Risk of heart disease and stroke among individuals with prehypertension or blood pressure progression: a national population-based cohort study.

OBJECTIVE: The purpose of our study was to analyze the association of blood pressure and blood pressure progression with heart disease and stroke among Chinese population. METHOD: We included a total of 10 122 adults aged 45 years and above free of heart disease or stroke at baseline from the China Health and Retirement Longitudinal Study cohort. We used Cox proportional hazards models to analyze the relationship between cardiovascular risk and prehypertension in subjects with or without progression to hypertension. RESULT: During a mean follow-up of 6.5 years, 1972 subjects were either diagnosed with heart disease or had a stroke (composite outcome). Compared with individuals with normotension at baseline, the fully adjusted hazard ratio (HR) [95% confidence interval (CI)] was 1.25 (1.10-1.42) and 1.52 (1.34-1.74) for composite outcome in individuals with prehypertension and hypertension at baseline, respectively. The subjects who progressed to hypertension had higher risk of cardiovascular outcomes than those who remained at normal blood pressure or prehypertension in a fully adjusted model. The subjects who progressed from prehypertension to hypertension had 1.72 times higher risk [HR (95% CI): 1.72 (1.37-2.16)] of cardiovascular outcomes than those who remained at normal blood pressure or prehypertension in a fully adjusted model. CONCLUSION: The cardiovascular risk of subjects with prehypertension is higher than that of subjects with normal blood pressure. After a diagnosis of hypertension, subjects who progressed from normal blood pressure to hypertension had an increased risk of heart disease and stroke.

Fine mapping of genes controlling pigment accumulation in oilseed rape (Brassica napus L.).

Purple/red appearance is one of the common phenotypic variations in leaves, stems, and siliques of oilseed rape (Brassica napus L.) but very rare in flowers. In this study, the causal genes for the purple/red traits in stems and flowers in two accessions of oilseed rape (DH_PR and DH_GC001, respectively) derived from the wide hybridization were fine mapped, and candidate genes were determined by methods combined with bulked segregant analysis (BSA) and RNA-seq analysis. Both traits of purple stem and red flowers were mapped to the locus as AtPAP2 homologous genes (BnaPAP2.C6a and BnaPAP2.A7b, respectively) belonging to the R2R3-MYB family. Sequence comparisons of full-length allelic genes revealed several InDels and SNPs in intron 1 as well as exons, and completely different promoter region of BnaPAP2.C6a and a 211 bp insertion was identified in the promoter region of BnaPAP2.A7b of DH_GC001. Our results not only contribute to a better understanding of anthocyanin inheritance in B. napus, but also provide a useful toolbox for future breeding of cultivars with purple/red traits through the combination of different functional alleles and homologs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01365-5.

Pan-cancer analysis of Homeobox B9 as a predictor for prognosis and immunotherapy in human tumors.

BACKGROUND: Although several animal and cell studies have described the association between HOXB9 and cancers, there is no pan-cancer investigation of HOXB9. In this article, we explored the expression levels and prognosis of HOXB9 in pan-cancer. We evaluated the correlation of HOXB9 expression level with the efficacy of immunotherapy. METHODS: We conducted a survival analysis of HOXB9 in various types of cancer using publicly available databases. We also examined the relationship between HOXB9 expression levels and several factors including prognosis, immune infiltration, immune checkpoint genes, tumor mutational burden, microsatellite instability, mismatch repair, and DNA methylation. TIMER2.0 tool was conducted to explore the immune cell infiltrations related to HOXB9 in this analysis. RESULTS: It was discovered through a comprehensive analysis of multiple public datasets that HOXB9 expression was highly expressed in most tumor tissues and cancer cell lines and that distinct associations exist between HOXB9 expression and tumor patient prognosis. Besides, HOXB9 expression was closely associated with immune cell infiltration and checkpoint genes in many cancers. Further, HOXB9 was associated with immune cell infiltration, TMB, MSI, MMR, and DNA methylation. It was also confirmed that HOXB9 was highly expressed in clinical GBM tissues. Experiments further revealed that knockdown of HOXB9 expression could suppress proliferation, migration, and invasion of glioma cells. CONCLUSIONS: The results revealed that HOXB9, a robust tumor biomarker, has a significant prognostic value. HOXB9 may act as a new predictor to assess cancer prognosis and therapeutic efficacy of the immune in various cancers.

