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In recent years, virtual idols have garnered considerable attention because they can perform activities similar to real idols. However, as they are fictitious idols with nonphysical presence, they cannot perform physical interactions such as handshake. Combining a robotic hand with a display showing virtual idols is the one of the methods to solve this problem. Nonetheless a physical handshake is possible, the form of handshake that can effectively induce the desirable behavior is unclear. In this study, we adopted a robotic hand as an interface and aimed to imitate the behavior of real idols. To test the effects of this behavior, we conducted step-wise experiments. The series of experiments revealed that the handshake by the robotic hand increased the feeling of intimacy toward the virtual idol, and it became more enjoyable to respond to a request from the virtual idol. In addition, viewing the virtual idols during the handshake increased the feeling of intimacy with the virtual idol. Moreover, the method of the hand-shake peculiar to idols, which tried to keep holding the user's hand after the conversation, increased the feeling of intimacy to the virtual idol.

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Lentiviral vectors (LVs) have been widely used as a tool for gene therapies. However, tissue-selective transduction after systemic delivery remains a challenge. Inducible degrader of low-density lipoprotein receptor is an attractive target for treating hypercholesterolemia. Here, a liver-targeted LV, CS8-LV-shIDOL, is developed by incorporating a hepatocyte-targeted peptide derived from circumsporozoite protein (CSP) into the lentivirus envelope for liver-targeted delivery of IDOL-shRNA (short hairpin RNA) to alleviate hypercholesterolemia. Tail-vein injection of CS8-LV-shIDOL results in extremely high accumulation in liver and nearly undetectable levels in other organs in mice. In addition, it shows superior therapeutic efficacy in lowering serum low-density lipoprotein cholesterol (LDL-C) and reducing atherosclerotic lesions over unmodified LV-shIDOL in hyperlipidemic mice. Mechanically, the envelope-engineered CS8-LV-shIDOL can enter liver cells via low-density lipoprotein receptor-related protein (LRP). Thus, this study provides a novel approach for liver-targeted delivery of IDOL-shRNA to treat hypercholesterolemia by using an envelope-engineered LV, and this delivery system has great potential for liver-targeted transgene therapy.

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BACKGROUND: Curcumin nicotinate (Curtn), derived from curcumin and niacin, reduces serum LDL-C levels, partly due to its influence on PCSK9. This study investigates IDOL's role in Curtn's lipid-lowering effects. OBJECTIVE: To elucidate Curtn's regulation of the IDOL/LDLR pathway and potential molecular mechanisms in hepatocytes. METHODS: Differential metabolites in Curtn-treated HepG2 cells were identified via LC-MS. Molecular docking assessed Curtn's affinity with IDOL. Cholesterol content and LDLR expression effects were studied in high-fat diet Wistar rats. In vitro evaluations determined Curtn's influence on IDOL overexpression's LDL-C uptake and LDLR expression in hepatocytes. RESULTS: Lipids were the main differential metabolites in Curtn-treated HepG2 cells. Docking showed Curtn's higher affinity to IDOL's FERM domain compared to curcumin, suggesting potential competitive inhibition of IDOL's binding to LDLR. Curtn decreased liver cholesterol in Wistar rats and elevated LDLR expression. During in vitro experiments, Curtn significantly enhanced the effects of IDOL overexpression in HepG2 cells, leading to increased LDL-C uptake and elevated expression of LDL receptors. CONCLUSION: Curtn modulates the IDOL/LDLR pathway, enhancing LDL cholesterol uptake in hepatocytes. Combined with its PCSK9 influence, Curtn emerges as a potential hyperlipidemia therapy.

