Angiotension II directly bind P2X7 receptor to induce myocardial ferroptosis and remodeling by activating human antigen R.

Continuous remodeling of the heart can result in adverse events such as reduced myocardial function and heart failure. Available evidence indicates that ferroptosis is a key process in the emergence of cardiac disease. P2 family purinergic receptor P2X7 receptor (P2X7R) activation plays a crucial role in numerous aspects of cardiovascular disease. The aim of this study was to elucidate any potential interactions between P2X7R and ferroptosis in cardiac remodeling stimulated by angiotensin II (Ang II), and P2X7R knockout mice were utilized to explore the role of P2X7R and elucidate its underlying mechanism through molecular biological methods. Ferroptosis is involved in cardiac remodeling, and P2X7R deficiency significantly alleviates cardiac dysfunction, remodeling, and ferroptosis induced by Ang II. Mechanistically, Ang II interacts with P2X7R directly, and LYS-66 and MET-212 in the in the ATP binding pocket form a binding complex with Ang II. P2X7R blockade influences HuR-targeted GPX4 and HO-1 mRNA stability by affecting the shuttling of HuR from the nucleus to the cytoplasm and its expression. These results suggest that focusing on P2X7R could be a possible therapeutic approach for the management of hypertensive heart failure.

Characterization of alkaloids and phenolics in Nitraria roborowskii Kom. fruit by UHPLC-triple-TOF-MS/MS and its sucrase and maltase inhibitory effects.

Nitraria roborowskii Kom (NRK), with high economic and ecological value, is mainly distributed in the Qaidam Basin, China. However, research on its chemical components and bioactivities is still rare. In this study, its chemical constituents (52) including 10 ß-carboline alkaloids, nine cyclic peptides, three indole alkaloids, five pyrrole alkaloids, eight phenolic acids and 17 flavonoids were identified tentatively using UPLC-triple-TOF-MS/MS. Notablely, one new ß-carboline alkaloid and five new cyclic peptides were confirmed using MS/MS fragmentation pathways. In addition, experiments in vitro indicated that NRK-C had strong maltase and sucrase inhibitory activities (IC50 of 0.202 and 0.103 mg/mL, respectively). Polysaccharide tolerance experiments confirmed NRK-C (400 mg/kg) was associated with decreased postprandial blood glucose (PBG) in diabetic mice. These results suggested that NRK fruit might be used as a functional ingredient in food products.

Extract of Silphium perfoliatum L. improve lipid accumulation in NAFLD mice by regulating AMPK/FXR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Globally, the incidence rate and number of patients with nonalcoholic fatty liver disease are increasing, which has become one of the greatest threats to human health. However, there is still no effective therapy and medicine so far. Silphium perfoliatum L. is a perennial herb native to North America, which is used to improve physical fitness and treat liver and spleen related diseases in the traditional medicinal herbs of Indian tribes. This herb is rich in chlorogenic acids, which have the functions of reducing blood lipids, losing weight and protecting liver. However, the effect of these compounds on nonalcoholic fatty liver disease remains unclear. AIM OF THE STUDY: Clarify the therapeutic effects and mechanism of the extract (CY-10) rich in chlorogenic acid and its analogues from Silphium perfoliatum L. on non-alcoholic fatty liver disease, and to determine the active compounds. MATERIALS AND METHODS: A free fatty acid-induced steatosis model of HepG2 cells was established to evaluate the in vitro activity of CY-10 in promoting lipid metabolism. Further, a high-fat diet-induced NAFLD model in C57BL/6 mice was established to detect the effects of CY-10 on various physiological and biochemical indexes in mice, and to elucidate the in vivo effects of the extract on regulating lipid metabolism, anti-inflammation and hepatoprotection, and nontarget lipid metabolomics was performed to analyze differential metabolites of fatty acids in the liver. Subsequently, western blotting and immunohistochemistry were used to analyze the target of the extract and elucidate its mechanism of action. Finally, the active compounds in CY-10 were elucidated through in vitro activity screening. RESULTS: The results indicated that CY-10 significantly attenuated lipid droplet deposition in HepG2 cells. The results of in vivo experiments showed that CY-10 significantly reduce HFD-induced mouse body weight and organ index, improve biochemical indexes, oxidation levels and inflammatory responses in the liver and serum, thereby protecting the liver tissue. It can promote the metabolism of unsaturated fatty acids in the liver and reduce the generation of saturated fatty acids. Furthermore, it is clarified that CY-10 can promote lipid metabolism balance by regulating AMPK/FXR/SREPB-1c/PPAR-γ signal pathway. Ultimately, the main active compound was proved to be cryptochlorogenic acid, which has a strong promoting effect on the metabolism of fatty acids in cells. Impressively, the activities of CY-10 and cryptochlorogenic acid were stronger than simvastatin in vitro and in vivo. CONCLUSION: For the first time, it is clarified that the extract rich in chlorogenic acids and its analogues in Silphium perfoliatum L. have good therapeutic effects on non-alcoholic fatty liver disease. It is confirmed that cryptochlorogenic acid is the main active compound and has good potential for medicine.

