolic profiles of neurons, oligodendrocytes, and astrocytes, and to elucidate the molecular consequences of mitochondrial dysfunction induced by chloramphenicol and oligomycin. Our findings indicate that neurons and oligodendrocytes primarily rely on oxidative phosphorylation (OXPHOS) for ATP production, whereas astrocytes predominantly utilize glycolysis. It is noteworthy that oligodendrocytes exhibited enriched pathways for cholesterol synthesis, fatty acid degradation, and heme catabolism-processes that are critical for myelin maintenance. Treatment with the mitochondrial function inhibitors chloramphenicol or oligomycin reduced the expression of OXPHOS enzymes in all cell types. This reduction was particularly pronounced in oligodendrocytes for glycolysis, cholesterol synthesis, heme degradation, and fatty acid degradation. These results suggest that oligodendrocytes are particularly vulnerable to mitochondrial dysfunction, which may play a pivotal role in the pathogenesis of age-related neurodegenerative disorders.

Animals↗
PubMed2025

Reprogramming neuroblastoma by diet-enhanced polyamine depletion.

Neuroblastoma is a highly lethal childhood tumour derived from differentiation-arrested neural crest cells1,2. Like all cancers, its growth is fuelled by metabolites obtained from either circulation or local biosynthesis3,4. Neuroblastomas depend on local polyamine biosynthesis, and the inhibitor difluoromethylornithine has shown clinical activity5. Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumour differentiation and profound survival gains in the Th-MYCN mouse model. Specifically, an arginine- and proline-free diet decreases the amount of the polyamine precursor ornithine and enhances tumour polyamine depletion by difluoromethylornithine. This polyamine depletion causes ribosome stalling, unexpectedly specifically at codons with adenosine in the third position. Such codons are selectively enriched in cell cycle genes and low in neuronal differentiation genes. Thus, impaired translation of these codons, induced by combined dietary and pharmacological intervention, favours a pro-differentiation proteome. These results suggest that the genes of specific cellular programmes have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of paediatric cancers.

Animals↗
PubMed2026

Ionizing radiation induces bidirectional transcriptomic reprogramming and dynamic NOS2/TREM2 regulation in triple-negative breast cancer cells.

PURPOSE: To characterize irradiation-associated transcriptomic changes in murine triple-negative breast cancer cells and examine dose- and time-response patterns of selected radiation-responsive candidates. MATERIALS AND METHODS: RNA sequencing (RNA-seq) was performed in 4T1 cells collected 24 h after 4 Gy irradiation, followed by Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and gene set enrichment analyses. Representative RNA-seq-derived genes were examined by reverse transcription quantitative PCR (RT-qPCR), and selected immune- and inflammation-related transcripts were further assessed across additional radiation doses and post-irradiation time points. Inducible nitric oxide synthase (NOS2) and triggering receptor expressed on myeloid cells 2 (TREM2) protein abundance was assessed by Western blotting, and nitrite accumulation in culture supernatants was measured using a Griess reagent-based assay as an indirect readout of nitric oxide production. RESULTS: RNA sequencing identified 757 differentially expressed genes, including 285 upregulated and 472 downregulated genes. Irradiation was associated with enrichment of inflammatory, interferon-related, immune-system, and cell-adhesion transcriptional signatures, whereas downregulated genes were enriched in cell-cycle-, chromosome-cohesion-, DNA-damage-response-, DNA-repair-, and SUMOylation-related pathways. Selected immune- and inflammation-related transcripts showed distinct temporal patterns. Nos2 mRNA increased across the examined 0-6 Gy dose range and at later post-irradiation time points, whereas NOS2 protein showed different kinetics, with an early peak after 4 Gy irradiation and no clear further increase above 6 Gy. Nitrite accumulation increased after irradiation. Trem2 showed the largest fold increase among strongly upregulated transcripts identified by RNA-seq, but RT-qPCR detected a significant increase only at 24 h, and TREM2 protein abundance remained unchanged across the examined doses and time points. CONCLUSIONS: Ionizing radiation was associated with broad bidirectional transcriptional remodeling in 4T1 cells, involving immune-, inflammatory-, and interferon-related signatures together with reduced representation of cell-cycle- and DNA-repair-related gene sets. The discordant mRNA and protein patterns of NOS2 and TREM2 indicate that transcript-level responses do not necessarily translate into corresponding protein-level changes. These findings define irradiation-associated molecular responses requiring further functional investigation.