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The marketing practice involved with virtual idols became popular, leading to the emergence of virtual idol marketing. However, there is a lack of scientific understanding of this emerging marketing field. To promote a fundamental understanding of virtual idol marketing, this study clarifies the conceptual boundary of virtual idols and provides meaningful insights into the definitions, benefits, and risks of virtual idol marketing. On this basis, this study further proposes an integrated framework established on the existing theories and research to explain the potential working mechanism of virtual idol marketing. This study can increase the accumulation of knowledge in the emerging field of virtual idol marketing, provide inspiration and decision-making assistance for brands to build connections with young consumers, especially Generation Z, and provide an avenue for future research in the field of virtual idol marketing.

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More than 20 natural products have been reported to modulate PCSK9-mediated cholesterol regulation, and small-molecule-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors continue to be developed and identified. Here, twelve undescribed clerodane-type diterpenes (1-9 and 12-14) and two known compounds were isolated from the chloroform-soluble extract of the dried fruits of Casearia grewiifolia Vent. using a PCSK9 mRNA expression monitoring assay. Among the undescribed compounds, the stereochemistry of two diastereomeric grewiifolins A and B (1 and 2) were extensively elucidated using 2D Nuclear Overhauser Effect Spectroscopy (NOESY) experiments, excitation-sculptured indirect detection experiments (EXSIDE), interproton distance analyses, and computational calculations that included quantum chemical shift calculations combined with DP4+ analysis. All isolates were assessed for their inhibitory activity against PCSK9 and IDOL mRNA expression. Among the compounds tested, compound 3 inhibited PCSK9 and IDOL mRNA expression.

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BACKGROUND: The suicide rate in Korea was the highest among the member countries of the Organization for Economic Cooperation and Development(OECD) for 2013-2016 and 2018-2020. In korea, suicide was the leading cause of death among individuals aged 10-39, and the second leading cause of death for aged 40-59. Thus, this study aimed to examine the Werther effect of the suicides of three Korean idol singers (Jonghyun: December 18, 2017, Sulli: October 14, 2019, and Hara Gu: November 24, 2019). METHODS: The study conducted Poisson regression and used the cause-of-death statistics microdata from 2016 to 2020 provided by Statistics Korea. The case periods ranged from the day of the suicide of each celebrity to 10 weeks after. The control periods were all weeks from 2016 to 2020, excluding the case periods. RESULTS: The suicide rates in Korea significantly increased by 1.21, 1.30, and 1.28 times after the deaths of Jonghyun, Sulli, and Hara Gu, respectively. The Werther effect was more evident in women than men. Suicide rate among individuals aged 10-29 years was greater than those for other age groups. CONCLUSIONS: This study confirmed that the rate of copycat suicides increased after three celebrity singers in Korea died by suicide. Nevertheless, the rate of suicide after the suicide of the three celebrity singers was lower than those in previous studies in Korea.

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Liver X receptor (LXR) signaling broadly restricts virus replication; however, the mechanisms of restriction are poorly defined. Here, we demonstrate that the cellular E3 ligase LXR-inducible degrader of low-density lipoprotein receptor (IDOL) targets the human cytomegalovirus (HMCV) UL136p33 protein for turnover. UL136 encodes multiple proteins that differentially impact latency and reactivation. UL136p33 is a determinant of reactivation. UL136p33 is targeted for rapid turnover by the proteasome, and its stabilization by mutation of lysine residues to arginine results in a failure to quiet replication for latency. We show that IDOL targets UL136p33 for turnover but not the stabilized variant. IDOL is highly expressed in undifferentiated hematopoietic cells where HCMV establishes latency but is sharply downregulated upon differentiation, a stimulus for reactivation. We hypothesize that IDOL maintains low levels of UL136p33 for the establishment of latency. Consistent with this hypothesis, knockdown of IDOL impacts viral gene expression in wild-type (WT) HCMV infection but not in infection where UL136p33 has been stabilized. Furthermore, the induction of LXR signaling restricts WT HCMV reactivation from latency but does not affect the replication of a recombinant virus expressing a stabilized variant of UL136p33. This work establishes the UL136p33-IDOL interaction as a key regulator of the bistable switch between latency and reactivation. It further suggests a model whereby a key viral determinant of HCMV reactivation is regulated by a host E3 ligase and acts as a sensor at the tipping point between the decision to maintain the latent state or exit latency for reactivation. IMPORTANCE Herpesviruses establish lifelong latent infections, which pose an important risk for disease particularly in the immunocompromised. Our work is focused on the betaherpesvirus human cytomegalovirus (HCMV) that latently infects the majority of the population worldwide. Defining the mechanisms by which HCMV establishes latency or reactivates from latency is important for controlling viral disease. Here, we demonstrate that the cellular inducible degrader of low-density lipoprotein receptor (IDOL) targets a HCMV determinant of reactivation for degradation. The instability of this determinant is important for the establishment of latency. This work defines a pivotal virus-host interaction that allows HCMV to sense changes in host biology to navigate decisions to establish latency or to replicate.

