Drying without dying: A genome database for desiccation-tolerant plants and evolution of desiccation tolerance.

Desiccation is typically fatal, but a small number of land plants have evolved vegetative desiccation tolerance (VDT), allowing them to dry without dying through a process called anhydrobiosis. Advances in sequencing technologies have enabled the investigation of genomes for desiccation-tolerant plants over the past decade. However, a dedicated and integrated database for these valuable genomic resources has been lacking. Our prolonged interest in VDT plant genomes motivated us to create the "Drying without Dying" database, which contains a total of 16 VDT-related plant genomes (including 10 mosses) and incorporates 10 genomes that are closely related to VDT plants. The database features bioinformatic tools, such as blast and homologous cluster search, sequence retrieval, Gene Ontology term and metabolic pathway enrichment statistics, expression profiling, co-expression network extraction, and JBrowser exploration for each genome. To demonstrate its utility, we conducted tailored PFAM family statistical analyses, and we discovered that the drought-responsive ABA transporter AWPM-19 family is significantly tandemly duplicated in all bryophytes but rarely so in tracheophytes. Transcriptomic investigations also revealed that response patterns following desiccation diverged between bryophytes and angiosperms. Combined, the analyses provided genomic and transcriptomic evidence supporting a possible divergence and lineage-specific evolution of VDT in plants. The database can be accessed at http://desiccation.novogene.com. We expect this initial release of the "Drying without Dying" plant genome database will facilitate future discovery of VDT genetic resources.

Endomyocardial fibrosis and apical calcification: A case report with unusual presentations of apical hypertrophic cardiomyopathy.

RATIONALE: Apical hypertrophic cardiomyopathy (ApHCM) is a phenotypic variant of hypertrophic cardiomyopathy. Endomyocardial fibrosis and endocardial calcification are especially rare in ApHCM. PATIENT CONCERNS: The main symptoms was chest tightness, palpitation, shortness of breath, and fatigue. Echocardiography and imaging examinations found apical hypertrophy along with endocardial calcification and endomyocardial fibrosis. Abnormal structural changes led to thrombosis and made the left ventricle a flat shape resembling an "apple." DIAGNOSES: The typical presentations, hypertrophic apex on echocardiography and an elevated N-terminal pro-brain natriuretic peptide level indicated the diagnosis of ApHCM and heart failure with preserved ejection fraction. INTERVENTIONS: Optimal medical therapy including the administration of ApHCM, heart failure and atrial fibrillation to improve symptoms and life quality. OUTCOMES: Since discharge, the patient could perform normal daily activities and had no discomfort based on the optimal medical therapy. LESSONS: We report a ApHCM patients with unusual presentations of endomyocardial fibrosis and apical calcification. This case highlights the importance of understanding the specific pathological changes of ApHCM for treatment and prognosis.

Co-production of lactate and volatile fatty acids through repeated-batch fermentation of fruit and vegetable waste: Effect of cycle time and replacement ratio.

In this study, repeated-batch fermentation was used to convert fruit and vegetable waste to lactate and volatile fatty acids (VFAs), which are essential carbon sources for medium-chain fatty acids (MCFAs) production. The effect of cycle time and replacement ratio on acidification in long-term fermentation was investigated. The results showed that they had a significant impact on product yield, productivity, and type of products. Considering the yield, productivity, and lactate/VFAs ratio, a replacement ratio of 30% and a cycle time of 2 d may be more suitable for further production of MCFAs. Its productivity and lactate/VFAs ratio were 4.07 ± 0.24 g/(L·d) and 5 ± 0.6, respectively. The lactic acid bacteria, such as Enterococcus (63%) and Lactobacillus (33%), stabilized in the reactor, resulting in the generation of both lactate and VFAs by heterolactic fermentation. The present study demonstrated a new strategy with the potential to recover high-value products from organic waste streams.

Three-year clinical outcomes of the novel sirolimus-eluting bioresorbable scaffold for the treatment of de novo coronary artery disease: A prospective patient-level pooled analysis of NeoVas trials.

