Versatile computer-aided design of free-form DNA nanostructures and assemblies.

Recent advances in structural DNA nanotechnology have been facilitated by design tools that continue to push the limits of structural complexity while simplifying an often-tedious design process. We recently introduced the software MagicDNA, which enables design of complex 3D DNA assemblies with many components; however, the design of structures with free-form features like vertices or curvature still required iterative design guided by simulation feedback and user intuition. Here, we present an updated design tool, MagicDNA 2.0, that automates the design of free-form 3D geometries, leveraging design models informed by coarse-grained molecular dynamics simulations. Our GUI-based, stepwise design approach integrates a high level of automation with versatile control over assembly and subcomponent design parameters. We experimentally validated this approach by fabricating a range of DNA origami assemblies with complex free-form geometries, including a 3D Nozzle, G-clef, and Hilbert and Trifolium curves, confirming excellent agreement between design input, simulation, and structure formation.

Thermally reversible pattern formation in arrays of molecular rotors.

Control over the mesoscale to microscale patterning of materials is of great interest to the soft matter community. Inspired by DNA origami rotors, we introduce a 2D nearest-neighbor lattice of spinning rotors that exhibit discrete orientational states and interactions with their neighbors. Monte Carlo simulations of rotor lattices reveal that they exhibit a variety of interesting ordering behaviors and morphologies that can be modulated through rotor design parameters. The rotor arrays exhibit diverse patterns including closed loops, radiating loops, and bricklayer structures in their ordered states. They exhibit specific heat peaks at very low temperatures for small system sizes, and some systems exhibit multiple order-disorder transitions depending on inter-rotor interaction design. We devise an energy-based order parameter and show via umbrella sampling and histogram reweighting that this order parameter captures well the order-disorder transitions occurring in these systems. We fabricate real DNA origami rotors which themselves can order via programmable DNA base-pairing interactions and demonstrate both ordered and disordered phases, illustrating how rotor lattices may be realized experimentally and used for responsive organization. This work establishes the feasibility of realizing structural nanomaterials that exhibit locally mediated microscale patterns which could have applications in sensing and precision surface patterning.

Steric Communication between Dynamic Components on DNA Nanodevices.

Biomolecular nanotechnology has helped emulate basic robotic capabilities such as defined motion, sensing, and actuation in synthetic nanoscale systems. DNA origami is an attractive approach for nanorobotics, as it enables creation of devices with complex geometry, programmed motion, rapid actuation, force application, and various kinds of sensing modalities. Advanced robotic functions like feedback control, autonomy, or programmed routines also require the ability to transmit signals among subcomponents. Prior work in DNA nanotechnology has established approaches for signal transmission, for example through diffusing strands or structurally coupled motions. However, soluble communication is often slow and structural coupling of motions can limit the function of individual components, for example to respond to the environment. Here, we introduce an approach inspired by protein allostery to transmit signals between two distal dynamic components through steric interactions. These components undergo separate thermal fluctuations where certain conformations of one arm will sterically occlude conformations of the distal arm. We implement this approach in a DNA origami device consisting of two stiff arms each connected to a base platform via a flexible hinge joint. We demonstrate the ability for one arm to sterically regulate both the range of motion and the conformational state (latched or freely fluctuating) of the distal arm, results that are quantitatively captured by mesoscopic simulations using experimentally informed energy landscapes for hinge-angle fluctuations. We further demonstrate the ability to modulate signal transmission by mechanically tuning the range of thermal fluctuations and controlling the conformational states of the arms. Our results establish a communication mechanism well-suited to transmit signals between thermally fluctuating dynamic components and provide a path to transmitting signals where the input is a dynamic response to parameters like force or solution conditions.

DNA origami tubes with reconfigurable cross-sections.

Structural DNA nanotechnology has enabled the design and construction of complex nanoscale structures with precise geometry and programmable dynamic and mechanical properties. Recent efforts have led to major advances in the capacity to actuate shape changes of DNA origami devices and incorporate DNA origami into larger assemblies, which open the prospect of using DNA to design shape-morphing assemblies as components of micro-scale reconfigurable or sensing materials. Indeed, a few studies have constructed higher order assemblies with reconfigurable devices; however, these demonstrations have utilized structures with relatively simple motion, primarily hinges that open and close. To advance the shape changing capabilities of DNA origami assemblies, we developed a multi-component DNA origami 6-bar mechanism that can be reconfigured into various shapes and can be incorporated into larger assemblies while maintaining capabilities for a variety of shape transformations. We demonstrate the folding of the 6-bar mechanism into four different shapes and demonstrate multiple transitions between these shapes. We also studied the shape preferences of the 6-bar mechanism in competitive folding reactions to gain insight into the relative free energies of the shapes. Furthermore, we polymerized the 6-bar mechanism into tubes with various cross-sections, defined by the shape of the individual mechanism, and we demonstrate the ability to change the shape of the tube cross-section. This expansion of current single-device reconfiguration to higher order scales provides a foundation for nano to micron scale DNA nanotechnology applications such as biosensing or materials with tunable properties.

