Genome-wide association studies dissect low-phosphorus stress response genes underling field and seedling traits in maize.

Phosphorus (P) is an essential element for plant growth, and its deficiency can cause decreased crop yield. This study systematically evaluated the low-phosphate (Pi) response traits in a large population at maturity and seedling stages, and explored candidate genes and their interrelationships with specific traits. The results revealed a greater sensitivity of seedling maize to low-Pi stress compared to that at maturity stage. The phenotypic response patterns to low-Pi stress at different stages were independent. Chlorophyll content was found to be a potential indicator for screening low-Pi-tolerant materials in the field. A total of 2900 and 1446 significantly associated genes at the maturity and seedling stages were identified, respectively. Among these genes, 972 were uniquely associated with maturity traits, while 330 were specifically detected at the seedling stage under low-Pi stress. Moreover, 768 and 733 genes were specifically associated with index values (low-Pi trait/normal-Pi trait) at maturity and seedling stage, respectively. Genetic network diagrams showed that the low-Pi response gene Zm00001d022226 was specifically associated with multiple primary P-related traits under low-Pi conditions. A total of 963 out of 2966 genes specifically associated with traits under low-Pi conditions or index values were found to be induced by low-Pi stress. Notably, ZmSPX4.1 and ZmSPX2 were sharply up-regulated in response to low-Pi stress across different lines or tissues. These findings advance our understanding of maize's response to low-Pi stress at different developmental stages, shedding light on the genes and pathways implicated in this response.

Genomic profiling informs therapies and prognosis for patients with hepatocellular carcinoma in clinical practice.

Hepatocellular carcinoma (HCC) genomic research has discovered actionable genetic changes that might guide treatment decisions and clinical trials. Nonetheless, due to a lack of large-scale multicenter clinical validation, these putative targets have not been converted into patient survival advantages. So, it's crucial to ascertain whether genetic analysis is clinically feasible, useful, and whether it can be advantageous for patients. We sequenced tumour tissue and blood samples (as normal controls) from 111 Chinese HCC patients at Qingdao University Hospital using the 508-gene panel and the 688-gene panel, respectively. Approximately 95% of patients had gene variations related to targeted treatment, with 50% having clinically actionable mutations that offered significant information for targeted therapy. Immune cell infiltration was enhanced in individuals with TP53 mutations but decreased in patients with CTNNB1 and KMT2D mutations. More notably, we discovered that SPEN, EPPK1, and BRCA2 mutations were related to decreased median overall survival, although MUC16 mutations were not. Furthermore, we found mutant MUC16 as an independent protective factor for the prognosis of HCC patients after curative hepatectomy. In conclusion, this study connects genetic abnormalities to clinical practice and potentially identifies individuals with poor prognoses who may benefit from targeted treatment or immunotherapy.

Exploring the phosphorus-starch content balance mechanisms in maize grains using GWAS population and transcriptome data.

Examining the connection between P and starch-related signals can help elucidate the balance between nutrients and yield. This study utilized 307 diverse maize inbred lines to conduct multi-year and multi-plot trials, aiming to explore the relationship among P content, starch content, and 100-kernel weight (HKW) of mature grains. A significant negative correlation was found between P content and both starch content and HKW, while starch content showed a positive correlation with HKW. The starch granules in grains with high-P and low-starch content (HPLS) were significantly smaller compared to grains with low-P high-starch content (LPHS). Additionally, mian04185-4 (HPLS) exhibited irregular and loosely packed starch granules. A significant decrease in ZmPHOs genes expression was detected in the HPLS line ZNC442 as compared to the LPHS line SCML0849, while no expression difference was observed in AGPase encoding genes between these two lines. The down-regulated genes in ZNC442 grains were enriched in nucleotide sugar and fatty acid anabolic pathways, while up-regulated genes were enriched in the ABC transporters pathway. An accelerated breakdown of fat as the P content increased was also observed. This implied that HPLS was resulted from elevated lipid decomposition and inadequate carbon sources. The GWAS analysis identified 514 significantly associated genes, out of which 248 were differentially expressed. Zm00001d052392 was found to be significantly associated with P content/HKW, exhibiting high expression in SCML0849 but almost no expression in ZNC442. Overall, these findings suggested new approaches for achieving a P-yield balance through the manipulation of lipid metabolic pathways in grains.

Molecular characterization, expression analysis and function identification of Pf_IL-12p35, Pf_IL-23p19 and Pf_IL-12p40 genes in yellow catfish (Pelteobagrus fulvidraco).

The interleukin-12 (IL-12) family is a class of heterodimeric cytokines that play crucial roles in pro-inflammatory and pro-stimulatory responses. Although some IL-12 and IL-23 paralogues have been found in fish, their functional activity in fish remains poorly understood. In this study, Pf_IL-12p35a/b, Pf_IL-23p19 and Pf_IL-12p40a/b/c genes were cloned from yellow catfish (Pelteobagrus fulvidraco), four α-helices were found in Pf_IL-12p35a/b and Pf_IL-23p19. The transcripts of these six genes were relatively high in mucus and immune tissues of healthy individuals, and in gill leukocytes. Following Edwardsiella ictaluri infection, Pf_IL-12p35a/b and Pf_IL-23p19 mRNAs were induced in brain and kidney (or head kidney), Pf_IL-12p40a mRNA was induced in gill, and Pf_IL-12p40b/c mRNAs were induced in brain and liver (or skin). The mRNA expression of these genes in PBLs was induced by phytohaemagglutinin (PHA) and polyinosinic-polycytidylic acid (poly I:C), while lipopolysaccharides (LPS) induced the mRNA expression of Pf_IL-12p35a and Pf_IL-12p40b/c in PBLs. After stimulation with recombinant (r) Pf_IL-12 and rPf_IL-23 subunit proteins, either alone or in combination, mRNA expression patterns of genes related to T helper cell development exhibited distinct differences. The results suggest that Pf_IL-12 and Pf_IL-23 subunits may play important roles in regulating immune responses to pathogens and T helper cell development.

Somatic mutations that affect early genetic progression and immune microenvironment in gastric carcinoma.

Gastric carcinoma (GC) is a high heterogeneity and malignant tumor with a poor prognosis. The current implementation of immunotherapy in GC is limited due to the insufficient exploration of immune-related mutations and speculated early mutation events. Therefore, we performed whole-exome sequencing on 40 patients with GC to explore their genetic characteristics, shedding light on the order of genetic events, somatic mutations impacting the immune microenvironment, and potential biomarkers for immunotherapy. Regarding genetic events, TP53 disruptions were identified as frequent and early events in GC progression, often occurring alongside other gene mutations. The mutations occurring in GANS, SMAD4, and POLE were early independent events. Patients harboring CSMD3, FAT4, FLG, KMT2C, LRP1B, MUC5B, MUC16, PLEC, RNF43, SYNE1, TP53, TTN, XIRP2, and ZFHX4 mutations tended to have decreased B cells, T cells, macrophage, neutrophil, and dendritic cells infiltration, except for the ARID1A gene mutations. We also found patients with microsatellite instability-high tumors had higher homologous recombination deficiency (HRD) scores. HRD showed a positive correlation with tumor mutational burden, which might serve as indirect evidence supporting the potential of HRD as a biomarker for GC. These findings highlighted GC's high heterogeneity and complexity and provided valuable insights into the somatic mutations that affect early genetic progression and immune microenvironment.