PLK1-ELAVL1/HuR-miR-122 signaling facilitates hepatitis C virus proliferation.

The liver-specific microRNA, miR-122, plays an essential role in the propagation of hepatitis C virus (HCV) by binding directly to the 5'-end of its genomic RNA. Despite its significance for HCV proliferation, the host factors responsible for regulating miR-122 remain largely unknown. In this study, we identified the cellular RNA-binding protein, ELAVL1/HuR (embryonic lethal-abnormal vision-like 1/human antigen R), as critically contributing to miR-122 biogenesis by strong binding to the 3'-end of miR-122. The availability of ELAVL1/HuR was highly correlated with HCV proliferation in replicon, infectious, and chronically infected patient conditions. Furthermore, by screening a kinase inhibitor library, we identified rigosertib, an anticancer agent under clinical trials, as having both miR-122-modulating and anti-HCV activities that were mediated by its ability to target polo-like kinase 1 (PLK1) and subsequently modulate ELAVL1/HuR-miR-122 signaling. The expression of PLK1 was also highly correlated with HCV proliferation and the HCV positivity of HCC patients. ELAVL1/HuR-miR-122 signaling and its mediation of PLK1-dependent HCV proliferation were demonstrated by performing various rescue experiments and utilizing an HCV mutant with low dependency on miR-122. In addition, the HCV-inhibitory effectiveness of rigosertib was validated in various HCV-relevant conditions, including replicons, infected cells, and replicon-harboring mice. Rigosertib was highly effective in inhibiting the proliferation of not only wild-type HCVs, but also sofosbuvir resistance-associated substitution-bearing HCVs. Our study identifies PLK1-ELAVL1/HuR-miR-122 signaling as a regulatory axis that is critical for HCV proliferation, and suggests that a therapeutic approach targeting this host cell signaling pathway could be useful for treating HCV and HCV-associated diseases.

Real-Time Visualizing Nucleation and Growth of Electrodes for Post-Lithium-Ion Batteries.

ConspectusUntil recently, most studies on nucleation and growth mechanisms have employed electrochemical transient measurements, and numerous models have been established on various metal electrode elements. Contrary to the conventional tip-induced nucleation and growth model, a base-induced nucleation and growth mode was discovered not so long ago, which highlighted the importance of direct real-time observations such as visualization. As analysis techniques developed, diverse in situ/operando imaging methods have spurred the fundamental understanding of complex and dynamic battery electrochemistry. Experimental observations of alkali Li and Na metals are limited and difficult because their high reactivity makes not only the fabrication but also the analysis itself challenging. Na metal has high reactivity to electrolytes. Accordingly, it is difficult to visualize the Na deposition in real-time due to gas evolution and resolution limitation. Only a few studies have examined the Na deposition and dissolution reactions in operando. It is generally believed that the Mg anode is free from the dendrite growth of Mg metal, and Mg deposition preferentially occurs along the surface direction. However, whether the Mg anode always follows the dendrite-free growth has currently become a controversial topic and is being discussed and redefined based on real-time imaging analyses. In addition, a variety of morphological evolutions in the metal anodes are required to be systematically distinguished by key parameters. Real-time imaging analysis can directly confirm the solid-liquid-solid multiphase conversion reactions of S and Se cathodes. S and Se elements belong to the same chalcogen group, but their crystal structures and morphological changes significantly differ in each electrode during deposition and dissolution reactions. Therefore, it is necessitated to discuss the nucleation and growth behaviors by examining intrinsic properties of each element in chalcogen cathodes. Considering that a mechanistic understanding of the Se cathode is in its infancy, its nucleation and growth behaviors must be further explored through fundamental studies. In this Account, we aim to discuss the nucleation and growth behaviors of metal (Li, Na, and Mg) anodes and chalcogen (S and Se) cathodes. To elucidate their nucleation and growth mechanisms, we overview the morphological evolutions on the electrode surface and interface by in situ/operando visualizations. Our recent studies covering Li, Na, Mg, S, and Se electrodes verified by operando X-ray imaging are used as critical resources in understanding their nucleation and growth behaviors. Overall, with validation of the complex and dynamic nucleation and growth behaviors of metal and chalcogen electrodes by in situ/operando visualization methods, we hope that this Account can contribute to supporting the fundamental knowledge for the development of high-energy-density metal and chalcogen electrodes.