Health assessment based on exposure to microplastics in tropical agricultural soil.

Microplastic (MP) pollution of agricultural soils has caused global alarm over its widespread distribution and potential risks to terrestrial ecosystems and human health. This study assessed human health based on exposure to soil MPs through a comprehensive investigation of the factors influencing their occurrence and spatial distribution on Hainan Island, South China. The results showed that the abundance of soil MPs was 1128.6 ± 391.5 items·kg-1, whereas the normalized abundance of MPs based on using a power-law function was 19,261.4 items·kg-1. Regarding the extent of population exposure to agricultural soil MPs, the average daily exposure dose (pADD) model revealed that using mass as an indicator to assess the health risks associated with MP intake is more reliable than using abundance. However, abundance-based exposure assessments are also relevant because MPs with smaller particle sizes are more harmful to human health. Moreover, for adults, the normalized pADD values based on abundance and mass were 1.68E-02 item MPs·kg BW-1·d-1 and 7.23E-02 mg MPs·kg BW-1·d-1, respectively. Although the multidimensionality of MPs should be further aligned and quantified, the preliminary findings of this study contribute to the development of human health risk assessment frameworks for soil MPs.

Inhibitory activities and rules of plant gallotannins with different numbers of galloyl moieties on sucrase, maltase and α-amylase in vitro and in vivo.

BACKGROUND: α-Glucosidase inhibitors could effectively reduce postprandial blood glucose (PBG) levels and control the occurrence of complications of diabetes. Gallotannins (GTs) in plants have attracted much attention due to their significant α-glucosidase inhibitory activities in vitro. However, there is still a lack of systematic comparative studies to further elucidate inhibitory activities in vivo and in vitro of these compounds against α-glucosidase, especially for mammalian sucrase and maltase, and analyze their structure-activity relationship. PURPOSE: Determine the in vitro and in vivo inhibitory activities of five GTs with different number of galloyl moieties (GMs) on sucrase, maltase and α-amylase, and elucidate the relationship between α-glucosidase inhibitory activities and the number and connection mode of GMs. METHODS: Molecular docking and dynamics were used to study the binding mode and binding ability of five GTs against sucrase, maltase and α-amylase. Then, the inhibitory activities and inhibitory mechanisms of these compounds on sucrase, maltase and α-amylase in vitro were studied using inhibitory assay and enzyme inhibition kinetics. Further, the hypoglycemic effects in vivo of these compounds were demonstrated by three polysaccharides tolerance experiments on diabetes model mice. RESULTS: The results of molecular docking showed that these compounds could bind to enzymes through hydrogen bonds, hydrophobic interactions, etc. In addition, the α-glucosidase inhibition comparative studies in vitro and in vivo demonstrated that the inhibitory activities of these compounds on all three sucrase, maltase and α-amylase were ranked as TA ≈ PGG > TeGG > TGG > 1GG, and their inhibitory activities increases with the increase in the number of GMs. Moreover, the hypoglycemic effects of 1,2,3,4,6-pentagalloylglucose (PGG) and tannic acid (TA) in vitro and in vivo were also confirmed to be equivalent to or even stronger than that of acarbose. CONCLUSION: α-Glucosidase inhibitory activities in vitro and in vivo of GTs were positively correlated with the number of GTs, and the more the number, the stronger the activity. However, PGG with five GTs and TA with ten GTs showed almost identical α-glucosidase inhibitory activities, possibly due to the reduced binding force with the enzyme caused by spatial hindrance.

