DNA methylation footprints during soybean domestication and improvement

Abstract Background In addition to genetic variation, epigenetic variation plays an important role in determining various biological processes. The importance of natural genetic variation to crop domestication and improvement has been widely investigated. However, the contribution of epigenetic variation in crop domestication at population level has rarely been explored. Results To understand the impact of epigenetics on crop domestication, we investigate the variation of DNA methylation during soybean domestication and improvement by whole-genome bisulfite sequencing of 45 soybean accessions, including wild soybeans, landraces, and cultivars. Through methylomic analysis, we identify 5412 differentially methylated regions (DMRs). These DMRs exhibit characters distinct from those of genetically selected regions. In particular, they have significantly higher genetic diversity. Association analyses suggest only 22.54% of DMRs can be explained by local genetic variations. Intriguingly, genes in the DMRs that are not associated with any genetic variation are enriched in carbohydrate metabolism pathways. Conclusions This study provides a valuable map of DNA methylation across diverse accessions and dissects the relationship between DNA methylation variation and genetic variation during soybean domestication, thus expanding our understanding of soybean domestication and improvement

Peroxisome Proliferator-Activated Receptor α Attenuates Hypertensive Vascular Remodeling by Protecting Vascular Smooth Muscle Cells from Angiotensin II-Induced ROS Production

Vascular remodeling is the fundamental basis for hypertensive disease, in which vascular smooth muscle cell (VSMC) dysfunction plays an essential role. Previous studies suggest that the activation of peroxisome proliferator-activated receptor α (PPARα) by fibrate drugs has cardiovascular benefits independent of the lipid-lowering effects. However, the underlying mechanism remains incompletely understood. This study explored the role of PPARα in angiotensin II (Ang II)-induced vascular remodeling and hypertension using VSMC-specific Ppara-deficient mice. The PPARα expression was markedly downregulated in the VSMCs upon Ang II treatment. A PPARα deficiency in the VSMC significantly aggravated the Ang II-induced hypertension and vascular stiffness, with little influence on the cardiac function. The morphological analyses demonstrated that VSMC-specific Ppara-deficient mice exhibited an aggravated vascular remodeling and oxidative stress. In vitro, a PPARα deficiency dramatically increased the production of mitochondrial reactive oxidative species (ROS) in Ang II-treated primary VSMCs. Finally, the PPARα activation by Wy14643 improved the Ang II-induced ROS production and vascular remodeling in a VSMC PPARα-dependent manner. Taken together, these data suggest that PPARα plays a critical protective role in Ang II-induced hypertension via attenuating ROS production in VSMCs, thus providing a potential therapeutic target for hypertensive diseases

Assessment of an exhaled breath test using ultraviolet photoionization time-of-flight mass spectrometry for the monitoring of kidney transplant recipients

Abstract Continuous monitoring for immunosuppressive status, infection and complications are a must for kidney transplantation (KTx) recipients. Traditional monitoring including blood sampling and kidney biopsy, which caused tremendous medical cost and trauma. Therefore, a cheaper and less invasive approach was urgently needed. We thought that a breath test has the potential to become a feasible tool for KTx monitoring. A prospective-specimen collection, retrospective-blinded assessment strategy was used in this study. Exhaled breath samples from 175 KTx recipients were collected in West China Hospital and tested by online ultraviolet photoionization time-of-flight mass spectrometry (UVP-TOF–MS). The classification models based on breath test performed well in classifying normal and abnormal values of creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN) and tacrolimus, with AUC values of 0.889, 0.850, 0.849 and 0.889, respectively. Regression analysis also demonstrated the predictive ability of breath test for clinical creatinine, eGFR, BUN, tacrolimus level, as the predicted values obtained from the regression model correlated well with the clinical true values (p < 0.05). The findings of this investigation implied that a breath test by using UVP-TOF–MS for KTx recipient monitoring is possible and accurate, which might be useful for future clinical screenings

Pollution Characteristics and Health Risk Assessment of Summertime Atmospheric Volatile Halogenated Hydrocarbons in a Typical Urban Area of Beijing, China