Transposon insertions within alleles of BnaFT.A2 are associated with seasonal crop type in rapeseed.

KEY MESSAGE: We identified two new transposon insertions within the promoter of BnaFT.A2 in addition to an existing 288 bp MITE within the second intron. Each insertion event corresponds to a distinct BnaFT.A2 haplotype and is closely associated with established crop seasonal ecotypes. Florigen, encoded by FLOWERING LOCUS T (FT), plays key roles not only as a flowering hormone, but also a universal growth factor affecting several aspects of plant architecture. In rapeseed, BnaFT.A2 has been revealed as one of the major loci associated with flowering time and different ecotypes. However, it is unclear how allelic variations of BnaFT.A2 affect its function in flowering time regulation and beyond. In this study, we confirmed an existing 288 bp miniature inverted-repeat transposable element (MITE) insertion within the second intron and identified two new insertions within the promoter of BnaFT.A2-a 3971 bp CACTA and a 1079 bp Helitron. Each insertion event corresponds to a distinct BnaFT.A2 haplotype and is closely associated with established crop seasonal ecotypes. These alleles have similar tissue-specific expression patterns but discrete transcriptional patterns tightly associated with rapeseed flowering time and ecotype. RNAi lines and mutants of BnaFT.A2 flowered significantly later than controls. Differentially expressed genes (DEGs), identified in transcriptomic profiling of seedling leaves from two loss-of-function mutants (Bnaft.a2-L1 and Bnaft.a2-L2) compared with controls, indicated significant enrichment for hormone metabolic genes and roles related to plant cell wall synthesis and photosynthesis. Plants with loss-of-function BnaFT.A2 had smaller leaves and lower net photosynthetic rate compared to controls. These findings not only further clarify the genetic basis of flowering time variation and ecotype formation in B. napus, but also provide an additional toolbox for genetic improvement of seasonal adaptation and production.

Functional homoeologous alleles of CONSTANS contribute to seasonal crop type in rapeseed.

KEY MESSAGE: Two CO paralogs in Brassica napus were confirmed and shown distinct expression pattern and function in promoting flowering and allelic variation s within BnaCO.A10 were found closely associated with ecotype divergence. CONSTANS (CO) is a key gene that responds to photoperiod and in Arabidopsis can promote flowering under long-day (LD) conditions. Brassica napus L. is a major oil crop and close relative of Arabidopsis, and arose via allopolyploidization from the diploids B. rapa (A genome) and B. oleracea (C genome). In this study, we confirmed that B. napus has two CO genes located on the A10 (BnaCO.A10) and C9 (BnaCO.C9) chromosomes. Significant differences in level and temporal pattern of transcription, as well as in protein function, of these homoeologous may have resulted from sequence variation in the promoter as well as in the coding region. Apart from two insertions of 527 bp and 2002 bp in the promoter of BnaCO.C9 that function as transcriptional enhancers, this gene is otherwise highly conserved in both promoter and coding region. However, BnaCO.A10 was classified into two haplotypes and transgene analysis in Arabidopsis and backcross analysis in rapeseed indicated that the winter-type haplotype had a greater effect in promoting flowering than the spring type. We discuss the contribution of CO alleles to species evolution, and for eco-geographic radiation following crop domestication, alongside scope for managing this locus in future breeding.

Development and internal validation of a multivariable prediction model for 6-year risk of stroke: a cohort study in middle-aged and elderly Chinese population.