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Lipids-lowering is considered as the most effective approach to decrease the risk of Atherosclerotic cardiovascular disease (ASCVD), of which atherosclerosis is the most common cause. Natural products containing a unique type of α-pyrone was reported to suppress atherosclerosis in which α-pyrone might be considered as an important pharmacore. In this study, an efficient one-pot intramolecular C-H activation strategy was applied to the synthesis of potentially bioactive α-pyrone derivatives. As the result, three different scaffolds were quickly and conveniently generated, including thiophenes, pyrrole and indole derivatives. Among of them, eight α-pyrone derivatives showed potential effects to promote the uptake of LDL in HepG2 cells. Active unique α-pyrones compounds exhibiting potent in vitro and in vivo lipids-lowering effects, and a novel mechanism associated with the regulation of LXR-IDOL-LDLR axis, the new pathway targeted pharmacologically to control plasma cholesterol levels, were disclosed firstly in this study.

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PURPOSE: The present study describes a new species of myxosporean, Sphaeromyxa cornuti n. sp. infecting the gallbladder of the Moorish idol, Zanclus cornutus (Linnaeus 1758) collected from Lakshadweep waters of the Arabian Sea. METHODS: Fish were collected using traps and cages. The morphology of mature spores recovered from the gallbladder of Z. cornutus was studied under Nomarski Differential Interference Contrast (DIC) optics. The molecular and phylogenetic analyses were based on SSU rDNA. RESULTS: Sphaeromyxa cornuti n. sp. is characterized by arcuate myxospores with tapering extremities and round ends in valvular, and slightly sigmoid in sutural views (19.2-24.7 µm × 4.1-5.7 µm). The two polar capsules are unequally elongate-ovoid in shape and positioned at opposite ends of the spore (6.2-9.7 µm × 1.7-2.6 µm). Each encloses an irregularly folded, ribbon-like polar tubule, which is oriented parallel to polar capsule axis. In molecular and phylogenetic analyses, the present myxosporean revealed significant differences with related forms and clustered together with S. hellandi within the 'incurvata' group of the Sphaeromyxa clade with high nodal support. CONCLUSIONS: Morphological, morphometric, molecular and phylogenetic differences between our material and previously described species of Sphaeromyxa, along with host and geographic variations indicate that the present myxosporean is unique and the name Sphaeromyxa cornuti n. sp. is proposed. This forms the first report of a myxosporean parasite-infecting Z. cornutus.