Triple-negative breast cancer↗
PubMed2026

HIF1A+CSF3R+ neutrophils-dominated hypoxic niche induced metabolic reprogramming for neoadjuvant therapy resistance in NSCLC.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the frequently occurring cancers characterized by molecular heterogeneity and multiple immune cell infiltration patterns, which are associated with treatment sensitivity and resistance. However, the specific microenvironmental cells and their mechanisms that lead to treatment resistance in patients need to be explored in greater depth. METHODS: On the basis of patients receiving neoadjuvant therapy in our center, a multicenter, multicohort NSCLC spatial transcriptome, single-cell transcriptome, T-cell receptor repertoire sequencing, bulk RNA transcriptome, phosphorylated proteome, genome mutation, and clinical data were included for a comprehensive assessment of the therapeutic and prognostic impact of HIF1A+ CSF3R+ neutrophils in NSCLC. In vitro experiments validated the functional phenotype of HIF1A+ CSF3R+ neutrophils and co-localization interactions with other cellular subpopulations. Gradient boosting machine (GBM) constructed region of interest (ROI) models for evaluation. Computer-aided drug design (CADD) was used to predict targeted small molecule drugs, and in vivo mouse models were constructed to assess the effectiveness of the combination treatment regimen. RESULTS: Centered on HIF1A+ CSF3R+ neutrophils, recruited exhausted T cells and stromal cells form a hypoxic niche within the tumor region, which was enriched in non-response patients. ROI composed of these specific cellular subpopulations, associated with senescence and glycolysis, accurately predicting NSCLC progression, prognosis, and microenvironment composition. CADD analysis identified that platycodin-D2 specifically targeted CSF3R, reducing HIF1A expression and inhibiting neutrophil activity. Combining navitoclax, platycodin-D2 with anti-programmed cell death protein 1 (PD-1) significantly suppressed tumor proliferation and improved the immunosuppressive microenvironment. CONCLUSION: Our study emphasized the role of HIF1A+ CSF3R+ neutrophils in immunotherapeutic resistance of NSCLC, constructed a microenvironmental immune dysregulation network in a hypoxic ecological niche with HIF1A+ CSF3R+ neutrophils as the center. Platycodin-D2 specifically targeted HIF1A+ CSF3R+ neutrophils, enhancing the efficacy of anti-PD-1 therapy in NSCLC.

Humans↗
PubMed2025

ALDOC and PGK1 coordinately induce glucose metabolism reprogramming and promote development of colorectal cancer.

Colorectal cancer (CRC) remains a significant health challenge globally, demanding a comprehensive understanding of its molecular underpinnings for effective management. In this study, we investigated the role of Aldolase C (ALDOC), a glycolytic enzyme, in CRC pathogenesis. Transcriptomic analysis of CRC tissues from The Cancer Genome Atlas (TCGA) revealed a substantial upregulation of ALDOC, correlating with adverse clinical outcomes. Immunohistochemical (IHC) staining of locally collected patient-derived tissues corroborated these findings, demonstrating elevated ALDOC expression in tumor tissues, particularly in advanced stages. Functional studies elucidated the regulatory role of ALDOC in CRC cell phenotypes. ALDOC knockdown significantly inhibited cell proliferation, induced apoptosis, arrested cell cycle progression, and suppressed cell migration in vitro. Moreover, in vivo studies using xenograft models confirmed that ALDOC knockdown attenuated tumor growth. Mechanistically, ALDOC was found to interact with hypoxia-inducible factor 1 alpha (HIF1A) and enhance its transcriptional activity on phosphoglycerate kinase 1 (PGK1), a key glycolytic enzyme. Dual-luciferase reporter assays and chromatin immunoprecipitation experiments validated the ALDOC-mediated transcriptional activation of PGK1. Further functional rescue experiments revealed a synergistic interplay between ALDOC and PGK1 in regulating CRC cell phenotypes. Additionally, ALDOC was implicated in promoting aerobic glycolysis in CRC cells, potentially through PGK1 regulation. Collectively, our findings unveil ALDOC as a critical regulator of CRC pathogenesis, offering insights into its potential as a therapeutic target and highlighting the ALDOC/PGK1 axis as a promising avenue for further investigation in CRC.

Humans↗
PubMed2026

Progressive salinity drives flavonoid branch reprogramming in Anoectochilus roxburghii.

