Metal element-based adsorbents for phosphorus capture: Chaperone effect, performance and mechanism.

Excessive phosphorus (P) enters the water bodies via wastewater discharges or agricultural runoff, triggering serious environmental problems such as eutrophication. In contrast, P as an irreplaceable key resource, presents notable supply-demand contradictions due to ineffective recovery mechanisms. Hence, constructing a system that simultaneously reduce P contaminants and effective recycling has profound theoretical and practical implications. Metal element-based adsorbents, including metal (hydro) oxides, layered double hydroxides (LDHs) and metal-organic frameworks (MOFs), exhibit a significant chaperone effect stemming from strong orbital hybridization between their intrinsic Lewis acid sites and P (Lewis base). This review aims to parse the structure-effect relationship between metal element-based adsorbents and P, and explores how to optimize the P removal properties. Special emphasis is given to the formation of the metal-P chemical bond, which not only depends on the type of metal in the adsorbent but also closely relates to its surface activity and pore structure. Then, we delve into the intrinsic mechanisms behind these adsorbents' remarkable adsorption capacity and precise targeting. Finally, we offer an insightful discussion of the prospects and challenges of metal element-based adsorbents in terms of precise material control, large-scale production, P-directed adsorption and effective utilization.

Rationally designed calcium carbonate multifunctional trap for contaminants adsorption.

Adsorption technology has been widely developed to control environmental pollution, which plays an important role in the sustainable development of modern society. Calcium carbonate (CaCO3) is characterized by its flexible pore design and functional group modification, which meet the high capacity and targeting requirements of adsorption. Therefore, its charm of "small materials for great use" makes it a suitable candidate for adsorption. Firstly, we comprehensively review the research progress of controlled synthesis and surface modification of CaCO3, and its application for adsorbing contaminants from water and air. Then, we systematically examine the structure-effect relationship between CaCO3 adsorbents and contaminants, while also intrinsic mechanism of remarkable capacity and targeted adsorption. Finally, from the perspective of material design and engineering application, we offer insightful discussion on the prospects and challenges of calcium carbonate adsorbents, providing a valuable reference for the further research in this field.

Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation.

Currently, human health due to corona virus disease 2019 (COVID-19) pandemic has been seriously threatened. The coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19. However, the efficacy is compromised by the SARS-CoV-2 evolvement and mutation. Here we report the SARS-CoV-2 S protein receptor-binding domain (RBD) inhibitor licorice-saponin A3 (A3) could widely inhibit RBD of SARS-CoV-2 variants, including Beta, Delta, and Omicron BA.1, XBB and BQ1.1. Furthermore, A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells, with EC50 of 1.016 µM. The mechanism was related with binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry (HDX-MS) analysis combined with quantum mechanics/molecular mechanics (QM/MM) simulations. Interestingly, phosphoproteomics analysis and multi fluorescent immunohistochemistry (mIHC) respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 MAPK pathways and rebalancing the corresponding immune dysregulation. This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

Protocol for characterizing the inhibition of SARS-CoV-2 infection by a protein of interest in cultured cells.

Here, we present a protocol to characterize the antiviral ability of a protein of interest to SARS-CoV-2 infection in cultured cells, using MUC1 as an example. We use SARS-CoV-2 ΔN trVLP system, which utilizes transcription and replication-competent SARS-CoV-2 virus-like particles lacking nucleocapsid gene. We describe the optimized procedure to analyze protein interference of viral attachment and entry into cells, and qRT-PCR-based quantification of viral infection. The protocol can be applied to characterize more antiviral candidates and clarify their functioning stage. For complete details on the use and execution of this protocol, please refer to Lai et al. (2022).

Generation of functionally competent hepatic stellate cells from human stem cells to model liver fibrosis in vitro.

