Fine Particulate Matter Exposure, Genetic Susceptibility, and the Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Both genetic factors and environmental air pollution contribute to the risk of stroke. However, it is unknown whether the association between air pollution and stroke risk is influenced by the genetic susceptibilities of stroke and its risk factors. METHODS: This prospective cohort study included 40 827 Chinese adults without stroke history. Satellite-based monthly fine particulate matter (PM2.5) estimation at 1-km resolution was used for exposure assessment. Based on 534 identified genetic variants from genome-wide association studies in East Asians, we constructed 6 polygenic risk scores for stroke and its risk factors, including atrial fibrillation, blood pressure, type 2 diabetes, body mass index, and triglyceride. The Cox proportional hazards model was applied to evaluate the hazard ratios and 95% CIs for the associations of PM2.5 and polygenic risk score with incident stroke and the potential effect modifications. RESULTS: Over a median follow-up of 12.06 years, 3147 incident stroke cases were documented. Compared with the lowest quartile of PM2.5 exposure, the hazard ratio (95% CI) for stroke in the highest quartile group was 2.72 (2.42-3.06). Among individuals at high genetic risk, the relative risk of stroke was 57% (1.57; 1.40-1.76) higher than those at low genetic risk. Although no statistically significant interaction was found, participants with both the highest PM2.5 and high genetic risk showed the highest risk of stroke, with ≈4× that of the lowest PM2.5 and low genetic risk group (hazard ratio, 3.55 [95% CI, 2.84-4.44]). Similar upward gradients were observed in the risk of stroke when assessing the joint effects of PM2.5 and genetic risks of blood pressure, type 2 diabetes, body mass index, atrial fibrillation, and triglyceride. CONCLUSIONS: Long-term exposure to PM2.5 was associated with a higher risk of incident stroke across different genetic susceptibilities. Our findings highlighted the great importance of comprehensive assessment of air pollution and genetic risk in the prevention of stroke.

Discordant High Remnant Cholesterol With LDL-C Increases the Risk of Stroke: A Chinese Prospective Cohort Study.

BACKGROUND: Previous studies focusing on assessing the effects of remnant cholesterol (RC) and low-density lipoprotein cholesterol (LDL-C) on stroke may not consider their mutual influence. We aimed to explore the associations of RC and discordant high RC with LDL-C with stroke, ischemic stroke (IS), and hemorrhagic stroke. METHODS: This prospective cohort study was conducted based on 3 cohorts of the China-PAR (Prediction for Atherosclerotic Cardiovascular Disease Risk in China) project. RC was calculated as non-high-density lipoprotein cholesterol minus LDL-C estimated by Martin/Hopkins equations. Concordant/discordant categories for RC versus LDL-C were determined based on cut-points of 130 mg/dL for LDL-C and equivalent percentile (32.50 mg/dL) for RC. Cox models were used to estimate adjusted hazard ratios and 95% CIs for incident stroke. RESULTS: Among 113 448 participants recruited at baseline, a total of 98 967 participants were eligible for the final analysis (mean age of 51.44 years; 40.45% were men). During 728 776.87 person-years of follow-up, 2859 stroke cases, 1811 IS cases, and 849 hemorrhagic stroke cases were observed. RC was positively associated with stroke and IS, but not hemorrhagic stroke, with adjusted hazard ratios (95% CIs) of 1.06 (1.02-1.10), 1.09 (1.04-1.13), and 0.95 (0.88-1.03) for per SD increase in RC. Compared with low LDL-C/low RC group, low LDL-C/high RC group had higher risks of stroke (adjusted hazard ratio, 1.15 [95% CI, 1.02-1.30]) and IS (1.19, 1.03-1.38), while high LDL-C/low RC group had no increased risk of stroke (1.07 [0.95-1.20]) and IS (1.09 [0.94-1.25]). CONCLUSIONS: Higher RC was associated with increased risks of stroke and IS but not hemorrhagic stroke. Discordantly high RC, not discordantly high LDL-C, conferred higher risks of stroke and IS. Our findings support further lowering RC by interventions to reduce residual IS risk.

Association of genetic variants related to combined lipid-lowering and antihypertensive therapies with risk of cardiovascular disease: 2 × 2 factorial Mendelian randomization analyses.

