Analysis of immunoinfiltration and EndoMT based on TGF-ß signaling pathway-related genes in acute myocardial infarction.

Acute myocardial infarction (AMI), a critical manifestation of coronary heart disease, presents a complex and not entirely understood etiology. This study investigates the potential role of immune infiltration and endothelial-mesenchymal transition (EndoMT) in AMI pathogenesis. We conducted an analysis of the GSE24519 and MSigDB datasets to identify differentially expressed genes associated with the TGF-ß signaling pathway (DE-TSRGs) and carried out a functional enrichment analysis. Additionally, we evaluated immune infiltration in AMI and its possible link to myocardial fibrosis. Key genes were identified using machine learning and LASSO logistic regression. The expression of MEOX1 in the ventricular muscles and endothelial cells of Sprague-Dawley rats was assessed through RT-qPCR, immunohistochemical and immunofluorescence assays, and the effect of MEOX1 overexpression on EndoMT was investigated. Our study identified five DE-TSRGs, among which MEOX1, SMURF1, and SPTBN1 exhibited the most significant associations with AMI. Notably, we detected substantial immune infiltration in AMI specimens, with a marked increase in neutrophils and macrophages. MEOX1 demonstrated consistent expression patterns in rat ventricular muscle tissue and endothelial cells, and its overexpression induced EndoMT. Our findings suggest that the TGF-ß signaling pathway may contribute to AMI progression by activating the immune response. MEOX1, linked to the TGF-ß signaling pathway, appears to facilitate myocardial fibrosis via EndoMT following AMI. These novel insights into the mechanisms of AMI pathogenesis could offer promising therapeutic targets for intervention.

Genome-Wide Association Analysis Combined With Quantitative Trait Loci Mapping and Dynamic Transcriptome Unveil the Genetic Control of Seed Oil Content in Brassica napus L.

Rapeseed, an allotetraploid oil crop, provides vegetable oil for human consumption. The growing demand for oilseeds has necessitated the development of rapeseed varieties with improved quality. Therefore, a clear understanding of the genetic basis underlying the seed oil content (SOC) is required. In this study, a natural population comprising 204 diverse accessions and recombinant inbred lines (RILs) derived from Brassica napus and Sinapis alba via distant hybridization were collected for genome-wide association analysis (GWAS) and quantitative trait loci (QTL) mapping of the SOC trait, respectively. The variable coefficient of the RIL and natural populations ranged from 7.43 to 10.43% and 8.40 to 10.91%. Then, a high-density linkage map was constructed based on whole genome re-sequencing (WGS); the map harbored 2,799 bin markers and covered a total distance of 1,835.21 cM, with an average marker interval of 0.66 cM. The QTLs for SOC on chromosome A07 were stably detected in both single and multiple environments. Finally, a novel locus qA07.SOC was identified as the major QTL for SOC based on the GWAS and RIL populations. In addition, the RNA-seq results showed that photosynthesis, lipid biosynthesis proteins, fatty acid metabolism, and unsaturated fatty acid biosynthesis were significantly different between the developed seeds of the two parents of the RIL population. By comparing the variation information and expression levels of the syntenic genes within qA07.SOC and its syntenic genomic regions, as well as through haplotype analysis via GWAS, BnaA07.STR18, BnaA07.NRT1, and BnaA07g12880D were predicted as candidate genes in the qA07.SOC interval. These stable QTLs containing candidate genes and haplotypes can potentially provide a reliable basis for marker-assisted selection in B. napus breeding for SOC.

MicroRNA-24-3p inhibition prevents cell growth of vascular smooth muscle cells by targeting Bcl-2-like protein 11.

