DNA Structure Research Articles

A Highly Tumor-Permeating DNA Nanoplatform for Efficient Remodeling of Immunosuppressive Tumor Microenvironments.

The immunosuppressive tumor microenvironment and limited intratumoral permeation have largely constrained the outcome of tumor therapy. Herein, we report a tailored DNA structure-based nanoplatform with striking tumor-penetrating capability for targeted remodeling of the immunosuppressive tumor microenvironment in vivo. In our design, chemo-immunomodulator (gemcitabine) can be precisely grafted on DNA sequences through a reactive oxygen species (ROS)-sensitive linker. After self-assembly, the gemcitabine-grafted DNA structure can site-specifically organize legumain-activatable melittin pro-peptide (promelittin) on each vertex for intratumoral delivery and further function as the template to load photosensitizers (methylene blue) for ROS production. The tailored DNA nanoplatform can achieve targeted accumulation, highly improved intratumoral permeation, and efficient immunogenic cell death of tumor cells by laser irradiation. Finally, the immunosuppressive tumor microenvironment can be successfully remodeled by reducing multi-type immunosuppressive cells and enhancing the infiltration of cytotoxic lymphocytes in the tumor. This rationally developed multifunctional DNA nanoplatform provides a new avenue for the development of tumor therapy.

A Highly Tumor‐Permeating DNA Nanoplatform for Efficient Remodeling of Immunosuppressive Tumor Microenvironments

AbstractThe immunosuppressive tumor microenvironment and limited intratumoral permeation have largely constrained the outcome of tumor therapy. Herein, we report a tailored DNA structure‐based nanoplatform with striking tumor‐penetrating capability for targeted remodeling of the immunosuppressive tumor microenvironment in vivo. In our design, chemo‐immunomodulator (gemcitabine) can be precisely grafted on DNA sequences through a reactive oxygen species (ROS)‐sensitive linker. After self‐assembly, the gemcitabine‐grafted DNA structure can site‐specifically organize legumain‐activatable melittin pro‐peptide (promelittin) on each vertex for intratumoral delivery and further function as the template to load photosensitizers (methylene blue) for ROS production. The tailored DNA nanoplatform can achieve targeted accumulation, highly improved intratumoral permeation, and efficient immunogenic cell death of tumor cells by laser irradiation. Finally, the immunosuppressive tumor microenvironment can be successfully remodeled by reducing multi‐type immunosuppressive cells and enhancing the infiltration of cytotoxic lymphocytes in the tumor. This rationally developed multifunctional DNA nanoplatform provides a new avenue for the development of tumor therapy.

Development of a novel computational technique to create DNA and cell geometrical models for Geant4-DNA

BackgroundThis study aimed to develop a novel human cell geometry for the Geant4-DNA simulation toolkit that explicitly incorporates all 23 chromosome pairs of the human cell. This approach contrasts with the existing, default human cell, geometrical model, which utilizes a continuous Hilbert curve. MethodsA Python-based tool named “complexDNA” was developed to facilitate the design of both simple and complex DNA geometries. This tool was employed to construct a human cell geometry with individual pairs of chromosomes. Subsequently, the performance of this chromosomal model was compared to the standard human cell model provided in the “molecularDNA” Geant4-DNA example. ResultsSimulations using the new chromosomal model revealed minimal discrepancies in DNA damage yield and fragment size distribution compared to the default human cell model. Notably, the chromosomal model demonstrated significant computational efficiency, requiring approximately three times less simulation time to achieve equivalent results. ConclusionsThis work highlights the importance of incorporating chromosomal structure into human cell models for radiation biology research. The “complexDNA” tool offers a valuable resource for creating intricate DNA structures for future studies. Further refinements, such as implementing smaller voxels for euchromatin regions, are proposed to enhance the model’s accuracy.

Chronic interferon-stimulated gene transcription promotes oncogene-induced breast cancer.