Hypoglycemic effect of Nitraria tangutorum fruit by inhibiting glycosidase and regulating IRS1/PI3K/AKT signalling pathway and its active ingredient identification by UPLC-MS.

The hypoglycemic effect of NTB-40 (40% ethanol fraction of Nitraria tangutorum fruit) in type I/II diabetic mice and its underlying mechanism and active ingredient structure were investigated. The postprandial blood glucose (PBG) lowering effect of NTB-40 treatment was confirmed by maltose, starch, and sucrose tolerance tests in alloxan-induced DM mice and sucrase and maltase inhibitory activities in vitro. More importantly, long-term dosing experiments in high-fat diet-STZ-induced diabetic mice further demonstrated that NTB-40 intervention could improve glycolipid metabolism disorder and insulin resistance (IR) by maintaining glucose homeostasis (FBG, OGTT, ITT, FINS, and HOMA-IR) and lipid homeostasis (TC, TG, HDL-C, LDL-C, and FFA), reducing inflammation (IL-6, IL-1ß, and TNF-α) and oxidative stress (SOD and MDA), ameliorating the liver's histological structural abnormalities, and modulating the IRS1/PI3K/AKT signaling pathway and downstream targets (FOXO1, GSK3ß, GLUT4) for decreasing hepatic gluconeogenesis and promoting glycogen synthesis and glucose uptake. All these results indicated that NTB-40 had an anti-diabetic effect by modulating the IRS1/PI3K/AKT signaling pathway and inhibiting α-glucosidase activity. Finally, the main chemical components of NTB-40, including phenolic acids, flavonoids, and alkaloids, were assigned by UPLC-Triple-TOF MS/MS.

Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. METHODS: Two independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients (n = 184) from heterozygous FH (HeFH, n = 376) and non-FH (n = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients. RESULTS: Beyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients. CONCLUSIONS: Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.

An unrecognized entry pathway of submicrometre plastics into crop root: The split of hole in protective layer.

Threats to food safety caused by the continuous accumulation of plastic particles in the terrestrial environment is currently a worldwide concern. To date, descriptions of how plastic particles pass the external biological barrier of crop root have been vague. Here, we demonstrated that submicrometre polystyrene particles passed unimpededly the external biological barrier of maize through the split of holes in the protective layer. We identified plastic particles induced the apical epidermal cells of root tips become round, thereby expanding the intercellular space. It further pulled apart the protective layer between the epidermal cells, and eventually formed the entry pathway for plastic particles. The enhancement of oxidative stress level induced by plastic particles was the main reason for the deformation of the apical epidermal cells (increased roundness values: 15.5%), comparing to the control. Our findings further indicated that the presence of cadmium was conducive to the "holes" formation. Our results highlighted the critical insights into the fracture mechanisms of plastic particles for the external biological barriers of crop roots, providing a strong incentive to access the risk of plastic particles in agriculture security.

Enrichment of Wheat Bread with Platycodon grandiflorus Root (PGR) Flour: Rheological Properties and Microstructure of Dough and Physicochemical Characterization of Bread.

