Functional & Integrative Genomics最新文献

Plants’ immobility renders them highly vulnerable to heat stress, which disrupts water relations, photosynthesis, respiration, and cellular homeostasis, ultimately reducing growth and yield. To survive, plants deploy a multifaceted heat stress response (HSR) that integrates calcium signaling, molecular chaperones, antioxidant enzymes, and phytohormonal networks. This review synthesizes recent advances in understanding the molecular crosstalk between phytohormones and protein synthesis during plant heat stress responses, with a particular focus on two key HSR modules: protein synthesis pathways, especially heat shock proteins (HSPs), and phytohormone signaling networks involving abscisic acid, cytokinins, ethylene, salicylic acid, and jasmonic acid. It also highlights the convergence of these pathways through calcium-dependent protein kinases (CDPKs) and reactive oxygen species (ROS) signaling. We present mechanistic insights into: (1) CDPK-mediated activation of heat shock transcription factors (HSFs) and hormone-responsive factors; (2) APX-driven ROS scavenging and its impact on crop thermotolerance; and (3) hormone-engineered strategies that enhance yield stability under high temperatures. By consolidating findings from recent meta-analyses and molecular studies, we identify critical nodes for biotechnological intervention, such as CDPK and APX overexpression, and propose field-oriented research priorities, including hormone-engineered crop trials and integrative breeding approaches. This forward-looking framework can help guide biotechnological interventions to enhance crop resilience and support the development of climate-smart crops aimed at safeguarding global food security in a warming world.

Although immunotherapy for late-stage non-small cell lung carcinoma (NSCLC) has been clinically utilized, its prognosis remains highly heterogeneous, prompting us to investigate novel predictive immunotherapy biomarkers for NSCLC. We analyzed the correlations between MED12 nonsynonymous mutations and survival, clinical, genomic, transcriptomic information, and immune infiltration information through data mining across multiple datasets. We also investigated the mechanism of MED12 using luciferase assay, Western blot, ChIP-PCR, and siRNA. MED12 is significantly associated with survival in completely independent immunotherapy datasets, including MSKCC (N = 350), Naiyer2015 (N = 34), our own (N = 295) and the pan-cancer dataset, but not in the TCGA dataset, where patients received non-immunotherapy regimens. Mutations in MED12 showed no significant correlation with known metrics (TMB, IPS/CTLA4/PD1 status, PD-1/PD-L1 expression, and TCR/BCR status) or DNA Damage Repair (DDR) pathway mutations, yet they carried independent prognostic information according to the Cox multivariate regression. On the other hand, MED12 mutation is significantly associated with multiple immune-related pathways and immune infiltration of CD8 + T cells and activated NK cells. Lactate dehydrogenase assay revealed that knockdown of TAP2 restored the upregulation of CD8 + T cell cytotoxicity triggered by MED12 knockdown. ChIP-PCR, luciferase assay and siRNA knock down assay indicate that MED12 binds to the promoter region of STAT1 to suppress its transcription, while the transcription factor STAT1 promotes the transcription of TAP2, thus inhibiting the antigen processing and presentation. Collectively, MED12 mutation is an independent and valuable biomarker for predicting the response to immune checkpoint inhibitor (ICI)therapy in NSCLC by modulating CD8 + T cell cytotoxicity via the STAT1/TAP2 axis.

Polycystic ovary syndrome (PCOS), a common endocrine condition affecting multiple systems, is tied to atherosclerosis (AS) progression among reproductive-aged women. The present study aimed to explore the underlying associations and uncover potential biological indicators for PCOS complicated with AS. Gene expression datasets for PCOS and AS were obtained from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) from PCOS tissues (granulosa cells, adipose tissue, skeletal muscle) and arterial wall of AS were analyzed via weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Immune infiltration and chemokine/receptor-immunocyte networks were constructed to explore immune cell recruitment. Key findings were validated in PCOS and AS murine models. The gradient boosting machine (GBM) and the extreme gradient boosting (XGBoost) algorithms were employed to identify potential biomarkers, further verified by the AS murine model, nomograms, and PCOS murine model. We identified 238, 60, and 76 secretory protein-encoding DEGs in PCOS tissues (granulosa cells, adipose tissue, and skeletal muscle) and 604 key AS-related DEGs. The enrichment analysis suggested associations between immune inflammation, dysregulated lipid metabolism, insulin signaling, and PCOS-related AS. Then, immunoinfiltration analysis revealed elevated naive B cell, follicular T helper cell, and neutrophil proportions in AS samples. In addition, six chemokines (CCL5, CCL20, CCL23, CCL28, CXCL1, and CXCL6) were involved in four immunocyte recruitments (B cells, neutrophils, NK cells, and CD4⁺ T cells) in AS, with CXCL1 and CXCL6 upregulated in the peripheral blood of PCOS mice. And CXCR2, the shared receptor for CXCL1/6, showed an increase in aortic tissues of both AS and PCOS mice. Machine learning identified five signature genes (LILRA5, CSF2RA, S100A8, CD6, and CCL24; AUC 0.856–0.983), two of which (CSF2RA and LILRA5) were verified in the AS murine model and the nomogram incorporating these genes showed strong predictive accuracy (AUC = 0.966). Finally, further validation in the PCOS murine model confirmed significantly elevated CSF2RA and reduced LILRA5 expression, suggesting a close association between PCOS and AS pathogenesis. This study identified potential associations between PCOS and AS, and screened the potential biological biomarkers for predicting PCOS-related AS, offering a foothold for future exploration of the diagnosis and risk stratification for PCOS-related AS.