OBJECTIVES: We aimed to evaluate the long-term outcomes of the novel NeoVas sirolimus-eluting bioresorbable scaffold (BRS) for the treatment of de novo coronary artery disease. BACKGROUND: The long-term safety and efficacy of the novel NeoVas BRS are still needed to be elucidated. METHODS: A total of 1103 patients with de novo native coronary lesions for coronary stenting were enrolled. The primary endpoint of target lesion failure (TLF) was defined as a composite of cardiac death (CD), target vessel myocardial infarction (TV-MI), or ischemia-driven-target lesion revascularization (ID-TLR). RESULTS: A three-year clinical follow-up period was available for 1,091 (98.9%) patients. The cumulative TLF rate was 7.2% with 0.8% for CD, 2.6% for TV-MI, and 5.1% for ID-TLR. Additionally, 128 (11.8%) patient-oriented composite endpoint and 11 definite/probable stent thromboses (1.0%) were recorded. CONCLUSIONS: The extended outcomes of the NeoVas objective performance criterion trial demonstrated a promising 3-year efficacy and safety of the NeoVas BRS in low-risk patients with low complexity in terms of lesions and comorbidities.

Effects of TCFA on stent neointimal coverage at 9 months after EXCEL drug-eluting stent implantation assessed by OCT.

BACKGROUND: The aim of this study was to investigate the effects of thin-cap fibroatheromas (TCFAs) on stent neointimal coverage at the 9­month follow-up after EXCEL stent implantation assessed by optical coherence tomography (OCT). METHODS: A total of 93 patients with non-ST elevation acute coronary syndrome (NSTEACS) who underwent EXCEL stent implantation were prospectively enrolled in the study and divided into a TCFA group (n = 47) and a non-TCFA group (n = 46) according to whether EXCEL stents covered the TCFAs. A TCFA was defined as a plaque with lipid content in more than one quadrant and fibrous cap thickness measuring less than 65 µm. The effect of TCFAs on stent neointimal coverage at the 9­month follow-up after stent implantation was evaluated by OCT. The primary study endpoints were the incidence of neointimal uncoverage and stent malapposition. RESULTS: At the 9­month follow-up, the minimal lumen diameter of the TCFA group tended to be smaller (2.8 ± 0.8 vs. 2.1 ± 0.8, p = 0.08) and the diameter of stenosis in the TCFA group tended to be larger (15.1 ± 10.3% vs. 26.3 ± 15.1%, p = 0.08) than those in the non-TCFA group. The mean intimal thickness of the TCFA group was significantly lower than that of the non-TCFA group (67.2 ± 35.5 vs. 145.1 ± 48.7, p < 0.001). The uncovered struts (10.1 ± 9.7 vs. 4.8 ± 4.3, p = 0.05) and malapposed struts (2.1 ± 4.7 vs. 0.3 ± 0.5, p = 0.003) in the TCFA group were more significant than those in the non-TCFA group. Multivariate analysis showed that TCFAs and lesion types were independent predictors of incomplete neointimal coverage (p < 0.05), and lesion types were independent predictors of stent malapposition (p < 0.05). CONCLUSION: In patients with NSTEACS, TCFAs delayed endothelium coverage at 9 months after stent implantation, and TCFAs were independent predictors of incomplete neointimal coverage of the stent.

Effect of salt stress and nitrogen supply on seed germination and early seedling growth of three coastal halophytes.