The MRE11 complex (comprising MRE11, RAD50, and NBS1) is integral to the maintenance of genome stability. We previously showed that a hypomorphic Mre11 mutant mouse strain (Mre11 ATLD1/ATLD1 ) was highly susceptible to oncogene-induced breast cancer. Here we used a mammary organoid system to examine which MRE11-dependent responses are tumor-suppressive. We found that Mre11 ATLD1/ATLD1 organoids exhibited an elevated interferon-stimulated gene (ISG) signature and sustained changes in chromatin accessibility. This Mre11 ATLD1/ATLD1 phenotype depended on DNA binding of a nuclear innate immune sensor, IFI205. Ablation of Ifi205 in Mre11 ATLD1/ATLD1 organoids restored baseline and oncogene-induced chromatin accessibility patterns to those observed in WT. Implantation of Mre11 ATLD1/ATLD1 organoids and activation of the oncogene led to aggressive metastatic breast cancer. This outcome was reversed in implanted Ifi205 -/- Mre11 ATLD1/ATLD1 organoids. These data reveal a connection between innate immune signaling and tumor development in the mammary epithelium. Given the abundance of aberrant DNA structures that arise in the context of genome instability syndromes, the data further suggest that cancer predisposition in those contexts may be partially attributable to chronic innate immune transcriptional programs.

Chloroplast genome sequencing and divergence analysis of 18 Pyrus species: insights into intron length polymorphisms and evolutionary processes

Pears constitute an essential temperate crop and are primarily produced through interspecific hybridization owing to self-incompatibility that complicates their breeding history. To address this, we sequenced the complete chloroplast (cp) genomes of 18 Pyrus and one Malus species using the Illumina HiSeq4000 platform. The cp genomes ranged from 159,885 bp to 160,153 bp and exhibited a conserved circular DNA structure with an average GC content of 36.5%. Each cp genome contained 127 genes, including 83 protein-coding, 36 tRNA, and 8 rRNA genes. Divergence analysis with mVISTA showed high conservation in the coding regions and notable variations in the non-coding regions. All species shared 17 intron-containing genes, with ycf3 and clpP each having two introns. Five intron-containing genes (ndhB, rpl2, rps12, trnA-UGC, and trnE-UUC) were located in the inverted repeat regions, while trnL-UAA was located in the large single-copy region, with conserved intron lengths across Pomoideae. We identified polymorphic intron sequences in the rpl22, petB, clpP, ndhA, and rps16 genes and designed primers for these regions. Notably, the two Pyrus ussuriensis accessions Doonggeullebae and Cheongdangrori showed intron-length polymorphisms despite being classified as the same species. Phylogenetic analysis of the cp genome sequences revealed two major clusters, indicating distinct maternal lineages and evolutionary origins. This study underscores the importance of cp gene polymorphisms in P. fauriei, P. calleryana, P. ussuriensis, and P. pyrifolia, providing valuable insights into Pyrus evolution as well as aiding in the conservation and breeding of pear germplasm.

In vitro and In Silico Molecular Modeling Studies of Newly Synthesized Pyrrole Derivatives for their Antimicrobial and Anticancer Properties

