Plant Hormone Pathway Is Involved in Regulating the Embryo Development Mechanism of the Hydrangea macrophylla Hybrid.

The research is aimed to elucidate the role of plant hormones in regulating the development of hybrid embryos in Hydrangea macrophylla. Fruits from the intraspecific cross of H. macrophylla 'Otaksa' × 'Coerulea' were selected at the globular, heart, and torpedo stages of embryo development. Transcriptome sequencing and differential gene expression analysis were conducted. The results showed that fruit growth followed a single "S-shaped growth curve, with globular, heart, and torpedo embryos appearing at 30, 40, and 50 d post-pollination, respectively, and the embryo maintaining the torpedo shape from 60 to 90 d. A total of 12,933 genes was quantified across the three developmental stages, with 3359, 3803, and 3106 DEGs in the S1_vs_S2, S1_vs_S3, and S2_vs_S3 comparisons, respectively. Among these, 133 genes related to plant hormone biosynthesis and metabolism were differentially expressed, regulating the synthesis and metabolism of eight types of plant hormones, including cytokinin, auxin, gibberellin, abscisic acid, and jasmonic acid. The pathways with the most differentially expressed genes were cytokinin, auxin, and gibberellin, suggesting these hormones may play crucial roles in embryo development. In the cytokinin pathway, CKX (Hma1.2p1_0579F.1_g182670.gene, Hma1.2p1_1194F.1_g265700.gene, and NewGene_12164) genes were highly expressed during the globular embryo stage, promoting rapid cell division in the embryo. In the auxin pathway, YUC (Hma1.2p1_0271F.1_g109005.gene and Hma1.2p1_0271F.1_g109020.gene) genes were progressively up-regulated during embryo growth; the early response factor AUX/IAA (Hma1.2p1_0760F.1_g214260.gene) was down-regulated, while the later transcriptional activator ARF (NewGene_21460, NewGene_21461, and Hma1.2p1_0209F.1_g089090.gene) was up-regulated, sustaining auxin synthesis and possibly preventing the embryo from transitioning to maturity. In the gibberellin pathway, GA3ox (Hma1.2p1_0129F.1_g060100.gene) expression peaked during the heart embryo stage and then declined, while the negative regulator GA2ox (Hma1.2p1_0020F.1_g013915.gene) showed the opposite trend; and the gibberellin signaling repressor DELLA (Hma1.2p1_1054F.1_g252590.gene) increased over time, potentially inhibiting embryo development and maintaining the torpedo shape until fruit maturity. These findings preliminarily uncover the factors affecting the development of hybrid H. macrophylla embryos, laying a foundation for further research into the regulatory mechanisms of H. macrophylla hybrid embryo development.

Targeting RNA N6-methyladenosine modification-- a novel therapeutic target for HER2- positive gastric cancer.

Gastric cancer is one of the most common cancers and is considered the 5th most frequent occurring cancer worldwide. It has gained great attention from the clinicians and researchers because of high mortality rate. It is generally treated with chemotherapy, radiotherapy, and surgery. Recently, additional treatment options including immunotherapy and targeted therapy and immunotherapy have been developed. However, poor prognosis, limited survival rate of patients, and drug resistance to treatment remain critical problems. To improve treatment options or to overcome the bottleneck of treatment, identification of diagnostic and prognostic markers, determining the most effective therapeutic options, and uncovering the molecular regulations associated with treatment strategies are required. In this regard n6-methyladenosine (m6A) regulation is considered important. This reversible modification plays a crucial role in progression, development and treatment of HER2-positive gastric cancer. Here, we discuss the role of m6A modification in HER2-positive gastric cancer progression through collecting related studies at present. We further discuss the association of m6A modification with therapeutic efficacy in HER2-positive gastric cancer and list some examples. We conclude that modification of m6A can be a new strategy for improving the prognosis and survival rate of HER2-positive gastric cancer patients.

Transcriptome, intestinal microbiome and histomorphology profiling of differences in the response of Chinese sea bass (Lateolabrax maculatus) to Aeromonas hydrophila infection.

