Catalysts with Trimetallic Sites on Graphene-like C2N for Electrocatalytic Nitrogen Reduction Reaction: A Theoretical Investigation.

Electrocatalytic nitrogen reduction reaction (NRR) is a green and highly efficient way to replace the industrial Haber-Bosch process. Herein, clusters consisting of three transition metal atoms loaded on C2N as NRR electrocatalysts are investigated using density functional theory (DFT). Meanwhile, Ca was introduced as a promoter and the role of Ca in NRR was investigated. It was found that Ca anchored to the catalyst can act as an electron donor and effectively promote the activation of N2 on M3. In both M3@C2N and M3Ca@C2N (M = Fe, Co, Ni), the limiting potential (UL) is less negative than that of the Ru(0001) surface and has the ability to suppress the competitive hydrogen evolution reaction (HER). Among them, Fe3@C2N is suggested to be the most promising candidate for NRR with high thermal stability, strong N2 adsorption ability, low limiting potential, and good NRR selectivity. The concepts of trimetallic sites and alkaline earth metal promoters in this work provide theoretical guidance for the rational design of atomically active sites in electrocatalytic NRR.

Association Between Dietary Factors and Chronic Sinusitis Among Korean Individuals: Insights From a Large Population-Based Study in Asia.

Objective: Population-based studies on chronic sinusitis have predominantly focused on Europe and the Americas, but research on chronic sinusitis within large Asian populations remains scarce. This study aims to explore the link between dietary factors and chronic sinusitis among ethnic Koreans in Asia. Design: A cross-sectional study. Setting: Data were collected from the Korean National Health and Nutrition Examination Survey (KNHANES) in 2012. Participants: Participants in the study were included based on a doctor's diagnosis of chronic sinusitis, as determined through the ear, nose, and throat examination questionnaires. Results: Adolescents [adjusted P value (aP) < .001, adjusted odds ratio (aOR) = 1.881, 95% confidence interval (CI) = 1.380-2.564] and individuals with college and higher education (aP = .042, aOR = 1.298, 95% CI = 1.009-1.669) were more likely to develop chronic rhinosinusitis. In addition, levels of dietary fat [P = .001, interquartile range (IQR) = 34.085] and energy intake (P = .004, IQR = 981.106) were associated with an increased risk of chronic sinusitis. Moreover, high dietary inflammatory index (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721), and high intake of fried pork chops (aP = .028, aOR = 1.335, 95% CI = 1.033-1.777), bread (aP = .024, aOR = 1.364, 95% CI = 1.042-1.786), and rice (aP = .021, aOR = 1.382, 95% CI = 1.051-1.818) were risk factors for chronic sinusitis, while cucumber consumption (aP < .001, aOR = 0.547, 95% CI = 0.415-0.721) was a protective factor for chronic sinusitis. Conclusion: This study revealed a significant correlation between diet and development of chronic sinusitis. These findings suggest that promoting an anti-inflammatory dietary pattern and providing guidance on healthy eating habits could help reduce the incidence of chronic sinusitis and enhance its management.

Selective Reduction of NO into N2 Catalyzed by Rh1-Doped Cluster Anions RhCe2O3-5.

Catalytic conversion of toxic nitrogen oxide (NO) and carbon monoxide (CO) into nitrogen (N2) and carbon dioxide (CO2) is imperative under the weight of the increasingly stringent emission regulations, while a fundamental understanding of the nature of the active site to selectively drive N2 generation is elusive. Herein, in combination with state-of-the-art mass-spectrometric experiments and quantum-chemical calculations, we demonstrated that the rhodium-cerium oxide clusters RhCe2O3-5- can catalytically drive NO reduction by CO and give rise to N2 and CO2. This finding represents a sharp improvement in cluster science where N2O is commonly produced in the rarely established examples of catalytic NO reduction mediated with gas-phase clusters. We demonstrated the importance of the unique chemical environment in the RhCe2O3- cluster to guide the substantially improved N2 selectivity: a triatomic Lewis "acid-base-acid" Ceδ+-Rhδ--Ceδ+ site is proposed to strongly adsorb two NO molecules as well as the N2O intermediate that is attached on the Rh atom and can facilely dissociate to form N2 assisted by both Ce atoms.

Size-Dependent Reactivity of Con- (n = 5-25) Cluster Anions toward Carbon Dioxide.

