A functional variant of CD40 modulates clearance of hepatitis B virus in hepatocytes via regulation of the ANXA2/CD40/BST2 axis.

More than 250 million people in the world are chronically infected with hepatitis B virus (HBV), which causes serious complications. Host genetic susceptibility is essential for chronic hepatitis B (CHB), and our previous genome-wide association study identified a single-nucleotide polymorphism (SNP), rs1883832, in the 5' untranslated region of CD40 predisposing to chronic HBV infection, but the underlying mechanism remains undefined. This study aimed to investigate whether rs1883832 was the real functional SNP (fSNP) of CD40 and how it modulated HBV clearance in hepatocytes. We determined the fSNP of CD40 and its regulatory protein(s) using luciferase reporter assays, electrophoretic mobility shift assay, flanking restriction enhanced pulldown and chromatin immunoprecipitation. The potential anti-HBV activity of CD40 and its downstream molecule BST2 was assessed in HBV-transfected and HBV-infected hepatoma cells and HBV-infected primary human hepatocytes. Moreover, the mechanism of CD40 was investigated by mRNA sequencing, quantitative real-time polymerase chain reaction, immunofluorescence and western blot. We revealed rs1883832 as the true fSNP of CD40 and identified ANXA2 as a negative regulatory protein that preferentially bound to the risk allele T of rs1883832 and hence reduced CD40 expression. Furthermore, CD40 suppressed HBV replication and transcription in hepatocytes via activating the JAK-STAT pathway. BST2 was identified to be the key IFN-stimulated gene regulated by CD40 after activating JAK-STAT pathway. Inhibition of JAK/STAT/BST2 axis attenuated CD40-induced antiviral effect. In conclusion, a functional variant of CD40 modulates HBV clearance via regulation of the ANXA2/CD40/BST2 axis, which may shed new light on HBV personalized therapy.

Genomic adaptations for arboreal locomotion in Asian flying treefrogs.

SignificanceTo adapt to arboreal lifestyles, treefrogs have evolved a suite of complex traits that support vertical movement and gliding, thus presenting a unique case for studying the genetic basis for traits causally linked to vertical niche expansion. Here, based on two de novo-assembled Asian treefrog genomes, we determined that genes involved in limb development and keratin cytoskeleton likely played a role in the evolution of their climbing systems. Behavioral and morphological evaluation and time-ordered gene coexpression network analysis revealed the developmental patterns and regulatory pathways of the webbed feet used for gliding in Rhacophorus kio.

Enzyme-Inspired Ligand Engineering of Gold Nanoclusters for Electrocatalytic Microenvironment Manipulation.

Natural enzymes intricately regulate substrate accessibility through specific amino acid sequences and folded structures at their active sites. Achieving such precise control over the microenvironment has proven to be challenging in nanocatalysis, especially in the realm of ligand-stabilized metal nanoparticles. Here, we use atomically precise metal nanoclusters (NCs) as model catalysts to demonstrate an effective ligand engineering strategy to control the local concentration of CO2 on the surface of gold (Au) NCs during electrocatalytic CO2 reduction reactions (CO2RR). The precise incorporation of two 2-thiouracil-5-carboxylic acid (TCA) ligands within the pocket-like cavity of [Au25(pMBA)18]- NCs (pMBA = para-mercaptobenzoic acid) leads to a substantial acceleration in the reaction kinetics of CO2RR. This enhancement is attributed to a more favorable microenvironment in proximity to the active site for CO2, facilitated by supramolecular interactions between the nucleophilic Nδ- of the pyrimidine ring of the TCA ligand and the electrophilic Cδ+ of CO2. A comprehensive investigation employing absorption spectroscopy, mass spectrometry, isotopic labeling measurements, electrochemical analyses, and quantum chemical computation highlights the pivotal role of local CO2 enrichment in enhancing the activity and selectivity of TCA-modified Au25 NCs for CO2RR. Notably, a high Faradaic efficiency of 98.6% toward CO has been achieved. The surface engineering approach and catalytic fundamentals elucidated in this study provide a systematic foundation for the molecular-level design of metal-based electrocatalysts.