The Chinese sea bass (Lateolabrax maculatus) is an important aquaculture fish, but diseases caused by Aeromonas hydrophila have led to severe economic losses to the aquaculture industry in recent years. To date, only a few studies have focused on the relationship between the intestinal immune response and changes in intestinal microbes by A. hydrophila infection. Here, we report the transcriptome and intestinal changes in infected sea bass. Histopathological results showed that severe steatosis and vacuolation occurred in the liver and that the intestinal villi and mesentery were seriously affected after infection. By extracting total RNA from intestinal tissue and studying the transcriptome profile, 1,678 genes (1,013 upregulated and 665 downregulated) were identified as significantly differentially expressed genes (DEGs). These genes are involved in many immune-related signalling pathways, such as the NOD-like receptor, C-type lectin receptor, and Toll-like receptor signalling pathways. Moreover, the intestinal microbes of sea bass changed significantly after infection. Interestingly, at the genus level, there was an increase in Serratia, Candida arthromitus and Faecalibacterium as well as a decrease in Akkermansia and Parabacteroides after infection. The results also indicated that some of the DEGs involved in the immune response were related to the genus level of intestinal microbiota. Finally, there was a relationship between gene expression patterns and the bacterial structure in the host intestine. Our study provides a reference for the study of the immune response and particular functions of intestinal microbes of sea bass after pathogen infection.

Effect of the R126C mutation on the structure and function of the glucose transporter GLUT1: A molecular dynamics simulation study.

Glucose transporter 1 (GLUT1) is responsible for basal glucose uptake and is expressed in most tissues under normal conditions. GLUT1 mutations can cause early-onset absence epilepsy and myoclonus dystonia syndrome (MDS), with MDS potentially lethal. In this study, the effect of the R126C mutation, which is associated with MDS, on structural stability and substrate transport of GLUT1 was investigated. Various bioinformatics tools were used to predict the stability of GLUT1, revealing that the R126C mutation reduces the structural stability of GLUT1. Molecular dynamics (MD) simulations were used to further characterize the effect of the R126C mutation on GLUT1 structural stability. Based on the MD simulations, specific conformational changes and dominant motions of the GLUT1 mutant were characterized by Principal component analysis (PCA). The mutation disrupts hydrogen bonds between substrate-binding residues and glucose, thus likely reducing substrate affinity. The R126C mutation reduces the conformational stability of the protein, and fewer intramolecular hydrogen bonds were present in the mutated GLUT1 when compared with that of wild-type GLUT1. The mutation increased the free energy of glucose transport through GLUT1 significantly, especially at the mutation site, indicating that passage of glucose through the channel is hindered, and this mutant may even release cytoplasmic glucose. This study provides a detailed atomic-level explanation for the reduced structural stability and substrate transport capacity of a GLUT1 mutant. The results aid our understanding of the structure of GLUT1 and provide a framework for developing drugs to treat GLUT1-related diseases, such as MDS.

Serum Anion Gap Is Associated with All-Cause Mortality among Critically Ill Patients with Congestive Heart Failure.

BACKGROUND: Congestive heart failure (CHF) is a complex clinical syndrome, with high morbidity and mortality. Serum anion gap (SAG) is associated with the severity of various cardiovascular diseases. However, the role of SAG indicators in CHF is unclear. METHODS AND RESULTS: A retrospective analysis of data from Multiparameter Intelligent Monitoring in Intensive Care III version 1.4 was conducted in critically ill patients with CHF. The clinical information of each patient, including demographic data, comorbidities, vital signs, scores, and laboratory indicators, were successfully obtained. Cox proportional hazards models were used to determine the relationship between SAG and mortality in patients with CHF, the consistency of which was further verified by subgroup analysis. RESULTS: A total of 7426 subjects met the inclusion criteria. Multivariate analysis showed that after adjusting for age, gender, ethnicity, and other potential confounders, increased SAG was significantly related to an increase in 30- and 90-day all-cause mortalities of critically ill patients with CHF compared with decreased SAG (tertile 3 versus tertile 1: adjusted hazard ratio, 95% confidence interval: 1.74, 1.46-2.08; 1.53, 1.32-1.77). Subgroup analysis indicated that the association between SAG and all-cause mortality presented similarities in most strata. CONCLUSION: SAG at admission could be a promising predictor of all-cause mortality in critically ill patients with CHF.