Platycodon grandiflorus (Jacq.) A.DC. root (PGR) flour is well known for its medical and edible values. In order to develop nutritionally fortified products, breads were prepared using wheat flour, partially replaced with PGR flour. The rheological properties and microstructure of dough and the physicochemical characterization of bread were investigated. Results showed that lower level of PGR addition (3 and 6 g/100 g) would improve the baking performance of breads, while the higher level of PGR addition (9 g/100 g) led to smaller specific volume (3.78 mL/g), increased hardness (7.5 ± 1.35 N), and unpalatable mouthfeel (21.8% of resilience and 92.6% of springiness) since its negative effect on the viscoelasticity and microstructure of dough. Moreover, sensory evaluation analysis also showed that the PGR3 and PGR6 breads exhibited a similar flavor to the control bread, but the 9 g/100 g addition of PGR provided bread with an unpleasant odor through its richer volatile components. As expected, the phenolic content and antioxidant capacity of bread increased significantly (p < 0.05) as PGR flour was added to the bread formulation. The total phenolic content (TPC) ranged from 14.23 to 22.36 g GAE/g; thus, DPPH• and ABTS•+ scavenging capacity increased from 10.44 and 10.06 µg Trolox/g to 14.69 and 15.12 µg Trolox/g, respectively. Therefore, our findings emphasized the feasibility of PGR flour partially replacing wheat flour in bread-making systems.

Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare inborn-errors-of-metabolism disorder characterized by devastatingly elevated low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. The gold standard for screening and diagnosing HoFH is genetic testing. In China, it is expensive and is always recommended for the most likely HoFH subjects with aggressive LDL-C phenotype. However, the LDL-C levels of HoFH patients and a substantial proportion of heterozygous FH (HeFH) patients overlapped considerably. Here, we performed a cost-effective metabolomic profiling on genetically diagnosed HoFH (n = 69) and HeFH patients (n = 101) with overlapping LDL-C levels, aiming to discovery a unique metabolic pattern for screening homozygotes in patients with severe FH. We demonstrated a differential serum metabolome profile in HoFH patients compared to HeFH patients. Twenty-one metabolomic alterations showed independent capability in differentiating HoFH from severe HeFH. The combined model based on seven identified metabolites yielded a corrected diagnosis in 91.3% of HoFH cases with an area under the curve value of 0.939. Collectively, this study demonstrated that metabolomic profiling serves as a useful and economical approach to preselecting homozygotes in FH patients with severe hypercholesterolemia and may help clinicians to conduct selective genetic confirmation testing and familial cascade screening.

Low-density lipoprotein receptor genotypes modify the sera metabolome of patients with homozygous familial hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is an extremely rare metabolism disorder usually caused by low-density lipoprotein receptor (LDLR) mutations. LDLR genotype is commonly known to determine blood concentrations of LDL cholesterol. However, effects of LDLR genotype on holistic metabolome remain unclear. Herein, we present metabolomic, genetic, and clinical datasets from a large multi-center panel of 142 patients with LDLR-mutated HoFH. We found that true homozygotes and compound heterozygotes showed few differences in clinical and metabolomic phenotypes. Compared with defective/defective mutation carriers, patients carrying one or two null mutation showed profound alterations in clinical laboratory lipids and serum cholesterol esters, lysophosphocholines, bile acids, and amino acids. Importantly, these altered metabolites are implicated in multiple biochemical reactions and associated with LDL cholesterol. This study extends the first map of different LDLR genotypes influencing the metabolome and suggests that the small-molecule metabolites serve as potential targets to mitigate the deleterious impact of LDLR mutations on HoFH.

Antagonistic effect of polystyrene nanoplastics on cadmium toxicity to maize (Zea mays L.).

