Knockout of stigmatic ascorbate peroxidase 1 (APX1) delays pollen rehydration and germination by mediating ROS homeostasis in Brassica napus L.

The successful interaction between pollen and stigma is a critical process for plant sexual reproduction, involving a series of intricate molecular and physiological events. After self-compatible pollination, a significant reduction in reactive oxygen species (ROS) production has been observed in stigmas, which is essential for pollen grain rehydration and subsequent pollen tube growth. Several scavenging enzymes tightly regulate ROS homeostasis. However, the potential role of these ROS-scavenging enzymes in the pollen-stigma interaction in Brassica napus remains unclear. Here, we showed that the activity of ascorbate peroxidase (APX), an enzyme that plays a crucial role in the detoxification of hydrogen peroxide (H2O2), was modulated depending on the compatibility of pollination in B. napus. We then identified stigma-expressed APX1s and generated pentuple mutants of APX1s using CRISPR/Cas9 technology. After compatible pollination, the BnaAPX1 pentuple mutants accumulated higher levels of H2O2 in the stigma, while the overexpression of BnaA09.APX1 resulted in lower levels of H2O2. Furthermore, the knockout of BnaAPX1 delayed the compatible response-mediated pollen rehydration and germination, which was consistent with the effects of a specific APX inhibitor, ρ-Aminophenol, on compatible pollination. In contrast, the overexpression of BnaA09.APX1 accelerated pollen rehydration and germination after both compatible and incompatible pollinations. However, delaying and promoting pollen rehydration and germination did not affect the seed set after compatible and incompatible pollination in APX1 pentuple mutants and overexpression lines, respectively. Our results demonstrate the fundamental role of BnaAPX1 in pollen rehydration and germination by regulating ROS homeostasis during the pollen-stigma interaction in B. napus.

Mutant p53 leads to low-grade IFN-I-induced inflammation and impairs cGAS-STING signalling in mice.

Type I interferons (IFN-Is) are a class of proinflammatory cytokines produced in response to viruses and environmental stimulations, resulting in chronic inflammation and even carcinogenesis. However, the connection between IFN-I and p53 mutation is poorly understood. Here, we investigated IFN-I status in the context of mutant p53 (p53N236S , p53S). We observed significant cytosolic double-stranded DNA (dsDNA) derived from nuclear heterochromatin in p53S cells, along with an increased expression of IFN-stimulated genes. Further study revealed that p53S promoted cyclic GMP-AMP synthase (cGAS) and IFN-regulatory factor 9 (IRF9) expression, thus activating the IFN-I pathway. However, p53S/S mice were more susceptible to herpes simplex virus 1 infection, and the cGAS-stimulator of IFN genes (STING) pathway showed a decline trend in p53S cells in response to poly(dA:dT) accompanied with decreased IFN-ß and IFN-stimulated genes, whereas the IRF9 increased in response to IFN-ß stimulation. Our results illustrated the p53S mutation leads to low-grade IFN-I-induced inflammation via consistent low activation of the cGAS-STING-IFN-I axis, and STAT1-IRF9 pathway, therefore, impairs the protective cGAS-STING signalling and IFN-I response encountered with exogenous DNA attack. These results suggested the dual molecular mechanisms of p53S mutation in inflammation regulation. Our results could be helping in further understanding of mutant p53 function in chronic inflammation and provide information for developing new therapeutic strategies for chronic inflammatory diseases or cancer.

The self-compatibility is acquired after polyploidization: a case study of Brassica napus self-incompatible trilinear hybrid breeding system.

