Single-cell RNA sequencing reveals the transcriptional heterogeneity of Tbx18-positive cardiac cells during heart development.

The T-box family transcription factor 18 (Tbx18) has been found to play a critical role in regulating the development of the mammalian heart during the primary stages of embryonic development while the cellular heterogeneity and landscape of Tbx18-positive (Tbx18+) cardiac cells remain incompletely characterized. Here, we analyzed prior published single-cell RNA sequencing (scRNA-seq) mouse heart data to explore the heterogeneity of Tbx18+ cardiac cell subpopulations and provide a comprehensive transcriptional landscape of Tbx18+ cardiac cells during their development. Bioinformatic analysis methods were utilized to identify the heterogeneity between cell groups. Based on the gene expression characteristics, Tbx18+ cardiac cells can be classified into a minimum of two distinct cell populations, namely fibroblast-like cells and cardiomyocytes. In terms of temporal heterogeneity, these cells exhibit three developmental stages, namely the MEM stage, ML_P0 stage, and P stage Tbx18+ cardiac cells. Furthermore, Tbx18+ cardiac cells encompass several cell types, including cardiac progenitor-like cells, cardiomyocytes, and epicardial/stromal cells, as determined by specific transcriptional regulatory networks. The scRNA-seq results revealed the involvement of extracellular matrix (ECM) signals and epicardial epithelial-to-mesenchymal transition (EMT) in the development of Tbx18+ cardiac cells. The utilization of a lineage-tracing model served to validate the crucial function of Tbx18 in the differentiation of cardiac cells. Consequently, these findings offer a comprehensive depiction of the cellular heterogeneity within Tbx18+ cardiac cells.

Analysis of morphology, nanostructure, and oxidation reaction of soot particulates from CI engines with dimethoxymethane-diesel blends under different loads and speeds.

Dimethoxymethane (DMM)-diesel blended fuels can simultaneously reduce exhaust emissions of soot and nitrogen oxide (NOX); several studies have been conducted in this regard. However, the influence of additive DMM on the production of inception and precursors of particulates, especially the relation between oxidation, morphology, and the nanostructure of soot particles has not been extensively investigated. In this study, a transmission electron microscope (TEM) and a thermogravimetric analyzer are introduced to acquire TEM images and conduct temperature-programmed-oxidation experiments. Aiming to study the influence of DMM addition on soot oxidation, morphology, and nanostructure, tests are conducted at different rotational speeds (1400 rpm and 2200 rpm), two engine loads (0.6 MPa and 1.2 MPa), and three fuels (D100, DMM6.4, and DMM13). The results show that the diameter distributions of all samples display a similar distribution, with the range of sample diameters being from 10 to 45 nm, and the addition of DMM reduces the dp (primary particle diameters) and the Df (fractal dimension), indicating a decreased structural compactness of aggregates, compared with diesel. Moreover, with increasing load and speed, La (the length of the fringe) increases and d (the distance between adjacent layer planes) decreases. Furthermore, with the addition of DMM, a more regular and higher degree of graphitization within soot particles can be observed in comparison to D100. The nanostructure influences the oxidation reaction of graphene segments with a line relation, leading to a difference in soot oxidation property.

Diesel soot combustion in air-NO environment: Evolution of functional groups on soot surfaces.

It is inevitable for NO to be involved in the soot combustion in diesel particulate filters (DPFs), so giving full play to the NO oxidation activity is one of the most effective means to improve the DPF regeneration performance. In this work, based on the results of programmed temperature oxidation (TPO) experiments, Fourier transfer inference spectroscopy, and X-ray photoelectron spectroscopy, the evolution of surface functional groups was seriously analyzed to explore the soot oxidation mechanism. The results revealed that with the presence of NO in the air atmosphere, the concentration of -ONO2 groups showed an increasing trend in the early oxidation stage of 0-20 % oxidation degree (OD) and then slowly decreased during 20-80 % OD, while the variations in CH functional group concentration were directly related to the concentration NO in the air atmosphere. COO functional group is easy to decompose, and NO promotes COO's generation and decomposition. The sp3/sp2 hybrid ratio is strongly correlated with CO (carbon­oxygen double bond), but the content of CO is also affected by the desorption of COO functional groups. It is worth noting that when the soot oxidation degree is at 50 %-80 % OD, CO groups are converted to CO functional groups.

