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Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies consisting essentially of adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although the diagnosis and treatment of ADC and SCC have been greatly improved in recent decades, there is still an urgent need to identify accurate transcriptome profile associated with the histological subtypes of NSCLC. The present study aims to identify the key dysregulated pathways and genes involved in the development of lung ADC and SCC and to relate them with the clinical traits. The transcriptional changes between tumour and normal lung tissues were investigated by RNA-seq. Gene ontology (GO), canonical pathways analysis with the prediction of upstream regulators, and weighted gene co-expression network analysis (WGCNA) to identify co-expressed modules and hub genes were used to explore the biological functions of the identified dysregulated genes. It was indicated that specific gene signatures differed significantly between ADC and SCC related to the distinct pathways. Of identified modules, four and two modules were the most related to clinical features in ADC and SCC, respectively. CTLA4, MZB1, NIP7, and BUB1B in ADC, as well as GNG11 and CCNB2 in SCC, are novel top hub genes in modules associated with tumour size, SUVmax, and recurrence-free survival. Our research provides a more effective understanding of the importance of biological pathways and the relationships between major genes in NSCLC in the perspective of searching for new molecular targets.

Crocus sativus is generally considered the source of saffron spice which is rich in apo-carotenoid compounds such as crocins, crocetin, picrocrocin, and safranal, which possess effective pharmacological activities. However, little is known about the exact genes involved in apo-carotenoid biosynthesis in saffron and the potential mechanism of specific accumulation in the stigma. In this study, we integrated stigmas at different developmental stages to perform in-depth transcriptome and dynamic metabolomic analyses to discover the potential key catalytic steps involved in apo-carotenoid biosynthesis in saffron. A total of 61 202 unigenes were obtained, and 28 regulators and 32 putative carotenogenic genes were captured after the co-expression network analysis. Moreover, 15 candidate genes were predicted to be closely related to safranal and crocin production, in which one aldehyde dehydrogenase (CsALDH3) was validated to oxidize crocetin dialdehyde into crocetin and a crocetin-producing yeast strain was created. In addition, a new branch pathway that catalyses the conversion of geranyl-geranyl pyrophosphate to copalol and ent-kaurene by the class II diterpene synthase CsCPS1 and three class I diterpene synthases CsEKL1/2/3 were investigated for the first time. Such gene to apo-carotenoid landscapes illuminate the synthetic charactersistics and regulators of apo-carotenoid biosynthesis, laying the foundation for a deep understanding of the biosynthesis mechanism and metabolic engineering of apo-carotenoids in plants or microbes.

Cardiovascular diseases are an array of age-related disorders, and accumulating evidence suggests a link between cardiac resident macrophages (CRMs) and the age-related disorders. However, how does CRMs alter with aging remains elusive. In the present study, aged mice (20 months old) have been employed to check for their cardiac structural and functional alterations, and the changes in the proportion of CRM subsets as well, followed by sorting of CRMs, including C-C Motif Chemokine Receptor 2 (CCR2) + and CCR2 – CRMs, which were subjected to Smart-Seq. Integrated analysis of the Smart-Seq data with three publicly available single-cell RNA-seq datasets revealed that inflammatory genes were drastic upregulated for both CCR2 + and CCR2 – CRMs with aging, but genes germane to wound healing were downregulated for CCR2 – CRMs, suggesting the differential functions of these two subsets. More importantly, inflammatory genes involved in damage sensing, complement cascades, and phagocytosis were largely upregulated in CCR2 – CRMs, implying the imbalance of inflammatory response upon aging. Our work provides a comprehensive framework and transcriptional resource for assessing the impact of aging on CRMs with a potential for further understanding cardiac aging.

Haberlea rhodopensis , a resurrection species, is the only plant known to be able to survive multiple extreme environments, including desiccation, freezing temperatures, and long-term darkness. However, the molecular mechanisms underlying tolerance to these stresses are poorly studied. Here, we present a high-quality genome of Haberlea and found that ~ 23.55% of the 44,306 genes are orphan. Comparative genomics analysis identified 89 significantly expanded gene families, of which 25 were specific to Haberlea. Moreover, we demonstrated that Haberlea preserves its resurrection potential even in prolonged complete darkness. Transcriptome profiling of plants subjected to desiccation, darkness, and low temperatures revealed both common and specific footprints of these stresses, and their combinations. For example, PROTEIN PHOSPHATASE 2C ( PP2C ) genes were substantially induced in all stress combinations, while PHYTOCHROME INTERACTING FACTOR 1 ( PIF1 ) and GROWTH RESPONSE FACTOR 4 ( GRF4 ) were induced only in darkness. Additionally, 733 genes with unknown functions and three genes encoding transcription factors specific to Haberlea were specifically induced/repressed upon combination of stresses, rendering them attractive targets for future functional studies. The study provides a comprehensive understanding of the genomic architecture and reports details of the mechanisms of multi-stress tolerance of this resurrection species that will aid in developing strategies that allow crops to survive extreme and multiple abiotic stresses.