Comparison of Particulate Steroid Injection vs Nonparticulate Steroid Injection for Lumbar Radicular Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: The objective of this study was to identify the difference on pain intensity and disability between particulate and nonparticulate steroid injections in patients with lumbar radicular pain. Subgroup analysis by study design, type of particulate steroid, and follow-up duration were performed. DATA SOURCES: We performed the literature search in the PubMed, Embase, and Cochrane Library up March, 2023. STUDY SELECTION: Studies, including randomized controlled trials (RCTs) and nonrandomized studies, that compared particulate steroid injection and nonparticulate steroid injection in patients with lumbar radicular pain were independently reviewed by 2 reviewers for eligibility for inclusion. DATA EXTRACTION: Outcomes of interest were pain intensity and disability. Two reviewers independently assessed the quality of included studies using the revised Cochrane Risk of Bias (RoB2.0) tool for RCTs and the Risk of Bias in Nonrandomized Studies of Interventions Tool (ROBINS-I) for nonrandomized studies. Effect sizes were estimated using mean difference (MD) and standardized mean difference (SMD). DATA SYNTHESIS: A total of 10 studies were included in this meta-analysis. The results showed no significant difference in visual analog scale, disability score and the numbers of patients with 50% pain reduction between particulate and nonparticulate steroid injection groups (P>.05). Particulate steroid injections showed significant better effect in pain scale in RCTs (MD=0.62; 95% CI 0.08-1.16, P=.02). In subgroup analysis with steroid types, methylprednisolone showed better effect compared with dexamethasone, while dexamethasone showed better effect compared with betamethasone. CONCLUSIONS: This meta-analysis suggested no significant differences between the particulate and nonparticulate steroid groups in pain or disability score. Therefore, considering the safety profile of nonparticulate steroids, nonparticulate steroid injection may be helpful in patients with lumbar radicular pain.

Near-flat top bandpass filter based on non-local resonance in a dielectric metasurface.

Localized light matter interaction at a resonant nanostructure facilitates spectrally selective transmission of light, which has led to demonstrations of ultrathin metasurface based optical filters. Unfortunately, due to the nature of Lorentzian spectral line shape in such resonances, it is inevitable to suffer significant spectral crosstalk. In this work, we demonstrate a conceptually new type of spectral filter which exhibits near flat-top bandpass with minimized spectral overlaps. To realize this, we leverage the recent development of non-local resonance in dielectric nanostructure to design a double-layered optical filter with performance comparable to the ideal spectral filters. The designed metasurface shows averaged transmission of more than 90% across the target spectral band and suppressed transmission of less than 10% out of the spectral band.

Anti-Inflammatory Effects of Tegoprazan in Lipopolysaccharide-Stimulated Bone-Marrow-Derived Macrophages.

The purpose of this study was to investigate the anti-inflammatory effect of tegoprazan (TEGO) in lipopolysaccharide (LPS)-stimulated bone-marrow-derived macrophages (BMMs). To this end, compared to methylprednisolone (MP; positive control), we evaluated whether TEGO effectively differentiates LPS-stimulated BMMs into M2-phenotype macrophages. Moreover, the expression of pro- and anti-inflammatory cytokines genes influenced by TEGO was measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. TEGO was found to reduce nitric oxide (NO) production in BMMs significantly. In addition, TEGO significantly decreased and increased the gene expression levels of pro-inflammatory and anti-inflammatory cytokines, respectively. In addition, we evaluated the phosphorylated values of the extracellular signal-regulatory kinase (ERK) and p38 in the mitogen-activated protein (MAP) kinase signaling pathway through Western blotting. TEGO significantly reduced the phosphorylated values of the ERK and p38. In other words, TEGO suppressed the various pro-inflammatory responses in LPS-induced BMMs. These results show that TEGO has the potential to be used as an anti-inflammatory agent.

HBV-Induced Increased N6 Methyladenosine Modification of PTEN RNA Affects Innate Immunity and Contributes to HCC.