Self-incompatibility plays a vital role in angiosperms, by preventing inbreeding depression and maintaining genetic diversity within populations. Following polyploidization, many angiosperm species transition from self-incompatibility to self-compatibility. Here, we investigated the S-locus in Brassicaceae and identified distinct origins for the sRNA loci, SMI and SMI2 (SCR Methylation Inducer 1 and 2), within the S-locus. The SMI loci were found to be widespread in Cruciferae, whereas the SMI2 loci were exclusive to Brassica species. Additionally, we discovered four major S-haplotypes (BnS-1, BnS-6, BnS-7, and BnS-1300) in rapeseed. Overexpression of BnSMI-1 in self-incompatible Brassica napus ('S-70S1300S6 ') resulted in a significant increase in DNA methylation in the promoter regions of BnSCR-6 and BnSCR-1300, leading to self-compatibility. Conversely, by overexpressing a point mutation of BnSmi-1 in the 'S-70S1300S6 ' line, we observed lower levels of DNA methylation in BnSCR-6 and BnSCR-1300 promoters. Furthermore, the overexpression of BnSMI2-1300 in the 'SI-326S7S6 ' line inhibited the expression of BnSCR-7 through transcriptional repression of the Smi2 sRNA from the BnS-1300 haplotype. Our study demonstrates that the self-compatibility of rapeseed is determined by S-locus sRNA-mediated silencing of SCR after polyploidization, which helps to further breed self-incompatible or self-compatible rapeseed lines, thereby facilitating the utilization of heterosis.

Alterations of lung microbiota in lung transplant recipients with pneumocystis jirovecii pneumonia.

BACKGROUND: Increasing evidence revealed that lung microbiota dysbiosis was associated with pulmonary infection in lung transplant recipients (LTRs). Pneumocystis jirovecii (P. jirovecii) is an opportunistic fungal pathogen that frequently causes lethal pneumonia in LTRs. However, the lung microbiota in LTRs with P. jirovecii pneumonia (PJP) remains unknow. METHODS: In this prospective observational study, we performed metagenomic next-generation sequencing (mNGS) on 72 bronchoalveolar lavage fluid (BALF) samples from 61 LTRs (20 with PJP, 22 with PJC, 19 time-matched stable LTRs, and 11 from LTRs after PJP recovery). We compared the lung microbiota composition of LTRs with and without P. jirovecii, and analyzed the related clinical variables. RESULTS: BALFs collected at the episode of PJP showed a more discrete distribution with a lower species diversity, and microbiota composition differed significantly compared to P. jirovecii colonization (PJC) and control group. Human gammaherpesvirus 4, Phreatobacter oligotrophus, and Pseudomonas balearica were the differential microbiota species between the PJP and the other two groups. The network analysis revealed that most species had a positive correlation, while P. jirovecii was correlated negatively with 10 species including Acinetobacter venetianus, Pseudomonas guariconensis, Paracandidimonas soli, Acinetobacter colistiniresistens, and Castellaniella defragrans, which were enriched in the control group. The microbiota composition and diversity of BALF after PJP recovery were also different from the PJP and control groups, while the main components of the PJP recovery similar to control group. Clinical variables including age, creatinine, total protein, albumin, IgG, neutrophil, lymphocyte, CD3+CD45+, CD3+CD4+ and CD3+CD8+ T cells were deeply implicated in the alterations of lung microbiota in LTRs. CONCLUSIONS: This study suggests that LTRs with PJP had altered lung microbiota compared to PJC, control, and after recovery groups. Furthermore, lung microbiota is related to age, renal function, nutritional and immune status in LTRs.

Genetic susceptibility and lifestyle modify the association of long-term air pollution exposure on major depressive disorder: a prospective study in UK Biobank.

BACKGROUND: Evidence linking air pollution to major depressive disorder (MDD) remains sparse and results are heterogeneous. In addition, the evidence about the interaction and joint associations of genetic risk and lifestyle with air pollution on incident MDD risk remains unclear. We aimed to examine the association of various air pollutants with the risk of incident MDD and assessed whether genetic susceptibility and lifestyle influence the associations. METHODS: This population-based prospective cohort study analyzed data collected between March 2006 and October 2010 from 354,897 participants aged 37 to 73 years from the UK Biobank. Annual average concentrations of PM2.5, PM10, NO2, and NOx were estimated using a Land Use Regression model. A lifestyle score was determined based on a combination of smoking, alcohol drinking, physical activity, television viewing time, sleep duration, and diet. A polygenic risk score (PRS) was defined using 17 MDD-associated genetic loci. RESULTS: During a median follow-up of 9.7 years (3,427,084 person-years), 14,710 incident MDD events were ascertained. PM2.5 (HR: 1.16, 95% CI: 1.07-1.26; per 5 µg/m3) and NOx (HR: 1.02, 95% CI: 1.01-1.05; per 20 µg/m3) were associated with increased risk of MDD. There was a significant interaction between the genetic susceptibility and air pollution for MDD (P-interaction < 0.05). Compared with participants with low genetic risk and low air pollution, those with high genetic risk and high PM2.5 exposure had the highest risk of incident MDD (PM2.5: HR: 1.34, 95% CI: 1.23-1.46). We also observed an interaction between PM2.5 exposure and unhealthy lifestyle (P-interaction < 0.05). Participants with the least healthy lifestyle and high air pollution exposures had the highest MDD risk when compared to those with the most healthy lifestyle and low air pollution (PM2.5: HR: 2.22, 95% CI: 1.92-2.58; PM10: HR: 2.09, 95% CI: 1.78-2.45; NO2: HR: 2.11, 95% CI: 1.82-2.46; NOx: HR: 2.28, 95% CI: 1.97-2.64). CONCLUSIONS: Long-term exposure to air pollution is associated with MDD risk. Identifying individuals with high genetic risk and developing healthy lifestyle for reducing the harm of air pollution to public mental health.