Background: Pyrroles are biologically active scaffolds that can have a number of different effects. They also have unique pharmacophores inside their ring system that make it easier to make molecules that are more active. Significantly, in the past ten years, research has been conducted on the anti-bacterial properties, with a particular emphasis on drug-resistant Gram-positive and Gram-negative pathogens such as mycobacteria. Additionally, scaffolds based on pyrroles were utilized in the production of anti-tumor medicines that function by modulating or suppressing genes. Objective: This research aimed to create new pyrrole derivatives by chemical means and evaluate their antimicrobial and anticancer properties. Methods: By reacting diverse 1H-pyrrole-2-carbohydrazide derivatives with benzaldehyde under normal conditions, a number of pyrrole variations were created. IR, mass spectroscopy, NMR, and elemental analysis were used to characterize the synthesized compounds. The serial dilution method was used to assess antimicrobial activity, along with a molecular docking study against the enzyme α-topoisomerase II (α-Topo II), which effectively controls the topology of DNA. This enzyme is strongly expressed in rapidly dividing cells and is crucial for transcription, replication, and chromosome structure. Pyrrole and its synthetic derivatives are known to exhibit strong anticancer activity by specifically targeting α-Topo II, which has led multiple researchers to investigate α-Topo II inhibitors as potential anticancer medicines. Consequently, designing pyrroline derivatives is interesting since the succinimide portion of the joined heteroaromatic molecule can selectively engage with the ATP binding pocket via the hydrogen bond network. Newer synthesized compounds were also docked via Schrodinger 2022-4 into the active pocket of the three-dimensional crystallographic structure of the ATP site of human topoisomerase IIα (htopo IIα) (PDB ID: 1zxm). Results: Among the newly synthesized pyrrole derivatives, compounds demonstrated significant anti- microbial activity. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Compounds 1a and 1h were found to have a stronger antiproliferative effect than compounds against MCF-07 breast cancer cell linen our study, ligands 1a and 1b exhibited better binding energies of -5.049 and -5.035 kcal/mol, respectively. Most of the synthesized pyrrole derivatives showed promising antiproliferative effects; however, further in vivo investigations are needed to confirm or refute these results. Conclusion: The results of this investigation show that pyrrole derivatives have the potential to be effective antimicrobial and anticancer agents. While resolving safety issues, the structural alterations carried out in this study enhanced the compounds' medicinal capabilities. To clarify the underlying mechanisms of action and enhance the pharmacological characteristics of these new pyrrole derivatives, further research is necessary.

Efficient Storage and Analysis of Genomic Data: A k-mer Frequency Mapping and Image Representation Method.

k-mer frequencies are crucial for understanding DNA sequence patterns and structure, with applications in motif discovery, genome classification, and short read assembly. However, the exponential increase in the dimension of frequency tables with increasing k-mer length poses storage challenges. In this study, we present a novel method for compressing k-mer data without information loss, aiming to optimize storage and analysis processes. We employed Chaos Game Representation (CGR) to map k-mers to coordinates and used these components to generate raster images of k-mers. The CGR maps were partitioned and labeled based on substrings, with each substring mapped to a subframe, creating a fractal-like structure. The entire k-mer frequency set of each genomic sequence was represented as a single image, with each pixel corresponding to a specific k-mer and its occurrence. This approach reduced file size by up to 16-fold compared to plain text and 3-fold compared to binary format. Furthermore, we demonstrated the feasibility of performing alignment-free similarity analyses on images derived from k-mer frequencies of whole genome sequences from 14 plant species. Our results highlight the potential of this method as a fast and efficient tool for accessing, processing, and analyzing large biological sequence datasets, enabling the retrieval of k-mer frequencies and image reconstruction.

Highly Efficient AIE-Active palmatine photosensitizer for photodynamic inactivation of Listeria monocytogenes in apple juice preservation

Photodynamic sterilization is a promising alternative to conventional antibacterial approaches with merits of high efficiency and safety. The exploration of aggregation-induced emission (AIE)-type photosensitizers from natural sources is highly valued by researchers and food industry. Herein, the use of palmatine (PA), an aggregation-induced emission-active natural product from traditional Chinese medicine, as photosensitizers for photodynamic inactivation of a tenacious foodborne pathogen of Listeria monocytogenes is investigated. Antibacterial and antibiofilm activity against L. monocytogenes of PA-mediated photodynamic process were first assessed. The results showed that PA-mediated photodynamic process could inhibit the growth of L. monocytogenes, and the minimum bactericidal concentration was determined as 80 μM. At this PA dosing level, well-established biofilms of L. monocytogenes can be effectively destroyed under light irritation. Afterward, cell- and gene-level investigations were conducted to explore the antibacterial mechanism. It is concluded that the exceptional photodynamic antibacterial activity of PA against L. monocytogenes is attributed to the disruption of the cell wall and membrane, increased cell permeability, leakage of functional proteins, and damage to DNA structure. Subsequently, PA-mediated photodynamic process was applied to reduce bacterial activity in apple juice while preserving its quality. Overall, this work highlights the significant potential of PA-mediated photodynamic strategy for controlling foodborne pathogens in food systems.