Numerous reports have shown that dysfunction of vascular smooth muscle cells (VSMCs) serves a critical function in the development of cardiovascular disease, including coronary heart disease (CHD). microRNAs (miRNAs/miRs) have been reported to play important roles in regulating the function of VSMCs. The present study aimed to determine the role of miR-24-3p in VSMCs and to uncover the underlying mechanism. The expression of miR-24-3p in the peripheral blood samples of CHD patients was measured by reverse transcription-quantitative (RT-q)PCR. It was found that the level of miR-24-3p in the peripheral blood of patients with CHD was significantly upregulated compared with that in healthy controls. A dual luciferase reporter assay was performed to determine whether Bcl-2-like protein 11 (Bcl-2L11) was a target gene of miR-24-3p, and it was identified that Bcl-2L11 was a direct target of miR-24-3p. The mRNA level and protein expression of Bcl-2L11 in the peripheral blood of patients with CHD were measured by RT-qPCR and western blotting, respectively. The findings suggested that Bcl-2L11 was downregulated in the peripheral blood of patients with CHD. In addition, it was found that downregulation of miR-24-3p suppressed VSMC proliferation and promoted VSMC apoptosis, while the effects of the miR-24-3p inhibitor on cell viability and apoptosis were reversed by Bcl-2L11-small interfering (si)RNA. Additionally, downregulation of miR-24-3p increased the levels of Bcl-2L11, caspase-3 and Bax, and decreased Bcl-2 expression in VSMCs; these changes were abolished by Bcl-2L11-siRNA. In conclusion, the aforementioned results indicated that miR-24-3p was an important regulator in VSMC proliferation and apoptosis by targeting Bcl-2L11, which suggested that miR-24-3p might be a potential therapeutic target for the treatment of CHD.

A recessive high-density pod mutant resource of Brassica napus.

In Brassica napus, pod number and pod density are critical factors to determine seed yield. Although the pod density is an essential yield trait, the regulation of yield formation in oil crops, as well as the genetic and molecular mechanisms, are poorly understood. In this study, we characterized a rapeseed high-density pod mutant (dpt247) from composite hybridization. To shed some light on the nature of this mutation, it was investigated morphologically, anatomically, physiologically, genetically and transcriptomically. The mutant plant showed noticeable phenotypic differences in comparison with the control plant, including reduced plant height and primary branch length, decreased number of primary branches, significantly increased number of pod on the main inflorescence, and more compact pod distribution. Besides, the mutant had higher levels of indole-3-acetic acid (IAA) and zeatin riboside (ZR) in the shoot apical meristem (SAM). The dense pod trait was controlled by two major recessive genes identified in the segregating genetic populations of GRE501 and dpt247. RNA sequencing indicated genes participated in auxin, cytokinin and WUS/CLV signalling pathway in dpt247 were more active in the mutant. These results provide important information for understanding the regulation of yield formation and high yield breeding in rapeseed.

[Research on influence of environment factors to yield and quality traits of Perilla frutescen].

The research is aimed to study of the influence of environmental factors on the yield and quality traits, and find out the regularity of the growth and development of perilla. The main environmental factor data in six ecological area in Guizhou province were collected, and the correlation analysis with yield and quality traits of 15 perilla strains was conducted. The results showed that the cultivation environment has significant effects on the yield and quality traits of perilla. The effect of environment on main yield composed traits, contained grain number in top spike, effective panicle number per plant, plant height, top spike length, growth period, and thousand seed weight was degressive. In the different environmental factors, the latitude showed positive correlation with yield, growth period and effective panicle number per plant, and negative correlation with top spike length and grain number in top spike. Elevation showed negative correlation with the growth period of perilla. The perilla yield increased at first and then decreased with altitude rising, with the maximum in the 800 m altitude. The 600-900 m altitude is suitable area for perilla. Except for positive correlation with the plant height, and negative correlation with top spike length, the longitude showed in apparent impact on other traits. Sunshine duration, temperature and rainfall accumulation showed different effect on the different perilla strains. For yield composed traits, the sunshine duration was negatively correlation with the plant length. The accumulated temperature and mean temperature showed negative correlation with the main spike length, the rainfall showed negative correlation with the precipitation and growth period, plant height, ear number. The environmental impact on the oil compounds decreased with oleic acid, stearic acid, linoleic acid, α-linolenic acid, palmitic acid and oil content. Correlation analysis showed that the significantly negative correlation between the oil content and palmitic acid and linoleic acid content, and the positive correlation between linolenic acid content, α-linolenic acid content showed significant negative correlation with other fatty acids composition, and palmitic acid, stearic acid, oleic acid, linoleic acid showed significant positive correlation with each other. The influence of different environmental factors on the quality of perilla were as follows: the oil content was positively associated with elevation and sunshine duration. α-Linolenic acid content showed negative correlation with longitude, latitude, accumulated temperature and mean temperature, but positive correlation with altitude, sunlight and rainfall capacity. The correlation between palmitic acid, stearic acid, oleic acid, linoleic acid and environmental factors showed contrast character of α-linolenic acid. This study detailed discussed the influence of environmental factors on the quality of perilla, which provided the foundation of ecological planting technology and geoherbalism research of perilla.

