The combined effect of MTHFR C677T and A1298C polymorphisms on the risk of digestive system cancer among a hypertensive population.

BACKGROUND AND PURPOSE: The enzyme methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in directing folate species towards nucleotide synthesis or DNA methylation. The MTHFR polymorphisms C677T and A1298C have been linked to cancer susceptibility, but the evidence supporting this association has been equivocal. To investigate the individual and joint associations between MTHFR C677T, A1298C, and digestive system cancer in a Chinese hypertensive population, we conducted a population-based case-control study involving 751 digestive system cancer cases and one-to-one matched controls from the China H-type Hypertension Registry Study (CHHRS). METHODS: We utilized the conditional logistic regression model to evaluate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) of digestive system cancer. RESULTS: The analysis revealed a significantly lower risk of digestive system cancer in individuals with the CT genotype (adjusted OR: 0.71; 95% CI 0.52, 0.97; P = 0.034) and TT genotype (adjusted OR: 0.57; 95% CI 0.40, 0.82; P = 0.003; P for trend = 0.003) compared to those with the 677CC genotype. Although A1298C did not show a measurable association with digestive system cancer risk, further stratification of 677CT genotype carriers by A1298C homozygotes (AA) and heterozygotes (AC) revealed a distinct trend within these subgroups. CONCLUSION: These findings indicate a potential protective effect against digestive system cancer associated with the T allele of MTHFR C677T. Moreover, we observed that the presence of different combinations of MTHFR polymorphisms may contribute to varying susceptibilities to digestive system cancer.

The complete chloroplast genome sequence of Begonia ferox, an endangered species in China.

Begonia ferox C.I Peng & Yan Liu (2013) was rated as endangered according to Red List of Chinese Plants. In this study, we report the complete chloroplast genome of B. ferox. The chloroplast genome is 169,114 bp in length as the circular, with the GC content of 35.5%, composed by a large single-copy (LSC) region of 75,887 bp, a small single-copy (SSC) region of 18,105 bp, and two inverted repeat regions (IRs) of 37,561 bp in each. The genome comprises 174 encoded genes in total, including 114 protein-coding genes, eight ribosomal RNA genes, and 52 transfer RNA genes. Phylogenetic analysis indicated that B. ferox is genetically closest to B. gulongshanensis.

Whole-genome assembly of A02 bacteria involved in nitrogen fixation within cassava leaves.

The endophytic nitrogen (N)-fixing bacterium A02 belongs to the genus Curtobacterium (Curtobacterium sp.) and is crucial for the N metabolism of cassava ( Manihot esculenta Crantz). We isolated the A02 strain from cassava cultivar SC205 and used the 15N isotope dilution method to study the impacts of A02 on growth and accumulation of N in cassava seedlings. Furthermore, the whole genome was sequenced to determine the N-fixation mechanism of A02. Compared with low N control (T1), inoculation with the A02 strain (T2) showed the highest increase in leaf and root dry weight of cassava seedlings, and 120.3 nmol/(mL·h) was the highest nitrogenase activity recorded in leaves, which were considered the main site for colonization and N-fixation. The genome of A02 was 3,555,568 bp in size and contained a circular chromosome and a plasmid. Comparison with the genomes of other short bacilli revealed that strain A02 showed evolutionary proximity to the endophytic bacterium NS330 (Curtobacterium citreum) isolated from rice (Oryza sativa) in India. The genome of A02 contained 13 nitrogen fixation (nif) genes, including 4 nifB, 1 nifR3, 2 nifH, 1 nifU, 1 nifD, 1 nifK, 1 nifE, 1 nifN, and 1 nifC, and formed a relatively complete N fixation gene cluster 8-kb long that accounted for 0.22% of the whole genome length. The nifHDK of strain A02 (Curtobacterium sp.) is identical to the Frankia alignment. Function prediction showed high copy number of the nifB gene was related to the oxygen protection mechanism. Our findings provide exciting information about the bacterial genome in relation to N support for transcriptomic and functional studies for increasing N use efficiency in cassava.

Editing of rice (Oryza sativa L.) OsMKK3 gene using CRISPR/Cas9 decreases grain length by modulating the expression of photosystem components.