ASSESSMENT OF DOSES FROM INGESTION OF RADIONUCLIDES 40 K, 137CS, 226RA AND 232TH IN EDIBLE COMMERCIAL MUSHROOMS FROM TAIWAN.

This study analyzed activity concentration and annual effective dose of radionuclides 40K, 137Cs, 226Ra and 232Th of 44 mushrooms collected from local markets in Taiwan. The 40K activity concentrations were 1570 ± 150 Bq/kg-dw (Agaricus bisporus) > 1084 ± 183 Bq/kg-dw (Flammulina velutipe) > 736 ± 150 Bq/kg-dw (Lentinula edodes). The activity concentrations of 226Ra were 5.04 ± 2.43, 4.00 ± 2.40 and 3.43 ± 2.69 Bq/kg-dw, and 232Th were 3.96 ± 2.18, 3.86 ± 1.43 and 2.90 ± 1.99 Bq/kg-dw for F. velutipe, L. edodes and A. bisporus, respectively. In seven of the 44 samples, 137Cs activity concentrations were detected, and the samples had an average of 1.55 ± 1.75 Bq/kg-dw. The total annual effective dose ranged from 0.90 to 3.50 µSv/y, with an average of 1.94 ± 0.62 µSv/y at an ingestion rate of 0.235 kg-dw/y.

Soil to tobacco component transfer factors for natural radionuclides 40K, 226Ra, and 232Th and the risk assessment of tobacco leaf in smoking.

This study determined the activity concentrations and corresponding transfer factors (TF) of 40K, 226Ra, and 232Th in three tobacco components (root, stem, and leaf). The radiation hazard index parameters were assessed for the tobacco leaf. The activity concentrations in the soil were 589-762, 32-43, and 49-59 Bq kg-dw-1 (dry weight) for 40K, 226Ra, and 232Th, respectively. The average activity concentrations of 40K, 226Ra, and 232Th were 447, 5.41 and 5.69 Bq/kg-dw for the root, 670, 9.64 and 7.61 Bq kg-dw-1 for the stem, and 793, 6.79 and 6.15 Bq kg-dw-1 for the leaf, respectively. The TF values were 0.42-1.42, 0.10-0.49 and 0.06-0.23 for 40K, 226Ra, and 232Th, respectively. The stem and leaf 40K TF values were significantly higher than the root values. The stem 226Ra TF values were significantly higher than the root values. The 226Ra and 232Th activity concentrations and TFs of tobacco components had a significant positive correlation. Based on the activity concentrations of the tobacco leaves, the annual inhalation effective dose to the lungs for an adult smoker was 0.32-0.81 mSv y-1 (average 0.60 mSv y-1). The Excess Lifetime Cancer Risk (ELCR) caused by smoking was an average of 2.39 × 10-3.

Activity concentrations and bioconcentration factors (BCFs) of natural radionuclides (40 K, 226Ra, and 232Th) from cultivated substrates to mushrooms.

This study examined 42 mushroom samples and corresponding cultivated substrates. The radionuclide activity concentrations and bioconcentration factor (BCF) from substrate-to-mushroom were determined. The substrate activity concentrations were 59.1-727.5, 4.5-37.6, and 4.0-53.0 Bq/kg dw (dry weight) for 40 K, 226Ra, and 232Th, respectively. The average 40 K concentrations were 1546.5, 1115.7, and 749.3 Bq/kg dw; the BCFs were 2.49, 3.56, and 5.58 for A. bisporus, F. velutipes, and L. edodes, respectively. The 40 K concentrations were insignificantly correlated with each species' corresponding substrate concentration. The 40 K BCFs had a significantly negative correlation with the substrate concentration for each species. Each mushroom species' 40 K concentration was almost stable, suggesting that 40 K has a regulated homeostasis for a given species. The average 226Ra concentrations were 5.5, 5.4, and 3.4 Bq/kg dw; the BCFs were 0.58, 0.17, and 0.50 for L. edodes, A. bisporus, and F. velutipes, respectively. The average 232Th concentrations were 4.7, 4.7, and 3.0 Bq/kg dw; the BCFs were 0.50, 0.11, and 0.53 for L. edodes, A. bisporus, and F. velutipes, respectively. The 226Ra and 232Th concentrations in mushrooms had a weak to moderate correlation with the cultivated substrate concentrations. The absorption of the 226Ra and 232Th from substrate-to-mushroom was similar to the hypothesis of the linear model that mushroom concentration yields a positive correlation with substrate concentration.