BACKGROUND: Lipid-lowering drugs and antihypertensive drugs are commonly combined for cardiovascular disease (CVD). However, the relationship of combined medications with CVD remains controversial. We aimed to explore the associations of genetically proxied medications of lipid-lowering and antihypertensive drugs, either alone or both, with risk of CVD, other clinical and safety outcomes. METHODS: We divided 423,821 individuals in the UK Biobank into 4 groups via median genetic scores for targets of lipid-lowering drugs and antihypertensive drugs: lower low-density lipoprotein cholesterol (LDL-C) mediated by targets of statins or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, lower systolic blood pressure (SBP) mediated by targets of ß-blockers (BBs) or calcium channel blockers (CCBs), combined genetically lower LDL-C and SBP, and reference (genetically both higher LDL-C and SBP). Associations with risk of CVD and other clinical outcomes were explored among each group in factorial Mendelian randomization. RESULTS: Independent and additive effects were observed between genetically proxied medications of lipid-lowering and antihypertensive drugs with CVD (including coronary artery disease, stroke, and peripheral artery diseases) and other clinical outcomes (ischemic stroke, hemorrhagic stroke, heart failure, diabetes mellitus, chronic kidney disease, and dementia) (P > 0.05 for interaction in all outcomes). Take the effect of PCSK9 inhibitors and BBs on CVD for instance: compared with the reference, PCSK9 group had a 4% lower risk of CVD (odds ratio [OR], 0.96; 95%CI, 0.94-0.99), and a 3% lower risk was observed in BBs group (OR, 0.97; 95%CI, 0.94-0.99), while combined both were associated with a 6% additively lower risk (OR, 0.94; 95%CI, 0.92-0.97; P = 0.87 for interaction). CONCLUSIONS: Genetically proxied medications of combined lipid-lowering and antihypertensive drugs have an independent and additive effects on CVD, other clinical and safety outcomes, with implications for CVD clinical practice, subsequent trials as well as drug development of polypills.

Stitching interferometry using alternating calibration of positioning and systematic errors.

Stitching interferometry is an essential technique for the non-contact, high-precision measurement of large apertures or complex optical surfaces. However, the accuracy of full-aperture surface reconstruction is significantly compromised by subaperture positioning and systematic errors. To address this challenge, this study introduces a novel stitching interferometry method utilizing alternating calibration of positioning and systematic errors (SIAC). This method calibrates one type of error while maintaining the other constant, and alternates between these processes to effectively decouple the two errors, facilitating accurate phase stitching. Within this calibration framework, an iterative weighted phase stitching model employing vertical projection for estimating overlapping areas was developed to calibrate positioning errors. Additionally, the rotation measurements of a single subaperture, in conjunction with a global fitting approach, were employed to correct reference errors. Numerical simulations have confirmed the efficacy of SIAC in calibrating these errors. Moreover, experimental measurements were performed on both a plane mirror and gullwing aspheres, with the resulting stitched full-aperture phase distributions and cross-testing outcomes affirming the method's accuracy and practicality. This research provides a novel solution for stitching interferometry, enhancing the precision of optical surface measurements.

Vibration-resistant Fizeau interferometry using three-cavity multiplexing.

This study demonstrates a three-cavity multiplexing vibration-resistant Fizeau interferometry (TCM). The method injects a vibration-measurement pass (VMP), which utilizes three-cavity hybrid interference for the transmission of phase and vibration information, to the Fizeau phase-measurement pass (PMP). Moreover, the VMP is demultiplexed using the temporal difference of mixed fringes and synchronous phase-shifting phase extraction of difference fringe to obtain the vibration information, which is then used to calculate the measured phase combined with PMP. The feasibility and performance of the TCM are demonstrated experimentally. To the best of our knowledge, this is the first proposal of the TCM that not only solves the effect of vibration and null-fringe demodulation but also features a common path, simple testing process, and low system complexity.

Discovery and biochemical characterization of two hexokinases from Crassostrea gigas.

Hexokinases (HKs) play a vital role in glucose metabolism, which controls the first committed step catalyzing the production of glucose-6-phosphate from glucose. Two HKs (CGIHK1 and CGIHK2) from the Pacific oyster Crassostrea giga were cloned and characterized. CGIHK1 and CGIHK2 were recombinantly expressed in Escherichia coli and successfully purified by the Ni-NTA column. The optimum pH of the two enzymes was pH 8.0 and 8.5, respectively. The optimum temperature of the two enzymes was 42 °C and 50 °C, respectively. Both enzymes showed a clear requirement for divalent magnesium and were strongly inhibited by SDS. CGIHK1 exhibited highly strict substrate specificity to glucose, while CGIHK2 could also catalyze other 11 monosaccharide substrates. This is the first report on the in vitro biosynthesis of glucose-6-phosphate by the hexokinases from Crassostrea gigas. The facile expression and purification procedures combined with different substrate specificities make CGIHK1 and CGIHK2 candidates for the biosynthesis of glucose-6-phosphate and other sugar-phosphates.

