LncRNA DANCR promotes macrophage lipid accumulation through modulation of membrane cholesterol transporters.

The progression of atherosclerosis (AS), the pathological foundation of coronary artery disease (CAD), is featured by massive lipid deposition in the vessel wall. LncRNAs are implicated in lipid disorder and AS, whereas the specific role of lncRNA DANCR in atherogenesis remains unknown. Here, we demonstrated that DANCR promotes macrophage lipid accumulation by regulating the expression of membrane cholesterol transport proteins. qPCR showed that compared to control groups, CAD patients and atherosclerotic mice had higher DANCR levels. Treating human THP-1 macrophages and mouse RAW264.7 macrophages with ox-LDL significantly upregulated the expression levels of DANCR. Oil Red O staining showed that the silence of DANCR robustly reduced, while overexpression of DANCR significantly increased the numbers and size of lipid droplets in ox-LDL-treated THP-1 macrophages. In contrast, the opposite phenomena were observed in DANCR overexpressing cells. The expression of ABCA1, ABCG1, SR-BI, and NBD-cholesterol efflux was increased obviously by DANCR inhibition and decreased by DANCR overexpression, respectively. Furthermore, transfection with DANCR siRNA induced a robust decrease in the levels of CD36, SR-A, and Dil-ox-LDL uptake, while DANCR overexpression amplified the expression of CD36, SR-A and the uptake of Dil-ox-LDL in lipid-laden macrophages. Lastly, we found that the effects of DANCR on macrophage lipid accumulation and the expression of membrane cholesterol transport proteins were not likely related to miR-33a. The present study unraveled the adverse role of DANCR in foam cell formation and its relationship with cholesterol transport proteins. However, the competing endogenous RNA network underlying these phenomena warrants further exploration.

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.

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.

Oridonin attenuates atherosclerosis by inhibiting foam macrophage formation and inflammation through FABP4/PPARγ signalling.

Both lipid accumulation and inflammatory response in lesion macrophages fuel the progression of atherosclerosis, leading to high mortality of cardiovascular disease. A therapeutic strategy concurrently targeting these two risk factors is promising, but still scarce. Oridonin, the bioactive medicinal compound, is known to protect against inflammatory response and lipid dysfunction. However, its effect on atherosclerosis and the underlying molecular mechanism remain elusive. Here, we showed that oridonin attenuated atherosclerosis in hyperlipidemic ApoE knockout mice. Meanwhile, we confirmed the protective effect of oridonin on the oxidized low-density lipoprotein (oxLDL)-induced foam macrophage formation, resulting from increased cholesterol efflux, as well as reduced inflammatory response. Mechanistically, the network pharmacology prediction and further experiments revealed that oridonin dramatically facilitated the expression of peroxisome proliferator-activated receptor gamma (PPARγ), thereby regulating liver X receptor-alpha (LXRα)-induced ATP-binding cassette transporter A1 (ABCA1) expression and nuclear factor NF-kappa-B (NF-κB) translocation. Antagonist of PPARγ reversed the cholesterol accumulation and inflammatory response mediated by oridonin. Besides, RNA sequencing analysis revealed that fatty acid binding protein 4 (FABP4) was altered responding to lipid modulation effect of oridonin. Overexpression of FABP4 inhibited PPARγ activation and blunted the benefit effect of oridonin on foam macrophages. Taken together, oridonin might have potential to protect against atherosclerosis by modulating the formation and inflammatory response in foam macrophages through FABP4/PPARγ signalling.

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.

[Influence of Different Types of Dewatering Agents on the Solidification Effect and Physical and Chemical Properties of Sediment].

In order to study the comprehensive effects of different types of dehydrating agents on the dewatering and solidification of dredged sediments, this study took the dredged sediments of Taihu Lake as the research object and selected microorganisms, polymeric iron aluminum salts, organic polymers, organic-inorganic composites, and aluminum salt microorganisms. These five types of composite dehydrating agents were used to conduct a three-month solidification test on the dredged sediment by means of geotechnical pipe bag solidification. The results of the study showed that the dehydration efficiency of organic polymers and organic-inorganic composite chemicals was better. After one month, the water content of sediment dropped to 61.78% and 63.26%, respectively, which then dropped to 40.56% and 32.16% after three months. Compared with that of the unsolidified sludge, the total nitrogen of the bottom sludge after solidification by the organic-inorganic composite agent was reduced by 74.82%, reaching 591 mg·kg-1, primarily due to the reduction in ammonia nitrogen. The solid sludge contained mainly aluminum-bound phosphorus, calcium-bound phosphorus, and iron-bound phosphorus. Among them, four groups (organic-inorganic composite) had the largest reduction in active phosphorus, with the lowest being 64.3 mg·kg-1. In addition, organic polymer agents had the best curing effect on heavy metals, the comprehensive ecological risk index of heavy metals was reduced by 51.3%, and the leaching toxicity concentration was far below the standard threshold. This study showed that organic polymers and organic-inorganic composite medicaments have a better effect on the dehydration and solidification of bottom sludge and thus have good application prospects.