Twenty-four-hour blood pressure variability plays a detrimental role in the neurological outcome of hemorrhagic stroke.

Background Blood pressure variability (BPV) is a modifiable risk factor for stroke. This study was performed to determine the prognostic role of BPV in patients with acute hemorrhagic stroke. Methods The data of 131 hospitalized hypertensive patients with spontaneous intracerebral hemorrhage (sICH) were collected. All patients underwent examinations using several neurological scales (Glasgow Coma Scale, National Institutes of Health Stroke Scale, and modified Rankin scale [mRS]) and BP measurements at different time points. Results Sex, age, hematoma volume, and neurological scores were not significantly different between patients with a favorable and unfavorable prognosis for sICH. However, significant differences were found in hypertension, diabetes, metabolic syndrome, atrial fibrillation, smoking, and stroke history. The standard deviation (SD), coefficient of variation (CV), and maximum-minimum range (Max-Min) of diastolic BP and the mean, SD, CV, and Max-Min of systolic BP significantly differed between the groups. Statistical analysis also demonstrated correlations between the 90-day mRS score and BPV and between systolic BPV and the 90-day mRS score. Conclusion High systolic or diastolic BPV within 24 hours of hemorrhagic stroke onset is associated with the 90-day neurological prognosis. The 24-hour BPV plays a critical role in the neurological outcome of hemorrhagic stroke.

Simultaneously Inducing and Tracking Cancer Cell Metabolism Repression by Mitochondria-Immobilized Rhenium(I) Complex.

Mitochondrial metabolism is essential for tumorigenesis, and the development of cancer is usually accompanied by alternations of mitochondrial function. Emerging studies have demonstrated that targeting mitochondria and mitochondrial metabolism is an effective strategy for cancer therapy. In this work, eight phosphorescent organometallic rhenium(I) complexes have been synthesized and explored as mitochondria-targeted theranostic agents, capable of inducing and tracking the therapeutic effect simultaneously. Complexes 1b-4b can quickly and efficiently penetrate into A549 cells, specifically localizing within mitochondria, and their cytotoxicity is superior to cisplatin against the cancer cells screened. Notably, complex 3b [Re(CO)3(DIP) (py-3-CH2Cl)]+ containing thiol-reactive chloromethylpyridyl moiety for mitochondria immobilization shows higher cytotoxicity and selectivity against cancer cells than other Re(I) complexes without mitochondria-immobilization properties. Mechanistic studies show that complexes 1b-4b induce a cascade of mitochondria-dependent events including mitochondrial damage, mitochondrial respiration inhibition, cellular ATP depletion, reactive oxygen species (ROS) elevation, and caspase-dependent apoptosis. By comparison, mitochondria-immobilized 3b causes more effective repression of mitochondrial metabolism than mitochondrial-nonimmobilized complexes. The excellent phosphorescence and O2-sensitive lifetimes of mitochondria-immobilized 3b can be utilized for real-time tracking of the morphological changes of mitochondria and mitochondrial respiration repression during therapy process, accordingly providing reliable information for understanding anticancer mechanisms.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.