Associations of body mass index trajectory, waist circumference trajectory, or both with type 2 diabetes mellitus risk in Chinese adults: The China-PAR project.

AIMS: To identify the trajectories of body mass index (BMI) and waist circumference (WC), and assess the associations of BMI trajectory, WC trajectory, or the two combined, with type 2 diabetes mellitus (T2DM) risk in Chinese adults. MATERIALS AND METHODS: This study was based on a prospective project-the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR). A total of 54 434 participants (39.21% men) who were measured on at least two occasions were included. Three slowly increasing trajectory patterns were identified for BMI, and four for WC, by latent mixed modelling. A nine-category variable was derived by combining the WC trajectory (low, moderate, moderate-high/high) and the BMI trajectory (low, moderate, high). Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The risk of developing T2DM increased with elevated BMI or WC trajectory levels (all ptrend <0.001). The risks were 2.85 (2.59-3.14) for high BMI trajectory and 4.34 (3.78-4.99) for high WC trajectory versus low trajectory groups, respectively. The association was more pronounced among younger individuals (pinteraction <0.001). In the joint analysis, compared to participants with low WC and BMI trajectory, those with moderate-high/high WC combined with high BMI trajectory had the highest risk of T2DM (OR 3.96, 95% CI 3.48-4.50); even those who maintained moderate-high/high WC but low BMI trajectory showed a higher T2DM risk (OR 3.00, 95% CI 2.31-3.91). CONCLUSIONS: This study suggests that simultaneous dynamic and continuous monitoring of BMI and WC may contribute more than single measurements to predicting T2DM risk and determining preventive strategies.

The AaERF64-AaTPPA module participates in cold acclimatization of Actinidia arguta (Sieb. et Zucc.) Planch ex Miq.

Actinidia arguta (A. arguta, kiwiberry) is a perennial deciduous vine with a strong overwintering ability. We hypothesized that trehalose metabolism, which plays a pivotal role in the stress tolerance of plants, may be involved in the cold acclimatization of A. arguta. Transcriptome analysis showed that the expression of AaTPPA, which encodes a trehalose-6-phosphate phosphatase (TPP), was upregulated in response to low temperatures. AaTPPA expression levels were much higher in lateral buds, roots, and stem cambia than in leaves in autumn. In AaTPPA-overexpressing (OE) Arabidopsis thaliana (A. thaliana), trehalose levels were 8-11 times higher than that of the wild type (WT) and showed different phenotypic characteristics from WT and OtsB (Escherichia coli TPP) overexpressing lines. AaTPPA-OE A. thaliana exhibited significantly higher freezing tolerance than WT and OtsB-OE lines. Transient overexpression of AaTPPA in A. arguta leaves increased the scavenging ability of reactive oxygen species (ROS) and the soluble sugar and proline contents. AaERF64, an ethylene-responsive transcription factor, was induced by ethylene treatment and bound to the GCC-box of the AaTPPA promoter to activate its expression. AaTPPA expression was also induced by abscisic acid. In summary, the temperature decrease in autumn is likely to induce AaERF64 expression through an ethylene-dependent pathway, which consequently upregulates AaTPPA expression, leading to the accumulation of osmotic protectants such as soluble sugars and proline in the overwintering tissues of A. arguta. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01475-8.

Arginase 2 is a Diagnostic and Prognostic Marker for Prostate Cancer and Is Associated with Metabolism.