Flavonoids play critical roles in plant adaptation to abiotic stress; however, how salt stress modulates metabolic flux distribution within flavonoid branches remains poorly understood, particularly in non-model medicinal plants. Here, we integrated targeted metabolomics, transcriptomics, and proteomics to examine flavonoid regulation in Anoectochilus roxburghii under 0, 50, 100, and 200 mmol·L- 1 NaCl. Metabolite profiling showed that salinity reshaped flavonoid composition rather than uniformly increasing flavonoid abundance. A metabolite-derived branch bias index (MI), representing the balance between reductive branch metabolites and flavonol products, increased under salt treatment, peaked at 100 mmol·L- 1 NaCl, and declined at 200 mmol·L- 1, indicating maximal branch bias under moderate stress followed by partial rebalancing under severe stress. Transcriptomic analysis showed induction of upstream phenylpropanoid and flavonoid entry genes, including PAL, 4CL, and CHS, whereas F3H was suppressed and FLS showed no induction. Furthermore, several short-chain dehydrogenase/reductase homologs (IFR-like SDR homologs) were upregulated, and the transcript-derived reductive branch index (EI) increased progressively across the salt gradient. EI was positively associated with MI, although the relationship was not strictly proportional under severe stress (200 mmol·L- 1 NaCl). Proteomic profiling further provided supportive evidence for sustained activation of upstream flavonoid biosynthesis, such as salt-induced accumulation of chalcone synthase (CHS) protein, complementing the transcriptomic and metabolomic datasets. Together, these results indicate that salt stress reorganizes flavonoid metabolism in A. roxburghii through persistent upstream activation and branch-specific regulation, favoring the reductive branch under moderate salinity.

Orchidaceae↗
PubMed2026

Epigenetic alterations of AKT1 orchestrate a metabolic reprogramming in advanced lipedema: translational insights from an integrated multi-omics study.

BACKGROUND: lipedema is a chronic, progressive adipose disorder predominantly affecting women, characterized by painful, symmetrical subcutaneous fat accumulation, and typically resistant to lifestyle interventions. The pathophysiology of advanced-stage lipedema remains poorly defined, and no validated biomarkers or targeted therapies are currently available. METHODS: in this observational study, we applied a comprehensive multi-omics approach to dissect the molecular and metabolic alterations underlying late-stage lipedema. RESULTS: Genome-wide DNA methylation profiling identified over 5,000 differentially methylated CpG sites affecting genes involved in receptor tyrosine kinase signaling, phospho-metabolism, and immune pathways. Transcriptomic analysis revealed profound downregulation of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and fatty acid β-oxidation, alongside disruption of the sirtuin pathway and extracellular matrix remodeling. Integrative analysis pinpointed AKT1 as a central regulatory node: its promoter region was hypomethylated, correlating with increased gene expression and protein phosphorylation. Metabolomic profiling confirmed AKT1-linked metabolic dysregulation, including altered levels of L-arginine, NADP+, ATP, guanosine, glycerol, and glutamate, indicating impaired redox balance and energy metabolism. Trans-omic network analysis positioned AKT1 at the intersection of multiple dysregulated pathways, suggesting its key role in advanced-stage lipedema. CONCLUSIONS: the consistent enhancing of AKT pathway signaling across omic layers highlights its potential not only as a biomarker for disease stratification but also as a putative druggable target for therapeutic intervention. These findings offer new mechanistic insights into lipedema pathophysiology and provide a rationale for future personalized treatment strategies guided by AKT1-centric molecular profiling.

Proto-Oncogene Proteins c-akt↗
PubMed1990

Reprogramming of gene expression in postischemic rat liver: induction of proto-oncogenes and hsp 70 gene family.

Steady-state levels of messenger RNA (mRNA) for different members of the heat-shock protein 70 gene family were studied in rat livers reperfused after non-necrogenic ischemia. The expression of constitutive hsc 73 gene decreases during ischemia, returns to normal upon reperfusion, and increases 4 hr after restoration of blood flow. Reperfusion induces the expression of another hsp 70 gene family member (the so-called inducible hsp 70 gene), which remains at high levels for at least 7 hr. The induction of hsp 70 family genes is preceded by activation of the cellular oncogene c-fos, the most prompt change in gene expression detected in reperfused liver. Run-on experiments demonstrate that the increased expression of these genes is largely dependent on activation of transcription. Changes in the amount of c-myc and ornithine decarboxylase mRNA are not evident, while the level of the mRNA for glucose-regulated protein GRP 78 increases later, concurrent with the onset of the acute phase response to surgical trauma. Analysis of polysomal and nonpolysomal fractions from sucrose gradients indicates that in postischemic liver, hsp 70 and hsc 73 mRNA are rapidly engaged on light polysomal or nonpolysomal complexes and are later shifted to polysomes. Albumin mRNA displays the same behavior, indicating that hsp 70 mRNA are not preferentially translated and that increased transcription is the major mechanism for enhanced hsp synthesis in postischemic liver. Damage by active oxygen species, pressure overload, and derangements of protein synthesis is likely to include the causative factors of increased expression of c-fos and the hsp 70 gene family in postischemic reperfused liver.

