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.

Effects of a PRECEDE-PROCEED Model-Based Intervention on Fatigue in Patients With Coronary Heart Disease: A Randomized Controlled Trial.

OBJECTIVE: This research aimed to determine how a 12-week PRECEDE-PROCEED model-based intervention affected fatigue in patients with coronary heart disease. METHODS: This cluster randomized controlled trial recruited participants diagnosed with coronary heart disease at 2 community health centers in China. Participants in the control group (n = 36) received routine health education, whereas those in the intervention group (n = 38) were given a 12-week PRECEDE-PROCEED model-based intervention and routine health education. The intervention consisted of 6 training sessions on coronary heart disease, fatigue, fatigue management, self-management skills and social support. A primary outcome (fatigue) and 4 secondary outcomes (knowledge of fatigue, self-management, quality of life and body mass index) were assessed using the Fatigue Scale-14, Fatigue Cognitive Questionnaire for Patients with Coronary Heart Disease, Coronary Artery Disease Self-Management Scale, Chinese Cardiovascular Questionnaire of Quality of Life, and electronic weighing scale, respectively. Data were collected 3 times over 12 weeks. RESULTS: Compared with the control group, the intervention group showed a statistically significant improvement in the level of fatigue (8.72 vs 7.06, P < .001), knowledge of fatigue (P < .001), self-management skills (P < .001), and quality of life (P < .001). However, there was no significant difference in body mass index between the 2 groups (P = .504). CONCLUSIONS: The findings suggest that a well-designed intervention based on the PRECEDE-PROCEED model could alleviate fatigue symptoms and increase knowledge of fatigue, self-management skills and quality of life in patients with coronary heart disease.

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.

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.

Highly Efficient Fractionation of Cornstalk into Noncondensed Lignin, Xylose, and Cellulose in Formic Acid.

Traditional pretreatment of lignocellulose is usually conducted under higher acidic and high temperature conditions, which leads to both the degradation of sugar and the condensation of lignin, hindering the subsequent conversion. An effective approach to fractionate lignocellulose into 93.9% of noncondensed lignin, 99.4% of cellulose, 17.8% of xylose, and 66.7% of xylooligosaccharides under mild conditions was developed using the formic acid solution at 80 °C for 100 min. The ß-O-4 bond content of lignin fractionated with formic acid (54.6 per 100 C9 units) was higher than dioxasolv lignin (48.4 per 100 C9 units), indicating that formic acid pretreatment well protected the ether bonds in lignin. Therefore, the hydrogenolysis of fractionated lignin contributed to 28.0% of aromatic monomer yield, which was comparable to dioxasolv lignin. As cellulose possesses a large amount of porosity because lignin was separated from lignocellulose, the hydrolysis of fractionated cellulose by molten salt hydrates gave a 96.4% of glucose yield.

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.

Effects of Teaching Resourcefulness in Patients with Coronary Heart Disease.

This cluster randomized controlled trial aimed to investigate the effects of an intervention to teach resourcefulness on depression and coping style of patients with coronary heart disease (CHD). A convenience sample of 72 patients in community settings took part. Participants in the intervention group (n = 36) received an 8-week intervention based on the concept of resourcefulness, plus routine health education. Participants in the control group (n = 36) received routine health education only. After the intervention, participants in the intervention group had significantly higher scores on resourcefulness and coping styles, and lower scores on depression than those in the control group (both ps < .001). The findings suggest that a well-developed intervention to teach resourcefulness could help patients with CHD to be more resourceful, improve their level of depression, and choose more effective strategies to cope with stress.

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.

Transcription Factor-7-Like-2 (TCF7L2) in Atherosclerosis: A Potential Biomarker and Therapeutic Target.

Transcription factor-7-like-2 (TCF7L2), a vital member of the T-cell factor/lymphoid enhancer factor (TCF/LEF) family, plays an important role in normal human physiological and pathological processes. TCF7L2 exhibits multiple anti-atherosclerotic effects through the activation of specific molecular mechanisms, including regulation of metabolic homeostasis, macrophage polarization, and neointimal hyperplasia. A single-nucleotide substitution of TCF7L2, rs7903146, is a genetic high-risk factor for type 2 diabetes and indicates susceptibility to cardiovascular disease as a link between metabolic disorders and atherosclerosis. In this review, we summarize the anti-atherosclerosis effect and novel mechanisms underlying the function of TCF7L2 to elucidate its potential as an anti-atherosclerosis biomarker and provide a novel therapeutic target for cardiovascular diseases.

Role of Exosomes in Brain Diseases.

Exosomes are a subset of extracellular vesicles that act as messengers to facilitate communication between cells. Non-coding RNAs, proteins, lipids, and microRNAs are delivered by the exosomes to target molecules (such as proteins, mRNAs, or DNA) of host cells, thereby playing a key role in the maintenance of normal brain function. However, exosomes are also involved in the occurrence, prognosis, and clinical treatment of brain diseases, such as Alzheimer's disease, Parkinson's disease, stroke, and traumatic brain injury. In this review, we have summarized novel findings that elucidate the role of exosomes in the occurrence, prognosis, and treatment of brain diseases.