Objective: Metabolism, a basic need and biochemical process for cell survival and proliferation, is closely connected with the pathogenesis and progression of prostate cancer. Methods: A four-gene signature construct that includes CKM (CKM), CD38, Enoyl Coenzyme A(EHHADH), and Arginase 2(ARG2) was created by bioinformatics. Finally, hub genes were validated by IHC and in vitro experiments. Results: The results showed the AUCs of the logistic regression and neural networks diagnostic model for the diagnosis of two subtypes were 0.920 and 0.936, respectively. The risk score demonstrated by univariable and multivariable Cox analysis is an independent predictive component of the prognostic signature for DFS. According to immunohistochemical analyses, ARG2 and CD38 expression levels were considerably under-expressed, but CKM and EHHADH expression levels were significantly overexpressed. Furthermore, The expression of ARG2 was significantly down-regulated in the late Gleason score. Finally, we found that ARG2 is lowly expressed in prostate cancer cells. Furthermore, based on the effect of ARG2 on the malignant phenotype of PCa in vitro, we also found that ARG2 may be a tumor suppressor that plays an important role in inhibiting proliferation, migration, and invasion. Conclusions: These findings suggest that ARG2 has been tentatively identified as a new target for research into how PCa develops in metabolism and for the development of innovative targeted treatments.

Toxicokinetics and bioavailability of indoxacarb enantiomers and their new metabolites in rats.

Indoxacarb is a chiral insecticide that consists of two enantiomers, S-(+)-indoxacarb and R-(-)-indoxacarb, of which only S-(+)-indoxacarb has insecticidal activity. Previous enantioselective toxicology studies of indoxacarb focused mostly on simple environmental model organisms. The lack of a toxicology evaluation of indoxacarb conducted in a mammalian system could mean that the extent of the potential health risk posed by the insecticide to humans is not adequately known. In this study, we reported on a new pair of enantiomers, S-IN-RM294 and R-IN-RM294, derived from the metabolic breakdown of S-(+)-indoxacarb and R-(-)-indoxacarb, respectively, in rats. The toxicokinetics of S-(+)-indoxacarb, R-(-)-indoxacarb, S-IN-RM294, and R-IN-RM294 in rats were evaluated to provide a more comprehensive risk assessment of these molecules. The bioavailability and excretion rates of both S-(+)-indoxacarb and R-(-)-indoxacarb were relatively low, which may be due to their faster metabolism and accumulation in the tissues. In addition, there were significant differences in the metabolism and distribution between the two indoxacarb enantiomers and their metabolites in vivo. S-(+)-Indoxacarb was found to be more easily metabolized in the blood compared with R-(-)-indoxacarb, as shown by the differences in pharmacokinetic parameters between oral and intravenous administration. Analysis of their tissue distribution showed that S-(+)-indoxacarb was less likely to accumulate in most tissues. The results obtained for the two metabolites were consistent with those of the two parent compounds. S-IN-RM294 was more readily cleared from the blood and less likely to accumulate in the tissues compared with R-IN-RM294. Therefore, whether from the perspective of insecticidal activity or from the perspective of mammalian and environmental friendliness, the application of optically pure S-(+)-indoxacarb in agriculture may be a more efficient and safer strategy.

Associations between socioeconomic status and rates of blood pressure changes among Chinese older adults: a longitudinal community-based cohort study.

OBJECTIVES: The relationships between socioeconomic status (SES) and blood pressure changes among older adults in China remain unclear. This study aimed to examine the associations between SES and rates of blood pressure changes among Chinese older adults. STUDY DESIGN: Community-based, prospective, longitudinal cohort study. METHODS: This study included 13,541 participants aged ≥65 years from the Chinese Longitudinal Healthy Longevity Survey between 2002 and 2018. SES was assessed by educational level, occupation, household yearly per capita income, and financial support. The estimated annual changes (EACs) of blood pressure were computed as the difference in blood pressure levels between any two adjacent surveys divided by the time interval. Associations between SES and EACs of blood pressure were evaluated using generalised estimating equations. RESULTS: Lower SES was significantly associated with greater annual increases of blood pressure among Chinese older adults. The effect of SES on EACs of blood pressure was more pronounced among non-hypertensive participants. Compared to EACs among non-hypertensive participants with high SES, multivariable-adjusted EACs among those with low SES increased by 0.57 mmHg (95% confidence interval [CI]: 0.16, 0.99), 0.32 mmHg (95% CI: 0.07, 0.57), and 0.40 mmHg (95% CI: 0.13, 0.66) for systolic blood pressure, diastolic blood pressure, and mean arterial pressure, respectively. CONCLUSIONS: This study revealed strong associations between SES and EACs of blood pressure among Chinese older adults, especially in the non-hypertensive population. Findings suggest that prevention strategies for hypertension should pay more attention to the older population with low SES.