Two aspartic proteases, BnaAP36s and BnaAP39s, regulate pollen tube guidance in Brassica napus.

Pollen tube (PT) growth towards the micropyle is critical for successful double fertilization. However, the mechanism of micropyle-directed PT growth is still unclear in Brassica napus. In this study, two aspartate proteases, BnaAP36s and BnaAP39s, were identified in B. napus. BnaAP36s and BnaAP39s were localized to the plasma membrane. The homologues of BnaAP36 and BnaAP39 were highly expressed in flower organs, especially in the anther. Sextuple and double mutants of BnaAP36s and BnaAP39s were then generated using CRISPR/Cas9 technology. Compared to WT, the seed-set of cr-bnaap36 and cr-bnaap39 mutants was reduced by 50% and 60%, respectively. The reduction in seed-set was also found when cr-bnaap36 and cr-bnaap39 were used as the female parent in a reciprocal cross assay. Like WT, cr-bnaap36 and cr-bnaap39 pollen were able to germinate and the relative PTs were able to elongate in style. Approximately 36% and 33% of cr-bnaap36 and cr-bnaap39 PTs, respectively, failed to grow towards the micropyle, indicating that BnaAP36s and BnaAP39s are essential for micropyle-directed PT growth. Furthermore, Alexander's staining showed that 10% of cr-bnaap39 pollen grains were aborted, but not cr-bnaap36, suggesting that BnaAP39s may also affect microspore development. These results suggest that BnaAP36s and BnaAP39s play a critical role in the growth of micropyle-directed PTs in B. napus. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01377-1.

Effect of body mass index trajectory on lifetime risk of cardiovascular disease in a Chinese population: A cohort study.

BACKGROUND AND AIMS: The longitudinal trajectories of body mass index (BMI) can reflect the pattern of BMI changes. Lifetime risk quantifies the cumulative risk of developing a disease over the remaining life of a person. We aimed to identify the trajectory of BMI and explore its association with cardiovascular disease (CVD) in the Chinese population. METHODS AND RESULTS: A total of 68,603 participants with a mean age of 55.46 years were included from the Kailuan cohort in Tangshan, China, who were free of CVD and cancer and with repeated measurements of BMI from 2006 to 2010. A latent mixture model was used to identify BMI trajectories. An improved Kaplan-Meier estimator was used to predict the lifetime risk of CVD according to BMI trajectories. During a median follow-up of 7.0 years, 3325 participants developed CVD. Five BMI trajectories were identified at three index ages (35, 45, and 55) respectively. For index age 35 years, compared with the stable low-normal weight group (22.7% [95% CI, 20.0%-25.4%]), the stable high-normal weight (27.6% [25.6%-29.5%]), stable overweight (29.4% [27.4%-31.4%]), stable-low obesity (32.8% [30.0%-35.5%]), and stable-high obesity (38.9% [33.3%-44.5%]) groups had a higher lifetime risk of CVD (P < 0.05). We observed similar patterns for stroke and myocardial infarction. Similarly, the lifetime risk of CVD was higher in the long-term overweight and obese groups at 45 and 55 index ages. CONCLUSIONS: Long-term overweight and obesity were associated with an increased lifetime risk of CVD. Our findings could assist in predicting the population burden of CVD.

Metabolic syndrome severity score and the progression of CKD.

