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G-quadruplex structures formed by guanine-rich nucleic acids are implicated in essential physiological and pathological processes and nanodevices. G-quadruplexes are normally composed of four Gn (n≥ 3) tracts assembled into a core of multiple stacked G-quartet layers. By dimethyl sulfate footprinting, circular dichroism spectroscopy, thermal melting, and photo-cross-linking, here we describe a unique type of intramolecular G-quadruplex that forms with one G₂ and three G₃ tracts and bears a guanine vacancy (G-vacancy) in one of the G-quartet layers. The G-vacancy can be filled up by a guanine base from GTP or GMP to complete an intact G-quartet by Hoogsteen hydrogen bonding, resulting in significant G-quadruplex stabilization that can effectively alter DNA replication in vitro at physiological concentration of GTP and Mg2+. A bioinformatic survey shows motifs of such G-quadruplexes are evolutionally selected in genes with unique distribution pattern in both eukaryotic and prokaryotic organisms, implying such G-vacancy–bearing G-quadruplexes are present and play a role in gene regulation. Because guanine derivatives are natural metabolites in cells, the formation of such G-quadruplexes and guanine fill-in (G-fill-in) may grant an environment-responsive regulation in cellular processes. Our findings thus not only expand the sequence definition of G-quadruplex formation, but more importantly, reveal a structural and functional property not seen in the standard canonical G-quadruplexes.

Nanobodies have emerged as promising tools in biomedicine due to their single-chain structure and inherent stability. They generally have convex paratopes, which potentially prefer different epitope sites in an antigen compared to traditional antibodies. In this study, a synthetic phage display nanobody library was constructed and used to identify nanobodies targeting a tumor-associated antigen, the human B7-H3 protein. Combining next-generation sequencing and single-clone validation, two nanobodies were identified to specifically bind B7-H3 with medium nanomolar affinities. Further characterization revealed that these two clones targeted a different epitope compared to known B7-H3-specific antibodies, which have been explored in clinical trials. Furthermore, one of the clones, dubbed as A6, exhibited potent antibody-dependent cell-mediated cytotoxicity (ADCC) against a colorectal cancer cell line with an EC50 of 0.67 nM, upon conversion to an Fc-enhanced IgG format. These findings underscore a cost-effective strategy that bypasses the lengthy immunization process, offering potential rapid access to nanobodies targeting unexplored antigenic sites.

Developing broad-spectrum influenza vaccines is crucial for influenza control and potential pandemic preparedness. Here, we reported a novel vaccine design utilizing circular RNA (circRNA) as a delivery platform for multi-subtype neuraminidases (NA) (influenza A N1, N2, and influenza B Victoria lineage NA) immunogens. Individual NA circRNA lipid nanoparticles (LNP) elicited robust NA-specific antibody responses with neuraminidase inhibition activity (NAI), preventing the virus from egressing and infecting neighboring cells. Additionally, the administration of circRNA LNP induced cellular immunity in mice. To achieve a universal influenza vaccine, we combined all three subtypes of NA circRNA-LNPs to generate a trivalent circRNA vaccine. The trivalent vaccine elicited a balanced antibody response against all three NA subtypes and a Th1-biased immune response in mice. Moreover, it protected mice against the lethal challenge of matched and mismatched H1N1, H3N2, and influenza B viruses, encompassing circulating and ancestral influenza virus strains. This study highlights the potential of delivering multiple NA antigens through circRNA-LNPs as a promising strategy for effectively developing a universal influenza vaccine against diverse influenza viruses.

G-quadruplexes (G4s) formed by guanine-rich nucleic acids play a role in essential biological processes such as transcription and replication. Besides the >1.5 million putative G-4–forming sequences (PQSs), the human genome features >640 million single-nucleotide variations (SNVs), the most common type of genetic variation among people or populations. An SNV may alter a G4 structure when it falls within a PQS motif. To date, genome-wide PQS–SNV interactions and their impact have not been investigated. Herein, we present a study on the PQS–SNV interactions and the impact they can bring to G4 structures and, subsequently, gene expressions. Based on build 154 of the Single Nucleotide Polymorphism Database (dbSNP), we identified 5 million gains/losses or structural conversions of G4s that can be caused by the SNVs. Of these G4 variations (G4Vs), 3.4 million are within genes, resulting in an average load of >120 G4Vs per gene, preferentially enriched near the transcription start site. Moreover, >80% of the G4Vs overlap with transcription factor–binding sites and >14% with enhancers, giving an average load of 3 and 7.5 for the two regulatory elements, respectively. Our experiments show that such G4Vs can significantly influence the expression of their host genes. These results reveal genome-wide G4Vs and their impact on gene activity, emphasizing an understanding of genetic variation, from a structural perspective, of their physiological function and pathological implications. The G4Vs may also provide a unique category of drug targets for individualized therapeutics, health risk assessment, and drug development.