Nanoplastics (NPs) (<1 µm) have gradually attracted worldwide attention owing to their widespread occurrence, distribution, and ecosystem risks. Few studies have explored the interaction between NPs and heavy metals in crops. In this study, we investigated the influence of polystyrene nanoplastics (PSNPs; 10 mg/L and 100 mg/L) and cadmium (2 mg/L and 10 mg/L) on the physiological and biochemical indices of maize plants, grown in Hoagland solution with contaminants, for 14 days. The fresh weight and growth of the maize plants were significantly reduced after exposure to high concentrations of PSNPs and Cd (p < 0.05). Specifically, the fresh weight decreased by 30.3% and 32.5% in the PSNPs and Cd treatment, respectively. Root length and shoot length decreased by 11.7% and 20.0%, and by 16.3% and 27.8%, in the PSNPs and Cd treatment, respectively. However, there were no significant effects on the fresh weight and growth of maize plants as Cd levels increased from 2 to 10 mg/L in the presence of PSNPs. Polystyrene nanoplastics alleviated the phytotoxicity of Cd in maize. Scanning electron microscopy (SEM) showed that PSNPs and Cd could enter maize roots and were transported upwards to the leaves through the vascular bundle. The activities of peroxidase (POD) and catalase (CAT) in maize leaves increased significantly under high concentrations of PSNPs, whereas superoxide dismutase (SOD) activity decreased (p < 0.05). The differences in SOD activity may be related to the absence of microelements such as Zn, Fe, and Mn. This study provides a scientific basis for further exploration of the combined toxicological effects of heavy metals and NPs on the environment.

Aerobic Exercise Inhibited P2X7 Purinergic Receptors to Improve Cardiac Remodeling in Mice With Type 2 Diabetes.

Background: Diabetic cardiomyopathy (DCM), the main complication of diabetes mellitus, presents as cardiac dysfunction by ventricular remodeling. In addition, the inhibition of P2X7 purinergic receptors (P2X7R) alleviates cardiac fibrosis and apoptosis in Type 1 diabetes. However, whether exercise training improves cardiac remodeling by regulating P2X7R remains unknown. Methods: Db/db mice spontaneously induced with type 2 diabetes and high-fat diet (HFD) and mice with streptozotocin (STZ)-induced type 2 diabetes mice were treated by 12-week treadmill training. Cardiac functions were observed by two-dimensional echocardiography. Hematoxylin-eosin staining, Sirius red staining and transmission electron microscopy were respectively used to detect cardiac morphology, fibrosis and mitochondria. In addition, real-time polymerase chain reaction and Western Blot were used to detect mRNA and protein levels. Results: Studying the hearts of db/db mice and STZ-induced mice, we found that collagen deposition and the number of disordered cells significantly increased compared with the control group. However, exercise markedly reversed these changes, and the same tendency was observed in the expression of MMP9, COL-I, and TGF-ß, which indicated cardiac fibrotic and hypertrophic markers, including ANP and MyHC expression. In addition, the increased Caspase-3 level and the ratio of Bax/Bcl2 were reduced by exercise training, and similar results were observed in the TUNEL test. Notably, the expression of P2X7R was greatly upregulated in the hearts of db/db mice and HFD + STZ-induced DM mice and downregulated by aerobic exercise. Moreover, we indicated that P2X7R knock out significantly reduced the collagen deposition and disordered cells in the DM group. Furthermore, the apoptosis levels and TUNEL analysis were greatly inhibited by exercise or in the P2X7R-/- group in DM. We found significant differences between the P2X7R-/- + DM + EX group and DM + EX group in myocardial tissue apoptosis and fibrosis, in which the former is significantly milder. Moreover, compared with the P2X7R-/- + DM group, the P2X7R-/- + DM + EX group represented a lower level of cardiac fibrosis. The expression levels of TGF-ß at the protein level and TGF-ß and ANP at the genetic level were evidently decreased in the P2X7R-/- + DM + EX group. Conclusion: Aerobic exercise reversed cardiac remodeling in diabetic mice at least partly through inhibiting P2X7R expression in cardiomyocytes.

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world, multi-center, cohort study.

BACKGROUND: There is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia. OBJECTIVE: To define the characteristics of phenotypic and genetic HoFH probands from mainland China. METHODS: We collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test. RESULTS: A total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH. CONCLUSIONS: This report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.

Hypoglycemic effects of Rhodiola crenulata (HK. f. et. Thoms) H. Ohba in vitro and in vivo and its ingredient identification by UPLC-triple-TOF/MS.