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The brand loyalty of fan consumers can be influenced by idol worship if certain celebrity figures are linked with a brand. Collaborating with idols is an effective marketing strategy that many companies use to enhance their appeal to fan consumers and increase their brand equity. Fan consumers demonstrate passion and admiration for their idols, and this psychological phenomenon affects their cognition of brands that are endorsed by their favorite celebrity figures. The purpose of this study was to explore the influence mechanism that propels fan consumers' brand loyalty and the mediating effects of brand passion and brand attachment. Our results revealed the following key findings: (1) brand personality attraction, perceived emotional value, brand-based self-realization, and relatedness needs satisfaction have a significant effect on brand passion; (2) perceived emotional value and relatedness needs satisfaction have a significant effect on brand passion attachment; (3) brand passion can directly affect brand loyalty, but it also indirectly affects brand loyalty through brand attachment; (4) brand personality appeal, brand-based self-realization, and relatedness needs satisfaction can influence brand attachment through brand passion and ultimately have an impact on brand loyalty; (5) brand perceived emotional value and relatedness needs satisfaction affect brand loyalty through brand attachment. These findings have several implications for enterprises that want to meet fan consumers' emotional needs, enhance brand loyalty through the use of idol brand endorsement, or implement brand campaigns that involve idols.

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Reference-based deconvolution methods use reference libraries of cell-specific DNA methylation (DNAm) measurements as a means toward deconvoluting cell proportions in heterogeneous biospecimens (e.g., whole-blood). As the accuracy of such methods depends highly on the CpG loci comprising the reference library, recent research efforts have focused on the selection of libraries to optimize deconvolution accuracy. While existing approaches for library selection work extremely well, the best performing approaches require a training data set consisting of both DNAm profiles over a heterogeneous cell population and gold-standard measurements of cell composition (e.g., flow cytometry) in the same samples. Here, we present a framework for reference library selection without a training dataset (RESET) and benchmark it against the Legacy method (minfi:pickCompProbes), where libraries are constructed based on a pre-specified number of cell-specific differentially methylated loci (DML). RESET uses a modified version of the Dispersion Separability Criteria (DSC) for comparing different libraries and has four main steps: (1) identify a candidate set of cell-specific DMLs, (2) randomly sample DMLs from the candidate set, (3) compute the Modified DSC of the selected DMLs, and (4) update the selection probabilities of DMLs based on their contribution to the Modified DSC. Steps 2-4 are repeated many times and the library with the largest Modified DSC is selected for subsequent reference-based deconvolution. We evaluated RESET using several publicly available datasets consisting of whole-blood DNAm measurements with corresponding measurements of cell composition. We computed the RMSE and R 2 between the predicted cell proportions and their measured values. RESET outperformed the Legacy approach in selecting libraries that improve the accuracy of deconvolution estimates. Additionally, reference libraries constructed using RESET resulted in cellular composition estimates that explained more variation in DNAm as compared to the Legacy approach when evaluated in the context of epigenome-wide association studies (EWAS) of several publicly available data sets. This finding has implications for the statistical power of EWAS. RESET combats potential challenges associated with existing approaches for reference library assembly and thus, may serve as a viable strategy for library construction in the absence of a training data set.

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Introduction: This study aimed to explore the psychological adaptation process of renouncing fanship due to para-loveshock in the context of fandom culture. Methods: We adopted netnography to explore social media platforms used by fans in China (Weibo, WeChat, and Douban) as research fields for 3 years. Results: (1) The process of "breaking up with" or renouncing an idol can be divided into three phases: the resistance phase with acute stress, the negotiation phase with bargaining, and the recovery phase with attachment reconstruction. In the resistance phase, fans displayed acute stress responses due to loveshock in psychological, physical, and behavioral aspects. In the negotiation phase, fans faced four barriers to renouncement: cognitive dissonance, emotional attachment, behavioral dependence, and social threat. They bargained within the three types of cognitive framework before deciding to "leave" or "re-follow" their idol. In the recovery phase, fans adopted two types of strategies to promote recovery: healing the past and facing the future. Healing the past involved public outcry, sharing their breakup plans, cognitive reconstruction, and seeking closure to the fan role. Facing the future involved switching environments, seeking new interests, and inhibiting the re-intrusion of trauma cues. (2) Internal factors affecting the psychological adaptation process of renouncement include the level of initiative, attribution styles, experience, attachment status and core belief systems, and alternative lifestyles; external factors include social support, peer pressure from the fan community, life stressors, and types and impact of traumatic events. (3) Based on the two dimensions of orientation and commitment, fans were classified into four types: short-term rational, short-term passionate, bounded loyal, and unconditionally loyal, corresponding to non-traumatic, stressful, accumulated, and traumatic breakup processes, respectively. (4) The post-renouncement growth of fans mainly manifested in the development of mental modes, coping skills toward trauma, emotional adaptation experience, and behavior patterns. Implications: This investigation of the recovery process from para-loveshock after renouncement of fanship can provide theoretical and practical insights into the development of psychological resilience for fans, reduction of the psychological distress and negative outcomes, and public governance on social media platform and cyber pop culture industry.