The detailed understanding of fibrogenesis has been hampered by a lack of important functional quiescence characteristics and an in vitro model to recapitulate hepatic stellate cell (HSC) activation. In our study, we establish robust endoderm- and mesoderm-sourced quiescent-like induced HSCs (iHSCs) derived from human pluripotent stem cells. Notably, iHSCs present features of mature HSCs, including accumulation of vitamin A in the lipid droplets and maintained quiescent features. In addition, iHSCs display a fibrogenic response and secrete collagen I in response to hepatoxicity caused by thioacetamide, acetaminophen, and hepatitis B and C virus infection. Antiviral therapy attenuated virally induced iHSC activation. Interestingly, endoderm- and mesoderm-derived iHSCs showed similar iHSC phenotypes. Therefore, we provide a novel and robust method to efficiently generate functional iHSCs from hESC and iPSC differentiation, which could be used as a model for hepatocyte toxicity prediction, anti-liver-fibrosis drug screening, and viral hepatitis-induced liver fibrosis.

TRIM56 impairs HBV infection and replication by inhibiting HBV core promoter activity.

Members of the tripartite motif (TRIM) protein family strongly induced by interferons (IFNs) are parts of the innate immune system with antiviral activity. However, it is still unclear which TRIMs could play important roles in hepatitis B virus (HBV) inhibition. Here, we identified that TRIM56 expression responded in IFN-treated HepG2-NTCP cells and HBV-infected liver tissues, which was a potent IFN-inducible inhibitor of HBV replication. Mechanistically, TRIM56 suppressed HBV replication via its Ring and C-terminal domain. C-terminal domain was essential for TRIM56 translocating from cytoplasm to nucleus during HBV infection. Further analysis revealed that TRIM56's Ring domain targeted IκBα for ubiquitination. This modification induced phosphorylation of p65, which subsequently inhibited HBV core promoter activity, resulting in the inhibition of HBV replication. The p65 was found to be necessary for NF-κB signal pathway to inhibit HBV replication. We verified our findings using HepG2-NTCP and primary human hepatocytes. Our findings reveal that TRIM56 is a critical antiviral immune effector and exerts an anti-HBV activity via NF-κB signal pathway, which is essential for inhibiting transcription of HBV covalently closed circular DNA.

Identified human breast milk compositions effectively inhibit SARS-CoV-2 and variants infection and replication.

The global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to public health. Human breast milk is a complex nutritional composition to nourish infants and protect them from different kinds of infectious diseases including COVID-19. Here, we identified that lactoferrin (LF), mucin1 (MUC1), and α-lactalbumin (α-LA) from human breast milk inhibit SARS-CoV-2 infection using a SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP). In addition, LF and MUC1 inhibited multiple steps including viral attachment, entry, and postentry replication, whereas α-LA inhibited viral attachment and entry. Importantly, LF, MUC1, and α-LA possess potent antiviral activities toward variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma), and B.1.617.1 (kappa). Taken together, our study provides evidence that human breast milk components (LF, MUC1, and α-LA) are promising antiviral and potential therapeutic candidates warranting further development for treating COVID-19.

Natural triterpenoids from licorice potently inhibit SARS-CoV-2 infection.

Introduction: The COVID-19 global epidemic caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a great public health emergency. Discovering antiviral drug candidates is urgent for the prevention and treatment of COVID-19. Objectives: This work aims to discover natural SARS-CoV-2 inhibitors from the traditional Chinese herbal medicine licorice. Methods: We screened 125 small molecules from Glycyrrhiza uralensis Fisch. (licorice, Gan-Cao) by virtual ligand screening targeting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. Potential hit compounds were further evaluated by ELISA, SPR, luciferase assay, antiviral assay and pharmacokinetic study. Results: The triterpenoids licorice-saponin A3 (A3) and glycyrrhetinic acid (GA) could potently inhibit SARS-CoV-2 infection, with EC50 of 75 nM and 3.17 µM, respectively. Moreover, we reveal that A3 mainly targets the nsp7 protein, and GA binds to the spike protein RBD of SARS-CoV-2. Conclusion: In this work, we found GA and A3 from licorice potently inhibit SARS-CoV-2 infection by affecting entry and replication of the virus. Our findings indicate that these triterpenoids may contribute to the clinical efficacy of licorice for COVID-19 and could be promising candidates for antiviral drug development.