Ionic liquids intercalation in titanium carbide MXenes: A first-principles investigation.

Herein, we present a density functional theory with dispersion correction (DFT-D) calculations that focus on the intercalation of ionic liquids (ILs) electrolytes into the two-dimensional (2D) Ti3C2Tx MXenes. These ILs include the cation 1-ethyl-3-methylimidazolium (Emim+), accompanied by three distinct anions: bis(trifluoromethylsulfonyl)imide (TFSA-), (fluorosulfonyl)imide (FSA-) and fluorosulfonyl(trifluoromethanesulfonyl)imide (FTFSA-). By altering the surface termination elements, we explore the intricate geometries of IL intercalation in neutral, negative, and positive pore systems. Accurate estimation of charge transfer is achieved through five population analysis models, such as Hirshfeld, Hirshfeld-I, DDEC6 (density derived electrostatic and chemical), Bader, and VDD (voronoi deformation density) charges. In this work, we recommend the DDEC6 and Hirshfeld-I charge models, as they offer moderate values and exhibit reasonable trends. The investigation, aimed at visualizing non-covalent interactions, elucidates the role of cation-MXene and anion-MXene interactions in governing the intercalation phenomenon of ionic liquids within MXenes. The magnitude of this role depends on two factors: the specific arrangement of the cation, and the nature of the anionic species involved in the process.

Ionic Pairs-Engineered Fluorinated Covalent Organic Frameworks Toward Direct Air Capture of CO2.

The covalent organic frameworks (COFs) possessing high crystallinity and capability to capture low-concentration CO2 (400 ppm) from air are still underdeveloped. The challenge lies in simultaneously incorporating high-density active sites for CO2 insertion and maintaining the ordered structure. Herein, a structure engineering approach is developed to afford an ionic pair-functionalized crystalline and stable fluorinated COF (F-COF) skeleton. The ordered structure of the F-COF is well maintained after the integration of abundant basic fluorinated alcoholate anions, as revealed by synchrotron X-ray scattering experiments. The breakthrough test demonstrates its attractive performance in capturing (400 ppm) CO2 from gas mixtures via O─C bond formation, as indicated by the in situ spectroscopy and operando nuclear magnetic resonance spectroscopy using 13C-labeled CO2 sources. Both theoretical and experimental thermodynamic studies reveal the reaction enthalpy of ≈-40 kJ mol-1 between CO2 and the COF scaffolds. This implies weaker interaction strength compared with state-of-the-art amine-derived sorbents, thus allowing complete CO2 release with less energy input. The structure evolution study from synchrotron X-ray scattering and small-angle neutron scattering confirms the well-maintained crystalline patterns after CO2 insertion. The as-developed proof-of-concept approach provides guidance on anchoring binding sites for direct air capture (DAC) of CO2 in crystalline scaffolds.

A genetic variant of CXCR4 predicts pegylated interferon-alpha treatment response in HBeAg-positive chronic hepatitis B patients.

Chemokine receptor 4 (CXCR4) plays a vital role in immunoregulation during hepatitis B virus (HBV) infection. This study aimed to screen single-nucleotide polymorphisms (SNPs) of CXCR4 for predicting pegylated interferon-alpha (PegIFNα) therapy response in chronic hepatitis B (CHB) patients. This retrospective cohort study enrolled a total of 945 CHB patients in two cohorts (Cohort 1, n = 238; Cohort 2, n = 707), and all the patients were hepatitis B e antigen (HBeAg)-positive and treated with PegIFNα for 48 weeks and followed up for 24 weeks. Twenty-two tag SNPs were selected in CXCR4 and its flanking region. A polygenic score (PGS) was utilized to evaluate the cumulative effect of multiple SNPs. The relationships between CXCR4 SNPs and PGS and PegIFNα treatment response were explored in the two cohorts. Among the 22 candidate SNPs of CXCR4, rs28367495 (T > C) was significantly linked to PegIFNα treatment response in both cohorts. In patients with more number of rs28367495 C allele, a higher rate of combined response (CR, defined as HBeAg seroconversion and HBV DNA level < 3.3 log10 IU/mL; P = 1.51 × 10-4), a lower mean hepatitis B surface antigen (HBsAg) level (P = 4.76 × 10-4), and a higher mean HBsAg decline (P = 3.88 × 10-4) at Week 72 were achieved. Moreover, a PGS integrating CXCR4_rs28367495 and five previously reported SNPs was strongly correlated with CR (P = 1.26 × 10-13), HBsAg level (P = 4.90 × 10-4), and HBsAg decline (P = 0.005) in all the patients of the two cohorts. CXCR4_rs28367495 is a promising indicator for predicting the responsiveness to PegIFNα treatment for HBeAg-positive CHB patients. The new PGS may further improve the prediction performance.