CRISPR/Cas9 technology is an efficient tool for site-specific livestock gene editing. However, to minimize potential disruption of host genome function, exogenous genes should be integrated into well-characterized genomic loci, such as H11 or Rosa26, which have been empirically validated for stable transgene expression. This study established a multi-dimensional assessment system to evaluate the biological applicability of the H11 locus and the widely used Rosa26 targeting platform as sites for targeted integration of exogenous genes in goats. Donor cells carrying the enhanced green fluorescent protein (EGFP) reporter gene at the H11 and Rosa26 loci were generated via CRISPR/Cas9-mediated homology-directed repair; this was followed by somatic cell nuclear transfer to produce transgenic cloned embryos and healthy offspring. Multi-dimensional analyses revealed the following. At the cellular level, there was stable and efficient EGFP expression at integration sites, with donor cells maintaining normal cell cycle progression, proliferation capacity, and apoptosis levels, and with no alterations in the transcriptional integrity of adjacent genes. At the embryonic level, there was sustained EGFP expression across pre-implantation embryonic stages, with developmental metrics statistically indistinguishable from wild-type embryos. Finally, at the individual level, cloned offspring exhibited growth phenotypes consistent with wild-type counterparts, and EGFP showed broad-spectrum expression in eight tissues. This study establishes the first CRISPR/Cas9-based crossscale (cellular–embryonic–individual) validation in goats, demonstrating that the H11 and Rosa26 loci support efficient and stable transgene integration in goats. These results provide a precise and predictable technical framework for livestock genetic improvement.

The MBTPS1 gene, which is located on chromosome 16q24, encodes the membrane-bound transcription factor protease site-1 (MBTPS1), commonly referred to as site-1 protease (S1P). S1P can process a variety of substrates independently or in conjunction with membrane-bound transcription factor protease site-2 (MBTPS2, also known as S2P), including sterol regulatory element binding proteins (SREBPs), activating transcription factor 6 (ATF6) and cyclic-AMP responsive element‑binding protein 3 (CREB3). Variants in the MBTPS1 gene can lead to multiple clinically distinct disorders with different phenotypes, including spondyloepiphyseal dysplasia of Kondo-Fu type (SEDKF), Cataract, alopecia, oral mucosal disorder, and psoriasis-like (CAOP) syndrome, and Silver-Russell-like syndrome (SRS). This review presents the structural and functional characteristics of S1P, enumerates the relevant substrates and elucidates the spectrum of associated disorders resulting from pathogenic variants of MBTPS1, and discusses the correlations investigates the genotype-phenotype correlations underlying these distinct clinical manifestations.

Endoplasmic reticulum (ER) stress and its associated unfolded protein response (UPR) have been demonstrated to play a crucial role in cancer’s progression, but their prognostic significance in breast cancer (BC) remains unclear. In this study, a reliable ER-related gene signature was developed for the purpose of predicting BC prognosis and investigating the associated immune landscape. By utilizing public datasets and analytical methods, we developed a 16 ER-related gene risk signature and verified its efficacy in predicting prognosis in independent patient groups. Patients in the high-risk group exhibited significantly poorer survival rates. Single-cell analysis revealed that the low-risk group exhibited stronger immune interactions. Conversely, the high-risk group exhibiting elevated immune checkpoints may signify an immunosuppressive microenvironment or heightened sensitivity to immune checkpoint inhibitor therapy. In vitro and vivo experiments confirmed that knocking down the expression of Marginal Zone B And B1 Cell Specific Protein (MZB1) significantly inhibited the proliferation, invasion, and tumorigenesis of breast cancer. The 16 ER-related gene signature is capable of effectively categorizing breast cancer patients into different risk levels, thereby providing a basis for personalized therapy. MZB1 has been identified as a significant regulatory factor, suggesting its potential as a target for the treatment of breast cancer.