Due to high salinity and low nutrient concentrations, the coastal zone is considered as one of the most vulnerable of the earth's habitats. Thus, the effect of salt and nitrogen on growth and development of coastal halophytes has been extensively investigated in recent years, but insufficient attention has been paid to the crucial stages of plant establishment, such as seed germination and seedling growth. Thus, we carried out a field experiment to evaluate the effects of salt stress (6, 10 and 20 g/kg NaCl) and nitrogen supply (0, 6 and 12 gm-2year-1) on seed germination and seedling growth of three coastal halophytes (including two dominant herb species Glehnia littoralis and Calystegia soldanella, one constructive shrub species Vitex rotundifolia) from September 2020 to June 2021. The results of our experiment showed that seeds of G. littoralis exhibited an explosive germination strategy in the early spring of 2021 with 70% of the seeds germinating. Conversely, the seeds of V. rotundifolia exhibited slow germination in the late spring of 2021 with only 60% of the seeds germinating. C. soldanella seed germination exhibited two obvious peak periods, but only 6% of the seeds germinated, which means that most seeds may be stored in the soil by stratification or died. All three halophytes showed greater sensitivity to nitrogen than salt stress during the seed germination stage. Nitrogen supply significantly delayed seed germination and reduced the cumulative germination percentage, particularly for G. littoralis. Despite the large impact of nitrogen on seed germination, nitrogen had a larger impact on seedling growth suggesting that the seedling growth stage of halophytes is more vulnerable to changes in nitrogen supply. Moreover, nitrogen supply significantly reduced the individual biomass of G. littoralis, C. soldanella and V. rotundifolia, with greater decreases seen in the dominant species than in the constructive species. Conversely, nitrogen supply increased underground biomass allocation of G. littoralis and C. soldanella, suggesting that the constructive species were less sensitive to nitrogen and exhibited a stronger anti-interference ability than the dominant species. Therefore, increasing nitrogen supply may firstly affect the seed germination and seedling growth of the dominant species, but not the constructive species.

Systolic blood pressure trajectories after acute ischemic strokes and clinical outcomes: A systematic review.

Blood pressure(BP) varies drastically during the acute phase after stroke onset. BP level and BP variability may have a major impact on acute ischemic stroke (AIS) prognosis. However, the association between trajectories of blood pressure over time and clinical outcomes have not been established. This review sought out existing evidences for associations of systolic blood pressure (SBP) trajectories on outcomes after stroke to determine the connection between SBP trajectories and stroke prognosis. According to a pre-designed search strategy, literature search was carried out in Embase, Pubmed and Web of Science. Two authors independently evaluated study eligibility and quality, and literature data were extracted. When the literature was eligible, we perform meta-analysis to determine associations of SBP trajectories with clinical outcomes. Seven studies were finally screened out of 52 studies retrieved. Seven studies received a good risk of bias rating and reported BP measurement methods and intervals, BP trajectories modeling methods, outcome measures, but it was found that final systolic BP trajectories in various papers were significantly different. All studies reported statistically significant associations between systolic blood pressure trajectories and prognosis. Methodological heterogeneity is observed in studies. However, this systematic review suggests that the high SBP group after AIS is related to poor clinical outcomes, while the rapid decline or medium-to-low or low SBP group is associated with relatively better clinical outcomes at different period after stroke. More prospective studies are needed to report the full methodology according to standardized criteria and explore relationships between SBP trajectories and prognosis of stroke.

Modeling and Measurement of Thermal-Mechanical-Stress-Creep Effect for RF MEMS Switch Up to 200 °C.

High-temperature processes, such as packaging and annealing, are challenges for Radio-Frequency Micro-Electro-Mechanical-Systems (RF MEMS) structures, which could lead to device failure. Coefficient of thermal expansion (CTE) mismatch and the material's creep effect affect the fabrication and performance of the MEMS, especially experiencing the high temperature. In this paper, the Thermal-Mechanical-Stress-Creep (TMSC) effect during thermal processes from room temperature (RT) to 200 °C is modeled and measured, in which an Au-cantilever-based RF MEMS switch is selected as a typical device example. A novel Isolation-Test Method (ITM) is used to measure precise TMSC variation. This method can achieve resolutions of sub-nanometer (0.5 nm) and attofarad (1 aF). There are three stages in the thermal processes, including temperature ramping up, temperature dwelling, and temperature ramping down. In different stages, the thermal-mechanical stress in anchor and cantilever, the grain growth of gold, and the thermal creep compete with each other, which result in the falling down and curling up of the cantilever. These influencing factors are decoupled and discussed in different stages. The focused ion beam (FIB) is used to characterize the change of the gold grain. This study shows the possibility of predicting the deformation of MEMS structures during different high-temperature processes. This model can be extended for material selection and package temperature design of MEMS cantilever in the further studies.