Engineering Nanostructured Interfaces of Hexagonal Boron Nitride-Based Materials for Enhanced Catalysis.

ConspectusHexagonal boron nitrides (h-BNs) are attractive two-dimensional (2D) nanomaterials that consist of alternating B and N atoms and layered honeycomb-like structures similar to graphene. They have exhibited unique properties and promising application potentials in the field of energy storage and transformation. Recent advances in utilizing h-BN as a metal-free catalyst in the oxidative dehydrogenation of propane have triggered broad interests in exploring h-BN in catalysis. However, h-BN-based materials as robust nanocatalysts in heterogeneous catalysis are still underexplored because of the limited methodologies capable of affording h-BN with controllable crystallinity, abundant porosity, high purity, and defect engineering, which played important roles in tuning their catalytic performance. In this Account, our recent progress in addressing the above issues will be highlighted, including the synthesis of high-quality h-BN-based nanomaterials via both bottom-up and top-down pathways and their catalytic utilization as metal-free catalysts or as supports to tune the interfacial electronic properties on the metal nanoparticles (NPs). First, we will focus on the large-scale fabrication of h-BN nanosheets (h-BNNSs) with high crystallinity, improved surface area, satisfactory purity, and tunable defects. h-BN derived from the traditional approaches using boron trioxide and urea as the starting materials generally contains carbon/oxygen impurities and has low crystallinity. Several new strategies were developed to address the issues. Using bulk h-BN as the precursor via gas exfoliation in liquid nitrogen, single- or few-layered h-BNNS with abundant defects could be generated. Amorphous h-BN precursors could be converted to h-BN nanosheets with high crystallinity assisted by a magnesium metallic flux via a successive dissolution/precipitation/crystallization procedure. The as-fabricated h-BNNS featured high crystallinity and purity as well as abundant porosity. An ionothermal metathesis procedure was developed using inorganic molten salts (NaNH2 and NaBH4) as the precursors. The h-BN scaffolds could be produced on a large scale with high yield, and the as-afforded materials possessed high purity and crystallinity. Second, utilization of the as-prepared h-BN library as metal-free catalysts in dehydrogenation and hydrogenation reactions will be summarized, in which they exhibited enhanced catalytic activity over the counterparts from the previous synthesis method. Third, the interface modulation between metal NPs with the as-prepared defects' abundant h-BN support will be highlighted. The h-BN-based strong metal-support interaction (SMSI) nanocatalysts were constructed without involving reducible metal oxides via the ionothermal procedure we developed by deploying specific inorganic metal salts, acting as robust nanocatalysts in CO oxidation. Under conditions simulated for practical exhaust systems, promising catalytic efficiency together with high thermal stability and sintering resistance was achieved. Across all of these examples, unique insights into structures, defects, and interfaces that emerge from in-depth characterization through microscopy, spectroscopy, and diffraction will be highlighted.

Supramolecular Complexation-enhanced CO2 Chemisorption in Amine-derived Sorbents.

A supramolecular complexation approach is developed to improve the CO2 chemisorption performance of solvent-lean amine sorbents. Operando spectroscopy techniques reveal the formation of carbamic acid in the presence of a crown ether. The reaction pathway is confirmed by theoretical simulation, in which the crown ether acts as proton acceptor and shuttle to drive the formation and stabilization of carbamic acid. Improved CO2 capacity and diminished energy consumption in sorbent regeneration was achieved.