Grain size is one of the most important agronomic traits for grain yield determination in rice. To better understand the proteins that are regulated by the grain size regulatory gene OsMKK3, this gene was knocked out using the CRISPR/Cas9 system, and tandem mass tag (TMT) labeling combined with liquid chromatograph-tandem mass spectrometry analysis was performed to study the regulation of proteins in the panicle. Quantitative proteomic screening revealed a total of 106 differentially expressed proteins (DEPs) via comparison of the OsMKK3 mutant line to the wild-type YexiangB, including 15 and 91 up-regulated and down-regulated DEPs, respectively. Pathway analysis revealed that DEPs were enriched in metabolic pathways, biosynthesis of secondary metabolites, phenylpropanoid biosynthesis, and photosynthesis. Strong interactions were detected among seven down-regulated proteins related to photosystem components in the protein-protein interaction network, and photosynthetic rate was decreased in mutant plants. The results of the liquid chromatography-parallel reaction monitoring/mass spectromery analysis and western blot analysis were consistent with the results of the proteomic analysis, and the results of the quantitative reverse transcription polymerase chain reaction analysis revealed that the expression levels of most candidate genes were consistent with protein levels. Overall, OsMKK3 controls grain size by regulating the protein content in cells. Our findings provide new candidate genes that will aid the study of grain size regulatory mechanisms associated with the mitogen-activated protein kinase (MAPK) signaling pathway.

Serum Serine and the Risk of All-Cause Mortality: A Nested Case-Control Study From the China Stroke Primary Prevention Trial (CSPPT).

Background: Serine plays a key role in numerous cellular processes, the levels and metabolism is therefore of critical importance. However, few data are available to illustrate the association of serine with long-term health effects, especially, the predictive value for long-term mortality. Objective: This study was conducted to evaluate the relationship between serum serine levels and all-cause mortality in general hypertensive patients in a longitudinal cohort, and to examine the potential effect modifiers. Methods: A nested case-control (NCC) study was conducted utilizing 20702 hypertensive participants from the China Stroke Primary Prevention Trial (CSPPT), a randomized, double-blind, actively controlled trial conducted from May 2008 to August 2013 in China. The current study included 291 cases of all-cause mortality and 291 controls matched on age (≤ 1 year), sex and treatment group. All-cause mortality was the main outcome in this analysis, which included death due to any reason. Results: With the increase in serum serine levels, the risk of all-cause mortality first increased before flattening. After adjusting for related variables, the risk of mortality increased significantly with the increase of serum serine levels. Compared with group Q1, the mortality risk of group Q2, Q3 and Q4 were significantly increased [ORs, 95% CI: Q2: 2.32, (1.32-4.07); Q3: 2.59, (1.48-4.54); and Q4: 1.85, (1.07-3.22)]. In the exploratory analysis, we observed three effect modifiers, total homocysteine, 5-Methyltetrahydrofolate, and estimated glomerular filtration rate significantly modified the serum serine and all-cause mortality association. Conclusion: Serum serine levels were significantly associated with an increased risk of all-cause mortality in hypertensive patients. Our results and findings, if confirmed further, suggest that serum serine should be considered as a marker for screening risk factors of mortality. Clinical Trial Registration: [https://www.clinicaltrials.gov/ct2/show/study/NCT00794885.], identifier [CSPPT, NCT00794885].

MeNPF4.5 Improves Cassava Nitrogen Use Efficiency and Yield by Regulating Nitrogen Uptake and Allocation.

Improving nitrogen use efficiency (NUE) is a very important goal of crop breeding throughout the world. Cassava is an important food and energy crop in tropical and subtropical regions, and it mainly use nitrate as an N source. To evaluate the effect of the nitrate transporter gene MeNPF4.5 on the uptake and utilization of N in cassava, two MeNPF4.5 overexpression lines (MeNPF4.5 OE-22 and MeNPF4.5 OE-34) and one MeNPF4.5 RNA interference (RNAi) line (MeNPF4.5 Ri-1) were used for a tissue culture experiment, combining with a field trial. The results indicated that MeNPF4.5 is a plasma membrane transporter mainly expressed in roots. The gene is induced by NO3 -. Compared with the wild type, MeNPF4.5 OE-22 exhibited improved growth, yield, and NUE under both low N and normal N levels, especially in the normal N treatment. However, the growth and N uptake of RNAi plants were significantly reduced, indicating poor N uptake and utilization capacity. In addition, photosynthesis and the activities of N metabolism-related enzymes (glutamine synthetase, glutamine oxoglutarate aminotransferase, and glutamate dehydrogenase) of leaves in overexpression lines were significantly higher than those in wild type. Interestingly, the RNAi line increased enzymatic activity but decreased photosynthesis. IAA content of roots in overexpressed lines were lower than that in wild type under low N level, but higher than that of wild type under normal N level. The RNAi line increased IAA content of roots under both N levels. The IAA content of leaves in the overexpression lines was significantly higher than that of the wild type, but showed negative effects on that of the RNAi lines. Thus, our results demonstrated that the MeNPF4.5 nitrate transporter is involved in regulating the uptake and utilization of N in cassava, which leads to the increase of N metabolizing enzyme activity and photosynthesis, along with the change of endogenous hormones, thereby improving the NUE and yield of cassava. These findings shed light that MeNPF4.5 is involved in N use efficiency use in cassava.