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BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide. In this study, we aimed to explore whether some genetic variants of the human IDOL gene were associated with CAD among Chinese population in Xinjiang. METHODS: We designed two independent case-control studies. The first one included in the Han population (448 CAD patients and 343 controls), and the second one is the Uygur population (304 CAD patients and 318 controls). We genotyped three SNPs (rs2072783, rs2205796, and rs909562) of the IDOL gene. RESULTS: Our results revealed that, in the Han female subjects, for rs2205796, the distribution of alleles, dominant model (TT vs. GG + GT) and the additive model (GG + TT vs. GT) showed significant differences between CAD patients and the control subjects (P = 0.048, P = 0.014, and P = 0.032, respectively). CONCLUSIONS: The rs2205796 polymorphism of the IDOL gene is associated with CAD in the Chinese Han female population in Xinjiang, China.

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Nardilysin (NRDC) has been shown to be involved in post-translational histone modifications, in addition to enhancement in ectodomain shedding of membrane-anchored protein, which play significant roles in various pathophysiology, including glucose homeostasis, inflammatory diseases and cancer. The present study sought to determine roles of NRDC in the liver on lipid and lipoprotein metabolism. We established liver-specific NRDC deficient mice by use of NRD1 floxed mice and albumin promoter-Cre recombinase (Cre) transgenic mice, and found that their serum low-density lipoprotein (LDL) cholesterol levels were significantly lower than those in control littermate mice. In the liver, LDL receptor (LDLR) mRNA expression was significantly upregulated, while inducible degrader of LDLR (IDOL) and microsomal triglyceride transfer protein (MTP) mRNA expression was significantly downregulated, in liver-specific NRDC deficient mice. Hepatic cell-surface LDLR expression levels were significantly elevated and serum pro-protein convertase subtilisin-kexin type 9 (PCSK9) levels were significantly reduced in mice with hepatic NRDC deficiency. In cultured hepatocytes, NRDC deficiency significantly reduced secreted PCSK9 and increased cell-surface LDLR expression. On the other hand, NRDC overexpression in cultured hepatocytes significantly increased secreted PCSK9 and lowered cell-surface LDLR expression. Thus, NRDC in murine hepatocytes appears to play key roles in cholesterol homeostasis, although the precise molecular mechanisms remain to be determined.

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Metabolic alterations occur in pathogenic infections, but the role of lipid metabolism in the progression of bacterial mastitis is unclear. Cross talk between lipid droplets (LDs) and invading bacteria occurs, and targeting of de novo lipogenesis inhibits pathogen reproduction. In this study, we investigate the role(s) of lipid metabolism in mammary cells during Streptococcus uberis infection. Our results indicate that S. uberis induces the synthesis of fatty acids and production of LDs. Importantly, taurine reduces fatty acid synthesis, the abundance of LDs and the in vitro bacterial load of S. uberis These changes are mediated, at least partly, by the E3 ubiquitin ligase IDOL, which is associated with the degradation of low-density lipoprotein receptors (LDLRs). We have identified a critical role for IDOL-mediated fatty acid synthesis in bacterial infection, and we suggest that taurine may be an effective prophylactic or therapeutic strategy for preventing S. uberis mastitis.

