BcaSOD1 enhances cadmium tolerance in transgenic Arabidopsis by regulating the expression of genes related to heavy metal detoxification and arginine synthesis.

Cadmium (Cd), which is a nonessential heavy metal element for organisms, can have a severe impact on the growth and development of organisms that absorb excessive Cd. Studies have shown that Brassica carinata, a semiwild oil crop, has strong tolerance to various abiotic stresses, and RNA-seq has revealed that the B. carinata superoxide dismutase gene (BcaSOD1) likely responds to Cd stress. To elucidate the BcaSOD1 function involved in tolerance of Cd stress, we cloned the coding sequences of BcaSOD1 from a purple B. carinata accession and successfully transferred it into Arabidopsis thaliana. The subcellular localization results demonstrated that BcaSOD1 was primarily located in the plasma membrane, mitochondria and nucleus. Overexpression of BcaSOD1 in transgenic Arabidopsis (OE) effectively decreased the toxicity caused by Cd stress. Compared to the WT (wild type lines), the OE lines exhibited significantly increased activities of antioxidant enzymes (APX, CAT, POD, and SOD) after exposure to 2.5 mM CdCl2. The Cd content of underground (root) in the OE line was dominantly higher than that in the WT; however, the Cd content of aboveground (shoot) was comparable between the OE and WT types. Moreover, the qRT‒PCR results showed that several heavy metal detoxification-related genes (AtIREG2, AtMTP3, AtHMA3, and AtNAS4) were significantly upregulated in the roots of OE lines under Cd treatment, suggesting that these genes are likely involved in Cd absorption in the roots of OE lines. In addition, both comparable transcriptome and qRT-PCR analyses revealed that exogenous BcaSOD1 noticeably facilitates detoxification by stimulating the expression of two arginine (Arg) biosynthesis genes (AtGDH1 and AtGDH2) while inhibiting the expression of AtARGAH1, a negative regulator in biosynthesis of Arg. The Arg content was subsequently confirmed to be significantly enhanced in OE lines under Cd treatment, indicating that BcaSOD1 likely strengthened Cd tolerance by regulating the expression of Arg-related genes. This study demonstrates that BcaSOD1 can enhance Cd tolerance and reveals the molecular mechanism of this gene, providing valuable insights into the molecular mechanism of Cd tolerance in plants.

Co-Expression Network Analysis of the Transcriptome Identified Hub Genes and Pathways Responding to Saline-Alkaline Stress in Sorghum bicolor L.

Soil salinization, an intractable problem, is becoming increasingly serious and threatening fragile natural ecosystems and even the security of human food supplies. Sorghum (Sorghum bicolor L.) is one of the main crops growing in salinized soil. However, the tolerance mechanisms of sorghum to saline-alkaline soil are still ambiguous. In this study, RNA sequencing was carried out to explore the gene expression profiles of sorghum treated with sodium bicarbonate (150 mM, pH = 8.0, treated for 0, 6, 12 and 24 h). The results show that 6045, 5122, 6804, 7978, 8080 and 12,899 differentially expressed genes (DEGs) were detected in shoots and roots after 6, 12 and 24 h treatments, respectively. GO, KEGG and weighted gene co-expression analyses indicate that the DEGs generated by saline-alkaline stress were primarily enriched in plant hormone signal transduction, the MAPK signaling pathway, starch and sucrose metabolism, glutathione metabolism and phenylpropanoid biosynthesis. Key pathway and hub genes (TPP1, WRKY61, YSL1 and NHX7) are mainly related to intracellular ion transport and lignin synthesis. The molecular and physiological regulation processes of saline-alkali-tolerant sorghum are shown by these results, which also provide useful knowledge for improving sorghum yield and quality under saline-alkaline conditions.

Overexpression of ApHIPP26 from the Hyperaccumulator Arabis paniculata Confers Enhanced Cadmium Tolerance and Accumulation to Arabidopsis thaliana.