Ni(II) Cylinders Damage DNA in Cancer Cells and Preferentially Bind Y-Shaped DNA Three-Way Junctions Blocking DNA Synthesis.

DNA three-way junctions are critical in various biological processes and hold significant potential for disease treatment and therapeutic applications. In this study, it is demonstrated that triple-stranded dinuclear [Ni2L3]4+ cylinders (L = C25H20N4) exhibit a preferential binding affinity for Y-shaped DNA three-way junctions (3WJs), even in the presence of an excess of competing DNA structures, including G-quadruplexes. Notably, the investigated Ni(II) cylinders are capable of halting DNA synthesis catalyzed by DNA polymerase by stabilizing the 3WJ on the template strand. Using an extended 1D nanoarchitecture model, it is further established the high affinity and selectivity of the cylinders for DNA 3WJs and explored their potential application in stabilizing short-armed 3WJs for constructing DNA nanomaterials. The combined use of Ni(II) cylinders and DNA damage response inhibitors also revealed that the cylinders promote DNA damage, leading to the formation of double-strand breaks. This effect is likely associated with i) the binding of cylinders to 3WJs and ii) the cytotoxic activity of the cylinders in cancer cells.

Metal Ion-Condensed DNA Nanoparticle Library: Phase Separation and Transition and Antisense Therapy Applications.

DNA condensation has long been investigated as a fundamental cellular activity and is known to be driven by the mediation of diverse condensing agents. The phase behaviors of DNA during condensation are particularly interesting because the complicated molecular structure of natural nucleotides fundamentally allows electrostatic, coordinate covalent, and various other secondary interactions with the condensing agents. Recently, metal ion (Mn+)-induced DNA condensation has emerged as a powerful approach to synthesizing nanoparticulate DNA structures suitable for therapeutic gene delivery. However, how the DNA phase changes during Mn+-induced DNA condensation has rarely been observed and is not understood yet. In this study, a library of Mn+-condensed DNA nanoparticles (Mn+-CDNPs) was established using 30 different types of Mn+s, and their phase behaviors during condensation were elucidated using spherical nucleic acids (SNAs) as electron microscopic labels. Importantly, the phase transition and separation of DNA were demonstrated to be driven by the Mn+s into either the growth of individual DNA particles or the fission of bulky DNA aggregates. Pt2+ and Eu3+ were chosen as model systems for the demonstration. The hard and soft acid nature of Mn+ is presumably the underlying driving force of these phase transitions. In addition, the Mn+-controlled anticancer therapeutic efficiency of the Mn+-CDNP library as a state-of-the-art gene delivery platform was demonstrated even for unmodified antisense oligonucleotides in association with the potential toxicity of the Mn+s released from the Mn+-CDNPs. This comprehensive study of the Mn+-dependent condensation of nucleic acids provides profound insights into the chemistry of the nucleic acid-Mn+ interactions and the reliable theragnostic applications of Mn+-CDNPs as functional nucleic acid nanostructures.

Evidence for a Miocene pulse of diversification of the tropical American clade of the Brazil nut family (Lecythidaceae)

ABSTRACT The tropical American species of the Brazil nut family, Lecythidaceae, are abundant in the tree flora, with some economically important species. Yet, the phylogenetic relationships and pace of diversification within this family are understudied. Here, we used shotgun sequencing data for 86 of the 228 currently accepted species in the exclusively tropical American subfamily Lecythidoideae in a phylogenomic context. For each sampled species, we built the full plastid DNA sequence, and also extracted nuclear DNA for 571 regions using the new bioinformatics pipeline REFMAKER, which we used to produce a time-calibrated phylogenetic hypothesis. Our analysis shows that phylogenetic inference from plastid and nuclear DNA alignments resulted in different topologies. The nuclear DNA topology strongly suggests that genus Lecythis should be split into at least four genera. Samples of the genus Eschweilera formed a monophyletic group, with the exception of one sampled species (Eschweilera amazoniciformis S.A.Mori). The Bertholletia clade, which contains the majority of the Lecythidoideae species, and all Lecythis and Eschweilera species, started diversifying around 27.5 Ma, with an accelerated rate of diversification starting in the middle Miocene (c. 12 Ma). The clade sister to Bertholletia (including Corythophora, Eschweilera, and Corrugata, Chartacea and Poiteaui clades) includes at least 124 species and it has diversified less than 10 Ma. This time frame of diversification coincides with major changes in tropical American landscapes and climate associated with the Andean uplift.