Twenty-three atmospheric volatile halogenated hydrocarbons (VHHs) were detected in a typical urban area of Beijing, China from 24 August to 4 September, 2012. The mean and range in daily mass concentrations of the 23 VHHs were 30.53 and 13.45&ndash;76.33 &micro;g/m3, respectively. Seven of those VHHs were controlled ozone-depleting substances in China, with a mean of 12.95 &micro;g/m3, accounting for 42.43% of the total. Compared with other national and international cities, the concentrations of the selected 11 VHHs in this study were relatively higher. Dichloroethane had the highest mass concentration, followed by difluorochloromethane. Maxima of total VHHs occurred within the period 8:30&ndash;9:00 a.m., while minima occurred during 1:30&ndash;2:00 p.m. Source apportionment suggested that the main sources of VHHs in the study area were solvents usage and industrial processes, leakage of chlorofluorocarbons banks, refrigerants, and fumigant usage. Among the selected 7 VHHs, trichloromethane, tetrachloromethane, 1,2-dichloroethane, and 1,4-dichlorobenzene posed potential carcinogenic risks to exposed populations, while none of the selected 11 VHHs posed appreciable non-carcinogenic risks to exposed populations. The carcinogenic risks from atmospheric VHHs in Beijing are higher than in other Chinese cities, indicating that it is necessary to implement immediate control measures for atmospheric VHHs in Beijing

CD38‐Specific CAR Integrated into CD38 Locus Driven by Different Promoters Causes Distinct Antitumor Activities of T and NK Cells

Abstract The robust and stable expression of CD38 in T‐cell acute lymphoblastic leukemia (T‐ALL) blasts makes CD38 chimeric antigen receptor (CAR)‐T/natural killer (NK) a potential therapy for T‐ALL. However, CD38 expression in normal T/NK cells causes fratricide of CD38 CAR‐T/NK cells. Here a “2‐in‐1” gene editing strategy is developed to generate fratricide‐resistant locus‐specific CAR‐T/NK cells. CD38‐specific CAR is integrated into the disrupted CD38 locus by CRISPR/Cas9, and CAR is placed under the control of either endogenous CD38 promoter (CD38KO/KI) or exogenous EF1α promoter (CD38KO/KIEF1α). CD38 knockout reduces fratricide and allows the expansion of CAR‐T cells. Meanwhile, CD38KO/KIEF1α results in higher CAR expression than CD38KO/KI in both CAR‐T and CAR‐NK cells. In a mouse T‐ALL model, CD38KO/KIEF1α CAR‐T cells eradicate tumors better than CD38KO/KI CAR‐T cells. Surprisingly, CD38KO/KI CAR‐NK cells show superior tumor control than CD38KO/KIEF1α CAR‐NK cells. Further investigation reveals that endogenous regulatory elements in NK cells lead to higher expression of CD38 CAR than in T cells, and the expression levels of CAR affect the therapeutic outcome of CAR‐T and CAR‐NK cells differently. Therefore, these results support the efficacy of CD38 CAR‐T/NK against T‐ALL and demonstrate that the “2‐in‐1” strategy can resolve fratricide and enhance tumor eradication, paving the way for clinical translation

The impacts of knowledge and attitude on behavior of antibiotic use for the common cold among the public and identifying the critical behavioral stage: based on an expanding KAP model

Abstract Background This study aims to explore the impacts of knowledge and attitude on the behavior of antibiotic use during the treatment of the common cold based on the expanding KAP model, and then identify the critical behavioral stage. Methods A cross-sectional study was conducted on 815 public from 21 community health centers (CHCs) in Chongqing, China. Based on the expanding KAP model, a self-administered questionnaire was designed to measure knowledge, attitude, multi-stage behavior, and perceived threat, in which multi-stage behavior was divided into pre-use antibiotic behavior, during-use antibiotic behavior, and post-use antibiotic behavior. A structural equation model was used to examine the model fit and the direct, indirect, mediating effects, and moderating effect of the variables. Results The expanding KAP showed good model fit indices with χ²/df = 0.537, RMSEA = 0.033, CFI = 0.973, GFI = 0.971, NFI = 0.934, TLI = 0.979. Knowledge had a positive effect on attitude (β = 0.503, p < 0.05), pre-use antibiotic behavior (β = 0.348, p < 0.05), during-use antibiotic behavior (β = 0.461, p < 0.001), and post-use antibiotic behavior (β = 0.547, p < 0.001). Attitude had a positive effect on during-use antibiotic behavior (β = 0.296, p < 0.001), and post-use antibiotic behavior (β = 0.747, p < 0.001). The mediating effect of attitude was positive among knowledge, during-use antibiotic behavior (β = 0.149, p < 0.05), and post-use antibiotic behavior (β = 0.376, p < 0.001). Perceived threat also had a positive moderating effect between knowledge and post-use antibiotic behavior (β = 0.021, p < 0.001). Conclusions Knowledge, attitude and perceived threat had different effects on different stages of antibiotic behavior. The critical behavioral stage prioritized the post-use antibiotic behavior and during-use antibiotic behavior over pre-use antibiotic behavior