Cadmium (Cd) is a toxic heavy metal that seriously affects metabolism after accumulation in plants, and it also causes adverse effects on humans through the food chain. The HIPP gene family has been shown to be highly tolerant to Cd stress due to its special domain and molecular structure. This study described the Cd-induced gene ApHIPP26 from the hyperaccumulator Arabis paniculata. Its subcellular localization showed that ApHIPP26 was located in the nucleus. Transgenic Arabidopsis overexpressing ApHIPP26 exhibited a significant increase in main root length and fresh weight under Cd stress. Compared with wild-type lines, Cd accumulated much more in transgenic Arabidopsis both aboveground and underground. Under Cd stress, the expression of genes related to the absorption and transport of heavy metals underwent different changes in parallel, which were involved in the accumulation and distribution of Cd in plants, such as AtNRAMP6 and AtNRAMP3. Under Cd stress, the activities of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase) in the transgenic lines were higher than those in the wild type. The physiological and biochemical indices showed that the proline and chlorophyll contents in the transgenic lines increased significantly after Cd treatment, while the malondialdehyde (MDA) content decreased. In addition, the gene expression profile analysis showed that ApHIPP26 improved the tolerance of Arabidopsis to Cd by regulating the changes of related genes in plant hormone signal transduction pathway. In conclusion, ApHIPP26 plays an important role in cadmium tolerance by alleviating oxidative stress and regulating plant hormones, which provides a basis for understanding the molecular mechanism of cadmium tolerance in plants and provides new insights for phytoremediation in Cd-contaminated areas.

The SbbHLH041-SbEXPA11 Module Enhances Cadmium Accumulation and Rescues Biomass by Increasing Photosynthetic Efficiency in Sorghum.

In plants, expansin genes are responsive to heavy metal exposure. To study the bioremediary potential of this important gene family, we discovered a root-expressed expansin gene in sorghum, SbEXPA11, which is notably upregulated following cadmium (Cd) exposure. However, the mechanism underlying the Cd detoxification and accumulation mediated by SbEXPA11 in sorghum remains unclear. We overexpressed SbEXPA11 in sorghum and compared wild-type (WT) and SbEXPA11-overexpressing transgenic sorghum in terms of Cd accumulation and physiological indices following Cd. Compared with the WT, we found that SbEXPA11 mediates Cd tolerance by exerting reactive oxygen species (ROS)-scavenging effects through upregulating the expression of antioxidant enzymes. Moreover, the overexpression of SbEXPA11 rescued biomass production by increasing the photosynthetic efficiency of transgenic plants. In the pot experiment with a dosage of 10 mg/kg Cd, transgenic sorghum plants demonstrated higher efficacy in reducing the Cd content of the soil (8.62 mg/kg) compared to WT sorghum plants (9.51 mg/kg). Subsequent analysis revealed that the SbbHLH041 transcription factor has the ability to induce SbEXPA11 expression through interacting with the E-box located within the SbEXPA11 promoter. These findings suggest that the SbbHLH041-SbEXPA11 cascade module may be beneficial for the development of phytoremediary sorghum varieties.

Identification and Genome-Wide Gene Expression Perturbation of a Trisomy in Chinese Kale (Brassica oleracea var. alboglabra).

Trisomy harbouring an extra copy of the chromosome generally causes a variety of physical and intellectual disabilities in mammals but is an extremely rare and important genetic stock in plants. In this study, a spontaneous trisomy plant in a Chinese kale accession (Brassica oleracea var. alboglabra, CC, 2n = 18) that showed significantly smaller plant architecture when compared to other normal plants was found and subsequently confirmed by cytological analysis in which the chromosome set of 2n = 19 and abnormal chromosome behaviour were observed. Then, based on the gene expression deviation determined by RNA-seq, the extra chromosome copy in this trisomy was identified as chromosome C2 (TC2). Compared to normal plants, TC2 not only showed generally upregulated differentially expressed genes (DEGs) on chromosome C2 (97.21% of 573 DEGs in chromosome C2) but also exhibited a whole-genome expression perturbation, in which 1329 DEGs (69.87% of total DEGs) were observed along two-copy chromosomes (trans-effect). The genes in the high (gene expression value > 100) and medium (100 > gene expression value > 10) groups were more prone to decreased gene expression, but the genes in the low group (10 > gene expression value > 0.1) showed upregulated expression deviation. In addition, GO (Gene ontology) annotation analysis revealed that the upregulated DEGs in the trans-effect group were overrepresented by the genes involved in the response to stress category, while the downregulated DEGs in the trans-effect group were mostly enriched in pathways related to DNA synthesis. In conclusion, we think our results can provide important resources for genetic analysis in B. oleracea and show some novel insights for understanding trisomy plant biology.