BACKGROUND: Metabolic syndrome severity, expressed by the continuous metabolic syndrome risk score (MetS score), has been demonstrated to be able to predict future health conditions. However, little is known about the association between MetS score and renal function. METHODS: A total of 22,719 participants with normal renal function abstracted from the Kailuan Study were followed from 2006 to 2016. The new onset of chronic kidney disease (CKD) was defined as eGFR <60 ml/min per 1.73 m2 and/or proteinuria >300 mg/dl. Progressive decline in renal function was defined as an annual change rate of eGFR below the 10th percentile of the whole population. RESULTS: In the multivariate-adjusted model, we found that the risk of progressive decline in renal function increased consistently with the MetS score, with an odds ratio of 1.49 (95% CI, 1.28, 1.73) for those subjects>75th percentile compared with those <25th percentile. Additionally, a high MetS score was found to be associated with an increased risk of CKD, with a hazard ratio of 1.53 (95% CI, 1.33, 1.78) for subjects >75th percentile compared with those <25th percentile. CONCLUSIONS: Our findings suggested that the MetS score was associated with an increased risk of a progressive decline in renal function and was also a strong and independent risk factor for the development of CKD. These findings provide evidence of the potential clinical utility of the MetS score for assessing metabolic syndrome severity to detect the risk of decreased renal function and CKD.

Lifetime risk of cardiovascular disease and life expectancy with and without cardiovascular disease according to changes in metabolic syndrome status.

BACKGROUND AND AIMS: The relationship between dynamic changes in metabolic syndrome (MetS) status and lifetime risk of cardiovascular disease (CVD) has not been reliably quantified. This study aimed to estimate lifetime risk of CVD and life expectancy with and without CVD according to dynamic MetS status. METHODS AND RESULTS: Dynamic changes in MetS status were assessed: MetS-free, MetS-chronic, MetS-developed, and MetS-recovery groups. We used Modified Kaplan-Meier method to estimate lifetime risk and used multistate life table method to calculate life expectancy. Participants free of CVD at index ages 35 (n = 40 168), 45 (n = 33 569), and 55 (n = 18 546) years. At index age 35 years, we recorded 1341 CVD events during a median follow-up of 6.1 years. Lifetime risk of 33.9% (95% CI: 26.9%-41.0%) in MetS-recovery group was lower than that of 39.4% (95% CI: 36.1%-42.8%) in MetS-chronic group. Lifetime risk of 37.8% (95% CI: 30.6%-45.1%) in MetS-developed group was higher than that of 26.4% (95% CI: 22.7%-30.0%) in MetS-free group. At index age 35 years, life expectancy free of CVD for MetS-recovery group (44.1 years) was higher than that for MetS-chronic group (38.8 years). Life expectancy free of CVD for MetS-developed group (41.9 years) was lower than that for MetS-free group (46.7 years). CONCLUSIONS: Recovery from MetS was associated with decreased lifetime risk of CVD and a longer life expectancy free of CVD, whereas development of MetS was associated with increased lifetime risk of CVD and a shorter life expectancy free of CVD.

Role of socioeconomic, lifestyle, and clinical factors in the progression of cardiometabolic multimorbidity in China: A 10-year prospective cohort study.

BACKGROUND AND AIMS: Cardiometabolic multimorbidity has become increasingly common over the past few decades. Little is known about how risk factors affect temporal progression of cardiometabolic multimorbidity. We aim to explore the role of socioeconomic, lifestyle, and clinical risk factors in the progression of cardiometabolic multimorbidity. METHODS AND RESULTS: This prospective cohort study included 56,587 participants aged ≥45 years who were free of diabetes, stroke, and heart disease. Three clusters of risk factors were assessed and each on a 5-point scale: socioeconomic, lifestyle, and clinical factors. We used multi-state models (MSMs) to examine the roles of risk factors in five transitions of multimorbidity trajectory: from healthy to first cardiometabolic disease, first cardiometabolic disease to cardiometabolic multimorbidity, health to mortality, first cardiometabolic disease to mortality, and cardiometabolic multimorbidity to mortality. In MSMs, socioeconomic (HR: 1.21; 95% CI: 1.19-1.25) and clinical (HR: 1.53; 95% CI: 1.51-1.56) scales were associated with the transition from health to first cardiometabolic. Socioeconomic (HR: 2.39; 95% CI: 2.24-2.54) and lifestyle (HR: 1.22; 95% CI: 1.18-1.26) scales were associated with the transitions from first disease to cardiometabolic multimorbidity. In addition, socioeconomic and lifestyle scales were associated with increased risk of mortality in people without cardiometabolic disease, with first cardiometabolic disease, and with cardiometabolic multimorbidity. CONCLUSIONS: Socioeconomic and lifestyle factors were not only important predictors of multimorbidity in those with existing cardiometabolic disease, but also important in shaping risk of mortality. However, clinical factors were the only key determinants of incidence of a first cardiometabolic disease.