Thermodynamics of volatile fatty acid degradation during anaerobic digestion under organic overload stress: The potential to better identify process stability.

Anaerobic digestion (AD) operating under organic overload stress usually increases the potential for process instability, leading to significant economic and ecological consequences. Volatile fatty acids (VFAs) accumulation is regularly considered a major factor during AD and their degradation is subject to thermodynamic constraints. To date, no study has systematically investigated the mechanisms of VFA degradation on process stability from the perspective of thermodynamics. Hence, increased substrate-to-inoculum ratio was applied in this study to simulate organic overload stress using batch tests with Hybrid Pennisetum. As a result, VFAs accumulation increased, accompanied by decreased methane yield, slower methane production kinetics and even severe process instability. Metagenomic analysis demonstrated that the accumulated propionate and butyrate were degraded by methyl-malonyl-CoA and the ß-oxidation pathway while syntrophic acetate oxidation was preferred during acetate degradation. The deviation of stability parameters to varying degrees from the recommended threshold values was observed. However, a subsequent thermodynamic analysis revealed that moderate organic overload stress merely retarded the syntrophic oxidation of propionate, butyrate, and acetate. As a result, the methanogenic activity decreased, and the lag phase of AD was extended, but no adverse thermodynamic effects actually occurred. Changes in the Gibbs free energy for syntrophic propionate and acetate oxidation have the potential to better identify process stability. This study provided novel insights into the underlying thermodynamic mechanisms of VFA degradation and may have important implications for improving the current diagnostic mode for AD process stability.

Effects of atorvastatin doses on serum level of procalcitonin and predictors for major adverse cardiovascular events in patients with acute myocardial infarction: a pilot study and post hoc analysis.

BACKGROUND: Inflammation plays an important role in acute myocardial infarction (AMI). Procalcitonin levels rise in response to proinflammatory stimuli. This study aimed to investigate the effects of different doses of atorvastatin on the serum inflammatory profiles, especially procalcitonin and major adverse cardiovascular events (MACEs) in patients with AMI during hospitalization. METHODS: The patients who were admitted to the Coronary Care Unit of The Third Medical Center of PLA General Hospital (Beijing, China) between January 2015 and December 2015 with a diagnosis of AMI were enrolled, and randomized to atorvastatin 20 mg/day postoperatively (20-mg group), 40 mg/day postoperatively (40-mg group) and 80 mg preoperatively+40 mg/day postoperatively (80/40-mg group). Serum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) were evaluated before and at 1 and 3 days after percutaneous coronary intervention (PCI). RESULTS: A total of 112 patients with AMI (23 women and 89 men) were prospectively eligible for the study. There were no significant differences in most clinical data among the three groups. The 80/40-mg group showed significantly reduced serum procalcitonin levels at 1 and 3 days after PCI (P < 0.001) and reduced hs-CRP levels at 3 days P = 0.001) compared with 20-mg and 40-mg groups. Serum procalcitonin (OR, 4.593; 95% CI, 1.476-8.387; P = 0.005), hs-CRP (OR, 1.149; 95% CI, 1.012-1.338; P = 0.018), highly sensitive cardiac troponin T (OR, 1.255; 95% CI, 1.004-1.569, P = 0.009) and Gensini score (OR, 1.022; 95% CI, 1.045-1.062; P = 0.013) were independently associated with MACEs during hospitalization. CONCLUSION: The use of atorvastatin 80 mg before and 40 mg/day after PCI in patients with AMI can effectively reduce serum inflammatory factors. procalcitonin and hs-CRP were independently associated with in-hospital MACEs.