Ketone Body ß-Hydroxybutyric Acid Ameliorates Dopaminergic Neuron Injury Through Modulating Zinc Finger Protein 36/Acyl-CoA Synthetase Long-Chain Family Member Four Signaling Axis-Mediated Ferroptosis.

ß-hydroxybutyrate (BHB) is one of main component of ketone body, which plays an important protective role in various tissues and organs. Whereas, its exact regulatory roles and mechanisms in Parkinson's disease (PD) have not been full elucidated. In this study, SN4741 cells and C57BL/6 mice were treated with 1-methyl-4-phenylpyridinium ion (MPP+)/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish the PD model in vitro and in vivo. Cell viability and damage to dopaminergic neurons were measured by cell counting kit 8, Calcein-AM/PI staining, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling and hematoxylin & eosin staining. Corresponding assay kits and BODIPY 581/591 C11 probe evaluated oxidative stress and intracellular iron levels. Western blot examined the ferroptosis-related proteins. MPTP/MPP+-treatment reduced cell viability but triggered oxidative stress and ferroptosis in SNA4741 cells and brain tissues of mice. However, these effects were dramatically reversed by BHB and Fer-1 treatment. Mechanistically, Zinc finger protein 36 (ZFP36) was a target of BHB, and its depletion could reverse the anti-oxidative stress and anti-ferroptosis roles of BHB. Moreover, ZFP36 could directly bound to acyl-CoA synthetase long-chain family member 4 (ACSL4) mRNA to decay its expression, thus negatively modulating ACSL4-mediated oxidative stress and ferroptosis. Summary, BHB alleviated oxidative stress and ferroptosis of dopaminergic neurons in PD via modulating ZFP36/ACSL4 axis, which provided some new understanding for PD prevention and treatment.

Cumulative mean arterial pressure and risks of adverse cardiac and cerebrovascular events: a prospective cohort study of 53,813 adults.

The association between cumulative mean arterial blood pressure (MAP) and risks of adverse cardiac and cerebrovascular events (CCVEs) has not been characterized. This prospective cohort study included 53,813 participants, free of prior myocardial infarction or stroke in or before 2010 (baseline) from a community-based cohort including 101,510 participants. Cumulative MAP was defined as the summed average MAP for each pair of consecutive examinations multiplied by the time interval with the data from previous surveys (2006- 2007, 2008 to 2009, 2010-2011). Incident adverse CCVEs were ascertained by both the information collection in biennial follow-up surveys (2012-2013, 2014-2015) and surveying each year's discharge lists from local hospitals and death certificates from state vital statistics offices by three experienced physicians blinded to the study design. The study population were stratified into quartiles based on cumulative MAP (<354.62 mmHg, n = 13,454; 354.62 to 392.82 mmHg, n = 13,452; 392.82 to 438.04 mmHg, n = 13 453; ≥ 438.04 mmHg, n = 13,454). We documented 1055 incident adverse CCVEs, including 271 myocardial infarction and 794 stroke (10 comorbid with myocardial infarction), which consisted of 673 ischemic stroke and 134 hemorrhagic stroke (13 comorbid with ischemic stroke). The incidence of adverse CCVEs increased with the increase of cumulative MAP with significant difference (p < 0.001). Cox proportional hazards regression models revealed the elevated cumulative MAP as an independent risk factor for adverse CCVEs, especially hemorrhagic stroke, after adjusting potential confounders. A J-shaped relationship between cumulative MAP and hemorrhagic stroke was also observed.

Correlation between clinic, cumulative, 24h-ambulatory systolic blood pressure, and chronic kidney damage in Chinese elderly.