Biomechanical analysis of subcondylar fracture fixation using miniplates at different positions and of different lengths.

BACKGROUND: Many types of titanium plates were used to treat subcondylar fracture clinically. However, the efficacy of fixation in different implant positions and lengths of the bone plate has not been thoroughly investigated. Therefore, the primary purpose of this study was to use finite element analysis (FEA) to analyze the biomechanical effects of subcondylar fracture fixation with miniplates at different positions and lengths so that clinicians were able to find a better strategy of fixation to improve the efficacy and outcome of treatment. METHODS: The CAD software was used to combine the mandible, miniplate, and screw to create seven different FEA computer models. These models with subcondylar fracture were fixed with miniplates at different positions and of different lengths. The right unilateral molar clench occlusal mode was applied. The observational indicators were the reaction force at the temporomandibular joint, von Mises stress of the mandibular bone, miniplate and screw, and the sliding distance on the oblique surface of the fracture site at the mandibular condyle. RESULTS: The results showed the efficacy of fixation was better when two miniplates were used comparing to only one miniplates. Moreover, using longer miniplates for fixation had better results than the short one. Furthermore, fixing miniplates at the posterior portion of subcondylar region would have a better fixation efficacy and less sliding distance (5.46-5.76 µm) than fixing at the anterolateral surface of subcondylar region (6.10-7.00 µm). CONCLUSION: Miniplate fixation, which was placed closer to the posterior margin, could effectively reduce the amount of sliding distance in the fracture site, thereby achieving greater stability. Furthermore, fixation efficiency was improved when an additional miniplate was placed at the anterior margin. Our study suggested that the placement of miniplates at the posterior surface and the additional plate could effectively improve stability.

Programmable Site-Specific Functionalization of DNA Origami with Polynucleotide Brushes.

Combining surface-initiated, TdT (terminal deoxynucleotidyl transferase) catalyzed enzymatic polymerization (SI-TcEP) with precisely engineered DNA origami nanostructures (DONs) presents an innovative pathway for the generation of stable, polynucleotide brush-functionalized DNA nanostructures. We demonstrate that SI-TcEP can site-specifically pattern DONs with brushes containing both natural and non-natural nucleotides. The brush functionalization can be precisely controlled in terms of the location of initiation sites on the origami core and the brush height and composition. Coarse-grained simulations predict the conformation of the brush-functionalized DONs that agree well with the experimentally observed morphologies. We find that polynucleotide brush-functionalization increases the nuclease resistance of DONs significantly, and that this stability can be spatially programmed through the site-specific growth of polynucleotide brushes. The ability to site-specifically decorate DONs with brushes of natural and non-natural nucleotides provides access to a large range of functionalized DON architectures that would allow for further supramolecular assembly, and for potential applications in smart nanoscale delivery systems.

Integrated computer-aided engineering and design for DNA assemblies.

Recently, DNA has been used to make nanodevices for a myriad of applications across fields including medicine, nanomanufacturing, synthetic biology, biosensing and biophysics. However, current DNA nanodevices rely primarily on geometric design, and it remains challenging to rationally design functional properties such as force-response or actuation behaviour. Here we report an iterative design pipeline for DNA assemblies that integrates computer-aided engineering based on coarse-grained molecular dynamics with a versatile computer-aided design approach that combines top-down automation with bottom-up control over geometry. This intuitive framework allows for rapid construction of large, multicomponent assemblies from three-dimensional models with finer control over the geometrical, mechanical and dynamical properties of the DNA structures in an automated manner. This approach expands the scope of structural complexity and enhances mechanical and dynamic design of DNA assemblies.

Programmable Transformations of DNA Origami Made of Small Modular Dynamic Units.