Leaf-root-soil N:P stoichiometry of ephemeral plants in a temperate desert in Central Asia.

Ephemeral plants are a crucial vegetation component in temperate deserts of Central Asia, and play an important role in biogeochemical cycle and biodiversity maintenance in desert ecosystems. However, the nitrogen (N) and phosphorus (P) status and interrelations of leaf-root-soil of ephemeral plants remain unclear. A total of 194 leaf-root-soil samples of eight ephemeral species at 37 sites in the Gurbantunggut Desert, China were collected, and then the corresponding N and P concentrations, and the N:P ratio were measured. Results showed that soil parameters presented no significant difference among the eight species. The total soil N:P was only 0.116 (geomean), indicating limited soil N, while the available soil N:P (4.896, geomean) was significantly larger than the total N:P. The leaf N (averagely 30.995 mg g-1) and P (averagely 1.523 mg g-1) concentrations were 2.64-8.46 and 0.93-3.99 times higher than the root N (averagely 8.014 mg g-1) and P (averagely 0.802 mg g-1) concentrations, respectively. Thus, leaf N:P (averagely 21.499) was 1.410-2.957 times higher than root N:P (averagely 11.803). Meanwhile, significant interspecific differences existed in plant stoichiometric traits. At the across-species level, N content scaled as the 3/4-power of P content in both leaves and roots. Leaf and root N:P ratios were mainly influenced by P; however, the leaf-to-root N or P ratio was dominated by roots. Leaf and root N, P contents and N:P were generally unrelated to soil nutrients, and the former presented lower variation than the latter, indicating a strong stoichiometric homeostasis for ephemerals. These results demonstrate that regardless of soil nutrient supply capacity in this region, the fast-growing ephemeral plants have formed a specific leaf-root-soil stoichiometric relation and nutrient use strategy adapting to the extreme desert environment.

Initial pH-driven production of volatile fatty acid from hybrid Pennisetum.

In this work, the impact of initial pH on the production of volatile fatty acids (VFAs) of hybrid Pennisetum was investigated. The batch experiments were conducted under six distinct beginning pH at a mesophilic temperature. Initial pH had an obvious effect on VFA yield and composition, and severe alkaline circumstances (pHin = 11.0) could boost VFA production and acetic acid selectivity. The highest VFAs yield and acetate proportion were obtained when the initial pH was 11.0, with 518 ± 29 mg g-1VS and 92%. Furthermore, microbial community analysis showed that alkaliphilic acetogenic anaerobe such as Amphibacillus, Tissierella, and Natronincola were the dominant species when the initial pH was 11.0. The Amphibacillus is the main hydrolysis bacterium under these conditions because of its high ability for xylan degradation at pH 9.0-10.0. Because of the increased VFA yield and superior acetic acid selectivity, the results suggest that adjusting the initial pH to 11.0 in batch mode would be possible for scaling-up purposes.

Is the Life History Flexibility of Cold Desert Annuals Broad Enough to Cope with Predicted Climate Change? The Case of Erodium oxyrhinchum in Central Asia.

Interannual seasonal variability in precipitation may strongly affect the life history and growth of desert annual plants. We compared the effects of dry and wet springs and dry and wet autumns on growth and F2 seed dormancy of plants from spring (SG)- and autumn (AG)-germinated seeds of the cold desert annual Erodium oxyrhinchum. Vegetative and reproductive growth and F2 seed dormancy and germination were monitored from September 2016 to November 2020 in the sandy Gurbantunggut Desert in NW China in Central Asia. Dry autumns decreased the density of AG plants, and dry springs decreased the density of SG plants and growth of SG and AG plants. In dry springs, SG plants were more sensitive to precipitation than AG plants, while in wet springs SG and AG plants had similar responses to precipitation. During growth in both dry and wet springs, most morphological characters of SG and AG plants initially increased rapidly in size/number and then plateaued or decreased, except for SG plants in dry springs. In dry springs, most morphological characters of AG plants were larger or more numerous than those of SG plants, and they were larger/more numerous for SG plants in wet than in dry springs. The percentage biomass allocated to reproduction in SG plants was slightly higher in a wet than in a dry spring. A much higher proportion of dormant seeds was produced by AG plants in a wet spring than in a dry spring. Projected changes in precipitation due to climate change in NW China are not likely to have much of an effect on the biology of this common desert annual plant.