Enhancing Multi-species Liver Microsomal Stability Prediction through Artificial Intelligence.

Liver microsomal stability, a crucial aspect of metabolic stability, significantly impacts practical drug discovery. However, current models for predicting liver microsomal stability are based on limited molecular information from a single species. To address this limitation, we constructed the largest public database of compounds from three common species: human, rat, and mouse. Subsequently, we developed a series of classification models using both traditional descriptor-based and classic graph-based machine learning (ML) algorithms. Remarkably, the best-performing models for the three species achieved Matthews correlation coefficients (MCCs) of 0.616, 0.603, and 0.574, respectively, on the test set. Furthermore, through the construction of consensus models based on these individual models, we have demonstrated their superior predictive performance in comparison with the existing models of the same type. To explore the similarities and differences in the properties of liver microsomal stability among multispecies molecules, we conducted preliminary interpretative explorations using the Shapley additive explanations (SHAP) and atom heatmap approaches for the models and misclassified molecules. Additionally, we further investigated representative structural modifications and substructures that decrease the liver microsomal stability in different species using the matched molecule pair analysis (MMPA) method and substructure extraction techniques. The established prediction models, along with insightful interpretation information regarding liver microsomal stability, will significantly contribute to enhancing the efficiency of exploring practical drugs for development.

Berberine improves cognitive impairment by alleviating brain atrophy and promoting white matter reorganization in diabetic db/db mice: a magnetic resonance imaging-based study.

Diabetic cognitive impairment is a common complication in type 2 diabetes. Berberine (BBR) is an isoquinoline alkaloid that has been shown to have neuroprotective effects against diabetes. This study aimed to investigate the effect of BBR on the gray and white matter of the brain by using magnetic resonance imaging (MRI) and to explore the underlying mechanisms. The study used diabetic db/db mice and administered BBR (50 and 100 mg/kg) intragastrically for twelve weeks. Morris water maze was applied to examine cognitive function. T2-weighted imaging (T2WI) was performed to assess brain atrophy, and diffusion tensor imaging (DTI) combined with fiber tracking was conducted to monitor the structural integrity of the white matter, followed by histological immunostaining. Furthermore, the protein expressions of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3ß (GSK-3ß) were detected. The results revealed that BBR significantly improved the spatial learning and memory of the db/db mice. T2WI exhibited ameliorated brain atrophy in the BBR-treated db/db mice, as evidenced by reduced ventricular volume accompanied by increased hippocampal volumes. DTI combined with fiber tracking revealed that BBR increased FA, fiber density and length in the corpus callosum/external capsule of the db/db mice. These imaging findings were confirmed by histological immunostaining. Notably, BBR significantly enhanced the protein levels of phosphorylated AKT at Ser473 and GSK-3ß at Ser9. Collectively, this study demonstrated that BBR significantly improved the cognitive function of the diabetic db/db mice through ameliorating brain atrophy and promoting white matter reorganization via AKT/GSK-3ß pathway.

Monolayer Fullerene Membranes for Hydrogen Separation.

Hydrogen separation membranes are a critical component in the emerging hydrogen economy, offering an energy-efficient solution for the purification and production of hydrogen gas. Inspired by the recent discovery of monolayer covalent fullerene networks, here we show from concentration-gradient-driven molecular dynamics that quasi-square-latticed monolayer fullerene membranes provide the best pore size match, a unique funnel-shaped pore, and entropic selectivity. The integration of these attributes renders these membranes promising for separating H2 from larger gases such as CO2 and O2. The ultrathin membranes exhibit excellent hydrogen permeance as well as high selectivity for H2/CO2 and H2/O2 separations, surpassing the 2008 Robeson upper bounds by a large margin. The present work points toward a promising direction of using monolayer fullerene networks as membranes for high-permeance, selective hydrogen separation for processes such as water splitting.

The Role of ALPK1 in Inhibiting Hepatitis B Virus Replication Facilitates the Identification of ALPK1 P660L Variant for Predicting Response to Pegylated Interferon α Therapy.