Association between serum 5-methyltetrahydrofolate and homocysteine in Chinese hypertensive participants with different MTHFR C677T polymorphisms: a cross-sectional study.

BACKGROUND AND AIMS: Clarifying the association between 5-methyltetrahydrofolate and homocysteine and the effect pattern of methylene tetrahydrofolate reductase (MTHFR C677T) may contribute to the management of homocysteine and may serve as a significant reference for a randomized controlled trial of 5-methyltetrahydrofolate intervention. This study aimed to reveal the association between these two biochemical indices. METHODS: Study population was drawn from the baseline data of the China Stroke Primary Prevention Trial (CSPPT), including 2328 hypertensive participants. 5-methyltetrahydrofolate and homocysteine were determined by stable-isotope dilution liquid chromatography-tandem mass spectrometry and automatic clinical analyzers, respectively. MTHFR C677T polymorphisms were detected using TaqMan assay. Multiple linear regression was performed to evaluate the association between serum 5-methyltetrahydrofolate and homocysteine. RESULTS: There was a significant inverse association between 5-methyltetrahydrofolate and homocysteine when 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T (per 1-ng/mL increment; All: ß = - 0.50, P <  0.001; CC: ß = - 0.14, P = 0.087; CT: ß = - 0.20, P = 0.011; TT: ß = - 1.19, P <  0.001). Moreover, the decline in trend in genotype TT participants was stronger than in genotype CC participants (P for difference <  0.001) and genotype CT participants (P for difference <  0.001), while there was no significant difference between genotype CC and genotype CT participants (P for difference = 0.757). CONCLUSIONS: Our data showed a non-linear association between serum homocysteine and 5-methyltetrahydrofolate among Chinese hypertensive adults, however, it could be inversely linearly fitted when serum 5-methyltetrahydrofolate was ≤ 10 ng/mL, and this association was modified by MTHFR C677T.

Association of serum choline levels and all-cause mortality risk in adults with hypertension: a nested case-control study.

BACKGROUND: Serum choline levels were associated with multiple chronic diseases. However, the association between serum choline and all-cause mortality in Chinese adults with hypertension remains unclear. The purpose of this study is to explore the association between serum choline concentrations and all-cause mortality risk in Chinese adults with hypertension, a high-risk population. METHODS: A nested, case-control study was conducted that included 279 patients with all-cause death, and 279 matched, living controls, derived from the China Stroke Primary Prevention Trial (CSPPT). Baseline serum choline concentrations were measured by liquid chromatography with tandem quadrupole mass spectrometry (LC-MS/MS). Multivariate logistic regression analysis was used to assess the association of serum choline levels and all-cause mortality risk, with adjustment of pertinent covariables, including folic acid and homocysteine. RESULTS: The median age of all participants was 64.13 years [interquartile range (IQR), 57.33-70.59 years]. The median serum choline concentration for cases (9.51 µg/mL) was higher than that in controls (7.80 µg/mL) (P = 0.009). When serum choline concentration was assessed as a continuous variable (per SD increased), there was a positive relation between serum choline levels and all-cause mortality risk [odds ratios (OR), 1.29; 95% confidence intervals (95%CI), 1.06-1.57; P = 0.010]. There was an increased all-cause mortality risk for participants in quartiles 2-4 (≥ 4.00 µg/mL; OR, 1.79; 95%CI, 1.15-2.78 compared with quartile 1 (< 4.00 µg/mL). In addition, non-drinking was found to promote the incidence of all-cause mortality for those with high choline concentrations. CONCLUSIONS: High serum choline concentrations were associated with increased all-cause mortality risk among Chinese adults with hypertension, compared to lower choline concentrations. Trial registration clinicaltrials.gov Identifier: NCT007948885; UTL: https://clinicaltrials.gov/ct2/show/NCT00794885?term=NCT00794885&draw=2&rank=1.