Conductive single-wall carbon nanotubes/extracellular matrix hybrid hydrogels promote the lineage-specific development of seeding cells for tissue repair through reconstructing an integrin-dependent niche.

BACKGROUND: The niche of tissue development in vivo involves the growth matrix, biophysical cues and cell-cell interactions. Although natural extracellular matrixes may provide good supporting for seeding cells in vitro, it is evitable to destroy biophysical cues during decellularization. Reconstructing the bioactivities of extracellular matrix-based scaffolds is essential for their usage in tissue repair. RESULTS: In the study, a hybrid hydrogel was developed by incorporating single-wall carbon nanotubes (SWCNTs) into heart-derived extracellular matrixes. Interestingly, insoluble SWCNTs were well dispersed in hybrid hydrogel solution via the interaction with extracellular matrix proteins. Importantly, an augmented integrin-dependent niche was reconstructed in the hybrid hydrogel, which could work like biophysical cues to activate integrin-related pathway of seeding cells. As supporting scaffolds in vitro, the hybrid hydrogels were observed to significantly promote seeding cell adhesion, differentiation, as well as structural and functional development towards mature cardiac tissues. As injectable carrier scaffolds in vivo, the hybrid hydrogels were then used to delivery stem cells for myocardial repair in rats. Similarly, significantly enhanced cardiac differentiation and maturation(12.5 ± 2.3% VS 32.8 ± 5%) of stem cells were detected in vivo, resulting in improved myocardial regeneration and repair. CONCLUSIONS: The study represented a simple and powerful approach for exploring bioactive scaffold to promote stem cell-based tissue repair.

Is Plant Life-History of Biseasonal Germination Consistent in Response to Extreme Precipitation?

Future climate is projected to increase in the intensity and frequency of extreme precipitation events, and the resulting ecological consequences are often more serious than those of normal precipitation events. In particular, in desert ecosystems, due to the low frequency and strong fluctuation of extreme precipitation, the destructive consequences for desert plants caused by extreme precipitation have not received enough attention for some time. Based on statistics of extreme precipitation events (1965-2018) in the Gurbantunggut Desert, we investigated the effects of extreme precipitation (+0%, CK; +50%, W1; +100%, W2; +200%, W3; maintenance of field capacity, W4) on the plant life-history of the spring-germinated (SG) and autumn-germinated (AG) ephemeral plant Erodium oxyrhynchum by monitoring seedling emergence, survival, phenology, organ size, biomass accumulation, and allocation. The results showed that extreme precipitation caused about 2.5% seedling emergence of E. oxyrhynchum in autumn 2018 and 3.0% seedling emergence in early spring 2019, which means that most seeds may be stored in the soil or have died. Meanwhile, extreme precipitation significantly improved the survival, organ size, and biomass accumulation of SG and AG plants, and W3 was close to the precipitation threshold of SG (326.70 mm) and AG (560.10 mm) plants corresponding to the maximum individual biomass; thus, AG plants with a longer life cycle need more water for growth. Conversely, W4 caused AG plants to enter the leaf stage in advance and led to death in winter, which indicates that extreme precipitation may not be good for AG plants. Root and reproduction biomass allocation of SG and AG plants showed a significantly opposite trend under extreme precipitation treatments, which might be related to their different life-history strategies. Therefore, when only taking into account the changing trend of extreme precipitation from the Coupled Model Intercomparison Project 6 (CMIP6) climate projections data, we speculate that extreme precipitation may promote the growth of SG and AG plants from the beginning to the middle of this century, but extreme precipitation in autumn exceeding a certain threshold may adversely affect the survival of AG plants at the end of the century.