Animals↗
PubMed1986

Reprograming of murine blastocoele formation.

The present study shows that there is communication between reaggregated asynchronous cleavage stage blastomeres that regulates blastocoele formation. Individual blastomeres from eight-cell murine embryos were transferred to empty zonae pellucidae, intact two-cell embryos, or enucleated two-cell embryos, and were examined over a period of 75 hours for development of cavitation. It was found that the isolated blastomeres cavitated concurrently with intact control eight-cell embryos, while intact control two-cell embryos cavitated 24 hours later. However, the embryos resulting from combining a two-cell embryo and a blastomere from an eight-cell embryo cavitated at a time in between the eight- and two-cell controls.

Animals↗
PubMed2026

Deficient arsenic methylation and global proteomic reprogramming in human keratinocytes during arsenic-induced skin carcinogenesis.

Chronic inorganic arsenic (iAs) exposure affects > 220 million people worldwide and skin cancer is a hallmark of long-term iAs exposure. Limited information exists regarding arsenic methylation by human keratinocytes and how methylation influences skin carcinogenesis. Inorganic arsenite (iAsIII) and its methylated metabolites disrupt diverse zinc finger proteins, leading to differential toxicity patterns. We examined arsenic methylation capacity in non-malignant human keratinocytes and interrogated proteomic remodeling across three stages of iAsIII induced malignant transformation using the well-established preclinical HaCaT model. Arsenic methylation was assessed by hydride generation cryotrapping inductively coupled-mass spectrometry and global proteomic changes were analyzed by tandem-mass tagging liquid chromatography-tandem mass spectrometry. Primary, hTERT-immortalized and HaCaT human keratinocytes exhibited negligible arsenic methylation, with iAsIII comprising at least 98.5% of total intracellular arsenic, attributable to minimal expression of arsenite methyltransferase. Proteomic profiling identified over 275 differentially expressed proteins at each stage of transformation, including multiple zinc finger proteins implicated in cell cycle control, RNA metabolism, and genome stability. Ingenuity® Pathway Analysis revealed progressive, coordinated disruption of cancer-associated pathways and regulatory networks over the transformation timeline, including zinc-coordinating upstream regulators that may explain widespread pathway dysregulation. Collectively, our findings suggest that iAsIII promotes skin carcinogenesis by disrupting C3H1- and C4-type zinc finger protein-centered regulatory networks that coordinate cancer-associated signaling and metabolic pathways in human keratinocytes, highlighting key candidates for future mechanistic studies.

Arsenic↗
PubMed2025

Whole genome duplication drives transcriptome reprogramming in response to drought in alfalfa.

Genome doubling did not enhance drought tolerance in alfalfa, but may set the stage for long-term adaptation to drought through a novel transcriptional landscape. Whole genome duplication (WGD) has been shown to enhance stress tolerance in plants. Cultivated alfalfa is autotetraploid, but diploid wild relatives are important sources of genetic variation for breeding. Investigating how WGD affects gene expression in stress conditions could provide better understanding for use of diploid genetic resources. In this work, we compared the drought response of neotetraploid plants obtained by bilateral sexual polyploidization with diploid full sibs, by measuring physiological and biochemical traits and RNA-seq. Without drought, 4x plants had lower photosynthetic potential than 2x plants per unit leaf area, but larger leaves allowed them to outperform the per leaf photosynthetic potential of 2x plants. Physiological and biochemical traits were significantly affected by drought in both 2x and 4x plants, but the differences between ploidies were small and nonsignificant. Proline levels were higher in 4x than 2x plants, both in control and drought conditions, indicating that larger cells with higher volume-to-surface ratio of 4x  plants require a higher osmolyte concentration. RNA-seq and gene network analyses showed that more genes were affected by drought at 4x than at 2x level, with downregulation of hundreds of genes involved in photosynthesis and stomatal movement at 4x level, suggesting that WGD made the 4x plants more responsive to drought. Genes involved in proline, phytormone and cell wall functions were also transcriptionally affected by drought in 4x plants. We conclude that WGD did not immediately enhance drought tolerance in alfalfa, but may set the stage for long-term adaptation to drought through a novel transcriptional landscape.

Medicago sativa↗
PubMed2026

Integrated Multi-omics Profiling of 2,4-dinitrochlorobenzene (DNCB)-induced Atopic Dermatitis in Mice Reveals a Coordinated Network of Barrier Dysfunction, Immune Activation, and Metabolic Reprogramming.