Visit-to-visit fasting blood glucose variability and lifetime risk of cardiovascular disease: a prospective study.

AIMS: Previous studies suggested an adverse association between higher fasting blood glucose (FBG) variability and cardiovascular disease (CVD). Lifetime risk provides an absolute risk assessment during the remainder of an individual's life. However, the association between FBG variability and the lifetime risk of CVD is uncertain. OBJECTIVE: We aimed to investigate the effect of the visit-to-visit FBG variability on the lifetime risk of CVD. METHODS: This study included participants from the Kailuan Study who did not have CVD at index ages 35, 45, and 55 years. The FBG variability was defined as the coefficient of variation (CV) of three FBG values that were measured during the examination periods of 2006-2007, 2008-2009, and 2010-2011. We used a modified Kaplan-Merrier method to estimate lifetime risk of CVD according to tertiles of FBG variability. RESULTS: At index age 35 years, the study sample comprised 46,018 participants. During a median follow-up of 7.0 years, 1889 participants developed CVD events. For index age 35 years, participants with high FBG variability had higher lifetime risk of CVD (32.5%; 95% confidence interval [CI]: 28.9-36.1%), compared with intermediate (28.3%; 95% CI: 25.5 -31.1%) and low (26.3%; 95% CI: 23.0-29.5%) FBG variability. We found that higher FBG variability was associated with increased lifetime risk of CVD in men but not women. Similar patterns were observed at index ages 45 and 55 years. CONCLUSIONS: Higher FBG variability was associated with increased lifetime risk of CVD at each index age. Focusing on the FBG variability may provide an insight to the clinical utility for reducing the lifetime risk of CVD.

Association between prenatal rare earth elements exposure and premature rupture of membranes: Results from a birth cohort study.

BACKGROUND: The widespread exploitation and application of rare earth elements (REE) have led to the risk of human exposure and might result in the adverse health effect on pregnant women. However, no epidemiological studies have explored the associations between prenatal REE exposure and premature rupture of membranes (PROM). OBJECTIVE: We aimed to investigate the associations of maternal urinary REE levels with the risk of PROM. METHODS: A total of 4897 mother-newborn pairs were recruited from a birth cohort study in Wuhan, China. Urinary concentrations of REE were measured by inductively coupled plasma mass spectrometry (ICP-MS). The associations of prenatal REE exposure with PROM were evaluated using logistic regression models. False discovery rate (FDR) was applied to adjust for multiple testing. Weighted quantile sum (WQS) regression was used to estimate the association of urinary REE mixture with PROM. RESULTS: With one unit increase (µg/g creatinine) in natural log-transformed urinary REE levels (Ce, Yb, La, Pr, Nd, Eu, Gd, Dy, Ho, Er, Tm), the adjusted ORs (95% CIs) for the PROM were from 1.143 (1.078, 1.211) to 1.317 (1.223, 1.419), and the associations were still observed after FDR adjustment (all PFDRs < 0.05). The associations were stronger among male infants than female infants. Furthermore, the urinary REE mixture was also associated with the risk of PROM, a quartile increase in the WQS index of REE resulted in ORs (95% CI) for the PROM of 1.494 (1.356, 1.645) in the adjusted model. CONCLUSIONS: Our findings suggested that prenatal exposure to REE (Ce, Yb, La, Pr, Nd, Eu, Gd, Dy, Ho, Er, and Tm) and REE mixture were associated with the increased risk of PROM. Further studies from different populations are needed to confirm the associations and to explore the mechanisms.

Visit-to-visit variability in the measurements of metabolic syndrome components and the risk of all-cause mortality, cardiovascular disease, and arterial stiffness.

