Emerging applications of single-cell profiling in precision medicine of atherosclerosis.

Atherosclerosis is a chronic, progressive, inflammatory disease that occurs in the arterial wall. Despite recent advancements in treatment aimed at improving efficacy and prolonging survival, atherosclerosis remains largely incurable. In this review, we discuss emerging single-cell sequencing techniques and their novel insights into atherosclerosis. We provide examples of single-cell profiling studies that reveal phenotypic characteristics of atherosclerosis plaques, blood, liver, and the intestinal tract. Additionally, we highlight the potential clinical applications of single-cell analysis and propose that combining this approach with other techniques can facilitate early diagnosis and treatment, leading to more accurate medical interventions.

The Role of Circular RNAs in Ischemic Stroke.

Ischemic stroke (IS), a devastating condition characterized by intracranial artery stenosis and middle cerebral artery occlusion leading to insufficient oxygen supply to the brain, is a major cause of death and physical disability worldwide. Recent research has demonstrated the critical role of circular RNAs (circRNAs), a class of covalently enclosed noncoding RNAs that are widespread in eukaryotic cells, in regulating various physiological and pathophysiological cellular processes, including cell apoptosis, autophagy, synaptic plasticity, and neuroinflammation. In the past few years, circRNAs have attracted extensive attention in the field of IS research. This review summarizes the current understanding of the mechanisms underlying the involvement of circRNAs in IS development. A better understanding of circRNA-mediated pathogenic mechanisms in IS may pave the way for translating circRNA research into clinical practice, ultimately improving the clinical outcomes of IS patients.

Integrating satellite and reanalysis precipitation products for SWAT hydrological simulation in the Jing River Basin, China.

In hydrological studies, satellite and reanalysis precipitation products are increasingly being used to supplement gauge observation data. This study designed the composite simulation index (COSI), considering two factors: F1 (data accuracy assessment) and F2 (hydrological simulation performance), to compare the performance of the latest satellite-based and reanalysis-based precipitation products (IMERG, ERA5, ERA5-Land), the prior precipitation products (TRMM, CMADS), and the multi-source weighted-ensemble precipitation (MSWEP). The Soil and Water Assessment Tool (SWAT) model was then applied to compare and analyze the hydrological simulation performance of four preferred products using three data fusion methods including simple model averaging, variance-based weighted averaging, and the latest quantile-based Bayesian model averaging (QBMA). The results can be summarized as follows: (1) Reanalysis products are superior to satellite-based products in terms of F1. However, the satellite-based precipitation products exhibit less BIAS and relatively higher F2, while the MSWEP has relatively high performance on both F1 and F2. (2) Among reanalysis-based precipitation products, CMADS has the best COSI value of 0.53. Although ERA5-Land shows good performance for individual parameters, the comprehensive assessment reveals that ERA5 outperforms ERA5-Land in terms of both F1 and F2. (3) IMERG and TRMM exhibit similar spatiotemporal patterns and similar F1, but IMERG is superior in F2. (4) QBMA outperformed traditional methods in F2, improving the NS coefficient of SWAT model from 0.74 to 0.85. These findings provide a useful reference for analyzing the strengths and limitations of satellite-based and reanalysis precipitation products, and also provide valuable ideas for the combined application of multi-source precipitation products in hydrological studies.

IGF­1 inhibits palmitic acid­induced mitochondrial apoptosis in macrophages.

Insulin growth factor­1 (IGF­1) is an endocrine regulator that plays an important role in normal growth and development. IGF­1 mediated effects may result in protecting macrophages from immunometabolic response. However, it is unclear whether IGF­1 has a protective effect on fatty acid­induced macrophages damage. In the present study, THP­1 cells were differentiated into macrophages and stimulated with palmitic acid (PA) in the absence or presence of IGF­1. Macrophages apoptosis was measured by Cell Counting Kit­8 assay, flow cytometry, Hoechst 33342 staining and western blotting. The mitochondrial damage was evaluated using JC­1 staining and mitochondrial reactive oxygen species detection. The activation of mitophagy was assessed using immunofluorescence and western blotting. As a result, IGF­1 significantly restored the survival rate in macrophages, while the apoptosis was inhibited through mitochondrial pathway. In addition, IGF­1 protected the mitochondrial damage induced by PA. Furthermore, PA induced mitophagy via phosphatase and tensin homolog­induced putative kinase protein 1/Parkin, which was reversed by IGF­1. Taken together, the present study demonstrated the protective effect of IGF­1 on PA­induced mitochondrial apoptosis in macrophages, which might provide a potential therapeutic strategy for treatment of lipotoxicity.

Histone Deacetylase 3: A Potential Therapeutic Target for Atherosclerosis.