Physiological and Proteomic Responses of the Tetraploid Robinia pseudoacacia L. to High CO2 Levels.

The increase in atmospheric CO2 concentration is a significant factor in triggering global warming. CO2 is essential for plant photosynthesis, but excessive CO2 can negatively impact photosynthesis and its associated physiological and biochemical processes. The tetraploid Robinia pseudoacacia L., a superior and improved variety, exhibits high tolerance to abiotic stress. In this study, we investigated the physiological and proteomic response mechanisms of the tetraploid R. pseudoacacia under high CO2 treatment. The results of our physiological and biochemical analyses revealed that a 5% high concentration of CO2 hindered the growth and development of the tetraploid R. pseudoacacia and caused severe damage to the leaves. Additionally, it significantly reduced photosynthetic parameters such as Pn, Gs, Tr, and Ci, as well as respiration. The levels of chlorophyll (Chl a and b) and the fluorescent parameters of chlorophyll (Fm, Fv/Fm, qP, and ETR) also significantly decreased. Conversely, the levels of ROS (H2O2 and O2·-) were significantly increased, while the activities of antioxidant enzymes (SOD, CAT, GR, and APX) were significantly decreased. Furthermore, high CO2 induced stomatal closure by promoting the accumulation of ROS and NO in guard cells. Through a proteomic analysis, we identified a total of 1652 DAPs after high CO2 treatment. GO functional annotation revealed that these DAPs were mainly associated with redox activity, catalytic activity, and ion binding. KEGG analysis showed an enrichment of DAPs in metabolic pathways, secondary metabolite biosynthesis, amino acid biosynthesis, and photosynthetic pathways. Overall, our study provides valuable insights into the adaptation mechanisms of the tetraploid R. pseudoacacia to high CO2.

Different Changing Patterns for Stroke Subtype Mortality Attributable to High Sodium Intake in China During 1990 to 2019.

BACKGROUND: It is unclear whether sodium intake had similar effects on mortality of stroke subtypes. The purpose of this study is to compare the long-term trends in mortality of stroke subtypes attributable to high sodium intake in China during 1990 to 2019. METHODS: Data for China in the GBD (Global Burden of Disease) 2019 study were obtained mainly from the Chinese surveillance systems and the KaiLuan Study. The trends in stroke mortality due to high sodium intake (>5 g/d) were evaluated using join-point regression and age-period-cohort methods adjusting for age, period, and cohort. RESULTS: The age-standardized mortality rates of stroke attributable to high sodium intake showed downward trends during 1990 to 2019 in China, with an average annual percentage change of -0.6 (95% CI, -0.8 to -0.4) for ischemic stroke, -2.5 (95% CI, -2.8 to -2.2) for intracerebral hemorrhage, and -6.1 (95% CI, -6.6 to -5.7) for subarachnoid hemorrhage. The curves of local drifts, which reflected the average annual percentage change of stroke mortality due to high sodium intake across age groups, showed a slow upward trend with age for ischemic stroke, a slow downward trend for intracerebral hemorrhage, and a sharp downward trend for subarachnoid hemorrhage. The high sodium-related mortality increased dramatically with age for ischemic stroke and intracerebral hemorrhage, while it reached a peak at 50 to 70 years old for subarachnoid hemorrhage. The period and cohort rate ratios of stroke mortality due to high sodium intake decreased in the past 3 decades, with the greatest decline for subarachnoid hemorrhage and the weakest decrease for ischemic stroke. Notably, men had higher high sodium-related mortality and risk but slighter declines for all stroke subtypes than women. CONCLUSIONS: Our results provided powerful evidence that high sodium-related age-standardized mortality rates and risk of stroke in China decreased in the past 3 decades, with diverse changing patterns for different stroke subtypes, highlighting that salt reduction had distinct impact on stroke subtypes.

Genetic dissection of maize (Zea mays L.) chlorophyll content using multi-locus genome-wide association studies.