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Inducible degrader of the low-density lipoprotein receptor (IDOL) is an E3 ubiquitin ligase mediating degradation of low-density lipoprotein (LDL) receptor (LDLR). IDOL also controls its own stability through autoubiquitination, primarily at lysine 293. Whether IDOL may undergo other forms of posttranslational modification is unknown. In this study, we show that IDOL can be modified by small ubiquitin-like modifier 1 at the K293 residue at least. The SUMOylation of IDOL counteracts its ubiquitination and augments IDOL protein levels. SUMOylation and the associated increase of IDOL protein are effectively reversed by SUMO-specific peptidase 1 (SENP1) in an activity-dependent manner. We further demonstrate that SENP1 affects LDLR protein levels by modulating IDOL. Overexpression of SENP1 increases LDLR protein levels and enhances LDL uptake in cultured cells. On the contrary, loss of SENP1 lowers LDLR levels in an IDOL-dependent manner and reduces LDL endocytosis. Collectively, our results reveal SUMOylation as a new regulatory posttranslational modification of IDOL and suggest that SENP1 positively regulates the LDLR pathway via deSUMOylation of IDOL and may therefore be exploited for the treatment of cardiovascular disease.

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BACKGROUND AND AIMS: Cholesterol metabolism is tightly regulated by transcriptional and post-transcriptional mechanisms. Accordingly, dysregulation of cholesterol metabolism is a major risk factor for the development of coronary artery disease and associated complications. In recent years, it has become apparent that next to the liver, the intestine plays a key role in systemic cholesterol metabolism by governing cholesterol absorption, secretion, and incorporation into lipoprotein particles. We have previously demonstrated that the Liver X receptor (LXR)-regulated E3 ubiquitin ligase inducible degrader of LDLR (IDOL) is a regulator of cholesterol uptake owing to its ability to promote the ubiquitylation of the low-density lipoprotein receptor (LDLR). However, whether the LXR-IDOL-LDLR axis regulates the LDLR in the intestine and whether this influences intestinal cholesterol homeostasis is not known. METHODS: In this study, we evaluated the role of the LXR-IDOL-LDLR axis in enterocyte cell models and in primary enterocytes isolated from Idol(-/-) and wild type mice. Furthermore, we studied the regulation of intestinal LDLR in Idol(-/-) and in wild type mice treated with the LXR agonist GW3965. Finally, we assessed ezetimibe-induced trans-intestinal cholesterol efflux in Idol(-/-) mice. RESULTS: We show that in a wide range of intestinal cell lines LXR activation decreases LDLR protein abundance, cell surface occupancy, and LDL uptake in an IDOL-dependent manner. Similarly, we find that pharmacological dosing of C57BL6/N mice with the LXR agonist GW3965 increases Idol expression across the intestine with a concomitant reduction in Ldlr protein. Conversely, primary enterocytes isolated from Idol(-/-) mice have elevated Ldlr. To test whether these changes contribute to trans-intestinal cholesterol efflux, we measured fecal cholesterol in mice following ezetimibe dosing, but found no differences between Idol(-/-) and control mice in this setting. CONCLUSIONS: In conclusion, our study establishes that the LXR-IDOL-LDLR axis is active in the intestine and is part of the molecular circuitry that maintains cholesterol homeostasis in enterocytes.