The Expression of miR-365 in Serum of Hypertension Patients with Left Ventricular Hypertrophy Was Up-Regulated, Which Was Positively Correlated with Left Ventricular Mass Index.

OBJECTIVE: The present study aims to investigate micro ribonucleic acid-365 (miR-365) serum expression and its correlation with left ventricular hypertrophy (LVH) in patients with hypertension (HT). METHODS: Eighty-four patients were selected as study subjects and divided into three groups: the experimental group (n = 28), the observation group (n = 29), and the control group (n = 27). The experimental group included patients with LVH-accompanied HT who were treated in the People's Hospital of Hebei Province between November 2019 and November 2020, the observation group included patients with HT unaccompanied by LVH, and the control group included healthy age and gender-matched subjects who underwent health examinations in our physical examination center. The cardiac echocardiography, 24-h Holter electrocardiogram, and circulating miR-365 levels in all subjects were measured. The differences in circulating miR-365 expression levels among the three groups were compared, and the correlations between the miR-365 expression levels and the blood pressure parameters (24-h mean systolic blood pressure [SBP] and 24-h mean diastolic blood pressure [DBP]), inter-ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular internal diameter (LVID), left ventricular mass (LVM), LVM index (LVMI), and LVH-related indicators were analyzed. RESULTS: The relative miR-365 expressions in the experimental, observation, and control groups were 2.08 (1.60, 2.34), 0.62 (0.44, 0.83), and 0.66 (0.35, 0.86), respectively. Patient miR-365 expression was significantly higher in the experimental group than in the observation group and the control group; the differences were statistically significant (p < 0.000). Furthermore, miR-365 expression was significantly correlated with SBP, DBP, IVST, LVPWT, LVID, LVM, and LVMI; the greatest correlation was with LVMI. Further univariate linear regression analysis revealed that miR-365 expression was linearly and positively correlated with LVMI and that miRNA-365 expression increased with the LVMI value. CONCLUSION: The miR-365 serum expression in patients with LVH-accompanied HT was increased compared with the observation group and the control group and positively correlated with the LVH degree.

Inhibition of cardiomyocyte apoptosis post-acute myocardial infarction through the efficient delivery of microRNA-24 by silica nanoparticles.

MicroRNA-24 (miR-24) is an apoptosis suppressor miRNA downregulated in cardiomyocytes after acute myocardial infarction (AMI). However, due to the lack of effective delivery strategies, the role of anti-apoptotic miR-24 in cardiomyocytes post-acute myocardial infarction remains unexplored. Here, we used a silica nanoparticle-based polyelectrolyte (polyethylenimine, PEI) delivery system to study the role of miR-24. These particles with good biocompatibility could be efficiently internalized into cells and release the loaded miR-24 into the cytoplasm. As a result, the overexpression of miR-24 resulted in the inhibition of the pro-apoptotic Bim, thereby inhibiting cardiomyocyte apoptosis in vitro. Furthermore, in vivo experiments revealed that over-expressed miR-24 additionally significantly improves ventricular remodeling and cardiac function in Sprague-Dawley (SD) rats after coronary artery ligation. In summary, our novel delivery system serves as a therapeutic miRNA formulation for cardiovascular disease treatment.

Effects of carbon nanotube-mediated Caspase3 gene silencing on cardiomyocyte apoptosis and cardiac function during early acute myocardial infarction.