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.

Carbonylative coupling of simple alkanes and alkenes enabled by organic photoredox catalysis.

A visible-light-driven direct carbonylative coupling of simple alkanes and alkenes via the combination of a hydrogen atom transfer process and photoredox catalysis has been demonstrated. Employing the N-alkoxyazinium salt as the oxidant and the precursor of an oxygen radical, a variety of α,ß-unsaturated ketones could be obtained in a metal-free fashion.

Visible-Light-Mediated Divergent Silylfunctionalization of Alkenes.

1,2-Silylfunctionalization of alkenes is an efficient way to construct highly functionalized silicon-containing compounds. However, examples of 1,2-silylfunctionalization of alkenes using readily available hydrosilanes are limited. Herein, we present a visible-light-mediated divergent 1,2-silylfunctionalization of alkenes using hydrosilane under ambient conditions. A series of ß-alkoxy, ß-alkylthio, ß-hydroxy, and ß-indolyl silanes was obtained in good to excellent yields. Moreover, vinylsilanes were successfully prepared in the absence of an additional nucleophile.

Photoinduced Oxidative Alkoxycarbonylation of Alkenes with Alkyl Formates.

A photoinduced oxidative alkoxycarbonylation of alkenes initiated by intermolecular addition of alkoxycarbonyl radicals has been demonstrated. Employing alkyl formates as alkoxycarbonyl radical sources, a range of α,ß-unsaturated esters were obtained with good regioselectivity and E selectivity under ambient conditions.

[Endogenous Pollution and Release Characteristics of Bottom Sediments of Hengshan Reservoir in Yixing City].

To clarify the endogenous pollution and release characteristics of the bottom sediment of Hengshan Reservoir in Yixing City, a typical section of the reservoir was sampled and analyzed. The research results show that the average concentrations of total nitrogen, total phosphorus, and organic matter in the surface sediments of Hengshan Reservoir are 2778 mg·kg-1, 899 mg·kg-1, and 3.1%, respectively. The endogenous pollution is serious, and the downstream sediments are highly polluted upstream of the reservoir. Phosphorus spectroscopic analysis results show that iron-bound phosphorus (Fe-P) and aluminum-bound phosphorus (Al-P) are the main bound phosphorus forms in the sediment, accounting for 28% and 39% of the total phosphorus, respectively. The average concentration of activated phosphorus in the sediment (combination of weakly adsorbed phosphorus, organic phosphorus, and iron phosphorus) is 255 mg·kg-1, accounting for 38% of the total phosphorus. The average release rates of nitrogen and phosphorus in sediments were 18.0 mg·(m2·d)-1 and 0.60 mg·(m2·d)-1. The correlation analysis results show that the organic matter content of the sediment is significantly correlated with the diffusion flux of phosphate, ammonia nitrogen, and ferrous iron (P<0.05), indicating that the mineralization of organic matter in the sediment may be the main release source of nitrogen and phosphorus in the sediment influencing factors.

Photoredox-Catalyzed α-C(sp3)-H Activation of Unprotected Secondary Amines: Facile Access to 1,4-Dicarbonyl Compounds.

A photoredox-catalyzed α-C(sp3)-H activation approach of unprotected secondary amines is reported. Such transformations provide facile access to various 1,4-dicarbonyl compounds using readily available amines and α,ß-unsaturated compounds as feedstocks under air conditions. The substrate scope of this method is broad, and a wide array of functional groups are tolerated.

[Fabrication of La-MHTC Composites for Phosphate Removal: Adsorption Behavior and Mechanism].