The aim of this study was to investigate whether clinic, cumulative, and 24h ambulatory systolic blood pressure (SBP) was associated with chronic kidney damage, defind as estimated glomerular filtration rate (eGFR) <60 ml/(min·1.73 m2) and/or microalbuminuria ≥30 mg/L, and, if so, which measurement of SBP is more associated with chronic kidney damage in Chinese elderly. A total of 1207 participants older than 60 years old were included in the final analysis. Clinical blood pressure, cumulative blood pressure exposure was calculated and ambulatory 24h blood pressure was assessed. Multiple logistic regression analysis showed that the clinic (p < .001), cumulative (p = .033), 24h average (p < .001), daytime (p = .001) and nighttime SBP (p = .001) were respectively associated with lower eGFR, and cumulative (p = .008), 24 average (p < .001), daytime (p < .001), and nighttime SBP (p < .001) were the risk factors of microalbuminuria. The degree of correlation were strongest between 24h average SBP and chronic kidney damage (odds ratio, 1.78; 95% confidence interval, 1.46-2.15; p < .001), clinic SBP and eGFR (odds ratio, 1.57; 95% confidence interval, 1.13-2.17; p = .007), nighttime SBP and microalbuminuria (odds ratio, 1.45; 95% confidence interval, 1.05-2.00; p = .024). The likelihood ratio test demonstrated that the introduction of 24h average SBP will improve the goodness of fit of the clinic SBP model(p < .05), while the introduction of cumulative SBP exposure has no such effect(p > .05). Cumulative SBP exposure seems inferior to other measurement in indentifying chronic kidney damage, including decreased GFR and microalbuminuria.

Longitudinal fasting blood glucose patterns and arterial stiffness risk in a population without diabetes.

OBJECTIVE: To identify long-term fasting blood glucose trajectories and to assess the association between the trajectories and the risk of arterial stiffness in individuals without diabetes. METHODS: We enrolled 16,454 non-diabetic participants from Kailuan cohort. Fasting blood glucose concentrations were measured in 2006, 2008, and 2010 survey. Brachial-ankle pulse wave velocities were measured during 2011 to 2016. Multivariate regression model was used to estimate the difference of brachial-ankle pulse wave velocity levels and logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of arterial stiffness risk, according to the fasting blood glucose trajectories. RESULTS: We identified five distinct fasting blood glucose trajectories and each of the trajectories was labeled according to its range and change over 2006-2010 survey: elevated-stable pattern (5.0% of participants), elevated-decreasing pattern (6.6%), moderate-increasing pattern (10.9%), moderate-stable pattern (59.3%), and low-stable pattern (18.2%). After adjustment for potential confounders, individuals with elevated-stable pattern had a 42.6 cm/s (95%CI: 24.7 to 60.6 cm/s) higher brachial-ankle pulse wave velocity level and a 37% (OR 1.37, 95%CI: 1.14 to 1.66) higher arterial stiffness risk, and individuals with moderate-increasing pattern had a 19.6 cm/s (95%CI: 6.9 to 32.3 cm/s) higher brachial-ankle pulse wave velocity level and a 17% (OR 1.17, 95%CI: 1.03 to 1.33) higher arterial stiffness risk, related to individuals with moderate-stable pattern. We did not find significant associations of the elevated-decreasing or low-stable patterns with arterial stiffness. Consistently, the cumulative average, variability, and increased rate of fasting blood glucose during 2006-2010 survey were significantly associated with the arterial stiffness risk. CONCLUSION: Discrete fasting blood glucose trajectories were associated with the arterial stiffness risk in non-diabetic individuals.

Correlation between the trajectory of systolic blood pressure and new renal damage in a nonhypertensive population.

