Effects of long-term exposure to ambient fine particulate matter and its specific components on blood pressure and hypertension incidence.

BACKGROUND: Epidemiological evidence on the association of PM2.5 (particulate matter with aerodynamic diameter ≤ 2.5 µm) and its specific components with hypertension and blood pressure is limited. METHODS: We applied information of participants from the World Health Organization's (WHO) Study on Global Ageing and Adult Health (SAGE) to estimate the associations of long-term PM2.5 mass and its chemical components exposure with blood pressure (BP) and hypertension incidence in Chinese adults ≥ 50 years during 2007-2018. Generalized linear mixed model and Cox proportional hazard model were applied to investigate the effects of PM2.5 mass and its chemical components on the incidence of hypertension and BP, respectively. RESULTS: Each interquartile range (IQR = 16.80 µg/m3) increase in the one-year average of PM2.5 mass concentration was associated with a 17 % increase in the risk of hypertension (HR = 1.17, 95 % CI: 1.10, 1.24), and the population attributable fraction (PAF) was 23.44 % (95 % CI: 14.69 %, 31.55 %). Each IQR µg/m3 increase in PM2.5 exposure was also related to increases of systolic blood pressure (SBP) by 2.54 mmHg (95 % CI:1.99, 3.10), and of diastolic blood pressure (DBP) by 1.36 mmHg (95 % CI: 1.04, 1.68). Additionally, the chemical components of SO42-, NO3-, NH4+, OM, and BC were also positively associated with an increased risk of hypertension incidence and elevated blood pressure. CONCLUSIONS: These results indicate that long-term exposure to PM2.5 mass and its specific components may be major drivers of escalation in hypertension diseases.

Joint Effects of Long-Term Exposure to Ambient Fine Particulate Matter and Ozone on Asthmatic Symptoms: Prospective Cohort Study.

BACKGROUND: The associations of long-term exposure to air pollutants in the presence of asthmatic symptoms remain inconclusive and the joint effects of air pollutants as a mixture are unclear. OBJECTIVE: We aimed to investigate the individual and joint associations of long-term exposure to ambient fine particulate matter (PM2.5) and daily 8-hour maximum ozone concentrations (MDA8 O3) in the presence of asthmatic symptoms in Chinese adults. METHODS: Data were derived from the World Health Organization Study on Global Ageing and Adult Health (WHO SAGE) cohort study among adults aged 50 years or older, which was implemented in 1 municipality and 7 provinces across China during 2007-2018. Annual average MDA8 O3 and PM2.5 at individual residential addresses were estimated by an iterative random forest model and a satellite-based spatiotemporal model, respectively. Participants who were diagnosed with asthma by a doctor or taking asthma-related therapies or experiencing related conditions within the past 12 months were recorded as having asthmatic symptoms. The individual associations of PM2.5 and MDA8 O3 with asthmatic symptoms were estimated by a Cox proportional hazards regression model, and the joint association was estimated by a quantile g-computation model. A series of subgroup analyses was applied to examine the potential modifications of some characteristics. We also calculated the population-attributable fraction (PAF) of asthmatic symptoms attributed to PM2.5 and MDA8 O3. RESULTS: A total of 8490 adults older than 50 years were included, and the average follow-up duration was 6.9 years. During the follow-up periods, 586 (6.9%) participants reported asthmatic symptoms. Individual effect analyses showed that the risk of asthmatic symptoms was positively associated with MDA8 O3 (hazard ratio [HR] 1.12, 95% CI 1.01-1.24, for per quantile) and PM2.5 (HR 1.18, 95% CI 1.05-1.31, for per quantile). Joint effect analyses showed that per equal quantile increment of MDA8 O3 and PM2.5 was associated with an 18% (HR 1.18, 95% CI 1.05-1.33) increase in the risk of asthmatic symptoms, and PM2.5 contributed more (68%) in the joint effects. The individual PAFs of asthmatic symptoms attributable to PM2.5 and MDA8 O3 were 2.86% (95% CI 0.17%-5.50%) and 4.83% (95% CI 1.42%-7.25%), respectively, while the joint PAF of asthmatic symptoms attributable to exposure mixture was 4.32% (95% CI 1.10%-7.46%). The joint associations were greater in participants with obesity, in urban areas, with lower family income, and who used unclean household cooking fuel. CONCLUSIONS: Long-term exposure to PM2.5 and MDA8 O3 may individually and jointly increase the risk of asthmatic symptoms, and the joint effects were smaller than the sum of individual effects. These findings informed the importance of joint associations of long-term exposure to air pollutants with asthma.