BACKGROUND: Alpha kinase 1 (ALPK1) agonist has recently been reported to demonstrate anti-hepatitis B virus (HBV) efficacy via activating NF-κB signaling, which is crucial for maximizing interferon (IFN) responses. Here, we investigated the impact of ALPK1 on HBV replication and explored ALPK1 variants for predicting the response to pegylated IFN-α (PegIFN-α) treatment. METHODS: The potential anti-HBV effect of ALPK1 was evaluated in HBV-integrated and HBV-infected hepatoma cells. The potentially functional genetic variants of ALPK1 were screened out, and their correlations with PegIFN-α treatment response were assessed in 945 hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB). RESULTS: We revealed that ALPK1 inhibited HBV replication in hepatocytes via activating the JAK-STAT pathway. ALPK1 overexpression improved the anti-HBV effect of IFN-α in cell models. A missense variant, rs35389530 (P660L), of ALPK1 was strongly associated with combined response (CR; namely, HBeAg seroconversion and HBV DNA level <3.3log10 IU/mL) to PegIFN-α treatment in patients with CHB (P = 2.12 × 10-6). Moreover, a polygenic score integrating ALPK1_rs35389530 and 2 additional genetic variants was further significantly associated with CR (Ptrend = 9.28 × 10-7), hepatitis B surface antigen (HBsAg) level (Ptrend = .0002), and HBsAg loss (Ptrend = .025). CONCLUSIONS: The anti-HBV effects of ALPK1 through activating JAK-STAT pathway provides a new perspective for CHB therapy. ALPK1_rs35389530 and polygenic score are potential biomarkers to predict PegIFN-α treatment response and may be used for optimizing CHB treatment.

Dynamic Monkey Bar Mechanism of Superionic Li-ion Transport in LiTaCl6.

The LiTaCl6 solid electrolyte has the lowest activation energy of ionic conduction at ambient conditions (0.165 eV), with a record high ionic conductivity for a ternary compound (11 mS cm-1 ). However, the mechanism has been unclear. We train machine-learning force fields (MLFF) on ab initio molecular dynamics (AIMD) data on-the-fly and perform MLFF MD simulations of AIMD quality up to the nanosecond scale at the experimental temperatures, which allows us to predict accurate activation energy for Li-ion diffusion (at 0.164 eV). Detailed analyses of trajectories and vibrational density of states show that the large-amplitude vibrations of Cl- ions in TaCl6 - enable the fast Li-ion transport by allowing dynamic breaking and reforming of Li-Cl bonds across the space in between the TaCl6 - octahedra. We term this process the dynamic-monkey-bar mechanism of superionic Li+ transport which could aid the development of new solid electrolytes for all-solid-state lithium batteries.

Significant Roles of Surface Hydrides in Enhancing the Performance of Cu/BaTiO2.8 H0.2 Catalyst for CO2 Hydrogenation to Methanol.

Tuning the anionic site of catalyst supports can impact reaction pathways by creating active sites on the support or influencing metal-support interactions when using supported metal nanoparticles. This study focuses on CO2 hydrogenation over supported Cu nanoparticles, revealing a 3-fold increase in methanol yield when replacing oxygen anions with hydrides in the perovskite support (Cu/BaTiO2.8 H0.2 yields ~146 mg/h/gCu vs. Cu/BaTiO3 yields ~50 mg/h/gCu). The contrast suggests that significant roles are played by the support hydrides in the reaction. Temperature programmed reaction and isotopic labelling studies indicate that BaTiO2.8 H0.2 surface hydride species follow a Mars van Krevelen mechanism in CO2 hydrogenation, promoting methanol production. High-pressure steady-state isotopic transient kinetic analysis (SSITKA) studies suggest that Cu/BaTiO2.8 H0.2 possesses both a higher density and more active and selective sites for methanol production compared to Cu/BaTiO3 . An operando high-pressure diffuse reflectance infrared spectroscopy (DRIFTS)-SSITKA study shows that formate species are the major surface intermediates over both catalysts, and the subsequent hydrogenation steps of formate are likely rate-limiting. However, the catalytic reactivity of Cu/BaTiO2.8 H0.2 towards the formate species is much higher than Cu/BaTiO3 , likely due to the altered electronic structure of interface Cu sites by the hydrides in the support as validated by density functional theory (DFT) calculations.