BACKGROUND AND AIMS: Epitranscriptomic modification of RNA has emerged as the most prevalent form of regulation of gene expression that affects development, differentiation, metabolism, viral infections, and most notably cancer. We have previously shown that hepatitis B virus (HBV) transcripts are modified by N6 methyladenosine (m6 A) addition. HBV also affects m6 A modification of several host RNAs, including phosphatase and tensin homolog (PTEN), a well-known tumor suppressor. PTEN plays a critical role in antiviral innate immunity and the development of hepatocellular carcinoma (HCC). Reports have shown that PTEN controlled interferon regulatory factor 3 (IRF-3) nuclear localization by negative phosphorylation of IRF-3 at Ser97, and PTEN reduced carcinogenesis by inhibiting the phosphatidylinositol-3-kinase (PI3K)/AKT pathway. APPROACH AND RESULTS: Here, we show that HBV significantly increases the m6 A modification of PTEN RNA, which contributes to its instability with a corresponding decrease in PTEN protein levels. This is reversed in cells in which the expression of m6 A methyltransferases is silenced. PTEN expression directly increases activated IRF-3 nuclear import and subsequent interferon synthesis. In the absence of PTEN, IRF-3 dephosphorylation at the Ser97 site is decreased and interferon synthesis is crippled. In chronic HBV patient biopsy samples, m6 A-modified PTEN mRNA levels were uniformly up-regulated with a concomitant decrease of PTEN mRNA levels. HBV gene expression also activated the PI3K/AKT pathway by regulating PTEN mRNA stability in HCC cell lines. CONCLUSIONS: The m6 A epitranscriptomic regulation of PTEN by HBV affects innate immunity by inhibiting IRF-3 nuclear import and the development of HCC by activating the PI3K/AKT pathway. Our studies collectively provide new insights into the mechanisms of HBV-directed immune evasion and HBV-associated hepatocarcinogenesis through m6 A modification of the host PTEN mRNAs.

Current Updates on COVID-19 Vaccines and Therapeutics: As of June 2022.

Since COVID-19, caused by SARS-CoV-2 infection, has become a global issue, many vaccines and therapeutic candidates have been developed or are being developed against the COVID-19 endemic and the next wave. However, it is difficult to overcome the spread and mutation rate of SARS-CoV-2 in the COVID-19 pandemic because development of vaccines and therapeutics involves considerable social cost and time, as well as research capabilities. Thus, assessing the development status of these agents is important for advancing efficient research strategies. In this review, we summarize the status of 141 vaccines and 345 therapeutic candidates under development worldwide, according to their development stage and characteristics. As of June 2022, 32 vaccines and 12 therapeutics have been approved for emergency use. Although the development of four of these therapeutics was terminated owing to their low efficacy against various variants of SARS-CoV-2, many new candidates that have completed phase 3 clinical trials have been awaiting phase 4 clinical trials or full approval by the Food and Drug Administration (FDA). These efforts are expected to contribute to establishing an efficient research strategy to overcome the COVID-19 pandemic and facilitate its transition toward an endemic phase. Electronic Supplementary Material ESM: The online version of this article (doi: 10.1007/s12257-022-0188-4) contains supplementary material, which is available to authorized users.

Arrayed CRISPR screen with image-based assay reliably uncovers host genes required for coxsackievirus infection.

Pooled CRISPR screens based on lentiviral systems have been widely applied to identify the effect of gene knockout on cellular phenotype. Although many screens were successful, they also have the limitation that genes conferring mild phenotypes or those essential for growth can be overlooked, as every genetic perturbation is incorporated in the same population. Arrayed screens, on the other hand, incorporate a single genetic perturbation in each well and could overcome these limitations. However, arrayed screens based on siRNA-mediated knockdown were recently criticized for low reproducibility caused by incomplete inhibition of gene expression. To overcome these limitations, we developed a novel arrayed CRISPR screen based on a plasmid library expressing a single guide RNA (sgRNA) and disrupted 1514 genes, encoding kinases, proteins related to endocytosis, and Golgi-localized proteins, individually using 4542 sgRNAs (three sgRNAs per gene). This screen revealed host factors required for infection by coxsackievirus B3 (CVB3) from Picornaviridae, which includes human pathogens causing diverse diseases. Many host factors that had been overlooked in a conventional pooled screen were identified for CVB3 infection, including entry-related factors, translational initiation factors, and several replication factors with different functions, demonstrating the advantage of the arrayed screen. This screen was quite reliable and reproducible, as most genes identified in the primary screen were confirmed in secondary screens. Moreover, ACBD3, whose phenotype was not affected by siRNA-mediated knockdown, was reliably identified. We propose that arrayed CRISPR screens based on sgRNA plasmid libraries are powerful tools for arrayed genetic screening and applicable to larger-scale screens.