RNA interference (RNAi) technology can achieve efficient and specific silencing of Caspase3 gene expression, thus providing new options for anti-apoptosis treatment. However, delivering siRNA to specific cells and tissues in the body is a significant challenge. Therefore, we aim to construct a functionalized single-walled carbon nanotube (F-CNT) bound to siRNA from Caspase3. The obtained gene transfer carrier F-CNT-siCas3 not only demonstrated a good water solubility and biocompatibility, but also had a high transfection efficiency of up to 82%, which significantly downregulated the expression level of the Caspase3 gene miRNA and protein in primary cardiomyocytes. Furthermore, it was verified by in vivo experiments that Caspase3 gene silencing had obvious protective effects on myocardial cell apoptosis, ventricular remodeling, and cardiac function in Sprague-Dawley (SD) rats after coronary artery ligation. This study may provide an important theoretical basis for the application of F-CNT in vivo siRNA gene therapy to treat cardiovascular diseases.

Mitochondria-Inspired Nanoparticles with Microenvironment-Adapting Capacities for On-Demand Drug Delivery after Ischemic Injury.

Stimuli-responsive nanoparticles (NPs), so-called "smart" NPs, possess great potentials in drug delivery. Presently, the intelligence of smart NPs is mainly based on their chemical or physical changes to stimuli, which are usually "mechanical" and fundamentally different from biological intelligence. Inspired by mitochondria (MT), a biosmart nanoparticle with microenvironment targeting and self-adaptive capacity (MTSNP) was fabricated for ischemic tissue repair. The nanoparticles were designed as shell@circular DNA@shell@core. The double shells were like the two-layered membranes of MT, the melatonin-loaded cores corresponded to the MT matrix, and the circular DNA corresponded to MTDNA. In function, melatonin-loaded cores simulated the cell-protective mechanism of MT, which naturally synthesized melatonin to resist ischemia, while circular DNA was constructed to mimic the biological oxygen-sensing mechanism, synthesizing VEGF for vascularization according to oxygen level, like the ATP supply by MT according to microenvironment demand. At the acute stage of ischemia, melatonin was rapidly released from MTSNP to scavenge reactive oxygen species and activated melatonin receptor I on MT to prevent cytochrome c release, which would activate apoptosis. During the chronic stage, circular DNA could sense hypoxia and actively secrete VEGF for revascularization as a response. Importantly, circular DNA could also receive feedback of revascularization and shut down VEGF secretion as an adverse response. Then, the therapeutic potentials of the MTSNP were verified in myocardial ischemia by the multimodality of the methods. Such nanoparticles may represent a promising intelligent nanodrug system.

Safety and efficacy of intracoronary prourokinase administration in patients with high thrombus burden.

OBJECTIVES: The study was designed to evaluate the effect of low-dose intracoronary prourokinase administration immediately after thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) presenting with a serious thrombus burden. METHODS: Consecutive STEMI patients with high thrombus burden received thrombus aspiration during primary percutaneous coronary intervention (PCI) were randomly assigned to study group (intracoronary prourokinase administration) or control group (intracoronary 0.9% sodium chloride administration). The primary endpoint was complete ST-segment resolution (STR) at 90 min after primary PCI, and the secondary endpoints included angiographic myocardial perfusion indexes. RESULTS: Patients in study group had a higher incidence of complete STR and myocardial blush grade 3 compared with those in control group (56.52% vs. 38.89%, P = 0.017 and 57.61% vs. 38.89%, P = 0.041). The peak cardiac troponin I value and corrected thrombolysis in myocardial infarction frame count were significantly lower in study group (52.16 ± 24.67 ng/mL vs. 60.91 ± 28.81 ng/mL, P = 0.029; and 19.57 ± 9.05 vs. 22.91 ± 10.22, P = 0.020). A significant improvement in left ventricular ejection fraction and major adverse cardiac events (MACEs)-free survival was observed in study group (55.22 ± 10.50% vs. 52.18 ± 9.39%, P = 0.041; 10.87% vs. 22.22%, P = 0.039) at the 6-month follow-up. The bleeding complication was similar in both groups (17.39% vs. 12.22%, P = 0.327). CONCLUSIONS: In STEMI patients with high thrombus burden, low-dose prourokinase intracoronary administered immediately after thrombus aspiration improves myocardial perfusion, cardiac function, and MACEs-free survival with no significant increase in major bleeding.