The enhancement role of Matrigel on HBV infection in HepG2-NTCP cells.

The hepatoma cell lines stably expressing sodium taurocholate cotransporting polypeptide (NTCP), the receptor of hepatitis B virus (HBV) infection, serve as important infection models for studying viral biology and drug discovery. However, the efficiency of infection greatly varies. In this study, we studied the effects and potential mechanisms of Matrigel® hESC-qualified (M-hq), a biological basement membrane matrix commonly used in cell culture, on promotion HBV in vitro infection in HepG2-NTCP cells. For the first time, our findings demonstrate that M-hq could enhance the infection efficiency of cell culture-derived HBV with no impact on the cell viability, the HBV transcription and response to antiviral treatments. The infection enhancement is reproducible and is suggested to occur at HBV attachment step. Our study suggests that this novel system is applicable for studying HBV biology and new drugs.

Hypermethylation of PI3K-AKT signalling pathway genes is associated with human neural tube defects.

Neural tube defects (NTDs) are a group of common and severe congenital malformations. The PI3K-AKT signalling pathway plays a crucial role in the neural tube development. There is limited evidence concerning any possible association between aberrant methylation in PI3K-AKT signalling pathway genes and NTDs. Therefore, we aimed to investigate potential associations between aberrant methylation of PI3K-AKT pathway genes and NTDs. Methylation studies of PI3K-AKT pathway genes utilizing microarray genome-methylation data derived from neural tissues of ten NTD cases and eight non-malformed controls were performed. Targeted DNA methylation analysis was subsequently performed in an independent cohort of 73 NTD cases and 32 controls to validate the methylation levels of identified genes. siRNAs were used to pull-down the target genes in human embryonic stem cells (hESCs) to examine the effects of the aberrant expression of target genes on neural cells. As a result, 321 differentially hypermethylated CpG sites in the promoter regions of 30 PI3K-AKT pathway genes were identified in the microarray data. In target methylation analysis, CHRM1, FGF19, and ITGA7 were confirmed to be significantly hypermethylated in NTD cases and were associated with increased risk for NTDs. The down-regulation of FGF19, CHRM1, and ITGA7 impaired the formation of rosette-like cell aggregates. The down-regulation of those three genes affected the expression of PAX6, SOX2 and MAP2, implying their influence on the differentiation of neural cells. This study for the first time reported that hypermethylation of PI3K-AKT pathway genes such as CHRM1, FGF19, and ITGA7 is associated with human NTDs.

Flat band carrier confinement in magic-angle twisted bilayer graphene.

Magic-angle twisted bilayer graphene has emerged as a powerful platform for studying strongly correlated electron physics, owing to its almost dispersionless low-energy bands and the ability to tune the band filling by electrostatic gating. Techniques to control the twist angle between graphene layers have led to rapid experimental progress but improving sample quality is essential for separating the delicate correlated electron physics from disorder effects. Owing to the 2D nature of the system and the relatively low carrier density, the samples are highly susceptible to small doping inhomogeneity which can drastically modify the local potential landscape. This potential disorder is distinct from the twist angle variation which has been studied elsewhere. Here, by using low temperature scanning tunneling spectroscopy and planar tunneling junction measurements, we demonstrate that flat bands in twisted bilayer graphene can amplify small doping inhomogeneity that surprisingly leads to carrier confinement, which in graphene could previously only be realized in the presence of a strong magnetic field.

The Genotype (A to H) Dependent N-terminal Sequence of HBV Large Surface Protein Affects Viral Replication, Secretion and Infectivity.