Extraction of Noncondensed Lignin from Poplar Sawdusts with p-Toluenesulfonic Acid and Ethanol.

The traditional pretreatment leads to the recalcitration of C-C bonds during lignin fractionation, thus hindering their depolymerization into aromatic monomers. It is essential to develop an applicable approach to extract noncondensed lignin for its high-value applications. In this work, noncondensed lignins were extracted from poplar sawdust using recyclable p-toluenesulfonic acid for cleaving lignin-carbohydrate complex bonds effectively and ethanol as a stabilization reagent to inhibit lignin condensation. Lignin yield of 83.74% was recovered by 3 mol/L acid in ethanol at 85 °C for 5 h, and carbohydrates were well preserved (retaining 98.97% cellulose and 50.01% hemicelluloses). During lignin fractionation, the acid concentration and extraction time were the major drivers of condensation. Ethanol reacted with lignin at the α-position to prevent the formation of the condensed structure. The extracted lignin depolymerized over the Pd/C catalysts gave a yield of 50.35% of aromatic monomers, suggesting that the novel extraction process provided a promising way for noncondensed lignin production.

Adsorption-Enhanced Glucan Oligomer Production from Cellulose Hydrolysis over Hyper-Cross-Linked Polymer in Molten Salt Hydrate.

Selective saccharification of cellulose into glucose is a critical step for utilization of lignocellulosic biomass. Molten salt hydrates (MSHs) have shown promising performance in selectively converting cellulose into glucose because of the high solubility of cellulose in the solvent. However, the separation of formed glucose from the MSHs is still a grand challenge. To address this issue, we developed a two-step process, where crystalline cellulose is hydrolyzed into short-chain glucan oligomers in MSHs followed by separation and subsequent hydrolysis of the formed oligomers into glucose under mild conditions. The two-step method provides an easy separation for glucan oligomers from the MSHs without sacrificing the selectivity to glucose. Application of the method for crystalline cellulose is, however, limited to a relatively low concentration, 26.2 mg/mL, because of the formation of byproducts in the MSH that facilitate oligomers degradation. In this work, reactive adsorption was employed to in situ remove the byproducts formed during cellulose hydrolysis in the MSH. It was found that hyper-cross-linked polymer (HCP) made from the polymerization of 4-vinylbenzyl chloride and divinylbenzene can selectively adsorb 5-hydroxymethylfurfural (5-HMF) and levulinic acid (LA) while showing negligible sugar adsorption in both water and the MSH. With the reactive adsorption approach, byproducts including 5-HMF and LA were removed from the reaction media under reaction conditions, and their negative effects on oligomer degradation were inhibited. In the presence of the HCP, the obtained glucan oligomer concentration was enhanced from less than 54.2 to 247.1 mg mL-1 when the weight ratio of cellulose was increased to MSH from 1:60 to 1:4, exhibiting an oligomer yield of 69.5%. The HCP can be effectively separated from the reaction media by filtration and regenerated by oxidation with hydrogen peroxide. Application of reactive adsorption with HCP for cellulose hydrolysis in the MSH provides a promising method to produce glucan oligomers and glucose with an improved yield and efficiency.

Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis.

Non-alcoholic fatty liver disease (NAFLD) is a quickly emerging global health problem representing the most common chronic liver disease in the world. Atherosclerotic cardiovascular disease represents the leading cause of mortality in NAFLD patients. Cholesterol metabolism has a crucial role in the pathogenesis of both NAFLD and atherosclerosis. The liver is the major organ for cholesterol metabolism. Abnormal hepatic cholesterol metabolism not only leads to NAFLD but also drives the development of atherosclerotic dyslipidemia. The cholesterol level in hepatocytes reflects the dynamic balance between endogenous synthesis, uptake, esterification, and export, a process in which cholesterol is converted to neutral cholesteryl esters either for storage in cytosolic lipid droplets or for secretion as a major constituent of plasma lipoproteins, including very-low-density lipoproteins, chylomicrons, high-density lipoproteins, and low-density lipoproteins. In this review, we describe decades of research aimed at identifying key molecules and cellular players involved in each main aspect of hepatic cholesterol metabolism. Furthermore, we summarize the recent advances regarding the biological processes of hepatic cholesterol transport and its role in NAFLD and atherosclerosis.

Secondary prevention of coronary heart disease: The effect of a nursing intervention using Cox's interaction model of client health behaviour.