RNA-Seq transcriptome analysis of renal tissue from spontaneously hypertensive rats revealed renal protective effects of dapagliflozin, an inhibitor of sodium-glucose cotransporter 2.

Hypertensive nephropathy (HTN) is a common complication of hypertension. Although various agents for treatment of hypertension exert significant effects, there is currently no effective treatment for hypertensive nephropathy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, such as dapagliflozin (DAPA), are a new class of hypoglycemic agents shown to improve the prognosis of patients with chronic kidney disease and diabetes mellitus. However, the mechanisms underlying the protective effects of DAPA remain unclear. RNA-sequencing (RNA-Seq)-based computational analysis was conducted to explore the transcriptomic changes to spontaneously hypertensive rats (SHRs) treated with DAPA for 8 weeks. Differentially expressed genes in SHRs were related to dysregulation of lipid metabolism, oxidation-reduction reaction, immunity and inflammation in HTN. Transcriptome analysis showed that 8 weeks of DAPA therapy exerted protective effects on the renal tissues of SHRs through the lysosomal, phagosomal, and autophagic pathways. VENN diagram analysis identified Zinc finger and BTB domain-containing 20 (Zbtb20) as the potential target of DAPA therapy. Consistent with the RNA-Seq findings, real-time quantitative PCR and immunohistochemical analyses revealed increased expression of Zbtb20 in the renal tissues of SHRs, whereas expression was decreased following 8 weeks of DAPA administration. The results of this study clarified the transcriptome signature of HTN and the beneficial effects of DAPA on renal tissues by alleviating dysregulation of metabolic processes and reducing inflammation.

Transcriptomic profile analysis of the left atrium in spontaneously hypertensive rats in the early stage.

Left atrial remodeling, characterized by enlargement and hypertrophy of the left atrium and increased fibrosis, was accompanied by an increased incidence of atrial fibrillation. While before morphological changes at the early stage of hypertension, how overloaded hypertension influences the transcriptomic profile of the left atrium remains unclear. Therefore, RNA-sequencing was performed to define the RNA expressing profiles of left atrium in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats as a control group. We also compared the changes in the RNA expression profiles in SHRs treated with an angiotensin receptor blocker (ARB) and angiotensin receptor-neprilysin inhibitor (ARNI) to assess the distinct effects on the left atrium. In total, 1,558 differentially expressed genes were found in the left atrium between WKY rats and SHRs. Bioinformatics analysis showed that these mRNAs could regulate upstream pathways in atrial remodeling through atrial fibrosis, inflammation, electrical remodeling, and cardiac metabolism. The regulated transcripts detected in the left atrial tissue in both the ARB-treated and ARNI-treated groups were related to metabolism. In contrast to the ARB-treated rates, the transcripts in ARNI-treated rats were mapped to the cyclic guanosine monophosphate-protein kinase G signaling pathway.

Effects of biodiesels on the physicochemical properties and oxidative reactivity of diesel particulates: A review.

Particulate emissions from the combustion of diesel have always been the main concern, especially in recent years, with continuously stringent particulate emission regulation for diesel engines. To alleviate the problem, biodiesel has been received great attention because of its being environment-friendly, widely available and renewable. The application of biodiesel in diesel engines changes the combustion process, thus varies physicochemical property of the particulate matter (PM) formed, which in turn influences the oxidative reactivity of soot particles. In view of this, it is particularly important to analyze soot particles from the diesel engine fueled with biodiesels. This review focus on the effects of biodiesels on the physicochemical properties of soot particles, such as surface morphology, nanostructure, active surface area, element composition, elemental and organic carbon contents, surface functional groups, sp2 and sp3 hybridizations, etc. The impact of engine operating conditions (i.e. engine load, engine speed, fuel injection timing, fuel injection pressure, exhaust gas recirculation, etc.) on characteristics of soot particles from diesel engines powered by biodiesel is also discussed. Whereafter, the relationships between soot physicochemical characteristics and soot oxidative reactivity are reviewed. Finally, the main conclusions are outlined as well as the proposed research work in the future.