Dynamic DNA origami has been employed for generating a rich repository of molecular nanomachines that are capable of sensing various cues and changing their conformations accordingly. The common design principle of the existing DNA origami nanomachines is that each dynamic DNA origami is programmed to transform in a specific manner, and the nanomachine needs to be redesigned to achieve a different form of transformation. However, it remains challenging to enable a multitude of controlled transformations in a single design of dynamic DNA nanomachine. Here we report a modular design method to programmatically tune the shapes of a DNA origami nanomachine. The DNA origami consists of small, modular DNA units, and the length of each unit can be selectively changed by toehold-mediated strand displacement. By use of different combinations of trigger DNA strands, modular DNA units can be selectively transformed, leading to the programmable reconfiguration of the overall dimensions and curvatures of DNA origami. The modular design of programmable shape transformation of DNA origami can find potential applications in more sophisticated molecular nanorobots and smart drug delivery nanocarriers.

An electrochemical biosensor exploiting binding-induced changes in electron transfer of electrode-attached DNA origami to detect hundred nanometer-scale targets.

The specific detection in clinical samples of analytes with dimensions in the tens to hundreds of nanometers, such as viruses and large proteins, would improve disease diagnosis. Detection of these "mesoscale" analytes (as opposed to their nanoscale components), however, is challenging as it requires the simultaneous binding of multiple recognition sites often spaced over tens of nanometers. In response, we have adapted DNA origami, with its unparalleled customizability to precisely display multiple target-binding sites over the relevant length scale, to an electrochemical biosensor platform. Our proof-of-concept employs triangular origami covalently attached to a gold electrode and functionalized with redox reporters. Electrochemical interrogation of this platform successfully monitors mesoscale, target-binding-induced changes in electron transfer in a manner consistent with coarse-grained molecular dynamics simulations. Our approach enables the specific detection of analytes displaying recognition sites that are separated by ∼40 nm, a spacing significantly greater than that achieved in similar sensor architectures employing either antibodies or aptamers.

Uncertainty quantification of a DNA origami mechanism using a coarse-grained model and kinematic variance analysis.

Significant advances have been made towards the design, fabrication, and actuation of dynamic DNA nanorobots including the development of DNA origami mechanisms. These DNA origami mechanisms integrate relatively stiff links made of bundles of double-stranded DNA and relatively flexible joints made of single-stranded DNA to mimic the design of macroscopic machines and robots. Despite reproducing the complex configurations of macroscopic machines, these DNA origami mechanisms exhibit significant deviations from their intended motion behavior since nanoscale mechanisms are subject to significant thermal fluctuations that lead to variations in the geometry of the underlying DNA origami components. Understanding these fluctuations is critical to assess and improve the performance of DNA origami mechanisms and to enable precise nanoscale robotic functions. Here, we report a hybrid computational framework combining coarse-grained modeling with kinematic variance analysis to predict uncertainties in the motion pathway of a multi-component DNA origami mechanism. Coarse-grained modeling was used to evaluate the variation in geometry of individual components due to thermal fluctuations. This variation was incorporated in kinematic analyses to predict the motion pathway uncertainty of the entire mechanism, which agreed well with experimental characterization of motion. We further demonstrated the ability to predict the probability density of DNA origami mechanism conformations based on analysis of mechanical properties of individual joints. This integration of computational analysis, modeling tools, and experimental methods establish the foundation to predict and manage motion uncertainties of general DNA origami mechanisms to guide the design of DNA-based nanoscale machines and robots.

Paper Origami-Inspired Design and Actuation of DNA Nanomachines with Complex Motions.

Significant progress in DNA nanotechnology has accelerated the development of molecular machines with functions like macroscale machines. However, the mobility of DNA self-assembled nanorobots is still dramatically limited due to challenges with designing and controlling nanoscale systems with many degrees of freedom. Here, an origami-inspired method to design transformable DNA nanomachines is presented. This approach integrates stiff panels formed by bundles of double-stranded DNA connected with foldable creases formed by single-stranded DNA. To demonstrate the method, a DNA version of the paper origami mechanism called a waterbomb base (WBB) consisting of six panels connected by six joints is constructed. This nanoscale WBB can follow four distinct motion paths to transform between five distinct configurations including a flat square, two triangles, a rectangle, and a fully compacted trapezoidal shape. To achieve this, the sequence specificity of DNA base-pairing is leveraged for the selective actuation of joints and the ion-sensitivity of base-stacking interactions is employed for the flattening of joints. In addition, higher-order assembly of DNA WBBs into reconfigurable arrays is achieved. This work establishes a foundation for origami-inspired design for next generation synthetic molecular robots and reconfigurable nanomaterials enabling more complex and controllable motion.

Cation-Activated Avidity for Rapid Reconfiguration of DNA Nanodevices.