Direct Injection of Hydrogels Embedding Gold Nanoparticles for Local Therapy after Spinal Cord Injury.

In this study, we created a hydrogel composed of glycol chitosan (gC) and oxidized hyaluronate (oHA). Gold nanoparticles (GNPs) were conjugated with ursodeoxycholic acid (UDCA). The GNP-UDCA complex was embedded into gC-oHA (CHA) hydrogels to form a CHA-GNP-UDCA gel. This CHA-GNP-UDCA gel was injected once into an epicenter of an injured region in SCI rats. Near-infrared (NIR) irradiation was then applied to the lesion as a means of local therapy. To optimize the viscosity for injection into a lesion, several volume ratios of gC and oHA were investigated using scanning electron microscopy and a rotating rheometer. The optimally synthesized CHA-GNP-UDCA gel under NIR irradiation suppressed the production of inflammatory cytokines in vitro. In addition, the optimized CHA-GNP-UDCA gel under NIR irradiation inhibited the cystic cavity of the lesion and significantly improved the hindlimb function. The production of inflammatory cytokines following SCI was significantly inhibited in the CHA-GNP-UDCA gel + NIR group. CHA-GNP-UDCA gels with NIR irradiation can therefore have therapeutic effects for those with spinal cord injuries.

Enhanced interfacial reaction of silicon carbide fillers onto the metal substrate in carbon nanotube paste for reliable field electron emitters.

Adhesion of carbon nanotube (CNT) onto a cathode substrate is very crucial for field electron emitters that are operating under high electric fields. As a supporting precursor of CNT field emitters, we adopted silicon carbide (SiC) nano-particle fillers with Ni particles and then enhanced interfacial reactions onto Kovar-alloy substrates through the optimized wet pulverization process of SiC aggregates for reliable field electron emitters. As-purchased SiC aggregates were efficiently pulverized from 20 to less than 1 micro-meter in a median value (D50). CNT pastes for field emitters were distinctively formulated by a mixing process of the pulverized SiC aggregates and pre-dispersed CNTs. X-ray photoelectron spectroscopy studies showed that the optimally pulverized SiC-CNT paste-emitter had a stronger Si 2p3/2 signal in the Ni2Si phase than the as-purchased one. The Si 2p3/2 signal would represent interfacial reaction of the SiC nano-particle onto Ni from the CNT paste and the Kovar substrate, forming the supporting layer for CNT emitters. The optimal paste-emitter even in a vacuum-sealed tube exhibited a highly reliable field emission current with a high current density of 100 mA cm-2 for over 50 h along with good reproducibility. The enhanced interfacial reaction of SiC filler onto the metal substrates could lead to highly reliable field electron emitters for vacuum electronic devices.

N6-methyladenosine modification of hepatitis B virus RNA differentially regulates the viral life cycle.

N6-methyladenosine (m6A) RNA methylation is the most abundant epitranscriptomic modification of eukaryotic messenger RNAs (mRNAs). Previous reports have found m6A on both cellular and viral transcripts and defined its role in regulating numerous biological processes, including viral infection. Here, we show that m6A and its associated machinery regulate the life cycle of hepatitis B virus (HBV). HBV is a DNA virus that completes its life cycle via an RNA intermediate, termed pregenomic RNA (pgRNA). Silencing of enzymes that catalyze the addition of m6A to RNA resulted in increased HBV protein expression, but overall reduced reverse transcription of the pgRNA. We mapped the m6A site in the HBV RNA and found that a conserved m6A consensus motif situated within the epsilon stem loop structure, is the site for m6A modification. The epsilon stem loop is located in the 3' terminus of all HBV mRNAs and at both the 5' and 3' termini of the pgRNA. Mutational analysis of the identified m6A site in the 5' epsilon stem loop of pgRNA revealed that m6A at this site is required for efficient reverse transcription of pgRNA, while m6A methylation of the 3' epsilon stem loop results in destabilization of all HBV transcripts, suggesting that m6A has dual regulatory function for HBV RNA. Overall, this study reveals molecular insights into how m6A regulates HBV gene expression and reverse transcription, leading to an increased level of understanding of the HBV life cycle.