BACKGROUND AND AIMS: The risk of adverse health conditions varied according to the number of metabolic syndrome components. We aimed to evaluate the risk of mortality and incident cardiovascular events according to the number of components with high variability. METHODS AND RESULTS: A total of 43,737 Kailuan Study participants with ≥3 examinations of waist circumference, fasting blood glucose, systolic blood pressure, triglyceride, and high-density lipoprotein during 2006-2013 were included in the present study. Visit-to-visit variability in each parameter was defined by the intraindividual standard deviation across visits. High variability was defined as the highest quartile of variability. Participants were classified numerically according to the number of high-variability components (e.g., a score of 0 indicated no high-variability component). There were 1551 deaths during a median follow-up of 5.9 years, and 950 incident cardiovascular disease (CVD) cases during a median follow-up of 4.9 years. In the multivariable adjusted model, compared with participants with low variability for all components, participants with ≥3 high-variability components had significantly higher risks for all-cause mortality (hazards ratio [HR], 1.61; 95 % confidence interval [CI], 1.35-1.91) and incident CVD event (HR, 1.45; 95 % CI, 1.16-1.82). Additionally, participants with ≥3 high-variability components had increased odds of arterial stiffness, as measured by brachia-ankle pulse wave velocity (odds ratio [OR], 1.39; 95 % CI, 1.19-1.63). CONCLUSIONS: Our findings suggest that participants with at least three metabolic parameters with high variability experienced increased risk of CVD and all-cause mortality.

Association between early-term birth and delayed neurodevelopment at the age of 2 years: results from a cohort study in China.

A growing body of evidence indicates that early-term births (37-38 weeks of gestational age) have an increased risk of short-term and long-term complications. Here, we sought to explore the association between early-term births and the risk of delayed neurodevelopment at age 2 years. Pregnant women and their live singleton birth were recruited from a single tertiary hospital between October 2013 and February 2017. Mental and Psychomotor Development Indexes (MDI and PDI) were assessed using the Bayley Scales of Infant Development (BSID). Delayed neurodevelopment was defined as scores of PDI or MDI less than -1SD relative to the mean score of the study population. In total, 1678 full-term infants and 727 early-term infants were assessed when they were 2 years old. After adjustment for potential confounders, early-term birth was related to 43% increased odds of neurodevelopmental delay in the PDI domain as compared with full-term birth (OR: 1.43; 95% CI: 1.12, 1.82). The observed associations were more prominent among those infants born by cesarean (OR: 1.44; 95% CI: 1.03, 2.00) and among males (OR: 1.66; 95% CI: 1.20, 2.28). No statistical difference in the MDI domain was found between early-term and full-term births.Conclusions: Our findings suggest that early-term birth was associated with increased odds of delayed neurodevelopment in the PDI domain as measured by BSID assessments at age 2 years. Health professionals should be aware of the influence of early-term birth on the risk of delayed neurodevelopment. What is Known: • Evidence indicates that early-term births have an increased risk of short-term and long-term complications. • The association between early-term births and delayed neurodevelopment at their early childhood has not been widely studied. What is New: • Early-term birth was associated with increased odds of delayed neurodevelopment in PDI domain as measured by BSID assessments at age 2 years. • The observed associations were more prominent among infants born by cesarean section and among male infants.

Association between maternal urinary manganese concentrations and newborn telomere length: Results from a birth cohort study.