A fundamental understanding of the reactivity evolution of nanosized clusters at an atomically precise level is pivotal to assemble desired materials with promising candidates. Benefiting from the tandem mass spectrometer coupled with a high-temperature ion-trap reactor, the reactions of mass-selected Con- (n = 5-25) clusters with CO2 were investigated and the increased reactivity of Co20-25- was newly discovered herein. This finding marks an important step to understand property evolution of subnanometer metal clusters (Co25-, ∼0.8 nm) atom-by-atom. The reasons behind the increased reactivity of Co20-25- were proposed by analyzing the reactions of smaller Co6-8- clusters that exhibit significantly different reactivity toward CO2, in which a lower electron affinity of Con contributes to the capture of CO2 while the flexibility of Con- could play vital roles to stabilize reaction intermediates and suppress the barriers of O-CO rupture and CO desorption.

Catalytic NO Reduction by Noble-Metal-Free Vanadium-Aluminum Oxide Cluster Anions.

By using state-of-the-art mass spectrometry and guided by the newly discovered single-electron mechanism (SEM; e.g., Ti3+ + 2NO → Ti4+-O•- + N2O), we determined experimentally that the vanadium-aluminum oxide clusters V4-xAlxO10-x- (x = 1-3) can catalyze the reduction of NO by CO and substantiated theoretically that the SEM still prevails in driving the catalysis. This finding marks an important step in cluster science in which a noble metal had been demonstrated to be indispensable in NO activation mediated by heteronuclear metal clusters. The results provide new insights into the SEM in which active V-Al cooperative communication favors the transfer of an unpaired electron from the V atom to NO attached to the Al atom on which the reduction reaction actually takes place. This study provides a clear picture for improving our understanding of related heterogeneous catalysis, and the electron hopping behavior induced by NO adsorption could be a fundamental chemistry for driving NO reduction.

Filtration of the preferred catalyst for reverse water-gas shift among Rhn- (n = 3-11) clusters by mass spectrometry under variable temperatures.

The key to optimizing energy-consuming catalytic conversions lies in acquiring a fundamental understanding of the nature of the active sites and the mechanisms of elementary steps at an atomically precise level, while it is challenging to capture the crucial step that determines the overall temperature of a real-life catalytic reaction. Herein, benefiting from a newly-developed high-temperature ion trap reactor, the reverse water-gas shift (CO2 + H2 → CO + H2O) reaction catalyzed by the Rhn- (n = 3-11) clusters was investigated under variable temperatures (298-783 K) and the critical temperature that each elementary step (Rhn- + CO2 and RhnO- + H2) requires to take place was identified. The Rh4- cluster strikingly surpasses other Rhn- clusters to drive the catalysis at a mild starting temperature (∼440 K). This finding represents the first example that a specifically sized cluster catalyst that works under an optimum condition can be accurately filtered by using state-of-the-art mass spectrometric experiments and rationalized by quantum-chemical calculations.

Transcriptome Analysis of Antrodia cinnamomea Mycelia from Different Wood Substrates.

Antrodia cinnamomea, an edible and medicinal fungus with significant economic value and application prospects, is rich in terpenoids, benzenoids, lignans, polysaccharides, and benzoquinone, succinic and maleic derivatives. In this study, the transcriptome of A. cinnamomea cultured on the wood substrates of Cinnamomum glanduliferum (YZM), C. camphora (XZM), and C. kanehirae (NZM) was sequenced using the high-throughput sequencing technology Illumina HiSeq 2000, and the data were assembled by de novo strategy to obtain 78,729 Unigenes with an N50 of 4,463 bp. Compared with public databases, about 11,435, 6,947, and 5,994 Unigenes were annotated to the Non-Redundant (NR), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genome (KEGG), respectively. The comprehensive analysis of the mycelium terpene biosynthesis-related genes in A. cinnamomea revealed that the expression of acetyl-CoA acetyltransferase (AACT), acyl-CoA dehydrogenase (MCAD), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), mevalonate pyrophosphate decarboxylase (MVD), and isopentenyl diphosphate isomerase (IDI) was significantly higher on NZM compared to the other two wood substrates. Similarly, the expression of geranylgeranyltransferase (GGT) was significantly higher on YZM compared to NZM and XZM, and the expression of farnesyl transferase (FTase) was significantly higher on XZM. Furthermore, the expressions of 2,3-oxidized squalene cyclase (OCS), squalene synthase (SQS), and squalene epoxidase (SE) were significantly higher on NZM. Overall, this study provides a potential approach to explore the molecular regulation mechanism of terpenoid biosynthesis in A. cinnamomea.

Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3ß/ß-catenin pathway.

OBJECTIVE: Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness. METHODS: A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3ß (GSK-3ß)/ß-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3ß/ß-catenin signaling pathway was detected. RESULTS: Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3ß/ß-catenin signaling pathway. Additionally, the desmin+/CD31+ ratio, rather than the number of CD31+ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3ß/ß-catenin signaling pathway were also inhibited in cells treated with serum from swimming group. CONCLUSION: Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3ß/ß-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3ß/ß-catenin pathway. J Integr Med. 2023; 21(2): 184-193.

Catalytic NO Reduction by NO Pre-Adsorbed RhCeO2 NO- Clusters.

A fundamental understanding on the dynamically structural evolution of catalysts induced by reactant gases under working conditions is challenging but pivotal in catalyst design. Herein, in combination with state-of-the-art mass spectrometry for cluster reactions, cryogenic photoelectron imaging spectroscopy, and quantum-chemical calculations, we identified that NO adsorption on rhodium-cerium bimetallic oxide cluster RhCeO2 - can create a Ce3+ ion in product RhCeO2 NO- that serves as the starting point to trigger the catalysis of NO reduction by CO. Theoretical calculations substantiated that the reduction of another two NO molecules into N2 O takes place exclusively on the Ce3+ ion while Rh behaves like a promoter to buffer electrons and cooperates with Ce3+ to drive NO reduction. Our finding demonstrates the importance of NO in regulating the catalytic behavior of Rh under reaction conditions and provides much-needed insights into the essence of NO reduction over Rh/CeO2 , one of the most efficient components in three-way catalysts for NOx removal.

Facile CO bond cleavage on polynuclear vanadium nitride clusters V4N5.

Identifying the structural configurations of precursors for CO dissociation is fundamentally interesting and industrially important in the fields of, e.g., Fischer-Tropsch synthesis. Herein, we demonstrated that CO could be dissociated on polynuclear vanadium nitride V4N5- clusters at room temperature, and a key intermediate, with CO in a N-assisted tilted bridge coordination where the C-O bond ruptures easily, was discovered. The reaction was characterized by mass spectrometry, photoelectron spectroscopy, and quantum-chemistry calculations, and the nature of the adsorbed CO on product V4N5CO- was further characterized by a collision-induced dissociation experiment. Theoretical analysis evidences that CO dissociation is predominantly governed by the low-coordinated V and N atoms on the (V3N4)VN- cluster and the V3N4 moiety resembles a support. This finding strongly suggests that a novel mode for facile CO dissociation was identified in a gas-phase cluster study.

Data mining for adverse drug reaction signals of daptomycin based on real-world data: a disproportionality analysis of the US Food and Drug Administration adverse event reporting system.

BACKGROUND: Previous reports on daptomycin's adverse drug reactions (ADRs) have been insufficient, often because of limited data. Pharmacovigilance risk signal detection is innovative and has been applied to the safety monitoring and reevaluation of drugs post-marketing. AIM: The study aimed to promote safe daptomycin prescribing by mining and evaluating the daptomycin ADR signals from the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHOD: A disproportionality analysis (reporting odds ratio ROR and proportional reporting ratio PRR) was utilized for FAERS data mining from the first quarter of 2004 to the second quarter of 2021 (the most recent quarterly data at the time of the study). Preferred Terms of ADR reports were categorized by System Organ Class (SOC) based on the Medical Dictionary for Regulatory Activities. RESULTS: This study retrieved 12,221 cases within the reporting period. A total of 140 repetitive signals were obtained by ROR and PRR, of which 53 new ADR signals were not recorded in the drug labels/datasheets. The top three ADR reports were "blood creatine phosphokinase elevation" (ROR, 56.66, 95% confidence interval (CI) 51.07-62.87, PRR 51.94), "eosinophilic pneumonia" (ROR 696.71, 95%CI 603.21-804.70, PRR 657.57), and "rhabdomyolysis" (ROR 22.85, 95%CI 19.94-26.18, PRR 21.83). The highest ROR of "antimicrobial susceptibility test resistant" was found at 9808.14. Reports of rare adverse events, such as "necrotizing fasciitis and compartment syndrome," have emerged. The significant SOCs were "Infections and Infestations" and "Investigations." CONCLUSION: New daptomycin ADR signals were detected. Clinicians should monitor these potential ADRs in patients receiving daptomycin.