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Hepatic abundance of the low-density lipoprotein receptor (LDLR) is a critical determinant of circulating plasma LDL cholesterol levels and hence development of coronary artery disease. The sterol-responsive E3 ubiquitin ligase inducible degrader of the LDLR (IDOL) specifically promotes ubiquitination and subsequent lysosomal degradation of the LDLR and thus controls cellular LDL uptake. IDOL contains an extended N-terminal FERM (4.1 protein, ezrin, radixin, and moesin) domain, responsible for substrate recognition and plasma membrane association, and a second C-terminal RING domain, responsible for the E3 ligase activity and homodimerization. As IDOL is a putative lipid-lowering drug target, we investigated the molecular details of its substrate recognition. We produced and isolated full-length IDOL protein, which displayed high autoubiquitination activity. However, in vitro ubiquitination of its substrate, the intracellular tail of the LDLR, was low. To investigate the structural basis for this, we determined crystal structures of the extended FERM domain of IDOL and multiple conformations of its F3ab subdomain. These reveal the archetypal F1-F2-F3 trilobed FERM domain structure but show that the F3c subdomain orientation obscures the target-binding site. To substantiate this finding, we analyzed the full-length FERM domain and a series of truncated FERM constructs by small-angle X-ray scattering (SAXS). The scattering data support a compact and globular core FERM domain with a more flexible and extended C-terminal region. This flexibility may explain the low activity in vitro and suggests that IDOL may require activation for recognition of the LDLR.

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MicroRNAs (miRNA) have emerged as important post-transcriptional regulators of metabolic pathways that contribute to cellular and systemic lipoprotein homeostasis. Here, we identify two conserved miRNAs, miR-224, and miR-520d, which target gene networks regulating hepatic expression of the low-density lipoprotein (LDL) receptor (LDLR) and LDL clearance. In silico prediction of miR-224 and miR-520d target gene networks showed that they each repress multiple genes impacting the expression of the LDLR, including the chaperone molecules PCSK9 and IDOL that limit LDLR expression at the cell surface and the rate-limiting enzyme for cholesterol synthesis HMGCR, which is the target of LDL-lowering statin drugs. Using gain- and loss-of-function studies, we tested the role of miR-224 and miR-520d in the regulation of those predicted targets and their impact on LDLR expression. We show that overexpression of miR-224 or miR-520d dose-dependently reduced the activity of PCSK9, IDOL, and HMGCR 3'-untranslated region (3'-UTR)-luciferase reporter constructs and that this repression was abrogated by mutation of the putative miR-224 or miR-520d response elements in the PCSK9, IDOL, and HMGCR 3'-UTRs. Compared to a control miRNA, overexpression of miR-224 or miR-520d in hepatocytes inhibited PCSK9, IDOL, and HMGCR mRNA and protein levels and decreased PCSK9 secretion. Furthermore, miR-224 and miR-520d repression of PCSK9, IDOL, and HMGCR was associated with an increase in LDLR protein levels and cell surface expression, as well as enhanced LDL binding. Notably, the effects of miR-224 and miR-520d were additive to the effects of statins in upregulating LDLR expression. Finally, we show that overexpression of miR-224 in the livers of Ldlr +/- mice using lipid nanoparticle-mediated delivery resulted in a 15% decrease in plasma levels of LDL cholesterol, compared to a control miRNA. Together, these findings identify roles for miR-224 and miR-520d in the posttranscriptional control of LDLR expression and function.

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BACKGROUND AND AIMS: The aim of this study is to determine the lead level in blood, workers expose to lead. METHODS: 42 subjects blood was analyzes for Lead. 21,14,2,5 persons are from fuel station workers, idol painters, application of lead containing pigment to eyes and garage workers respectively. Studied from January 2012 to 2017. Analysis blood by method of inductivity coupled atomic emission spectroscopy. RESULTS: 21 fuel outlet works 11 (45.83%) Lead levels in blood were from 35.4 to 190 (mean 72.77) mcg/dl, remaining 10 lead levels were <10 mcg/dl. Out of 14 idol painters 9 (64.28%) persons blood Lead levels were 10.06 to 18.57 (12.57) mcg/dl, remaining 5 it was <10 mcg/dl. 2 Surma application to eyes their Lead levels were 29.22 and 10.93 respectively. 5 garage workers Lead levels were 13.54 to 46.75 (mean23.52) mcg/dl. CONCLUSION: Occupation exposure to lead containing fuel, paints, surma and garage workers blood levels of lead is significant.