BACKGROUND: The chlorophyll content (CC) is a key factor affecting maize photosynthetic efficiency and the final yield. However, its genetic basis remains unclear. The development of statistical methods has enabled researchers to design and apply various GWAS models, including MLM, MLMM, SUPER, FarmCPU, BLINK and 3VmrMLM. Comparative analysis of their results can lead to more effective mining of key genes. RESULTS: The heritability of CC was 0.86. Six statistical models (MLM, BLINK, MLMM, FarmCPU, SUPER, and 3VmrMLM) and 1.25 million SNPs were used for the GWAS. A total of 140 quantitative trait nucleotides (QTNs) were detected, with 3VmrMLM and MLM detecting the most (118) and fewest (3) QTNs, respectively. The QTNs were associated with 481 genes and explained 0.29-10.28% of the phenotypic variation. Additionally, 10 co-located QTNs were detected by at least two different models or methods, three co-located QTNs were identified in at least two different environments, and six co-located QTNs were detected by different models or methods in different environments. Moreover, 69 candidate genes within or near these stable QTNs were screened based on the B73 (RefGen_v2) genome. GRMZM2G110408 (ZmCCS3) was identified by multiple models and in multiple environments. The functional characterization of this gene indicated the encoded protein likely contributes to chlorophyll biosynthesis. In addition, the CC differed significantly between the haplotypes of the significant QTN in this gene, and CC was higher for haplotype 1. CONCLUSION: This study's results broaden our understanding of the genetic basis of CC, mining key genes related to CC and may be relevant for the ideotype-based breeding of new maize varieties with high photosynthetic efficiency.

Flexible stitching interferometry for gull-wing asphere using variable-sign curvature compensation.

Aspheres have widespread applications in modern optical systems; however, the high-precision testing of the gull-wing asphere (GWA) is still challenging. In this Letter, flexible stitching interferometry (FSI) has been reported using variable-sign curvature compensation (VSCC) to realize accurate GWA testing. The method involves varying the sign and magnitude of the outgoing wavefront curvature by relative translation of VSCC to compensate for the curvatures of subapertures, and alternating optimization stitching is utilized to obtain the full-aperture absolute phase. The feasibility and performance of the proposed method are demonstrated experimentally. To our knowledge, such a stitching interferometry using VSCC is here proposed for the first time, and could contribute to general aspheric interferometry.

High-precision wavelength measurement using a virtual Fizeau cavity.

Fizeau wavelength measurement plays an important role in the fields of laser technology, optical communication, and optical metrology. The accuracy of the traditional multistage Fizeau wavemeter is limited owing to the degradation of the stripe symmetry and finesse caused by variations in the cavity length. Herein, we propose a virtual Fizeau cavity (VFC) based on the principle of phase difference to address this issue. The principle analysis and simulation of this measurement system are presented, along with experiments that verified the feasibility and performance of the VFC method. The wavelength measurement accuracy of this system is superior to 60 MHz in the 350-1100 nm wavelength range. The design concept of "virtual-real combined" cavities first proposed in this paper to our knowledge introduces possibilities for the development of high-accuracy Fizeau wavelength measurements.

Dual-shearing interferometer for multi-modal hyperspectral imaging.

A dual-shearing interferometer (DSI) for multimodal hyperspectral imaging is presented. Two orthogonally stacked pairs of coherent beams are generated by a pair of novel, to the best of our knowledge, birefringent lateral shearing splitters. Consequently, two sets of interferograms with full pixel resolution are captured alternately in a time sequence in the double Nyquist frequency mode. Modals of dual-field-of-view hyperspectral imaging and differential-polarization hyperspectral imaging are introduced, and verification experiments are performed. The feasibility of other modals is discussed. The proposed method can effectively improve the instrument's performance in terms of the field of view, polarization, spectral resolution, and spectral range.

The genetic architecture of prolificacy in maize revealed by association mapping and bulk segregant analysis.

KEY MESSAGE: Here, we revealed maize prolificacy highly correlated with domestication and identified a causal gene ZmEN1 located in one novel QTL qGEN261 that regulating maize prolificacy by using multiple-mapping methods. The development of maize prolificacy (EN) is crucial for enhancing yield and breeding specialty varieties. To achieve this goal, we employed a genome-wide association study (GWAS) to analyze the genetic architecture of EN in maize. Using 492 inbred lines with a wide range of EN variability, our results demonstrated significant differences in genetic, environmental, and interaction effects. The broad-sense heritability (H2) of EN was 0.60. Through GWAS, we identified 527 significant single nucleotide polymorphisms (SNPs), involved 290 quantitative trait loci (QTL) and 806 genes. Of these SNPs, 18 and 509 were classified as major effect loci and minor loci, respectively. In addition, we performed a bulk segregant analysis (BSA) in an F2 population constructed by a few-ears line Zheng58 and a multi-ears line 647. Our BSA results identified one significant QTL, qBEN1. Importantly, combining the GWAS and BSA, four co-located QTL, involving six genes, were identified. Three of them were expressed in vegetative meristem, shoot tip, internode and tip of ear primordium, with ZmEN1, encodes an unknown auxin-like protein, having the highest expression level in these tissues. It suggested that ZmEN1 plays a crucial role in promoting axillary bud and tillering to encourage the formation of prolificacy. Haplotype analysis of ZmEN1 revealed significant differences between different haplotypes, with inbred lines carrying hap6 having more EN. Overall, this is the first report about using GWAS and BSA to dissect the genetic architecture of EN in maize, which can be valuable for breeding specialty maize varieties and improving maize yield.