Atopic dermatitis (AD) is caused by a combination of epidermal barrier defect and immune imbalance. However, the molecular networks between these structural abnormalities and metabolic variations are unclear. This study aim of this research was to examine the concurrent molecular alterations in skin barrier damage and metabolic disorders in an AD-like mouse model by a multi-omics strategy. A 2,4-dinitrochlorobenzene (DNCB)-induced AD-like mouse model was established and the skin tissues were examined through the combination of transcriptomic, quantitative proteomic, and metabolomic analyses. Cross-omics correlation and network analyses were performed to identify consistently abnormal molecular pathways and crucial regulatory molecules. DNCB treatment caused severe epidermal hyperplasia, and prominent infiltration of CD3⁺ T cells, F4/80⁺ macrophages, and mast cells. Transcriptomic and proteomic analysis indicated significant disruption in keratinocyte differentiation, extracellular matrix organization, and cornified envelope formation pathways. Combined analysis detected 171 molecules which were simultaneously altered at both mRNA and protein levels, and network analysis identified FLG2 and KRT6B as central barrier-related molecules. Pathway enrichment analysis consistently showed the participation of AMPK and PPAR signaling pathways. Metabolomic analysis also revealed coordinated changes in lipid and amino acid metabolism which were closely associated with cornified envelope-associated genes and collagen-modifying enzymes. These findings indicate a close relationship between barrier, immune and metabolic regulation in DNCB-induced dermatitis and provide a multi-omics resource for future mechanistic studies of atopic skin inflammation.

Animals↗
PubMed1992

Drosophila salivary glands exhibit a regional reprogramming of gene expression during the third larval instar.

In D. virilis salivary glands transcripts of two early gland protein genes, Egp-1 and Egp-2, which encode putative secretory proteins, accumulate in all cells from the first to mid third larval instar. Subsequently the transcripts disappear from the cytoplasm of the corpus cells, but not from their nuclei, where they accumulate at the chromosomal site of their synthesis. In the collum cells, however, Egp-transcripts continue to be detectable in the cytoplasm until the end of larval life. In the salivary glands of transgenic D. melanogaster the presence of a Egp-1/lacZ fusion protein shows the same regional shift as the cytoplasmic Egp-transcripts in D. virilis. We predict that the expression of Egp-genes is related to an early secretory function of the larval salivary glands which is executed by all cells during earlier larval stages but becomes restricted exclusively to the collum cells during the third larval instar.

Amino Acid Sequence↗
PubMed2026

Beyond the salt barrier: CRISPR-mediated DNA reprogramming to uncouple yield from tolerance in Rice: A review.

Rice (Oryza sativa L.) feeds half of humanity, yet its cultivation is increasingly threatened by soil salinization, which now affects 1.4 billion hectares globally. Decades of breeding and engineering have focused on Na+ exclusion, principally through the Saltol QTL and the xylem-unloading transporter OsHKT1;5, yet this strategy has reached a physiological ceiling. Excluder genotypes survive salinity but fail to fill grain, because the ATP-intensive cost of continuous ion extrusion starves reproductive sinks, while ABA-mediated stomatal closure imposes chronic carbon limitation. The resulting "survival-yield gap" exposes a fundamental flaw in single-trait approaches to a polygenic stress. In this review, we argue that durable, yield-stable salt tolerance requires a coordinated systems-level intervention spanning five mechanistic tiers: (i) CRISPR/Cas9-mediated removal of negative regulatory brakes (OsRR22, RST1, PC1) that suppress plant's latent stress-adaptive capacity; (ii) reinforcement of actin-myosin cytoskeletal transport to sustain SOS1, NHX1, and HKT1;5 delivery under ionic stress; (iii) importation of halophyte design principles from Oryza coarctata, including salt gland architecture and superior Na+ compartmentalization; (iv) recalibration of the ROS-photosynthesis axis via the DHHC09-STRK1-CatC molecular switch and stomatal density engineering; and (v) pyramiding these modules into a "Salt-Shield Rice" genotype through multiplex editing, marker-assisted introgression, speed breeding, and genomic selection. We propose a phased ten-year roadmap that integrates synthetic biology circuit design with conventional breeding to deliver field-ready, multi-module varieties with greater than 70% yield stability at 8-10 dS m-1. This remains an aspirational design target rather than a demonstrated outcome, as three of the five tiers-halophyte-derived structural traits, cytoskeletal reinforcement, and full multi-module pyramiding-remain unvalidated in rice.

CRISPR/Cas9↗