The Influence of Ions on the Electrochemical Stability of Aqueous Electrolytes.

The electrochemical stability window of water is known to vary with the type and concentration of dissolved salts. However, the underlying influence of ions on the thermodynamic stability of aqueous solutions has not been fully understood. Here, we investigated the electrolytic behaviors of aqueous electrolytes as a function of different ions. Our findings indicate that ions with high ionic potentials, i.e., charge density, promote the formation of their respective hydration structures, enhancing electrolytic reactions via an inductive effect, particularly for small cations. Conversely, ions with lower ionic potentials increase the proportion of free water molecules-those not engaged in hydration shells or hydrogen-bonding networks-leading to greater electrolytic stability. Furthermore, we observe that the chemical environment created by bulky ions with lower ionic potentials impedes electrolytic reactions by frustrating the solvation of protons and hydroxide ions, the products of oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively. We found that the solvation of protons plays a more substantial role than that of hydroxide, which explains a greater shift for OER than for HER, a puzzle that cannot be rationalized by the notion of varying O-H bond strengths of water. These insights will help the design of aqueous systems.

Selective Formation of Acetic Acid and Methanol by Direct Methane Oxidation Using Rhodium Single-Atom Catalysts.

Atomically dispersed catalysts such as single-atom catalysts have been shown to be effective in selectively oxidizing methane, promising a direct synthetic route to value-added oxygenates such as acetic acid or methanol. However, an important challenge of this approach has been that the loading of active sites by single-atom catalysts is low, leading to a low overall yield of the products. Here, we report an approach that can address this issue. It utilizes a metal-organic framework built with porphyrin as the linker, which provides high concentrations of binding sites to support atomically dispersed rhodium. It is shown that up to 5 wt% rhodium loading can be achieved with excellent dispersity. When used for acetic acid synthesis by methane oxidation, a new benchmark performance of 23.62 mmol·gcat-1·h-1 was measured. Furthermore, the catalyst exhibits a unique sensitivity to light, producing acetic acid (under illumination, up to 66.4% selectivity) or methanol (in the dark, up to 65.0% selectivity) under otherwise identical reaction conditions.

Harnessing the Hybridization of a Metal-Organic Framework and Superbase-Derived Ionic Liquid for High-Performance Direct Air Capture of CO2.

Direct air capture (DAC) of CO2 has emerged as the most promising "negative carbon emission" technologies. Despite being state-of-the-art, sorbents deploying alkali hydroxides/amine solutions or amine-modified materials still suffer from unsolved high energy consumption and stability issues. In this work, composite sorbents are crafted by hybridizing a robust metal-organic framework (Ni-MOF) with superbase-derived ionic liquid (SIL), possessing well maintained crystallinity and chemical structures. The low-pressure (0.4 mbar) volumetric CO2 capture assessment and a fixed-bed breakthrough examination with 400 ppm CO2 gas flow reveal high-performance DAC of CO2 (CO2 uptake capacity of up to 0.58 mmol g-1 at 298 K) and exceptional cycling stability. Operando spectroscopy analysis reveals the rapid (400 ppm) CO2 capture kinetics and energy-efficient/fast CO2 releasing behaviors. The theoretical calculation and small-angle X-ray scattering demonstrate that the confinement effect of the MOF cavity enhances the interaction strength of reactive sites in SIL with CO2 , indicating great efficacy of the hybridization. The achievements in this study showcase the exceptional capabilities of SIL-derived sorbents in carbon capture from ambient air in terms of rapid carbon capture kinetics, facile CO2 releasing, and good cycling performance.

TRIM16 E121D variant affects the risk and prognosis of hepatocellular carcinoma by modulating the Wnt/ß-catenin pathway.