Rhodiola crenulata (HK. f. et. Thoms) H. Ohba (RC), mainly distributed in the highly cold region of China, has long been used as a medicine/healthy food for eliminating fatigue and increasing blood circulation. This study aimed to evaluate the inhibitory effects of the RCRS extract on α-amylase and α-glucosidase (sucrase and maltase) in vitro and in vivo, and tentatively analyze and identify its chemical ingredients using UPLC-Triple-TOF/MS. The Rhodiola crenulata RCRS extract had strong inhibitory activities against α-amylase, sucrase and maltase with an IC50 of 0.031 mg mL-1, 0.142 mg mL-1 and 0.214 mg mL-1, respectively. Furthermore, the RCRS extract could significantly decrease the postprandial blood glucose (PBG) level of normal mice in a starch tolerance test, and reduce the PBG levels of diabetic mice in a starch/maltose/sucrose tolerance test. UHPLC-Triple-TOF-MS/MS analysis indicated that hydroxybenzoic acids, hydroxycinnamic acids, alcohol glycosides, flavonols and their derivatives were the main active ingredients in the RCRS extract. The results demonstrate that the RCRS extract of Rhodiola crenulata could be employed as a healthy food or medicine for controlling postprandial blood glucose levels.

Effect of "Natural Polypill", Xuezhikang on Serum Cholesterol Metabolism Markers in Early Menopausal Women with Hypercholesterolemia.

OBJECTIVE: To analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism. METHODS: A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention. RESULTS: Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range. CONCLUSIONS: Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."

Prognostic value of coronary flow velocity reserve in patients with homozygous familial hypercholesterolemia.

BACKGROUND: Coronary flow velocity reserve (CFVR) can provide useful quantitative information on the functional status of coronary artery circulation, and an impaired CFVR (< 2.0) was associated with a significant increase in the occurrence of cardiac events. Coronary artery disease (CAD) is the leading cause of death in homozygous familial hypercholesterolemia (HoFH), but the relationship between impaired CFVR and outcome in HoFH has never been discussed before METHODS: To explore the long-term prognostic value of CFVR in patients with HoFH, 39 HoFH patients with CFVR data (mean age with 16.7 years) were enrolled from the Genetic and Imaging of Familial Hypercholesterolemia in Han Nationality Study. All patients were divided into impaired CFVR (CFVR < 2.0, n = 17) and preserved CFVR (CFVR≥2.0, n = 22) group. Follow-up was performed until a major adverse cardiac event (MACE) occurred or up to June 30, 2020 RESULTS: During a median follow-up of 89 months, 16 events were registered, 12 of which were occurred in the impaired CFVR group and four occurred in the preserved CFVR group. The event-free survival rate of impaired CFVR group was significantly lower than that in the preserved CFVR group (29.4% vs 81.8%, P < .001), and CFVR < 2.0 was independently associated with prognosis before and after adjustment for related risk factors (HR 5.197, 95% CI 1.669 to 16.178, P = .004 and HR 5.488, 95% CI 1.470 to 20.496, P = .011, respectively) CONCLUSIONS: an impaired CFVR predicts a worse outcome in HoFH. CFVR shows an independent value in the prediction of long-term outcome in HoFH.

The Effects of Waste Cement on the Bioavailability, Mobility, and Leaching of Cadmium in Soil.