OBJECTIVE: Telomere length (TL) is a biomarker for biological aging, and the initial setting of TL at birth is a determinant factor of TL in later life. Newborn TL is sensitive to maternal metals concentrations, while study about the association between maternal manganese (Mn) concentrations and newborn TL was not found. Our study aimed to investigate whether newborn TL is related to maternal Mn concentrations. METHODS: Data were collected from a birth cohort study of 762 mother-newborn pairs conducted from November 2013 to March 2015 in Wuhan, China. We measured the Mn concentrations in spot urine samples collected during three trimesters by inductively coupled plasma mass spectrometry (ICP-MS) and relative cord blood TL by quantitative real-time polymerase chain reaction (qPCR). We applied multiple informant models to investigate the associations between maternal Mn concentrations and cord blood TL. RESULTS: The geometric mean of creatinine-corrected urinary Mn concentrations were 1.58 µg/g creatinine, 2.53 µg/g creatinine, and 2.62 µg/g creatinine in the first, second, and third trimester, respectively. After adjusting for potential confounders, a doubling of maternal urinary Mn concentration during the second trimester was related to a 2.10% (95% CI: 0.25%, 3.99%) increase in cord blood TL. Mothers with the highest tertile of urinary Mn concentrations during the second trimester had a 9.67% (95% CI: 2.13%, 17.78%) longer cord blood TL than those with the lowest tertile. This association was more evident in male infants. No relationship was found between maternal urinary Mn concentrations and cord blood TL during the first and third trimesters in our study. CONCLUSIONS: Our findings suggested that maternal Mn concentration during the second trimester was positively associated with newborn TL. These results might provide an epidemiology evidence on the protective role of maternal Mn for newborn TL and offer clues for the early prevention of telomere shortening related diseases.

Cytosolic malate dehydrogenase 4 modulates cellular energetics and storage reserve accumulation in maize endosperm.

Cytosolic malate dehydrogenase (MDH) is a key enzyme that regulates the interconversion between malate and oxaloacetate (OAA). However, its role in modulating storage compound accumulation in maize endosperm is largely unknown. Here, we characterized a novel naturally occurring maize mdh4-1 mutant, which produces small, opaque kernels and exhibits reduced starch but enhanced lysine content. Map-based cloning, functional complementation and allelism analyses identified ZmMdh4 as the causal gene. Enzymatic assays demonstrated that ZmMDH4 predominantly catalyses the conversion from OAA to malate. In comparison, the activity of the mutant enzyme, which lacks one glutamic acid (Glu), was completed abolished, demonstrating that the Glu residue was essential for ZmMDH4 function. Knocking down ZmMdh4 in vivo led to a substantial metabolic shift towards glycolysis and a dramatic disruption in the activity of the mitochondrial complex I, which was correlated with transcriptomic alterations. Taken together, these results demonstrate that ZmMdh4 regulates the balance between mitochondrial respiration and glycolysis, ATP production and endosperm development, through a yet unknown feedback regulatory mechanism in mitochondria.

Prenatal second-hand smoke exposure and newborn telomere length.

BACKGROUND: Cigarette smoking is associated with shorter telomere lengths in adults, but evidence on the effect of prenatal tobacco exposure is limited. We aimed to investigate the association between prenatal second-hand smoke exposure and newborn telomere length. METHODS: We recruited 762 mother-newborn pairs from Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital) between November 2013 and March 2015. Information on second-hand smoke exposure was obtained via questionnaires. Relative telomere length was measured in DNA extracted from umbilical cord blood. We used linear regression to assess the associations between prenatal second-hand smoke exposure and newborn telomere length. RESULTS: In the fully adjusted model, prenatal second-hand smoke exposure was associated with 9.7% shorter newborn telomere length (percent difference: -9.7%; 95% confidence interval (CI): -15.0, -4.0). The estimate for boys was lower (percent difference: -10.9%; 95% CI: -18.6, -2.5) than that for girls (percent difference: -8.5%; 95% CI: -15.8, -0.5), but the interaction term between newborn sex and prenatal second-hand smoke was not significant (P = 0.751). CONCLUSIONS: This study demonstrated that prenatal second-hand smoke exposure may be a preventable risk factor for accelerated biological aging in the intrauterine stage, and further suggested possible sex differences in the susceptibility to prenatal second-hand smoke.

Higher Numbers of Pregnancies Associated With an Increased Prevalence of Gestational Diabetes Mellitus: Results From the Healthy Baby Cohort Study.