Atherosclerosis, the pathological basis of most cardiovascular disease, is characterized by plaque formation in the intima. Secondary lesions include intraplaque hemorrhage, plaque rupture, and local thrombosis. Vascular endothelial function impairment and smooth muscle cell migration lead to vascular dysfunction, which is conducive to the formation of macrophage-derived foam cells and aggravates inflammatory response and lipid accumulation that cause atherosclerosis. Histone deacetylase (HDAC) is an epigenetic modifying enzyme closely related to chromatin structure and gene transcriptional regulation. Emerging studies have demonstrated that the Class I member HDAC3 of the HDAC super family has cell-specific functions in atherosclerosis, including 1) maintenance of endothelial integrity and functions, 2) regulation of vascular smooth muscle cell proliferation and migration, 3) modulation of macrophage phenotype, and 4) influence on foam cell formation. Although several studies have shown that HDAC3 may be a promising therapeutic target, only a few HDAC3-selective inhibitors have been thoroughly researched and reported. Here, we specifically summarize the impact of HDAC3 and its inhibitors on vascular function, inflammation, lipid accumulation, and plaque stability in the development of atherosclerosis with the hopes of opening up new opportunities for the treatment of cardiovascular diseases.

Effect of sulfamethazine on anaerobic digestion of manure mediated by biochar.

Antibiotic contamination from animal production and wastewater treatment process will release antibiotic resistant genes to the environment and potentially threaten human health. Meanwhile, the residual antibiotic in manure could have inactive impacts on anaerobic digestion (AD). This study explores the effect of sulfamethazine on manure AD mediated by biochar. The results show that biochar weakens the adverse effects of sulfamethazine on AD by adsorption sulfamethazine during the initial stage (0-3 days) of AD and promoting the growth of hydrolytic bacteria (especially Firmicutes and Bacteroidetes) and methanogens (especially Methanothrix and Methanosarcina). Besides, the presence of biochar improves the biogas production capacity of AD and promotes microbial diversity and community richness. Thus, the addition of biochar greatly reduces sulfamethazine and is testified to be a desirable strategy to mitigate the inhibition of sulfamethazine on AD.

Development of a hydraulically controlled piston-pressurized pulsed water jet device and its application potential for hard rock breaking.

To improve the efficiency of hard rock breaking by a pulsed water jet (PWJ), a hydraulically controlled piston-pressurized PWJ (HCPPPWJ) device has been developed, by which the large amplitude pressurization of the jet could be realized through the motion coupling of the piston and the valve core inside the device without requiring additional control or ultra-high-pressure components. Under the continuous injection of low-pressure hydraulic oil, the device has a stable pressurization effect and controllable pulse pressure and pulse frequency. The jet pressure varies periodically with the alternation of high and low pressures; in the rising stage of the pulse pressure, the jet morphology presents an umbrella-like thin-layer structure, which ensures an effective initial impact force of the jet in contact with the target. With the addition of high-frequency stress waves and water wedge pressure, local flaky exfoliation was observed when the granite surface was eroded, and the maximum radius and volume of the erosion pit were greater than those in the case of employing a continuous water jet. Compared with the interrupted PWJ, the HCPPPWJ efficiently utilizes the jet energy during the erosion process, and the specific energy is lower. The results prove that the HCPPPWJ device is an advanced tool in the field of hard rock breaking.

Endocan: A Key Player of Cardiovascular Disease.

Endothelial dysfunction is considered to be an early change in atherosclerosis. Endocan, also known as endothelial cell specific molecule-1, is a soluble proteoglycan mainly secreted by endothelial cells. Inflammatory factors such as IL-1ß and TNF-α can up regulate the expression of endocan and then affect the expression of cell adhesion molecules, such as ICAM-1 and VCAM-1, which play an important role in promoting leukocyte migration and inflammatory response. Elevated plasma levels of endocan may reflect endothelial activation and dysfunction, and is considered to be a potential immuno-inflammatory marker that may be related to cardiovascular disease. In the case of hypertension, diabetes, angina pectoris and acute myocardial infarction, the increase or decrease of serum endocan levels is of great significance. Here, we reviewed the current research on endocan, and emphasis its possible clinical value as a prognostic marker of cardiovascular disease. Endocan may be a useful biomarker for the prognosis of cardiovascular disease, but more research is needed on its mechanism of action.

Emerging roles of growth differentiation factor-15 in brain disorders (Review).

Brain disorders, such as Alzheimer's and Parkinson's disease and cerebral stroke, are an important contributor to mortality and disability worldwide, where their pathogenesis is currently a topic of intense research. The mechanisms underlying the development of brain disorders are complex and vary widely, including aberrant protein aggregation, ischemic cell necrosis and neuronal dysfunction. Previous studies have found that the expression and function of growth differentiation factor-15 (GDF15) is closely associated with the incidence of brain disorders. GDF15 is a member of the TGFß superfamily, which is a dimer-structured stress-response protein. The expression of GDF15 is regulated by a number of proteins upstream, including p53, early growth response-1, non-coding RNAs and hormones. In particular, GDF15 has been reported to serve an important role in regulating angiogenesis, apoptosis, lipid metabolism and inflammation. For example, GDF15 can promote angiogenesis by promoting the proliferation of human umbilical vein endothelial cells, apoptosis of prostate cancer cells and fat metabolism in fasted mice, and GDF15 can decrease the inflammatory response of lipopolysaccharide-treated mice. The present article reviews the structure and biosynthesis of GDF15, in addition to the possible roles of GDF15 in Alzheimer's disease, cerebral stroke and Parkinson's disease. The purpose of the present review is to summarize the mechanism underlying the role of GDF15 in various brain disorders, which hopes to provide evidence and guide the prevention and treatment of these debilitating conditions.