OBJECTIVE: To develop and internally validate a prediction model for 6-year risk of stroke and its primary subtypes in middle-aged and elderly Chinese population. DESIGN: This is a retrospective cohort study from a prospectively collected database. PARTICIPANTS: We included a total 3124 adults aged 45-80 years, free of stroke or myocardial infarction at baseline in the 2009-2015 cohort of China Health and Nutrition Survey. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcome of the prediction model was stroke. Investigated predictors were: age, gender, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), hypertension (HBP), drinking status, smoking status, diabetes and site. Stepwise multiple Cox regression was applied to identify independent predictors. A nomogram was constructed to predict 6-year risk of stroke based on the multiple analysis results. Bootstraps with 1000 resamples were applied to both C-index and calibration curve. RESULT: The overall incidence of overall stroke was 2.98%. Age, gender, HBP and TC were found as significant risk predictors for overall stroke; age, gender, HBP and LDL-C were found as significant risk predictors for ischaemic stroke; age, gender, HBP, BMI and HDL-C were found as significant risk predictors for haemorrhagic stroke. The nomogram was constructed using significant variables included in the model, with a C-index of 0.74 (95% CI: 0.72 to 0.76), 0.74 (95% CI: 0.71 to 0.77), and 0.81 (95% CI: 0.78 to 0.84) for overall stroke, ischaemic stroke, and haemorrhagic stroke model, respectively. The calibration curves demonstrated the good agreements between predicted and observed 6-year risk probability. CONCLUSION: Our nomogram could be convenient, easy to use and effective prognoses for predicting 6-year risk of stroke in middle-aged and elderly Chinese population.

Alternatively Spliced BnaPAP2.A7 Isoforms Play Opposing Roles in Anthocyanin Biosynthesis of Brassica napus L.

Brassica napus L. (rapeseed, oilseed rape, and canola) and varieties of its two diploid parents, B. oleracea and B. rapa, display a large amount of variation in anthocyanin pigmentation of the leaf, stem, and fruit. Here, we demonstrate that BnaPAP2.A7, an ortholog of the B. oleracea anthocyanin activator BoMYB2 that confers purple traits, positively regulates anthocyanin biosynthesis in leaves of B. napus. Sequencing of BnaPAP2.A7 and transgenic analysis suggests that activation of this gene in purple rapeseed may result from a single nucleotide and/or 2bp insertion in its promoter region. BnaPAP2.A7 gives rise to three splice variants, designated BnaPAP2.A7-744, BnaPAP2.A7-910, and BnaPAP2.A7-395 according to the length of the transcripts. While BnaPAP2.A7-744 encodes a full-length R2R3-MYB, both BnaPAP2.A7-910 and BnaPAP2.A7-395 encode truncated proteins that lack both a partial R3 repeat and the complete C terminal domain, and so in vitro are unable to interact with the Arabidopsis bHLH protein AtTT8. Although expression of either BnaPAP2.A7-910 or BnaPAP2.A7-395 in green rapeseed does not result in purple leaves, both genes do modify genome-wide gene expression, with a strong repression of anthocyanin-related genes. We have demonstrated that BnaPAP.A7 regulates anthocyanin accumulation in leaves of B. napus and propose a potential mechanism for modulation of anthocyanin biosynthesis by alternative splicing.

[Anti-gastric cancer effect of melatonin and Bcl-2, Bax, p21 and p53 expression changes].

In order to investigate the role of melatonin in inhibiting the proliferation of murine gastric cancer and the underlying molecular mechanism, we performed an in vivo study by inoculating murine foregastric carcinoma (MFC) cells in mice, and then tumor-bearing mice were treated with different concentrations of melatonin (i.p.). The changes of Bcl-2, Bax, p21 and p53 expressions in tumor tissue were detected by using real-time fluorescence quantitative RT-PCR and Western blot. We found that: (1) melatonin resulted in reductions of tumor's volume and weight in the gastric cancer-bearing mice and thus showed anti-cancer effect; (2) melatonin reduced Bcl-2 expression, but increased the expression of Bax, p53 and p21 in tumor tissue. Our results suggest that melatonin could inhibit the growth of tumors in gastric cancer-bearing mice through accelerating the apoptosis of tumor cells.