The ability to design and control DNA nanodevices with programmed conformational changes has established a foundation for molecular-scale robotics with applications in nanomanufacturing, drug delivery, and controlling enzymatic reactions. The most commonly used approach for actuating these devices, DNA binding and strand displacement, allows devices to respond to molecules in solution, but this approach is limited to response times of minutes or greater. Recent advances have enabled electrical and magnetic control of DNA structures with sub-second response times, but these methods utilize external components with additional fabrication requirements. Here, we present a simple and broadly applicable actuation method based on the avidity of many weak base-pairing interactions that respond to changes in local ionic conditions to drive large-scale conformational transitions in devices on sub-second time scales. To demonstrate such ion-mediated actuation, we modified a DNA origami hinge with short, weakly complementary single-stranded DNA overhangs, whose hybridization is sensitive to cation concentrations in solution. We triggered conformational changes with several different types of ions including mono-, di-, and trivalent ions and also illustrated the ability to engineer the actuation response with design parameters such as number and length of DNA overhangs and hinge torsional stiffness. We developed a statistical mechanical model that agrees with experimental data, enabling effective interpretation and future design of ion-induced actuation. Single-molecule Förster resonance energy-transfer measurements revealed that closing and opening transitions occur on the millisecond time scale, and these transitions can be repeated with time resolution on the scale of one second. Our results advance capabilities for rapid control of DNA nanodevices, expand the range of triggering mechanisms, and demonstrate DNA nanomachines with tunable analog responses to the local environment.

Three-dimensional structural dynamics of DNA origami Bennett linkages using individual-particle electron tomography.

Scaffolded DNA origami has proven to be a powerful and efficient technique to fabricate functional nanomachines by programming the folding of a single-stranded DNA template strand into three-dimensional (3D) nanostructures, designed to be precisely motion-controlled. Although two-dimensional (2D) imaging of DNA nanomachines using transmission electron microscopy and atomic force microscopy suggested these nanomachines are dynamic in 3D, geometric analysis based on 2D imaging was insufficient to uncover the exact motion in 3D. Here we use the individual-particle electron tomography method and reconstruct 129 density maps from 129 individual DNA origami Bennett linkage mechanisms at ~ 6-14 nm resolution. The statistical analyses of these conformations lead to understanding the 3D structural dynamics of Bennett linkage mechanisms. Moreover, our effort provides experimental verification of a theoretical kinematics model of DNA origami, which can be used as feedback to improve the design and control of motion via optimized DNA sequences and routing.

Association between PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma in Asian chronic hepatitis C patients: A longitudinal study.

BACKGROUND/PURPOSE: Prdevious meta-analyses assess whether or not patatin-like phospholipase domain containing 3 (PNPLA3) (rs738409 C > G) was associated with increased risk of hepatocellular carcinoma (HCC) in Caucasians patients with hepatitis C virus (HCV)-related cirrhosis, these meta-analyses did not provide firm conclusions. Only one cross-sectional study involving Asian patients has previously been conducted to explore this issue. We aim to investigate this in a longitudinal cohort of Asian chronic hepatitis C (CHC) patients. METHODS: We consecutively enrolled 1011 CHC patients who underwent liver biopsy before initiating interferon-based therapy. These patients were followed-up and screened for HCC up to a median of 6.9 years. The influence of rs738409 (GG) genotype on the occurrence of HCC was assessed using the Kaplan-Meier method, then according to the multivariate Cox model. RESULTS: During follow-up, 143 (14.1%) patients developed HCC. rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.634). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.12). Among 261 patients with liver cirrhosis, rs738409 (GG) genotype was not associated with time-to-HCC development on multivariate Cox regression (P = 0.737). When considering the occurrence of these events over time, rs738409 (GG) genotype did not influence the risk of HCC development (log-rank = 0.72). CONCLUSION: In this longitudinal study with liver biopsy to stage liver fibrosis, we affirm there is no influence of the rs738409 (GG) genotype on the occurrence of HCC in Asian CHC patients, including cirrhotic patients.

Dynamic noninvasive markers predict hepatocellular carcinoma in chronic hepatitis C patients without sustained virological response after interferon-based therapy: Prioritize who needs urgent direct-acting antiviral agents.