Vegetable oil is an essential constituent of the human diet and renewable raw material for industrial applications. Enhancing oil production by increasing seed oil content in oil crops is the most viable, environmentally friendly, and sustainable approach to meet the continuous demand for the supply of vegetable oil globally. An in-depth understanding of the gene networks involved in oil biosynthesis during seed development is a prerequisite for breeding high-oil-content varieties. Rapeseed (Brassica napus) is one of the most important oil crops cultivated on multiple continents, contributing more than 15% of the world’s edible oil supply. To understand the phasic nature of oil biosynthesis and the dynamic regulation of key pathways for effective oil accumulation in B. napus, comparative transcriptomic profiling was performed with developing seeds and silique wall (SW) tissues of two contrasting inbred lines with ~13% difference in seed oil content. Differentially expressed genes (DEGs) between high- and low-oil content lines were identified across six key developmental stages, and gene enrichment analysis revealed that genes related to photosynthesis, metabolism, carbohydrates, lipids, phytohormones, transporters, and triacylglycerol and fatty acid synthesis tended to be upregulated in the high-oil-content line. Differentially regulated DEG patterns were revealed for the control of metabolite and photosynthate production in SW and oil biosynthesis and accumulation in seeds. Quantitative assays of carbohydrates and hormones during seed development together with gene expression profiling of relevant pathways revealed their fundamental effects on effective oil accumulation. Our results thus provide insights into the molecular basis of high seed oil content (SOC) and a new direction for developing high-SOC rapeseed and other oil crops.

Background Drought stress is an adverse factor with deleterious effects on several aspects of rice growth. However, the mechanism underlying drought resistance in rice remains unclear. To understand the molecular mechanism of the drought response in rice, drought-sensitive CSSL (Chromosome Single-substitution Segment Line) PY6 was used to map QTLs of sensitive phenotypes and to reveal the impact of the QTLs on transcriptional profiling. Results The QTL dss-1 was mapped onto the short arm of chromosome 1 of rice. According to transcriptomic analysis, the identified differentially expressed genes (DEGs) exhibited a downregulated pattern and were mainly enriched in photosynthesis-related GO terms, indicating that photosynthesis was greatly inhibited under drought. Further, according to weighted gene coexpression network analysis (WGCNA), specific gene modules (designating a group of genes with a similar expression pattern) were strongly correlated with H 2 O 2 (4 modules) and MDA (3 modules), respectively. Likewise, GO analysis revealed that the photosynthesis-related GO terms were consistently overrepresented in H 2 O 2 -correlated modules. Functional annotation of the differentially expressed hub genes (DEHGs) in the H 2 O 2 and MDA-correlated modules revealed cross-talk between abiotic and biotic stress responses for these genes, which were annotated as encoding WRKYs and PR family proteins, were notably differentially expressed between PY6 and PR403. Conclusions We speculated that drought-induced photosynthetic inhibition leads to H 2 O 2 and MDA accumulation, which can then trigger the reprogramming of the rice transcriptome, including the hub genes involved in ROS scavenging, to prevent oxidative stress damage. Our results shed light on and provide deep insight into the drought resistance mechanism in rice.

Halophyte plants could successfully survive in severe saline lands. However, the spatiotemporal responses of halophyte trees to salt stress are still largely unclear. Here, comprehensive transcriptome profiling analyses in the roots of T. chinensis tree in response to salt stress were conducted. After treatments with 300 mM NaCl for 12, 24 and 48 h, 4452, 4836 and 5222 differentially expressed genes (DEGs) were respectively identified. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis indicated that these DEGs identified at different treatment times were enriched in the same pathways. Further transcriptomic analyses demonstrated that gene encoding transcription factor genes, such as bHLH , Dof , MYB and NAC , and oxidative stress and sugar metabolism related genes, were differentially and time specifically expressed, especially at the time point of 12 h treatment. The results of this study will provide fundamental information for future study on the mechanism of halophyte plants in response to salt stress, and for the identification of new candidates genes usable for the molecular breeding of plant varieties with promoted tolerance to abiotic stress.