Water-Gas Shift Catalyzed by Iridium-Vanadium Oxide Clusters IrVO2- with Iridium in a Rare Oxidation State of -II.

The discovery of compounds containing transition metals with an unusual and well-established oxidation state is vital to enrich our horizon on formal oxidation state. Herein, benefiting from the study of the water-gas shift reaction (CO + H2O → CO2 + H2) mediated with the iridium-vanadium oxide cluster IrVO2-, the missing -II oxidation state of iridium was identified. The reactions were performed by using our newly developed double ion trap reactors that can spatially separate the addition of reactants and are characterized by mass spectrometry and quantum-chemical calculations. This finding makes an important step that all the proposed 13 oxidation states of iridium (+IX to -III) have been known. The iridium atom in the IrVO2- cluster features the Ir═V double bond and resembles chemically the coordinated oxygen atom. A reactivity study demonstrated that the flexible role switch of iridium between an oxygen-atom like (Ir-IIVO2-) and a transition-metal-atom like behavior (Ir+IIVO3-) in different species can drive the water-gas shift reaction in the gas phase under ambient conditions. This result parallels and well rationalizes the extraordinary reactivity of oxide-supported iridium single-atom catalysts in related condensed-phase reactions.

Reverse water-gas shift reaction catalyzed by diatomic rhodium anions.

The reverse water-gas shift (RWGS, CO2 + H2 → CO + H2O, ΔH298 = +0.44 eV) reaction mediated by the diatomic anion Rh2- was successfully constructed. The generation of a gas-phase H2O molecule and ion product [Rh2(CO)ads]- was identified unambiguously at room temperature and the only elementary step that requires extra energy to complete the catalysis is the desorption of CO from [Rh2(CO)ads]-. This experimentally identified Rh2- anion represents the first gas-phase species that can drive the RWGS reaction because it is challenging to design effective routes to yield H2O from CO2 and H2. The reactions were performed by using our newly developed double ion trap reactors and characterized by mass spectrometry, photoelectron spectroscopy, and high-level quantum-chemical calculations. We found that the order that the reactants (CO2 or D2) were fed into the reactor did not have a pronounced impact on the reactivity and the final product distribution (D2O and Rh2CO-). The atomically precise insights into the key steps to guide the reaction toward the RWGS direction were provided.

Aerobic exercise suppresses hepatocellular carcinoma by downregulating dynamin-related protein 1 through PI3K/AKT pathway.

OBJECTIVE: Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis. METHODS: Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise. RESULTS: The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 µmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor. CONCLUSION: Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.

Water Gas Shift Reaction Catalyzed by Rhodium-Manganese Oxide Cluster Anions.

Fundamental understanding of the nature of active sites in real-life water gas shift (WGS) catalysts that can convert CO and H2O into CO2 and H2 is crucial to engineer related catalysts performing under ambient conditions. Herein, we identified that the WGS reaction can be, in principle, catalyzed by rhodium-manganese oxide clusters Rh2MnO1,2- in the gas phase at room temperature. This is the first example of the construction of such a potential catalysis in cluster science because it is challenging to discover clusters that can abstract the oxygen from H2O and then supply the anchored oxygen to oxidize CO. The WGS reaction was characterized by mass spectrometry, photoelectron spectroscopy, and quantum-chemical calculations. The coordinated oxygen in Rh2MnO1,2- is paramount for the generation of an electron-rich Mn+-Rh- bond that is critical to capture and reduce H2O and giving rise to a polarized Rh+-Rh- bond that functions as the real redox center to drive the WGS reaction.

An IrVO4+ Cluster Catalytically Oxidizes Four CO Molecules: Importance of Ir-V Multiple Bonding.

The generation and characterization of multiple metal-metal (M-M) bonds between early and late transition metals is vital to correlate the nature of multiple M-M bonds with the related reactivity in catalysis, while the examples with multiple M-M bonds have been rarely reported. Herein, we identified that the quadruple bonding interactions were formed in a gas-phase ion IrV+ with a dramatically short Ir-V bond. Oxidation of four CO molecules by IrVO4+ is a highly exothermic process driven by the generation of stable products IrV+ and CO2, and then IrV+ can be oxidized by N2O to regenerate IrVO4+. This finding overturns the general impression that vanadium oxide clusters are unwilling to oxidize multiple CO molecules because of the strong V-O bond and that at most two oxygen atoms can be supplied from a single V-containing cluster in CO oxidation. This study emphasizes the potential importance of heterobimetallic multiple M-M bonds in related heterogeneous catalysis.