TRIM16 has been identified as a tumor suppressor in hepatocellular carcinoma (HCC). This study aimed to investigate whether there are genetic variants in TRIM16 influencing HCC risk and/or prognosis and explore the mechanisms. We performed a gene-wide single-nucleotide polymorphism (SNP) mining in TRIM16. The associations of SNPs with both HCC risk and prognosis were assessed through two independent cohorts respectively. Functional experiments were performed to investigate the underlying mechanisms. A missense variant rs2074890 (G > T, resulting in an amino acid substitution from glutamate to aspartate at code 121, E121D) of TRIM16 was found to be associated with both HCC risk (odds ratio = 0.806, p = 0.023) and prognosis (hazard ratio = 0.44, p = 0.034). Compared to the rs2074890 G allele (corresponding to TRIM16121E ) homozygote carriers, the rs2074890 T allele (corresponding to TRIM16121D ) carriers showed lower HCC risk and better overall survival. Mechanistically, TRIM16121D has stronger ability to inhibit proliferation, migration, and invasion of HCC cells. Furthermore, TRIM16121D could bind to ß-catenin better and mediate K48-linked ubiquitination to degrade ß-catenin, which leads to inhibition of Wnt/ß-catenin pathway. In conclusion, TRIM16 E121D variant impacts both risk and prognosis of HCC via regulation of Wnt/ß-catenin pathway, which may lead to better understanding the pathogenesis of HCC.

CXCL13 variant predicts pegylated-interferon α treatment response in HBeAg-positive chronic hepatitis B patients.

As a key immune cytokine, C-X-C motif chemokine ligand 13 (CXCL13) has been reported to play critical roles in immune control of hepatitis B virus (HBV) infection. We aimed to screen single-nucleotide polymorphisms (SNPs) of CXCL13 for predicting response to pegylated interferon-alpha (PegIFNα) therapy of chronic hepatitis B (CHB) patients. Two independent cohorts with a total of 945 (Cohort 1, n = 238; Cohort 2, n = 707) hepatitis B e antigen (HBeAg)-positive CHB patients treated with PegIFNα were enrolled in this retrospective cohort study. Eight candidate SNPs were selected through gene-wide SNP mining within or flanking CXCL13. A polygenic score (PGS) was utilized to assess the cumulative effects of multiple SNPs. The associations of candidate SNPs and PGS with combined response (CR, defined as the combination of HBeAg seroconversion and HBV DNA level <3.3log10 IU/mL) and hepatitis B surface antigen (HBsAg) level were evaluated. Among the eight candidate SNPs, rs76084459 which is located at upstream of CXCL13 was significantly associated with both CR (p = 0.002) and HBsAg level (p = 0.015). A PGS integrating CXCL13_rs76084459 and five other SNPs, which were previously identified as predictors of PegIFNα treatment response, was further strongly correlated with CR (p = 1.759 × 10-10 ) and HBsAg level (p = 0.004). This study demonstrated that CXCL13_rs76084459 can predict response to PegIFNα treatment of HBeAg-positive CHB patients. A PGS composed of six SNPs including CXCL13_rs76084459 predicts PegIFNα treatment response better.

Hydrogen-mediated polarity compensation on the (110) surface terminations of ABO3 perovskites.

Polar surfaces undergo polarity compensation, which can lead to significantly different surface chemistry from their nonpolar counterparts. This process in turn can substantially alter the binding of adsorbates on the surface. Here, we find that hydrogen binds much more strongly to the polar (110) surface than the nonpolar (100) surface for a wide range of ABO3 perovskites, forming a hydroxyl layer on the O24- termination and a hydride layer on the ABO4+ termination of the (110) surface. The stronger adsorption on the polar surfaces can be explained by polarity compensation: hydrogen atoms can act as electron donors or acceptors to compensate for the polarity of perovskite surfaces. The relative stability of the surface terminations is further compared under different gas environments and several perovskites have been found to form stable surface hydride layers under oxygen-poor conditions. These results demonstrate the feasibility of creating stable surface hydrides on perovskites by polarity compensation which might lead to new hydrogenation catalysts based on ABO3 perovskites.