Waste cement is a construction and demolition waste produced from old buildings' demolition and transformation. In recent years, the recycling of recycled concrete is limited to the use of recycled aggregate, and the research on the utilization of waste cement in waste concrete is scarce. This study explored the effective application of waste cement for the adsorption of cadmium (Cd2+) from an aqueous solution and the bioavailability and immobility of Cd2+ in soil. Results showed that the maximum adsorption capacities of ordinary Portland cement(OPC) paste, fly ash cement (FAC) paste, and zeolite cement (ZEC) paste for Cd2+ were calculated to be 10.97, 9.47, 4.63 mg·g-1, respectively. The possible mechanisms for Cd2+ adsorption in the solution by waste cement mainly involve precipitation by forming insoluble Cd2+ compounds in alkaline conditions, and ion exchange for Cd2+ with the exchangeable calcium ions in waste cement, which were confirmed by XRD and SEM. Results from diethylene triaminepentaacetic acid (DTPA) extraction and toxicity characteristic leaching procedure (TCLP) implied reduction of the Cd2+ mobility. DTPA-extractable Cd2+ decreased by 52, 48 and 46%, respectively, by adding 1% OPC, FAC and ZEC. TCLP-extractable Cd2+ decreased by 89.0, 80.3, and 56.0% after 1% OPC, FAC, and ZEC treatment, respectively. BCR analyses indicate that OPC, FAC, and ZEC applications increased the percentage of Cd2+ in residual fraction and induced a high reduction in the acid-soluble Cd2+ proportion. The leaching column test further confirmed a reduction in Cd2+ mobility by waste cement treated under continuous leaching of simulated acid rain (SAR). Therefore, waste cement exhibited a significant enhancement in the immobilization of Cd2+ under simulated acid rain (SAR) leaching. In summary, the application of alkaline waste cement could substantially remove Cd2+ from wastewater and reduce Cd2+ mobility and bioavailability in contaminated soil.

Effect of Pyrolysis Temperature on the Characterisation of Dissolved Organic Matter from Pyroligneous Acid.

Dissolved organic matter (DOM) greatly influences the transformation of nutrients and pollutants in the environment. To investigate the effects of pyrolysis temperatures on the composition and evolution of pyroligneous acid (PA)-derived DOM, DOM solutions extracted from a series of PA derived from eucalyptus at five pyrolysis temperature ranges (240-420 °C) were analysed with Fourier transform infrared spectroscopy, gas chromatography-mass spectroscopy, and fluorescence spectroscopy. Results showed that the dissolved organic carbon content sharply increased (p < 0.05) with an increase in pyrolysis temperature. Analysis of the dissolved organic matter composition showed that humic-acid-like substances (71.34-100%) dominated and other fluorescent components (i.e., fulvic-acid-like, soluble microbial by-products, and proteinlike substances) disappeared at high temperatures (>370 °C). The results of two-dimensional correlation spectroscopic analysis suggested that with increasing pyrolysis temperatures, the humic-acid-like substances became more sensitive than other fluorescent components. This study provides valuable information on the characteristic evolution of PA-derived DOM.

Integrated analysis of microRNA and mRNA expression profiles in homozygous familial hypercholesterolemia patients and validation of atherosclerosis associated critical regulatory network.

Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder characterized by an extremely elevated serum level of low-density lipoprotein cholesterol (LDL-C) and accelerated premature atherosclerotic cardiovascular diseases (ASCVD). However, the detailed mechanism of how the pathogenic mutations of HoFH trigger the acceleration of ASCVD is not well understood. Therefore, we performed high-throughput RNA and small RNA sequencing on the peripheral blood RNA samples of six HoFH patients and three healthy controls. The gene and miRNA expression differences were analyzed, and seven miRNAs and six corresponding genes were screened out through regulatory network analysis. Validation through quantitative PCR of genes and miRNAs from 52 HoFH patients and 20 healthy controls revealed that the expression levels of hsa-miR-486-3p, hsa-miR-941, and BIRC5 were significantly upregulated in HoFH, while ID1, PLA2G4C, and CACNA2D2 were downregulated. Spearman correlation analysis found that the levels of ID1, hsa-miR-941, and hsa-miR-486-3p were significantly correlated with additional ASCVD risk factors in HoFH patients. This study represents the first integrated analysis of transcriptome and miRNA expression profiles in patients with HoFH, a rare disease, and as a result, six differentially expressed miRNAs/genes that may be related to atherosclerosis in HoFH are reported. The miRNA-mRNA regulatory network may be the critical regulation mechanism by which ASCVD is accelerated in HoFH.