Lanthanum (La)-based materials have shown great potential for phosphate removal owing to the strong affinity between La and phosphate. In this study, magnetic hydrothermal biochar immobilized La(OH)3 (La-MHTC) were prepared and used as phosphate adsorbents. Hydrochar was produced by the hydrothermal carbonization process (220℃, 2 h). Magnetic La-MHTC with different La-to-Fe mass ratios were synthesized by the co-precipitation method. Subsequently, La-MHTC was applied to remove phosphate from wastewater. Results indicate that La-MHTC (with a La-to-Fe mass ratio of 2:1) exhibited excellent magnetic properties for easy recovery and high phosphate adsorption capacity up to 100.25 mg·g-1. Effective phosphate removal was obtained over a wide pH range of 3-10. The absorption isotherm and kinetics were better fitted by the Langmuir model and the pseudo second-order model, respectively, which showed a fast adsorption rate and exhibited superior La utilization efficiency. The La-MHTC has strong selectivity for phosphate in the presence of coexisting ions (Cl-, NO3-, and SO42-). The adsorption-desorption experiment suggested its excellent stability and cyclic utilization. In addition, La-MHTC was applied to treat real domestic wastewater, efficiently reducing the phosphate concentration (from 0.87 mg·L-1 to 0.05 mg·L-1). Electrostatic attraction and inner-sphere complexation between La(OH)3 and P via ligand exchange were the main mechanisms of phosphate adsorption by La-MHTC.

Performance of physical and chemical methods in the co-reduction of internal phosphorus and nitrogen loading from the sediment of a black odorous river.

The continuous release of nutrients from sediment is a major barrier to the remediation of black odorous rivers. This study used a long-term laboratory incubation experiment to investigate the effectiveness of sediment dredging, intermittent aeration, and in situ inactivation with modified clays to reduce the internal loading of sediment from a seriously polluted river. The results indicated that intermittent aeration and in situ inactivation were effective in reducing the TN and NH4+ concentrations in the water column. However, sediment dredging did not consistently reduce the TN and NH4+ concentrations in the water column. In contrast, the three methods were all effective in controlling the TP and PO43- concentrations in the water column. Except for dredging, >30% of NH4+ and 40% of PO43- fluxes from sediment were reduced when compared with a control sample after 120 days of remediation. Dredging induced a significant release of NH4+ from sediment. Dredging and aeration made nearly no change to the amount of extractable nitrogen in the sediment. However, inactivation may increase sediment-extractable ammonium in deep sediment layers with time due to vertical transportation of clay by intensive bioturbation. Dredging is the most effective way to reduce surface mobile phosphorus over time while the transported clays can reduce a large percentage of the mobile phosphorus in deeper sediment. The relative abundance of Nitrospira in the surface sediment increased significantly with each remediation measure, creating favorable conditions for the reduction of the ammonium released from sediment. Altogether, the results of this study indicated that clay inactivation is the best method for controlling the internal loading of both phosphorus and nitrogen in seriously polluted river sediment.

Efficacy of dredging engineering as a means to remove heavy metals from lake sediments.

Dredging is used worldwide to remove polluted sediments from water bodies. However, the dredging efficacy remains hard to identify. Here, we studied the efficacy of dredging engineering as a means to remove Cu, Cd, and Pb from polluted lake sediments, after six years of completion. Dissolved metals and DGT-labile metals were quantified in the non-dredged and post-dredged sediments by high-resolution dialysis (HR-Peeper) and diffusive gradients (DGT) in thin films techniques. April and July measurements showed that dredging was effectively remediate the polluted sediments. The dissolved Pb, Cd, and Cu contents decreased up to 30%, 44%, and 26%, and the DGT-labile contents decreased up to 51%, 27%, and 33% compared with the contents in the non-dredged zone. Dredging was thus proven efficient in decreasing the labile metal fractions, increasing the capacity of available solids to bind metals, and slowing the leaching of metals from available solids in the post-dredged sediments. In October and January, the dredging efficacy was counteracted by the decomposition of algae, which increased the dissolved and DGT-labile metal concentrations in the post-dredged zone.

Seasonal antimony pollution caused by high mobility of antimony in sediments: In situ evidence and mechanical interpretation.

Antimony (Sb) mobilization in sediments and its impact on water quality remained to be studied. In this study, high-resolution dialysis (HR-Peeper) and diffusive gradients in thin films (DGT) technique were used to measure soluble Sb and labile Sb in sediment-overlying water profiles for a full year in a eutrophic region of Lake Taihu. Results showed that the highest mean concentrations of soluble Sb in overlying water (11.27 and 6.99 µg/L) appeared in December 2016 and January 2017, due to oxidation of Sb(III) to Sb(V) by Mn and Fe oxides, all of which exceeded the surface or drinking water limits set by China, United States and European Union. From April to November 2016, the concentrations of soluble Sb remained low with small monthly fluctuations and mean values ranging from 1.79 to 2.93 µg/L. This was attributed to the predominance of insoluble Sb(III) in sediments under anoxic conditions. The concentration of soluble Sb was slightly higher in summer than in autumn, due to the complexation of Sb(III) with DOM, as shown under anaerobic incubation. The mobility of inorganic Sb in sediments was mostly determined by the transition between Sb(III) and Sb(V), with Sb pollution in bottom water during winter being of concern.