CTRP1 decreases ABCA1 expression and promotes lipid accumulation through the miR-424-5p/FoxO1 pathway in THP-1 macrophage-derived foam cells.

Prevention of ATP binding cassette transporter A1 (ABCA1)-dependent cholesterol efflux leads to lipid accumulation in macrophages and atherosclerosis development. C1q tumor necrosis factor-related protein 1 (CTRP1), a conserved paralog of adiponectin, has been shown to aggravate atherosclerosis via its proinflammatory property. However, very little is known about its effects on ABCA1 expression and macrophage lipid accumulation. In the current studies, we found that CTRP1 downregulated ABCA1 expression, inhibited cholesterol efflux to apoA-I and promoted lipid accumulation in THP-1 macrophage-derived foam cells. Forkhead box O1 (FoxO1), a transcriptional repressor of ABCA1, was identified as a direct target of miR-424-5p. Mechanistically, CTRP1 attenuated miR-424-5p levels and then augmented FoxO1 expression in the nucleus, which led to downregulation of ABCA1 expression and inhibition of cholesterol efflux. In conclusion, these findings suggest that CTRP1 restrains cholesterol efflux and facilitates macrophage lipid accumulation through the miR-424-5p/FoxO1/ABCA1 signaling pathway, thereby providing a novel mechanistical insight into its proatherosclerotic action.

Activation of Carbon Dioxide by CoCDn- (n = 0-4) Anions.

Laser ablation generated CoCDn- (n = 0-4) anions were mass selected and then reacted with CO2 in an ion trap reactor. The reactions were characterized by mass spectrometry and quantum chemical calculations. The experimental results demonstrated that the CoC- anion can convert CO2 into CO. In contrast, the bare Co- anion is inert toward CO2. Coordinated D ligands can modify the reactivity of CoCD1-4- in which CoCD1-3- can reduce CO2 into CO selectively and CoCD4- can only adsorb CO2. The crucial roles of the coordinated C and D ligands to tune the reactivity of CoCDn- (n = 0-4) toward CO2 were rationalized by theoretical calculations. Note that the hydrogenation process that is usually observed in the reactions of gas-phase metal hydrides with CO2 is completely suppressed for the reactions CoCDn- + CO2. This study provides insights into the molecular-level origin for the observations that CO can be selectively generated from CO2 catalyzed by cobalt-containing carbides in heterogeneous catalysis.

CTRP12 ameliorates atherosclerosis by promoting cholesterol efflux and inhibiting inflammatory response via the miR-155-5p/LXRα pathway.

C1q tumor necrosis factor-related protein 12 (CTRP12), a conserved paralog of adiponectin, is closely associated with cardiovascular disease. However, little is known about its role in atherogenesis. The aim of this study was to examine the influence of CTRP12 on atherosclerosis and explore the underlying mechanisms. Our results showed that lentivirus-mediated CTRP12 overexpression inhibited lipid accumulation and inflammatory response in lipid-laden macrophages. Mechanistically, CTRP12 decreased miR-155-5p levels and then increased its target gene liver X receptor α (LXRα) expression, which increased ATP binding cassette transporter A1 (ABCA1)- and ABCG1-dependent cholesterol efflux and promoted macrophage polarization to the M2 phenotype. Injection of lentiviral vector expressing CTRP12 decreased atherosclerotic lesion area, elevated plasma high-density lipoprotein cholesterol levels, promoted reverse cholesterol transport (RCT), and alleviated inflammatory response in apolipoprotein E-deficient (apoE-/-) mice fed a Western diet. Similar to the findings of in vitro experiments, CTRP12 overexpression diminished miR-155-5p levels but increased LXRα, ABCA1, and ABCG1 expression in the aortas of apoE-/- mice. Taken together, these results suggest that CTRP12 protects against atherosclerosis by enhancing RCT efficiency and mitigating vascular inflammation via the miR-155-5p/LXRα pathway. Stimulating CTRP12 production could be a novel approach for reducing atherosclerosis.

LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis.

Kcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE-/- mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE-/- mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.