OBJECTIVE: This study aims to investigate the correlation between the trajectory of systolic blood pressure (SBP) and new renal damage in a nonhypertensive population. PATIENTS AND METHODS: This prospective cohort study included a total of 14 382 nonhypertensive individuals, employees of Kailuan Group of Companies, who took part in five healthy examinations in 2006-2007, 2008-2009, 2010-2011, 2012-2013, and 2014-2015, and had complete data. These individuals were divided into four groups according to the different trajectories of SBP: low-low, low-stable, middle-high, and high-high groups. The correlation between the trajectory of SBP and new renal damage in a nonhypertensive population was analyzed using a multivariate Cox's proportional hazard regression model. RESULTS: (a) A total of 14 382 individuals had complete data and the average age of these individuals was 44.6±10.8 years. Among these, 10 888 (75.7%) individuals were men and 3494 (24.3%) individuals were women. (b) These individuals were divided into four groups according to different trajectories of blood pressure: low-low group, accounting for 13.15% (blood pressure was <106 mmHg); low-stable group, accounting for 53.91% (blood pressure was between 115 and 116 mmHg); middle-high group, accounting for 28.77% (blood pressure was between 125 and 131 mmHg); and high-high group, accounting for 4.6% (blood pressure was between 126 and 151 mmHg). (c) With the increase in the trajectory of SBP, the detection rate of renal damage increased gradually. From the low-low group to the high-high group, the detection rates of estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 m were 2.3, 2.4, 3.6, and 4.3%, respectively; the positive rates of urinary protein were 1.7, 2.9, 3.8, and 5.5%, respectively; and the detection rates of eGFR less than 60 ml/min/1.73 m or positive urinary protein were 4, 5.2, 7.3, and 9.3%, respectively (P<0.05). (d) After adjustment for other confounding factors, multivariate Cox's proportional hazard regression analysis showed that compared with the low-low group, the risk of eGFR less than 60 ml/min/1.73 m increased by nearly 1.5 times in the high-high group and in the low-stable, middle-high, and high-high groups, the risks of positive urinary protein, eGFR less than 60 ml/min/1.73 m, or positive urinary protein increased by 1.48-2.34 and 1.20-1.70 times, respectively. CONCLUSION: In a nonhypertensive population, the high trajectory of SBP is a risk factor for kidney damage.

Association of Cumulative Exposure to Resting Heart Rate with Risk of Stroke in General Population: The Kailuan Cohort Study.

BACKGROUND AND PURPOSE: It remains unclear whether resting heart rate (RHR), particularly cumulative exposure to resting heart rate (cumRHR), is associated with stroke. The aim of our study was to prospectively explore the relationship between cumRHR and stroke morbidity. MATERIALS AND METHODS: The Kailuan study is a prospective longitudinal cohort study on cerebrovascular events and cardiovascular factors. Hazard ratios (HRs) with 95% confidence interval (CI) were calculated using a Cox competing risk model. RESULTS: A total of 46,568 participants were included in the final analysis. In the observation population, we identified 851 stroke events and 1012 incident death cases in the 4.98 ± .51 year followed-up. Each 46.74 (beats/min) × year increase in heart rate was associated with a 12% increase in the risk of stroke (HR = 1.12, 95% CI = 1.05-1.20). In the categorical model, the highest quartile had an increased risk of stroke (HR = 1.43, 95% CI = 1.13-1.81), compared with the bottom quartile. Gender and age had no interaction with cumRHR for the risk of stroke. CONCLUSION: Increase of exposure to cumulative heart rate is independently associated with a higher risk of stroke in the general population.

Cumulative Resting Heart Rate Exposure and Risk of All-Cause Mortality: Results from the Kailuan Cohort Study.

The relationship between cumulative exposure to resting heart rate (cumRHR) and mortality remain unclear in the general population. In the Kailuan cohort study, resting heart rate (RHR) was repeatedly measured at baseline and at years 2 and 4 by electrocardiogram among 47,311 adults aged 48.70 ± 11.68. The cumRHR was defined as the summed average RHR between two consecutive examinations multiplied by the time interval between with two examinations [(beats/min) * year]. A higher RHR was defined as ≥80 beats/min, and the number of visits with a higher RHR was counted. During a median of 4.06 years of follow-up, a total of 1,025 participants died. After adjusting for major traditional cardiovascular risk factors and baseline RHR, the hazard ratio for the highest versus lowest quartile of cumRHR was 1.39 (95% CI: 1.07-1.81) for all-cause mortality. Each 1-SD increment in cumRHR was associated with a 37% (HR: 1.37, 95% CI: 1.23-1.52) increased risk of death and displayed a J-shaped relationship. Compared with no exposure, adults who had a higher RHR at all 3 study visits were associated with a 1.86-fold higher risk (95% CI: 1.33-2.61) of mortality. In summary, cumulative exposure to higher RHR is independently associated with an increased risk of mortality.