Genetic variability has significant impacts on biological characteristics and pathogenicity of hepatitis B virus (HBV), in which the N-terminal sequence of the presurface 1 (preS1) region of HBV large surface protein (LHBs) displays genotype (GT) dependent genetic heterogeneity. However, the influence of this heterogeneity on its biological roles is largely unknown. By analyzing 6560 full-length genome sequences of GTA-GTH downloaded from HBVdb database, the preS1 N-terminal sequences were divided into four representative types, namely C-type (representative of GTA, GTB, and GTC), H-type (GTF and GTH), E-type (GTE and GTG), and D-type (GTD), respectively. We artificially substituted the preS1 N-termini of GTC and GTD plasmids or viral strains with each sequence of the four representative types. The roles of preS1 N-terminus on HBV replication, secretion and infectivity were investigated using HepG2 or HepG2-NTCP cells. In the transfection experiments, the results showed that the extracellular HBsAg levels and HBsAg secretion coefficients in D- and E-type strains were significantly higher than those in C- and H-type strains. D-type strain produced more extracellular HBV DNA than C-type strain. We further observed that D-, H-, and E-type strains increased the levels of intracellular replicative HBV DNAs, comparing with C-type strain. In the infection experiments, the levels of extracellular HBeAg, intracellular HBV total RNA and pgRNA/preC mRNA in D- and E-type strains were markedly higher than C and H-type ones. Our data suggest that the preS1 N-termini affect HBV replication, secretion and infectivity in a genotype dependent manner. The C- and H-type strains prefer to attenuate HBsAg secretion, while the strains of D- and E-type promoted infectivity. The existence and function of the intergenotypic shift of preS1 in naturally occurring recombination requires further investigation, as the data we acquired are mostly related to recombinant preS1 region between N-terminus of preS1 from genotypes A-H and the remaining preS1 portion of GTC or GTD.

A novel cell culture model reveals the viral interference during hepatitis B and C virus coinfection.

Coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may result in severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests that HBV replication is suppressed by replicating HCV and often rebounds after treatment with drugs against HCV. Thus, a highly efficient cell culture system permissive for HBV/HCV would facilitate investigation on the interaction and pathogenesis after coinfection. Here we reported a robust HBV/HCV coinfection cell culture model by overexpressing human sodium-taurocholate cotransporting polypeptide (NTCP), CD81 and Mir122 into HepG2 cells and investigated interactions between HBV and HCV. In this system, HepG2-NTCP/CD81/Mir122 cells not only supported robust infection and replication of HBV and HCV, but also allowed HBV/HCV coinfection in the single cell level. Our result showed cells with replicating HBV still supported HCV infection. However, HBV replication was suppressed by HCV through the inhibition of HBV core promoter and S promoter II activity, and this inhibition was attenuated by the interferon alpha (IFNα) treatment, suggesting HCV influence on HBV at transcriptional level. Coinfection of HBV/HCV in this system did not block IFN stimulated genes expression. Inhibition of HCV by direct-acting antiviral drugs restored HBV replication and expression of viral genes. Conclusions: HepG2-NTCP/CD81/Mir122 fully supports HBV/HCV coinfection, replication and interaction. This novel cell model offers a platform to advance our understanding of the molecular details of the interaction, pathogenesis and outcomes of HBV/HCV coinfection.

Evidence of flat bands and correlated states in buckled graphene superlattices.

Two-dimensional atomic crystals can radically change their properties in response to external influences, such as substrate orientation or strain, forming materials with novel electronic structure1-5. An example is the creation of weakly dispersive, 'flat' bands in bilayer graphene for certain 'magic' angles of twist between the orientations of the two layers6. The quenched kinetic energy in these flat bands promotes electron-electron interactions and facilitates the emergence of strongly correlated phases, such as superconductivity and correlated insulators. However, the very accurate fine-tuning required to obtain the magic angle in twisted-bilayer graphene poses challenges to fabrication and scalability. Here we present an alternative route to creating flat bands that does not involve fine-tuning. Using scanning tunnelling microscopy and spectroscopy, together with numerical simulations, we demonstrate that graphene monolayers placed on an atomically flat substrate can be forced to undergo a buckling transition7-9, resulting in a periodically modulated pseudo-magnetic field10-14, which in turn creates a 'post-graphene' material with flat electronic bands. When we introduce the Fermi level into these flat bands using electrostatic doping, we observe a pseudogap-like depletion in the density of states, which signals the emergence of a correlated state15-17. This buckling of two-dimensional crystals offers a strategy for creating other superlattice systems and, in particular, for exploring interaction phenomena characteristic of flat bands.