Biotechnology and sustainable strategies are the way forward for increasing global food production. The use of plant growth-promoting bacteria to increase the productivity of important food crops helps reduce the need for land expansion, improves soil fertility and plant tolerance to adverse abiotic conditions, and increases the ability to combat phytopathogens. Paenibacillus brasilensis strain PB24 is an endospore-forming bacterium that promotes plant growth through various direct and indirect mechanisms. To improve the understanding of its ability to inhibit the fungus Fusarium oxysporum, which causes numerous agricultural pathologies, the potential of P. brasilensis PB24 as a producer of antifungal compounds was investigated. In vitro assays demonstrated fungicidal activity against F. oxysporum hyphae. Additionally, genome mining of P. brasilensis PB24 was conducted to identify biocontrol and plant growth-promoting traits. For the first time, these traits were compared with those of other Paenibacillus species, and several genetic similarities were identified. Genome mining revealed that strain PB24 produces several antimicrobial compounds, similar to fusaricidin and sevadicin, but retains substantial differences in their monomers, suggesting that they may be novel lipopeptides. A unique genetic cluster was characterized in the PB24 genome as a potential resource for the discovery of new compounds. The results demonstrate the biotechnological potential of P. brasilensis PB24 for plant growth and biocontrol of phytopathogens and provide a basis for the future development of sustainable biocontrol strategies and commercial bacterial formulations.

Plastome evolution in species-rich angiosperm lineages remains poorly understood despite recent advances in phylogenomics, particularly regarding the mechanistic drivers of codon usage bias (CUB) and their relationship to adaptive evolution. The genus Bidens (Asteraceae), comprising approximately 280 species, represents a morphologically diverse lineage with significant medicinal and economic value. Here, we assembled the complete plastid genome (plastome) of Bidens alba and conducted comprehensive comparative analyses across 31 Bidens species, integrating structural characterization, simple sequence repeat (SSR) distribution, codon usage bias assessment, and selection pressure analysis through Ka/Ks ratios and phylogenomic reconstruction. All plastomes exhibited the canonical angiosperm quadripartite structure (150,490 − 151,856 bp) with consistent AT bias (average GC content: 37.48%) and mononucleotide SSR predominance (37.43%). Twenty-nine high-frequency codons displayed strong AT preference, with multiple analytical approaches confirming natural selection as the primary driver of codon usage bias. The non-synonymous (Ka) /synonymous (Ks) substitution ratios revealed that most protein-coding genes showed evidence of purifying selection (Ka/Ks < 0.5), though the ycf2 and accD genes displayed elevated ratios suggesting adaptive evolution. Phylogenomic reconstruction supported Bidens monophyly with high bootstrap values and resolved species relationships with high confidence. Comparative structural analysis revealed exceptional genomic conservation across the genus, suggesting that while sequence evolution has occurred, the fundamental genomic architecture remains stable. These findings provide crucial insights into significant structural conservation across Bidens plastomes while demonstrating active sequence-level evolution, providing crucial insights into plastome evolutionary mechanisms within rapidly diversifying lineages and establish a robust genomic framework for understanding ecological adaptation and phylogenetic relationships in this ecologically important lineage.

The cytosine base editor (CBE) enables precise C-to-T substitution without inducing DNA double-strand breaks, which offering a promising tool for editing livestock genomes to enhance economically valuable traits. In this study, using Hu sheep, characterized by high reproductive performance but suboptimal meat production as the research subject, two CBE-editing sgRNAs (sgM1 and sgM2) targeting the negative regulator Myostatin (MSTN) gene were designed. The results revealed a 75% editing efficiency of sgM2 at the parthenogenetically activated embryonic level with no detectable off-target effects. Thirty-four zygotes from five Hu sheep microinjected with sgM2 and CBE mRNA mixtures were transferred into four Hu sheep recipient ewes, yielding four lambs with confirmed MSTN editing and no off-target activity. Statistical analysis of growth performance data revealed that MSTN-edited Hu sheep exhibited significantly (P < 0.05) higher body weights at 120–180 days, and significantly (P < 0.05) enlarged muscle fiber cross-sectional areas compared to wild-type controls. Edited Hu sheep displayed reduced MSTN protein expression, elevated p-AKT levels, and diminished p-ERK and p-p38 signaling. In conclusion, MSTN-edited Hu sheep were highly efficient generated using CBE, and further analysis demonstrate that MSTN editing activates the AKT pathway while suppressing MAPK signaling, leading to muscle fiber hypertrophy and accelerated growth, which provides technical methodologies and breeding materials for developing fast-growing, meat-type Hu sheep-germplasm.