Seasonal changes of lead mobility in sediments in algae- and macrophyte-dominated zones of the lake.

This study examined lead (Pb) pollution in algae- and macrophytes-dominated sediments, using diffusive gradient in thin films (DGT) and dialysis (HR-Peeper) techniques. Lead pollution varied by season in the two different ecotype sediments. In the algae-dominated zone, the highest concentrations of DGT-labile Pb and dissolved Pb occurred in April and July, respectively. The reductive dissolution of Fe/Mn oxides was identified as an important driver for Pb releases in April and July. This was supported by the decrease of the reducible fraction of Pb in sediments during those sampling periods. Furthermore, dissolved organic matter (DOM) complexation with Pb in sediments also significantly increased the dissolved Pb concentrations in July. The Pb-DOM complexes accounted for 95% of the total chemical species of Pb in pore water, calculated by Visual MINTEQ 3.1 model. Low concentrations of labile and dissolved Pb were observed in October and January; these resulted from the formation of Pb-sulfide precipitates and adsorption by Fe/Mn oxides. It was supported by the high rate of Pb(HS)2 precipitation (saturation index > 0), at 36%, in October samples and the high reducible fraction of Pb in sediments in January samples. In the macrophytes-dominated region, there was a decrease of labile and dissolved Pb concentrations in April and July. It is likely because of the uptake of Pb by submerged macrophyte roots and the Fe/Mn plaques in the root surface. High concentrations of labile and dissolved Pb were observed in October and January, likely resulting from the DOM complexation with Pb in sediments. This was supported by the fact that the Pb-DOM complexes accounted for 90% and 87% of the total chemical species of Pb in October and January, respectively.

High-performance and versatile electrochemical aptasensor based on self-supported nanoporous gold microelectrode and enzyme-induced signal amplification.

Herein, novel and versatile electrochemical aptasensors were constructed on a self-supported nanoporous gold (np-Au) microelectrode, integrating with an exonuclease III (Exo III) induced signal amplification strategy. Self-supported np-Au microelectrode with 3D bicontinuous nanoporous structures possesses tremendously large specific area, clean surface, high stability and biocompatibility, bringing about significant advantages in both molecular recognition and signal response. As paradigms, two analytes of bisphenol A (BPA) and ochratoxin A (OTA) were selected to demonstrate the superiority and versatility of designed aptasensors. Trace amounts of mDNA (associated with BPA or OTA concentration) hybridized with cDNA strands assembled on np-Au microelectrode, activating the cleavage reaction with Exo III. Thus, cDNA was digested and mDNA was released to undergo a new hybridization and cleavage cycle. Finally, residual cDNA strands were recognized by methylene blue labelled rDNA/AuNPs with the assistance of hDNA to generate the electrochemical signals, which were used to quantitatively monitor targets. Under the optimized conditions, prepared aptasensors exhibited wide linear ranges (25pg/mL to 2ng/mL for BPA, 10pg/mL to 5ng/mL for OTA) with ultralow detection limits (10pg/mL for BPA, 5pg/mL for OTA), excellent selectivity and stability, and reliable detection in real samples. This work opens a new horizon for constructing promising electrochemical aptasensors for environmental monitoring, medical diagnostics and food safety.

Enhanced Azo-Dyes Degradation Performance of Fe-Si-B-P Nanoporous Architecture.

Nanoporous structures were fabricated from Fe76Si9B10P5 amorphous alloy annealed at 773 K by dealloying in 0.05 M H2SO4 solution, as a result of preferential dissolution of α-Fe grains in form of the micro-coupling cells between α-Fe and cathodic residual phases. Nanoporous Fe-Si-B-P powders exhibit much better degradation performance to methyl orange and direct blue azo dyes compared with gas-atomized Fe76Si9B10P5 amorphous powders and commercial Fe powders. The degradation reaction rate constants of nanoporous powders are almost one order higher than those of the amorphous counterpart powders and Fe powders, accompanying with lower activation energies of 19.5 and 26.8 kJ mol-1 for the degradation reactions of methyl orange and direct blue azo dyes, respectively. The large surface area of the nanoporous structure, and the existence of metalloids as well as residual amorphous phase with high catalytic activity are responsible for the enhanced azo-dyes degradation performance of the nanoporous Fe-Si-B-P powders.