BACKGROUND: Pregnancy leads to substantial maternal metabolic and lifestyle alterations. However, it is still unclear whether repeated exposure to these changes will influence the development of gestational diabetes mellitus (GDM). In the present study, we aimed to investigate the association between the number of pregnancies and GDM among Chinese women. METHODS: A total of 7,008 subjects from the Healthy Baby Cohort study were included in this study. The number of pregnancies was classified into three categories: 1, 2, or ≥3 pregnancies. GDM was diagnosed using International Association of Diabetes and Pregnancy Study Groups criteria. Multivariate logistic regression models were used. RESULTS: In the fully adjusted model, women with ≥3 pregnancies had a 1.27-fold (95% confidence interval [CI], 1.05-1.54) higher risk of GDM. Among women ≥30 years old, 2 and ≥3 pregnancies were associated with a higher risk of GDM (odds ratio [OR] 1.32; 95% CI, 1.01-1.73 and OR 1.54; 95% CI, 1.17-2.01, respectively). Among women with a pre-pregnancy BMI <24 kg/m2, ≥3 pregnancies were associated with a 1.35-fold (95% CI, 1.09-1.67) higher risk of GDM. CONCLUSIONS: Our findings suggested that higher numbers of pregnancies is an independent risk factor of GDM. The association between number of pregnancies and GDM was more prominent among women who were ≥30 years old or with a pre-pregnancy BMI <24 kg/m2.

Earlier maternal menarche is associated with shorter newborn telomere length.

The aim of our study was to investigate the relationship between maternal age at menarche and newborn telomere length which has been linked to lifespan and many age-related diseases. There were 734 mother-newborn pairs recruited from Wuhan Children's Hospital Wuhan, Hubei Province, China. Age at menarche was self-reported and categorized into three groups (≤ 12 years, 13 years, and ≥ 14 years). Telomere length in cord blood was measured using quantitative real-time polymerase chain reaction and expressed as the ratio of telomere copy number to single-copy gene number (T/S). The mean age at menarche of 734 mothers was 13.1 (± 1.1) years and the adjusted geometric means in the T/S of newborn telomeres in the three groups were 0.693, 0.721, and 0.748 respectively. Earlier age at menarche (≤ 12 years), compared with later age at menarche ≥ 14 years, was significantly associated with 7.32% (95% CI - 13.70%, - 0.23%) shorter telomere length in offspring after adjusting for potential confounders.Conclusion: Mothers with earlier age at menarche were more likely to give birth newborn with shorter telomere length. Our study provides evidences for the effect of earlier menarche on fetal telomere programming in offspring. What is Known: • Newborn telomere length is considered an indicator of lifespan and health outcomes in later life. • The adverse effects of earlier menarche age to their offspring have been found, but its relationship with newborn telomere length has not been assessed before. What is New: • This is the first study to explore the relationship of maternal menarche age with newborn telomere length. • We provided primary evidence that earlier maternal age at menarche was associated with shorter newborn telomere length.

Traditional and cortical trajectory screws of static and dynamic lumbar fixation- a finite element study.

BACKGROUND: Two types of screw trajectories are commonly used in lumbar surgery. Both traditional trajectory (TT) and cortical bone trajectory (CBT) were shown to provide equivalent pull-out strengths of a screw. CBT utilizing a laterally-directed trajectory engaging only cortical bone in the pedicle is widely used in minimal invasive spine posterior fusion surgery. It has been demonstrated that CBT exerts a lower likelihood of violating the facet joint, and superior pull-out strength than the TT screws, especially in osteoporotic vertebral body. No design yet to apply this trajectory to dynamic fixation. To evaluate kinetic and kinematic behavior in both static and dynamic CBT fixation a finite element study was designed. This study aimed to simulate the biomechanics of CBT-based dynamic system for an evaluation of CBT dynamization. METHODS: A validated nonlinearly lumbosacral finite-element model was used to simulate four variations of screw fixation. Responses of both implant (screw stress) and tissues (disc motion, disc stress, and facet force) at the upper adjacent (L3-L4) and fixed (L4-L5) segments were used as the evaluation indices. Flexion, extension, bending, and rotation of both TT and CBT screws were simulated in this study for comparison. RESULTS: The results showed that the TT static was the most effective stabilizer to the L4-L5 segment, followed by CBT static, TT dynamic, and the CBT dynamic, which was the least effective. Dynamization of the TT and CBT fixators decreased stability of the fixed segment and alleviate adjacent segment stress compensation. The 3.5-mm diameter CBT screw deteriorated stress distribution and rendered it vulnerable to bone-screw loosening and fatigue cracking. CONCLUSIONS: Modeling the effects of TT and CBT fixation in a full lumbosacral model suggest that dynamic TT provide slightly superior stability compared with dynamic CBT especially in bending and rotation. In dynamic CBT design, large diameter screws might avoid issues with loosening and cracking.