Torsion is a Dynamic Regulator of DNA Replication Stalling and Reactivation.

The inherent helical structure of DNA dictates that a replisome must rotate relative to DNA during replication, presenting inevitable topological challenges to replication. However, little is known about how the replisome progresses against torsional stress. Here, we developed a label-free, high-resolution, real-time assay to monitor replisome movement under torsion. We visualized the replisome rotation of DNA and determined how the replisome slows down under torsion. We found that while helicase or DNA polymerase (DNAP) individually is a weak torsional motor, the replisome composed of both enzymes is the most powerful DNA torsional motor studied to date. It generates ∼ 22 pN·nm of torque before stalling, twice the stall torque of E. coli RNA polymerase. Upon replisome stalling, the specific interaction between helicase and DNAP stabilizes the fork junction; without it, the fork can regress hundreds of base pairs. We also discovered that prolonged torsion-induced stalling inactivates the replisome. Surprisingly, DNAP exchange, mediated by the helicase, is highly effective in facilitating replication restart, but only if excess DNAP is present during stalling. Thus, helicase and DNA polymerase work synergistically as a powerful torsional motor, and their dynamic and fluid interactions are crucial for maintaining fork integrity under torsional stress. This work demonstrates that torsion is a strong regulator of DNA replication stalling and reactivation.

DDX41 dissolves G-quadruplexes to maintain erythroid genome integrity and prevent cGAS-mediated cell death.

Deleterious germline DDX41 variants constitute the most common inherited predisposition disorder linked to myeloid neoplasms (MNs). The role of DDX41 in hematopoiesis and how its germline and somatic mutations contribute to MNs remain unclear. Here we show that DDX41 is essential for erythropoiesis but dispensable for the development of other hematopoietic lineages. Using stage-specific Cre models for erythropoiesis, we reveal that Ddx41 knockout in early erythropoiesis is embryonically lethal, while knockout in late-stage terminal erythropoiesis allows mice to survive with normal blood counts. DDX41 deficiency induces a significant upregulation of G-quadruplexes (G4), noncanonical DNA structures that tend to accumulate in the early stages of erythroid precursors. We show that DDX41 co-localizes with G4 on the erythroid genome. DDX41 directly binds to and dissolves G4, which is significantly compromised in MN-associated DDX41 mutants. Accumulation of G4 by DDX41 deficiency induces erythroid genome instability, defects in ribosomal biogenesis, and upregulation of p53. However, p53 deficiency does not rescue the embryonic death of Ddx41 hematopoietic-specific knockout mice. In parallel, genome instability also activates the cGas-Sting pathway, which is detrimental to survival since cGas-deficient and hematopoietic-specific Ddx41 knockout mice are viable without detectable hematologic phenotypes, although these mice continue to show erythroid ribosomal defects and upregulation of p53. These findings are further supported by data from a DDX41 mutated MN patient and human iPSC-derived bone marrow organoids. Our study establishes DDX41 as a G4 dissolver, essential for erythroid genome stability and suppressing the cGAS-STING pathway.

Platinum(II)-Salphen Complexes as DNA Binders and Photosensitisers.