Virus-based SELEX (viro-SELEX) allows development of aptamers targeting knotty proteins.

It has been 100 years since the worst flu (Spanish flu) mankind has ever experienced. Rapid, accurate diagnosis and subtyping of flu are still an urgent unmet medical need. By using surrogate virus-based SELEX (viro-SELEX), we report here multiple advances incorporated into the field of flu diagnostics: (i) aptamers that can bind to the native virus well even though they cannot bind strongly to a recombinant protein (hemagglutinin); (ii) a couple of aptamers that can target a broad range of strains belonging to the H1N1 subtype and detect only the H1N1 subtype and nothing else; (iii) a highly sensitive lateral flow assay system (limit of detection is 0.08 HAU) using fluorescence-tagged aptamers. The viro-SELEX method of aptamer selection in conjunction with a fluorescent tag on aptamers is a very useful approach to develop highly sensitive, specific, portable, rapid, and quantitative point-of-care testing diagnostic tools for the future.

Double layers of gold nanoparticles immobilized titanium implants improve the osseointegration in rabbit models.

Osseointegration is important in osteopenia and osteoporosis patients due to their low bone densities. Gold nanoparticles (GNPs) are greatly beneficial materials as osteogenic agents. The aim of this study is to investigate osseointegration between bones and double layers of GNP-immobilized titanium (Ti) implants. The physicochemical properties of the Ti surface were evaluated by scanning electron microscopy, by atomic force microscopy, by means of the contact angle using water drops, and by x-ray photoelectron spectroscopy. Osteogenic differentiation of human bone-marrow-derived mesenchymal stem cells was analyzed and showed the higher values in double layers of GNP (GNP2) groups. In addition, we performed an in vivo study using hydroxyapatite (HA) and GNP2 spine pedicle screws in ovariectomized (OVX) and SHAM rabbits. Osseointegration parameters also showed higher values in GNP2 than in HA groups. These findings suggest that implants with double layers of GNPs can be a useful alternative in osteoporotic patients.

The impact of smoking cessation attempts on stress levels.

BACKGROUND: Cigarette smoking is a major health risk, particularly in male South Koreans. Smoking cessation can benefit health; however, the process of quitting smoking is difficult to some smokers and shows its relationship to their stress level. The hypothesis of this study is that who has failed attempts to stop smoking induce more stress than habitual smoking. METHODS: To test this, the analysis on the association between smoking cessation attempts and stress levels in smokers was performed. The Korean Community Health Survey (2011-2016) data with the total of 488,417 participants' data were used for this study. Survey data were analyzed using the chi-square test and logistic regression. As the dependent variable, self-reported level of stress was selected. RESULTS: Of the subject population, 78.3% (63.3% males, 81.4% females) felt stressed. Among participants who successfully stopped smoking, 73.0% (72.6% males, 78.1% females) reported feeling stressed. In contrast, of those who failed to stop smoking, 83.3% (83.6% males, 86.3% females) reported high stress levels. Among those who did not attempt smoking cessation, 81.1% (81.2% males, 80.3% females) responded that they experienced stress. Those who failed to stop smoking had higher odds of stress than those who did not attempt smoking cessation [odds ratio (OR) 1.11, 95% confidence interval (CI) 1.09-1.14, p < 0.001]. Those who successfully stopped smoking had lower odds of stress than those who did not attempt smoking cessation (OR 0.87, 95% CI 0.86-0.89, p < 0.001). CONCLUSION: The study found an association between unsuccessful smoking cessation and stress level. As the result, people who failed smoking cessation showed higher stress. These data should be considered in health policy recommendations for smokers.