Comparative transcriptomic analyses of glucosinolate metabolic genes during the formation of Chinese kale seeds.

BACKGROUND: To understand the mechanism of glucosinolates (GSs) accumulation in the specific organs, combined analysis of physiological change and transcriptome sequencing were applied in the current study. Taking Chinese kale as material, seeds and silique walls were divided into different stages based on the development of the embryo in seeds and then subjected to GS analysis and transcriptome sequencing. RESULTS: The main GS in seeds of Chinese kale were glucoiberin and gluconapin and their content changed with the development of the seed. During the transition of the embryo from torpedo- to the early cotyledonary-embryo stage, the accumulation of GS in the seed was accompanied by the salient decline of GS in the corresponding silique wall. Thus, the seed and corresponding silique wall at these two stages were subjected to transcriptomic sequencing analysis. 135 genes related to GS metabolism were identified, of which 24 genes were transcription factors, 81 genes were related to biosynthetic pathway, 25 genes encoded catabolic enzymes, and 5 genes matched with transporters. The expression of GS biosynthetic genes was detected both in seeds and silique walls. The high expression of FMOGS-OX and AOP2, which is related to the production of gluconapin by side modification, was noted in seeds at both stages. Interestingly, the expression of GS biosynthetic genes was higher in the silique wall compared with that in the seed albeit lower content of GS existed in the silique wall than in the seed. Combined with the higher expression of transporter genes GTRs in silique walls than in seeds, it was proposed that the transportation of GS from the silique wall to the seed is an important source for seed GS accumulation. In addition, genes related to GS degradation expressed abundantly in the seed at the early cotyledonary-embryo stage indicating its potential role in balancing seed GS content. CONCLUSIONS: Two stages including the torpedo-embryo and the early cotyledonary-embryo stage were identified as crucial in GS accumulation during seed development. Moreover, we confirmed the transportation of GS from the silique wall to the seed and proposed possible sidechain modification of GS biosynthesis may exist during seed formation.

Fuzzy logic and Gagné learning hierarchy for assessing mathematics skills.

This study developed a fuzzy logic and Gagné learning hierarchy (FL-GLH) for assessing mathematics skills and identifying learning barrier points. Fuzzy logic was used to model the human reasoning process in linguistic terms. Specifically, fuzzy logic was used to build relationships between skill level concepts as inputs and learning achievement as an output. Gagné learning hierarchy was used to develop a learning hierarchy diagram, which included learning paths and test questions for assessing mathematics skills. First, the Gagné learning hierarchy was used to generate learning path diagrams and test questions. In the second step, skill level concepts were grouped, and their membership functions were established to fuzzify the input parameters and to build membership functions of learning achievement as an output. Third, the inference engine generated fuzzy values by applying fuzzy rules based on fuzzy reasoning. Finally, the defuzzifier converted fuzzy values to crisp output values for learning achievement. Practical applications of the FL-GLH confirmed its effectiveness for evaluating student learning achievement, for finding student learning barrier points, and for providing teachers with guidelines for improving learning efficiency in students.

Clinical and genetic analysis of classical Ehlers-Danlos syndrome patient caused by synonymous mutation in COL5A2.