Some patients with hepatitis C virus (HCV) infections who fail to achieve sustained virological responses (SVRs) after interferon (IFN) therapy do not develop hepatocellular carcinoma (HCC). Risk stratification of these patients may help identify those who would benefit most from treatment with direct-acting antivirals (DAAs).A total of 552 HCV-infected patients with non-SVR status were enrolled. Laboratory data before and after IFN treatment were analyzed to determine the relationship of changes in serum markers with development of HCC during the 7-year study period.HCC developed in 93 patients. The risk factors for HCC were pre-existing liver cirrhosis, low hemoglobin level at baseline, low pretreatment platelet count, high post-treatment alpha-fetoprotein (AFP) level (≥15 ng/mL), and high post-treatment Fibrosis 4 (FIB4) index (>3.25). For patients without pre-existing cirrhosis, those with high post-treatment AFP level and FIB4 index had the highest risk of HCC (1 year: 6.7%; 3 years: 10.9%; 5 years: 29.7%), followed by those with high post-treatment AFP level and low post-treatment FIB4 index (5 years: 25%), and those with low post-treatment AFP level and high post-treatment FIB4 index (1 year: 3.7%; 3 years: 5.2%; 5 years: 10.6%). The risk was even lower for patients with low post-treatment AFP level and FIB4 index (1 year: 0%; 3 years: 0.4%; 5 years: 2.5%). None of the patients with FIB4 indexes consistently below 1.45 developed HCC.The combined use of post-treatment AFP level and FIB4 index was useful for risk stratification of HCV-infected patients with non-SVR status after IFN therapy. These data may help clinicians to identify patients who most urgently need DAA treatment.

Impact of PNPLA3 and IFNL3 polymorphisms on hepatic steatosis in Asian patients with chronic hepatitis C.

BACKGROUND AND AIMS: A recent meta-analysis revealed that the genotype PNPLA3 rs738409 GG is associated with a higher risk of hepatic steatosis (HS) in Caucasian patients with chronic hepatitis C (CHC). However, controversial results were found regarding Asian populations. Furthermore, previous studies have shown a negative association between interferon lambda 3 (IFNL3) rs12979860 CC and HS in Caucasian CHC patients, but there have been no reports indicating any such association in Asian populations. In this study, then, we investigated the association of PNPLA3 and IFNL3 polymorphisms with HS in Asian CHC patients. METHODS: We enrolled consecutive CHC patients who underwent liver biopsy prior to antiviral therapy. We excluded those patients with decompensated liver disease, any co-existing chronic liver disease, or HIV or HBV co-infection. RESULTS: 1080 CHC patients were enrolled, and HS was found in 453 (41.9%) patients. The frequency distribution of the G allele was significantly associated with HS (P<0.001), and this conferred a higher risk to G allele homozygotes (OR: 2.06, 95% CI: 1.46-2.88, P <0.001) than to G allele carriers (OR: 1.98, 95% CI: 1.52-2.58, P<0.001). There was a borderline significant difference in the prevalence of HS in rs12979860 CC versus non-CC (40.8% versus 49.3%, P = 0.059). After adjustment for age, sex, body mass index, diabetes, and excessive alcohol intake, the rs738409 G allele homozygote carriers still carried a higher risk for HS (OR: 1.93, 95% CI: 1.35-2.77, P = 0.003). CONCLUSION: The PNPLA3 rs738409 GG genotype is positively associated with HS, while the IFNL3 rs 12979860 CC genotype may be negatively associated with HS, in Asian CHC patients.

MicroRNA-122 as a predictor of HBsAg seroclearance in hepatitis B and C dual infected patients treated with interferon and ribavirin.

It has been demonstrated that microRNA-122 (miR-122) plays key roles in the modulation of hepatitis B virus (HBV) replication. This study examined the role of miR-122 in patients with hepatitis C virus (HCV)-HBV dual infection with active hepatitis C who received pegylated interferon-α and ribavirin dual therapy. We enrolled 121 patients with HCV-HBV dual infection after dual therapy. Stored serum was collected before treatment. RT-PCR was used to analyze miR-122. HBsAg seroclearance was noted in 37 (30.1%) cases during a median follow-up period of 5.4 years. miR-122 was significantly lower in HBsAg seroclearance patients than in non-HBsAg seroclearance patients (P < 0.014). Multivariate analysis showed that miR-122 was an independent factor of HBsAg seroclearance (OR: 0.30, 95% CI: 0.09-0.98, P = 0.046). miR-122 was significantly higher in patients who were qHBsAg > 100 IU/mL versus ≤100 IU/mL (P < 0.001). We concluded that in patients with HBV-HCV dual infection with active hepatitis C, miR-122 was associated with HBsAg seroclearance after therapy and qHBsAg level before therapy, indicating that miR-122 plays key roles in modulating HBV replication.