G-quadruplex (G4) structures formed by guanine-rich nucleic acids are implicated in essential physiological processes and serve as important drug targets. The genome-wide detection of G4s in living cells is important for exploring the biological role of G4s but has not yet been achieved due to the lack of a suitable G4 probe. We engineered a 6.7 kDa G4 probe (G4P) protein that binds G4s with high affinity and specificity. We used it to capture G4s in living human, mouse, and chicken cells with the ChIP-Seq technology, yielding genome-wide landscape as well as details on the positions, frequencies, and sequence identities of G4 formation in these cells. Our results indicate that transcription is accompanied by a robust formation of G4s in genes. In human cells, we detected up to >123,000 G4 peaks, of which >1/3 had a fold increase of ≥5 and were present in >60% promoters and ~70% genes. Being much smaller than a scFv antibody (27 kDa) or even a nanobody (12-15 kDa), we expect that the G4P may find diverse applications in biology, medicine, and molecular devices as a G4 affinity agent. Competing Interest Statement The authors have declared no competing interest. Footnotes * https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE133379

Random needle embroidery (RNE) is a graceful art enrolled in the world intangible cultural heritage. In this paper, we study the stitch layout problem and propose a controllable stitch layout strategy for RNE. Using our method, a user can easily change the layout styles by adjusting several high-level layout parameters. This approach has three main features: firstly, a stitch layout rule containing low-level stitch attributes and high-level layout parameters is designed; secondly, a stitch neighborhood graph is built for each region to model the spatial relationship among stitches; thirdly, different stitch attributes (orientations, lengths, and colors) are controlled using different reaction-diffusion processes based on a stitch neighborhood graph. Moreover, our method supports the user in changing the stitch orientation layout by drawing guide curves interactively. The experimental results show its capability for reflecting various stitch layout styles and flexibility for user interaction.

Two kinds of 90Cu10 Ni tubes with different service lives（more than 3 years and only 1 year,respectively）under identical working conditions were studied by an immersion test in a 3.5 wt% NaCl solution and the electron backscattered diffraction（EBSD） technique.The morphology after immersion showed severer corrosion attack at the grain boundaries of the tube with shorter service life compared with the tube with longer service life.The grain boundary characterization distributions（GBCDs） of the two tubes obtained by EBSD revealed more Σ3 boundaries and twins,and larger random boundary meshes in the tube with longer service life.A short immersion test in a modified Livingston＇s solution was conducted to evaluate the tendency to corrosion attack of different types of the grain boundaries.SEM and AFM were used to characterize the corrosion morphologies of the boundaries.A strong correlation between varying depths of corrosion grooves and types of the grain boundaries was obtained.The influence of deviation angle of low Σ boundaries on corrosion resistance of the grain boundaries was also discussed.It is concluded that a special ‘‘grain boundary engineering＇＇（GBE） treatment has been performed on the tube with longer service life.It is proposed that the optimized GBCD is responsible for the better service performance of the tube.

Electrochemical noise data in the presence of different corrosion types were analyzed. A correlation between the corrosion type of the observed noise and the entropy rate was recognized. A sequence was transformed from each set of original electrochemical noise signal, then the Markov process M and stationary distribution μ were calculated. Finally, entropy rate of each sequence was obtained by the definition. From the entropy rate, it has been observed that local corrosion showed a lower entropy rate, while uniform corrosion showed a higher entropy rate.

The combustion process of Yangquan anthracite(YQ) with the addition of 0.045wt%, 0.211wt%, 1.026wt%, and 2.982wt% chlorine was investigated using a thermogravimetric method from an ambient temperature to 1173 K in an air atmosphere. Results show that the YQ combustion characteristics are not significantly affected by an increase in chlorine content. Data acquired for combustion conversion are then further processed for kinetic analysis. Average apparent activation energies determined using the model-free method(specifically the KAS method) are 103.025, 110.250, 99.906, and 110.641 k J/mol, respectively, and the optimal kinetic model for describing the combustion process of chlorine-containing YQ is the nucleation kinetic model, as determined by the z(α) master plot method. The mechanism function of the nucleation kinetic model is then employed to estimate the pre-exponential factor, by making use of the compensation effect. The kinetic models to describe chlorine-containing YQ combustion are thus obtained through advanced determination of the optimal mechanism function, average apparent activation energy, and the pre-exponential factor.

The combustion process of Yangquan anthracite（YQ） with the addition of 0.045wt%, 0.211wt%, 1.026wt%, and 2.982wt% chlorine was investigated using a thermogravimetric method from an ambient temperature to 1173 K in an air atmosphere. Results show that the YQ combustion characteristics are not significantly affected by an increase in chlorine content. Data acquired for combustion conversion are then further processed for kinetic analysis. Average apparent activation energies determined using the model-free method（specifically the KAS method） are 103.025, 110.250, 99.906, and 110.641 k J/mol, respectively, and the optimal kinetic model for describing the combustion process of chlorine-containing YQ is the nucleation kinetic model, as determined by the z（α） master plot method. The mechanism function of the nucleation kinetic model is then employed to estimate the pre-exponential factor, by making use of the compensation effect. The kinetic models to describe chlorine-containing YQ combustion are thus obtained through advanced determination of the optimal mechanism function, average apparent activation energy, and the pre-exponential factor.