ABSTRACT Acute myeloid leukaemia (AML) with isolated trisomies (ITs) represents a distinct cytogenetic subgroup with heterogeneous clinical behaviour and incompletely defined molecular features. To explore its genomic and transcriptomic landscape, we performed next‐generation sequencing (NGS) on 14 AML patients harbouring isolated trisomies of chromosomes 8, 9, 10, 13, 14, 21 and 22. RNA sequencing (RNA‐Seq) was conducted on 15 samples, including 12 with IT and 3 cytogenetically normal AML cases (normal karyotype, NK‐AML) serving as controls. Trisomy 8 was most frequent, followed by chromosomes 13, 14 and 21. Recurrent mutations were identified in epigenetic regulators (DNMT3A, IDH1/2, ASXL1, TET2). Transcriptomic profiling stratified cases into IT‐8, IT‐21 and IT‐13+22 subgroups. Gene set enrichment analysis (GSEA) revealed shared downregulation of cell cycle‐related pathways (e.g., G2M checkpoint) and subgroup‐specific patterns: oxidative stress and unfolded protein response in IT‐8; epithelial‐mesenchymal transition and oxidative phosphorylation in IT‐21; inflammatory signalling (IL‐6/JAK/STAT, TNF‐α/NF‐κB) in IT‐13+22. A core set of 60 differentially expressed genes (DEGs) was shared, with nine hub genes related to cell cycle (MCM4, CDC7, CDC25A, DHFR), proteostasis (HSPA5, DNAJC3, CALR, HSP90B1) and inflammation. Drug sensitivity profiling revealed subgroup‐specific vulnerabilities: IT‐8 to DNA damage checkpoint inhibitors, IT‐21 to PLK/mTOR inhibitors and IT‐13+22 to BRAF/EGFR‐targeted agents. These findings highlight AML‐IT heterogeneity and therapeutic potential.

Background Sarcandra glabra is an evergreen and traditional Chinese herb with anti-oxidant, anti-bacterial, anti-inflammatory, and anti-tumor effects. Light is one of the most influential factor affecting the growth and quality of herbs. In recent times, the introduction of Light Emission Diode (LED) technology has been widely used for plants in greenhouse. However, the impact of such lights on plant growth and the regulatory mechanism of phenylpropanoid-derived compounds in S. glabra remain unclear. Results The red LED light (RL) substantially increased the plant height and decreased the stem diameter and leaf area relative to the white LED light (WL), while the blue LED light (BL) significantly reduced the height and leaf area of S. glabra . According to transcriptomic profiling, 861, 378, 47, 10,033, 7917, and 6379 differentially expressed genes (DEGs) were identified among the groups of leaf tissue under BL (BY) vs. leaf tissue under RL (RY), BY vs. leaf tissue under WL (WY), RY vs. WY, root tissue under WL (WG) vs. WY, stem tissue under WL (WJ) vs. WG, and WJ vs. WY, respectively. We identified 46 genes encoding for almost all known enzymes involved in phenylpropanoid biosynthesis, e.g., phenylalanine ammonia lyase (PAL), chalcone synthase (CHS), and flavonol synthase (FLS). We found 53 genes encoding R2R3-MYB proteins and bHLH proteins, respectively, where several were related to flavonoids biosynthesis. A total of 454 metabolites were identified based on metabolomic profiling, of which 44, 87, and 296 compounds were differentially produced in WY vs. RY, WY vs. BY, and WY vs. WG. In BY there was a substantial reduction in the production of esculetin, caffeic acid, isofraxidin, and fraxidin, while the yields of quercitrin and kaempferol were significantly up-regulated. In RY, the contents of cryptochlorogenic acid, cinnamic acid, and kaempferol decreased significantly. Besides, in WG, the production of metabolites (e.g. chlorogenic acid, cryptochlorogenic acid, and scopolin) declined, while their yields increased significantly (e.g. esculetin, fraxetin, isofraxidin, and fraxidin). Conclusion These results provide further insight into the regulatory mechanism of accumulation patterns of phenylpropanoid-derived compounds in S. glabra under various light conditions, allowing optimum breeding conditions to be developed for this plant.

BackgroundAge-related diminished ovarian reserve (DOR) is not absolute. Some advanced maternal age (AMA) still have normal ovarian reserve (NOR) and often show better pregnancy outcomes. Exploring the transcriptomic profile of granulosa cells (GCs) in AMA could lead to new ideas for mitigating age-related diminished ovarian reserve.AimThis study aimed to analyze the transcriptomic profile of GCs in AMA with different ovarian reserve.ResultsIn total, 6273 statistically significant differential expression genes (DEGs) (|log2fc|> 1, q < 0.05) were screened from the two groups, among which 3436 genes were upregulated, and 2837 genes were downregulated in the DOR group. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the potential functions of dysregulated genes in AMA with DOR or NOR were predicted. The GO enrichment analysis revealed that the DEGs were mainly enriched in obsolete oxidation–reduction process, mitochondrion, metal ion binding, ATP binding, etc. The KEGG pathway enrichment analysis revealed that the above-mentioned DEGs were mainly enriched in ferroptosis, regulation of actin cytoskeleton, oxidative phosphorylation, etc. Meanwhile, verification of the mRNA expression levels of DEGs revealed the possible involvement of “ferroptosis” in age-related diminished ovarian reserve.ConclusionsFrom a new clinical perspective, we presented the first data showing the transcriptomic profile in GCs between AMA with different ovarian reserve. At the same time, we identified the role of ferroptosis in the GCs of AMA, providing a new biological basis for studying ovarian aging and improving pregnancy outcomes of AMA.