Association of Long-Term Exposure to Ambient Fine Particulate Matter with Atherosclerotic Cardiovascular Disease Incidence Varies across Populations with Different Predicted Risks: The China-PAR Project.

Previous studies have established a significant link between ambient fine particulate matter (PM2.5) exposure and atherosclerotic cardiovascular disease (ASCVD) incidence, but whether this association varies across populations with different predicted ASCVD risks was uncertain previously. We included 109,374 Chinese adults without ASCVD at baseline from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. We obtained PM2.5 data of participants' residential address from 2000 to 2015 using a satellite-based spatiotemporal model. Participants were classified into low-to-medium and high-risk groups according to the ASCVD 10-year and lifetime risk prediction scores. Hazard ratios (HRs) and 95% confidence intervals (CIs) for PM2.5 exposure-related incident ASCVD, as well as the multiplication and additive interaction, were calculated using stratified Cox proportional hazard models. The additive interaction between risk stratification and PM2.5 exposure was estimated by the synergy index (SI), the attributable proportion due to the interaction (API), and the relative excess risk due to interaction (RERI). Over the follow-up of 833,067 person-years, a total of 4230 incident ASCVD cases were identified. Each 10 µg/m3 increment of PM2.5 concentration was associated with 18% (HR: 1.18; 95% CI: 1.14-1.23) increased risk of ASCVD in the total population, and the association was more pronounced among individuals having a high predicted ASCVD risk than those having a low-to-medium risk, with the HR (95% CI) of 1.24 (1.19-1.30) and 1.11 (1.02-1.20) per 10 µg/m3 increment in PM2.5 concentration, respectively. The RERI, API, and SI were 1.22 (95% CI: 0.62-1.81), 0.22 (95% CI: 0.12-0.32), and 1.37 (95% CI: 1.16-1.63), respectively. Our findings demonstrate a significant synergistic effect on ASCVD between ASCVD risk stratification and PM2.5 exposure and highlight the potential health benefits of reducing PM2.5 exposure in Chinese, especially among those with high ASCVD risk.

Identification of novel loci associated with starch content in maize kernels by a genome-wide association study using an enlarged SNP panel.

Starch is a major component of cereals, comprising over 70% of dry weight. It serves as a primary carbon source for humans and animals. In addition, starch is an indispensable industrial raw material. While maize (Zea mays) is a key crop and the primary source of starch, the genetic basis for starch content in maize kernels remains poorly understood. In this study, using an enlarged panel, we conducted a genome-wide association study (GWAS) based on best linear unbiased prediction (BLUP) value for starch content of 261 inbred lines across three environments. Compared with previous study, we identified 14 additional significant quantitative trait loci (QTL), encompassed a total of 42 genes, and indicated that increased marker density contributes to improved statistical power. By integrating gene expression profiling, Gene Ontology (GO) enrichment and haplotype analysis, several potential target genes that may play a role in regulating starch content in maize kernels have been identified. Notably, we found that ZmAPC4, associated with the significant SNP chr4.S_175584318, which encodes a WD40 repeat-like superfamily protein and is highly expressed in maize endosperm, might be a crucial regulator of maize kernel starch synthesis. Out of the 261 inbred lines analyzed, they were categorized into four haplotypes. Remarkably, it was observed that the inbred lines harboring hap4 demonstrated the highest starch content compared to the other haplotypes. Additionally, as a significant achievement, we have developed molecular markers that effectively differentiate maize inbred lines based on their starch content. Overall, our study provides valuable insights into the genetic basis of starch content and the molecular markers can be useful in breeding programs aimed at developing maize varieties with high starch content, thereby improving breeding efficiency. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01437-6.