Hepatitis B Virus-Induced Parkin-Dependent Recruitment of Linear Ubiquitin Assembly Complex (LUBAC) to Mitochondria and Attenuation of Innate Immunity.

Hepatitis B virus (HBV) suppresses innate immune signaling to establish persistent infection. Although HBV is a DNA virus, its pre-genomic RNA (pgRNA) can be sensed by RIG-I and activates MAVS to mediate interferon (IFN) λ synthesis. Despite of the activation of RIG-I-MAVS axis by pgRNA, the underlying mechanism explaining how HBV infection fails to induce interferon-αß (IFN) synthesis remained uncharacterized. We demonstrate that HBV induced parkin is able to recruit the linear ubiquitin assembly complex (LUBAC) to mitochondria and abrogates IFN ß synthesis. Parkin interacts with MAVS, accumulates unanchored linear polyubiquitin chains on MAVS via LUBAC, to disrupt MAVS signalosome and attenuate IRF3 activation. This study highlights the novel role of parkin in antiviral signaling which involves LUBAC being recruited to the mitochondria. These results provide avenues of investigations on the role of mitochondrial dynamics in innate immunity.

Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation.

Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct-acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their use in treating patients with chronic hepatitis C in interferon-sparing regimens occasionally produces undesirable side effects such as fatigue, migraine, and other conditions, which may be linked to mitochondrial dysfunction. Here, we show that clinically prescribed DAAs, including sofosbuvir, affect mitochondrial dynamics. To counter these adverse effects, we examined HCV-induced and DAA-induced aberrant mitochondrial dynamics modulated by ginsenoside, which is known to support healthy mitochondrial physiology and the innate immune system. We screened several ginsenoside compounds showing antiviral activity using a robust HCV cell culture system. We investigated the role of ginsenosides in antiviral efficacy, alteration of mitochondrial transmembrane potential, abnormal mitochondrial fission, its upstream signaling, and mitophagic process caused by HCV infection or DAA treatment. Only one of the compounds, ginsenoside Rg3 (G-Rg3), exhibited notable and promising anti-HCV potential. Treatment of HCV-infected cells with G-Rg3 increased HCV core protein-mediated reduction in the expression level of cytosolic p21, required for increasing cyclin-dependent kinase 1 activity, which catalyzes Ser616 phosphorylation of dynamin-related protein 1. The HCV-induced mitophagy, which follows mitochondrial fission, was also rescued by G-Rg3 treatment. CONCLUSION: G-Rg3 inhibits HCV propagation. Its antiviral mechanism involves restoring the HCV-induced dynamin-related protein 1-mediated aberrant mitochondrial fission process, thereby resulting in suppression of persistent HCV infection. (Hepatology 2017;66:758-771).

Association of self-reported sedentary time with insulin resistance among Korean adults without diabetes mellitus: a cross-sectional study.

BACKGROUND: A more sedentary lifestyle can result in insulin resistance. However, few research studies have assessed the association between insulin resistance and sedentary lifestyle in Asian populations. Therefore, this study aimed to investigate the association of sedentary time with insulin resistance. In addition, we also investigate the moderate effect of employment status, moderate-to-vigorous physical activity (MVPA), and body mass index (BMI) in this association. METHODS: Data from 2573 individuals who participated in the 2015 Korean National Health and Nutrition Examination Survey were analyzed. Sedentary time was measured using self-administered questionnaires, and IR data were estimated using the homeostasis model assessment-insulin resistance index (HOMA-IR). Adjusted odds ratio (OR) and 95% confidence intervals (CIs) from a multivariable logistic regression model were generated for all participants. Subgroup analysis was only performed between sedentary time and HOMA-IR stratified by employment status, because moderate effects were not significant in the tests for interaction for MVPA and BMI. For all analyses, the individuals were categorized as having high or normal HOMA-IR values (> 1.6 and ≤ 1.6, respectively). RESULTS: A HOMA-IR > 1.6 was observed in 40.3% of the sedentary time Q1 (low) group (< 5.0 h/day), 41.4% of the sedentary time Q2 (middle-low) group, 44.2% of the sedentary time Q3 (middle-high) group, and 48.4% of the sedentary time Q4 (high) group (≥10.0 h/day). When the low level sedentary time group was used as the reference group, the high level sedentary time group was significantly associated with high IR value (HOMA-IR > 1.6) (OR = 1.40, 95% CI: 1.060-1.838). However, this association was not significant across the other sedentary time groups. Moreover, participants reporting a high sedentary time and were employed had 1.67 times the odds of having a high IR value (HOMA-IR > 1.6) compared to those who reported having a low sedentary time and were employed (OR = 1.67, 95% CI: 1.184-2.344). In the unemployed participants, sedentary time was not associated with IR. CONCLUSIONS: High sedentary time (≥10.0 h/day) was associated with elevated HOMA-IR among Korean adults without diabetes mellitus. Furthermore, the association between high sedentary time and HOMA-IR values was more pronounced in the employed population.

Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence.

Mitochondrial dynamics is crucial for the regulation of cell homeostasis. Our recent findings suggest that hepatitis C virus (HCV) promotes Parkin-mediated elimination of damaged mitochondria (mitophagy). Here we show that HCV perturbs mitochondrial dynamics by promoting mitochondrial fission followed by mitophagy, which attenuates HCV-induced apoptosis. HCV infection stimulated expression of dynamin-related protein 1 (Drp1) and its mitochondrial receptor, mitochondrial fission factor. HCV further induced the phosphorylation of Drp1 (Ser616) and caused its subsequent translocation to the mitochondria, followed by mitophagy. Interference of HCV-induced mitochondrial fission and mitophagy by Drp1 silencing suppressed HCV secretion, with a concomitant decrease in cellular glycolysis and ATP levels, as well as enhanced innate immune signaling. More importantly, silencing Drp1 or Parkin caused significant increase in apoptotic signaling, evidenced by increased cytochrome C release from mitochondria, caspase 3 activity, and cleavage of poly(ADP-ribose) polymerase. These results suggest that HCV-induced mitochondrial fission and mitophagy serve to attenuate apoptosis and may contribute to persistent HCV infection.

Mitochondrial dynamics and viral infections: A close nexus.

Viruses manipulate cellular machinery and functions to subvert intracellular environment conducive for viral proliferation. They strategically alter functions of the multitasking mitochondria to influence energy production, metabolism, survival, and immune signaling. Mitochondria either occur as heterogeneous population of individual organelles or large interconnected tubular network. The mitochondrial network is highly susceptible to physiological and environmental insults, including viral infections, and is dynamically maintained by mitochondrial fission and fusion. Mitochondrial dynamics in tandem with mitochondria-selective autophagy 'mitophagy' coordinates mitochondrial quality control and homeostasis. Mitochondrial dynamics impacts cellular homeostasis, metabolism, and innate-immune signaling, and thus can be major determinant of the outcome of viral infections. Herein, we review how mitochondrial dynamics is affected during viral infections and how this complex interplay benefits the viral infectious process and associated diseases.

A soft biomolecule actuator based on a highly functionalized bacterial cellulose nano-fiber network with carboxylic acid groups.

Upcoming human-related applications such as soft wearable electronics, flexible haptic systems, and active bio-medical devices will require bio-friendly actuating materials. Here, we report a soft biomolecule actuator based on carboxylated bacterial cellulose (CBC), ionic liquid (IL), and poly (3,4-ethylenedioxythiophene)-poly(styrenesulfonate) ( PEDOT: PSS) electrodes. Soft and biocompatible polymer-IL composites were prepared via doping of CBC with ILs. The highly conductive PEDOT: PSS layers were deposited on both sides of the CBC-IL membranes by a dip-coating technique to yield a sandwiched actuator system. Ionic conductivity and ionic exchange capacity of the CBC membrane can be increased up to 22.8 times and 1.5 times compared with pristine bacterial cellulose (BC), respectively, resulting in 8 times large bending deformation than the pure BC actuators with metallic electrodes in an open air environment. The developed CBC-IL actuators show significant progress in the development of biocompatible and soft actuating materials with quick response, low operating voltage and comparatively large bending deformation.