AIMS: Secondary prevention of coronary heart disease is of utmost importance to facilitate people to achieve health outcomes and behaviours. This study was to investigate the effect of a nursing intervention based on Cox's interaction model of client health behaviour to improve health outcomes and behaviours of secondary prevention of coronary heart disease. DESIGN: This study is a cluster randomised controlled trial. METHODS: Participants were recruited between August and November 2019 in two community settings in Hengyang city, Hunan province, China. Participants in the intervention group received a nursing intervention based on Cox's interaction model of client health behaviour and routine health education, while those in the control group received routine health education only. The outcome variables included self-management, physical activity, medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, blood pressure, body mass index (BMI), and low-density lipoprotein cholesterol (LDL-C). The influential statistical tests applied to analyse the data included χ2 tests and t tests. RESULTS: Seventy-seven participants completed this study. Compared with the control group (n = 40), the intervention group (n = 37) showed statistically significant better health outcomes and behaviours regarding self-management, physical activity (except for high energy consumption), medication compliance, anxiety, sexual knowledge, the ability to identify sexual health education needs, systolic blood pressure, BMI, and LDL-C. However, there was no statistically significant difference in diastolic blood pressure and high energy consumption for physical activity. CONCLUSION: A well-developed nursing intervention based on Cox's interaction model of client health behaviour could successfully improve health outcomes and behaviours of secondary prevention of coronary heart disease. Such an intervention may be incorporated into community healthcare practice by nurses to improve patient care. IMPACT: This study provides a valuable insight to facilitate further development of effective nursing interventions to improve secondary prevention of coronary heart disease in community settings.

N6-Adenosine Methylation (m6A) RNA Modification: an Emerging Role in Cardiovascular Diseases.

N6-methyladenosine (m6A) is the most abundant and prevalent epigenetic modification of mRNA in mammals. This dynamic modification is regulated by m6A methyltransferases and demethylases, which control the fate of target mRNAs through influencing splicing, translation and decay. Recent studies suggest that m6A modification plays an important role in the progress of cardiac remodeling and cardiomyocyte contractile function. However, the exact roles of m6A in cardiovascular diseases (CVDs) have not been fully explained. In this review, we summarize the current roles of the m6A methylation in the progress of CVDs, such as cardiac remodeling, heart failure, atherosclerosis (AS), and congenital heart disease. Furthermore, we seek to explore the potential risk mechanisms of m6A in CVDs, including obesity, inflammation, adipogenesis, insulin resistance (IR), hypertension, and type 2 diabetes mellitus (T2DM), which may provide novel therapeutic targets for the treatment of CVDs.

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.

The Effect of Resourcefulness Training on Depression and Coping Styles of Patients With Coronary Heart Disease in China [RETRACTED].

BACKGROUND: Coronary heart disease (CHD) is one of the leading causes of mortality worldwide. Previous research has demonstrated that resourcefulness interventions can help individuals identify effective coping strategies to manage their conditions, reduce the incidence of depression, and improve their quality of life. However, little is known about such interventions for people with CHD in China. OBJECTIVE: This study aimed to investigate the effects of a resourcefulness training intervention on depression and coping style of patients with CHD in China. METHODS: A cluster randomized controlled trial design was used. A convenience sample of 72 patients in community settings took part in the study. Participants in the intervention group (n = 36) received an 8-week intervention based on the concept of resourcefulness, plus routine health education. Participants in the control group (n = 36) received routine health education only. Three outcomes (resourcefulness, depression, and coping styles) were measured using the Resourcefulness Scale, Center for Epidemiological Studies Depression Scale, and Medical Coping Mode Questionnaire. Data were collected at baseline and post intervention, and analyzed using frequencies, percentages, means, standard deviations, independent sample t tests, and χ tests. RESULTS: After the intervention, participants in the intervention group had significantly higher scores on resourcefulness and coping styles, and lower scores on depression than those in the control group (both Ps < .001). CONCLUSIONS: It is suggested that a well-developed resourcefulness intervention could help patients with CHD in China and beyond to be more resourceful, improve their level of depression, and choose more effective strategies to cope with stress.

Insights into the effect of aggregation on lignin fluorescence and its application for microstructure analysis.

As a natural fluorescent material, the fluorescent property and mechanism of lignin were elusive until now, which hindered the high value application of lignin fluorescence. Herein, we firstly probed the previous studies on lignin fluorescence and the results indicated that lignin microstructure was an important factor for its complex fluorescence property because of fluorophore interaction and aggregation behavior. Following the rules, lignin fluorescence was explored by analyzing its aggregation fluorescence behaviors and basic fluorescence properties based on the theory of traditional conjugated luminescence and aggregation-induced emission. It was demonstrated that intermicellar aggregation of loose lignin micelle made no substantial effect on lignin fluorescence, while intramicellar aggregation could induce the enhancement of lignin fluorescence before the micellar compactness exceeded a critical value. Combined with the physicochemical structures and fluorescence properties of lignin, aggregation-induced conjugation from phenylpropane units was believed as the main sources of the visible emission of lignin and different phenylpropane aggregates consequently formed the multi-fluorophore system in lignin micelle. Furthermore, lignin aggregation fluorescence behavior has great potential in its microstructure analysis and a case study of pH/ionic strength-induced solution behavior analysis was presented. This work provided a totally new prospective for lignin fluorescence.