BACKGROUND: Classical Ehlers-Danlos syndrome (cEDS) is a heterogeneous connective tissue disorder that mainly results from the germline mutation of COL5A1 and COL5A2. The majority of the COL5A2 mutations reported to date represent structural mutations, including missense or in-frame exon-skipping splice mutations. The only reported synonymous mutation was expected to affect on splicing of exon 29 by prediction programs which should be further confirmed. METHODS: Whole exome sequencing was performed to identify the genetic variants of a Chinese boy who was characterized by skin hyperextensibility, abnormal scarring, hypermobile joints and scoliosis. Sanger sequencing was used to validate the variants in his parents. Reverse transcription polymerase chain reaction (RT-PCR) was performed to analyze the functional effects of the variant. RESULTS: A de novo heterozygous synonymous variant (NM_000393.5:c.1977 G>A) of COL5A2 gene was identified in the patient. The results of RT-PCR revealed that the synonymous variant led to skipping of exon 29 in the RNA transcript. CONCLUSIONS: Our study supplies further supporting evidence that the synonymous COL5A2 mutation c.1977 G>A can cause skipping of exon 29 in the RNA transcript, thus resulting in the production of mutant α2(V)-chains and clinical phenotype of cEDS. This result highlights the need to include splicing-altering synonymous mutations into the screening for cEDS.

Integration of Small RNA and Transcriptome Sequencing Reveal the Roles of miR395 and ATP Sulfurylase in Developing Seeds of Chinese Kale.

Seed development is closely related to plant production and reproduction, and MicroRNAs (miRNA) is widely involved in plant development including seed development. Chinese kale, as a Brassicaceae vegetable, mainly depends on seed for proper reproduction. In the present study, Chinese kale seed and silique at different stages were selected to establish small RNA (sRNA) libraries including silique wall sRNA libraries at torpedo-embryo stage (PC), silique wall sRNA libraries at cotyledonary-embryo stage (PD), seed sRNA libraries at torpedo-embryo stage (SC), and seed sRNA libraries at cotyledonary-embryo stage (SD). The results showed that miRNA expressed differentially in the seeds and corresponding siliques at different stages. To further clarify the functional mode of miRNA in the process of seed development, Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis was performed on target genes of the differentially expressed miRNAs, and these target genes were mainly enriched in plant hormone signal transduction, primary and secondary metabolic pathways. After joint analysis with the transcriptome change of the corresponding period, miR156-SPL10/SPL11, miR395-APS3, and miR397-LAC2/LAC11 modules were identified to be directly involved in the development of Chinese kale seeds. What's more, modified 5'RLM-RACE and Agrobacteria-mediated Chinese kale transient transformation suggest miR395b_2 is involved in sulfur metabolism during seed development by regulating its target gene APS3.

Trace levels of mitomycin C disrupt genomic integrity and lead to DNA damage response defect in long-term-cultured human embryonic stem cells.

How to maintain the genetic integrity of cultured human embryonic stem (hES) cells is raising crucial concerns for future clinical use in regenerative medicine. Mitomycin C(MMC), a DNA damage agent, is widely used for preparation of feeder cells in many laboratories. However, to what extent MMC affects the karyotypic stability of hES cells is not clear. Here, we measured residual MMC using High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry following each step of feeder preparation and found that 2.26 ± 0.77 and 3.50 ± 0.92 ng/ml remained in mouse feeder cells and human feeder cells, respectively. In addition, different amounts of MMC caused different chromosomal aberrations in hES cells. In particular, one abnormality, dup(1)(p32p36), was the same identical to one we previously reported in another hES cell line. Using Affymetrix SNP 6.0 arrays, the copy number variation changes of the hES cells maintained on MMC-inactivated feeders (MMC-feeder) were significantly more than those cultured on γ-inactivated feeder (IR-feeder) cells. Furthermore, DNA damage response (DDR) genes were down-regulated during long-term culture in the MMC-containing system, leading to DDR defect and shortened telomeres of hES cells, a sign of genomic instability. Therefore, MMC-feeder and MMC-induced genomic variation present an important safety problem that would limit such hES from being applied for future clinic use and drug screening.