Impact of carbon chain length of alcohols on the physicochemical properties and reactivity of exhaust soot.

Particle is the main pollutant in diesel engine exhaust, which seriously endangers human health and the atmospheric environment. The use of alcohol fuels in diesel engines can effectively reduce particle emissions, but alcohol fuels with different carbon chain lengths will affect the generation process of particles, which in turn changes the physicochemical properties and oxidation characteristics of the particles. Therefore, it is particularly important to study the properties of particle emitted by diesel engines fueling alcohol fuels with different carbon chain lengths. The physicochemical properties of soot emitted from commercial diesel engines were studied by thermogravimetric analyzer, HRTEM (high-resolution transmission electron microscopy), and XPS (X-ray photoelectron spectroscopy) in this paper, respectively. The diesel engine used alcohol-diesel blends of different carbon chain lengths with the same oxygen content as fuels, such as methanol/diesel blend (M10), n-butanol/diesel blend (NB25), and n-octanol/diesel blend (NO45), and pure diesel fuel was used as a reference. The results showed that the use of alcohols reduced the fractal dimension (Df) of particles, and the NB25 particles had the smallest Df. Moreover, the particles of blended fuels had smaller primary particle diameter (dp) compared to pure diesel. However, with the use of short-chain to long-chain alcohols, an increasing tendency of dp was observed. In terms of the nanostructure, as the use of short-chain to long-chain alcohols, the La (fringe length) increased, both the d (fringe separation distance) and Tf (fringe tortuosity) reduced, which was not favorable for the oxidation of the particles. In addition, in terms of oxygenated surface functional groups (SFGs), the CO group occupied a higher proportion in most working conditions relative to the groups of CO and COO. Further analysis showed that the dp and nanostructure had more influence on the oxidation behavior of soot than Df and oxygenated SFGs.

[Analyzing the clinical phenotype of heart disease caused by the double mutation of p.Gly743Arg and p.Glu1389Lys carrying the myosin heavy chain gene].

OBJECTIVE: To investigate the relationship between double mutations of myosin heavy chain gene (MYH6) p.Gly743Arg and p.Glu1389Lys and the cardiac phenotype. METHODS: Patients carrying double mutations in the MYH6 gene p.Gly743Arg and p.Glu1389Lys were screened from 52 unrelated left ventricular hypertrophy (LVH) who were admitted to the Second Hospital of Chongqing Medical University from 2015 to 2020, and the genetic testing of peripheral blood of patients by second-generation whole-exome sequencing assay technology and genomic DNA of their family members Sanger sequencing was performed to validate the genomic DNA of the family members. The cardiac phenotype was evaluated by electrocardiogram, coronary computed tomography angiography (CTA), echocardiography, and cardiac magnetic resonance imaging (MRI) as adjuncts. RESULTS: All whole-exome gene were detected in 52 unrelated patients with LVH, of which 1 patient (1.9%) had double mutations in MYH6 gene p.Gly743Arg and p.Glu1389Lys (proband). Two members of the maternal line of this patient carried p.Glu1389Lys mutation, but there was no obvious clinical phenotype. Two members of the paternal line carried p.Gly743Arg mutation and had obvious clinical phenotype of bradycardia, but there was no LVH. The male proband, aged 21 years old, presented with LVH and sinus bradycardia but no coronary artery stenosis on CTA before treatment, MRI showed that the left ventricular end diastolic diameter was 58 mm. After treatment with angiotensin receptor-enkephalinase inhibitor (ARNI), electrocardiogram showed that the heart rate increased significantly (from 43 bpm to 72 bpm). Echocardiography showed that the left ventricular end diastolic diameter decreased significantly (from 60 mm to 49 mm). CONCLUSIONS: The p.Glu1389Lys mutation of the MYH6 gene may not manifest the phenotype of heart disease. MYH6 gene p.Gly743Arg mutation may be manifested asymptomatic sinus bradycardia, but there is no LVH phenotype. The cardiac disease phenotype caused by the double mutations of p.Gly743Arg and p.Glu1389Lys in the MYH6 gene is more obvious. Asymptomatic LVH and sinus bradycardia can appear in adolescence, but the LVH phenotype can be reversed in a short period of time after ARNI treatment.