Charge order and broken rotational symmetry in magic-angle twisted bilayer graphene.

Bilayer graphene can be modified by rotating (twisting) one layer with respect to the other. The interlayer twist gives rise to a moiré superlattice that affects the electronic motion and alters the band structure1-4. Near a 'magic angle' of twist2,4, where the emergence of a flat band causes the charge carriers to slow down3, correlated electronic phases including Mott-like insulators and superconductors were recently discovered5-8 by using electronic transport. These measurements revealed an intriguing similarity between magic-angle twisted bilayer graphene and high-temperature superconductors, which spurred intensive research into the underlying physical mechanism9-14. Essential clues to this puzzle, such as the symmetry and spatial distribution of the spectral function, can be accessed through scanning tunnelling spectroscopy. Here we use scanning tunnelling microscopy and spectroscopy to visualize the local density of states and charge distribution in magic-angle twisted bilayer graphene. Doping the sample to partially fill the flat band, we observe a pseudogap phase accompanied by a global stripe charge order that breaks the rotational symmetry of the moiré superlattice. Both the pseudogap and the stripe charge order disappear when the band is either empty or full. The close resemblance to similar observations in high-temperature superconductors15-21 provides new evidence of a deeper link underlying the phenomenology of these systems.

Visualizing Strain-Induced Pseudomagnetic Fields in Graphene through an hBN Magnifying Glass.

Graphene's remarkable properties are inherent to its two-dimensional honeycomb lattice structure. Its low dimensionality, which makes it possible to rearrange the atoms by applying an external force, offers the intriguing prospect of mechanically controlling the electronic properties. In the presence of strain, graphene develops a pseudomagnetic field (PMF) that reconstructs the band structure into pseudo Landau levels (PLLs). However, a feasible route to realizing, characterizing and controlling PMFs is still lacking. Here we report on a method to generate and characterize PMFs in a graphene membrane supported on nanopillars. A direct measure of the local strain is achieved by using the magnifying effect of the moiré pattern formed against a hexagonal boron nitride substrate under scanning tunneling microscopy. We quantify the strain-induced PMF through the PLLs spectra observed in scanning tunneling spectroscopy. This work provides a pathway to strain induced engineering and electro-mechanical graphene-based devices.

High thermoelectricpower factor in graphene/hBN devices.

Fast and controllable cooling at nanoscales requires a combination of highly efficient passive cooling and active cooling. Although passive cooling in graphene-based devices is quite effective due to graphene's extraordinary heat conduction, active cooling has not been considered feasible due to graphene's low thermoelectric power factor. Here, we show that the thermoelectric performance of graphene can be significantly improved by using hexagonal boron nitride (hBN) substrates instead of SiO2 We find the room temperature efficiency of active cooling in the device, as gauged by the power factor times temperature, reaches values as high as 10.35 W⋅m-1⋅K-1, corresponding to more than doubling the highest reported room temperature bulk power factors, 5 W⋅m-1⋅K-1, in YbAl3, and quadrupling the best 2D power factor, 2.5 W⋅m-1⋅K-1, in MoS2 We further show that the Seebeck coefficient provides a direct measure of substrate-induced random potential fluctuations and that their significant reduction for hBN substrates enables fast gate-controlled switching of the Seebeck coefficient polarity for applications in integrated active cooling devices.