Current anticancer therapies suffer from issues such as off-target side effects and the emergence of drug resistance; therefore, the discovery of alternative therapeutic approaches is vital. These can include the development of drugs with different modes of action, and the exploration of new biomolecular targets. For the former, there has been increasing interest in drugs that are activated by an external stimulus (e. g. light irradiation) to generate cytotoxic chemicals such as reactive oxygen species (ROS). For the latter, significant efforts are being directed to explore non-canonical DNA and RNA structures (e. g. guanine-quadruplexes), as alternative biomolecular targets. Herein we report the synthesis of a library of 21 new platinum(II)-Salphen complexes (square planar platinum(II) complexes coordinated to tetradentate O,N,N,O-Schiff base ligands), and the investigation, for all complexes, of their photophysical and photochemical properties, their interactions with duplex and quadruplex DNA, and their cytotoxicity against HeLa cancer cells both in the dark and upon light irradiation. Thanks to the intrinsic phosphorescence of the platinum(II) complexes, confocal microscopy was used for six of the complexes to determine their cellular permeability and localisation in two cancer cell lines (HeLa and U2OS). Altogether, these studies have allowed us to identify two lead platinum(II) complexes with high guanine-quadruplex DNA affinity and selectivity, good cell permeability and nuclear localisation, and high cytotoxicity against HeLa cancer cells upon irradiation with no detected cytotoxicity in the dark.

Repeat-mediated recombination results in Complex DNA structure of the mitochondrial genome of Trachelospermum jasminoides

BackgroundTrachelospermum jasminoides has medicinal and ornamental value and is widely distributed in China. Although the chloroplast genome has been documented, the mitochondrial genome has not yet been studied.ResultsThe mitochondrial genome of T. jasminoides was assembled and functionally annotated using Illumina and nanopore reads. The mitochondrial genome comprises a master circular molecular structure of 605,764 bp and encodes 65 genes: 39 protein-coding genes, 23 transfer RNA (tRNA) genes and 3 ribosomal RNA genes. In addition to the single circular conformation, we found many alternative conformations of the T. jasminoides mitochondrial genome mediated by 42 repetitive sequences. Six repetitive sequences (DRS01–DRS06) were supported by nanopore long reads, polymerase chain reaction (PCR) amplifications, and Sanger sequencing of the PCR products. Eleven homologous fragments were identified by comparing the mitochondrial and chloroplast genome sequences, including three complete tRNA genes. Moreover, 531 edited RNA sites were identified in the protein-coding sequences based on RNA sequencing data, with nad4 having the highest number of sites (54).ConclusionTo our knowledge, this is the first description of the mitochondrial genome of T. jasminoides. Our results demonstrate the existence of multiple conformations. These findings lay a foundation for understanding the genetics and evolutionary dynamics of Apocynaceae.

Management biofouling of uranium extraction from seawater by ultraviolet technique: Effect of UV wavelength

Marine biofouling is one of the primary limiting factors in uptake of uranium (U(VI)) from seawater. The effects of ultraviolet (UV) wavelength on its elimination capacity for marine biofouling were investigated in detail. V. alginolyticus was used as the representative of marine microorganisms in this work. UV254 irradiation can well reduce the adhesion of V. alginolyticus on poly(amidoxime) (PAO) surface and enhance U(VI) adsorption. The adsorption capacity of PAO for U(VI) increases from 40.7 mg/g to 67.1 mg/g at pH 8.2 and 298 K under UV254 irradiation condition. UV254 irradiation can well damage the DNA structure of V. alginolyticus by photochemistry reaction, and further reduce its extracellular polymeric substances (EPS). The increase of NO3- concentrations promote the yield of ˙OH by UV254 irradiation, and increase the inactivation of V. alginolyticus cells. Biological community results indicate that UV254 irradiation can intercept the reproduction and break the bottleneck of marine microorganisms, and would enhance the extraction of U(VI) from seawater.

The Avoidance of Purine Stretches by Cancer Mutations

Purine stretches, sequences of adenine (A) and guanine (G) in DNA, play critical roles in binding regulatory protein factors and influence gene expression by affecting DNA folding. This study investigates the relationship between purine stretches and cancer development, considering the aromaticity of purines, quantified by methods like Hückel’s rule and NICS calculations, and the importance of the flanking sequence context. A pronounced avoidance of long purine stretches by typical cancer mutations was observed in public data on the intergenic regions of cancer patients, suggesting a role of intergenic sequences in chromatin reorganization and gene regulation. A statistically significant shortening of purine stretches in cancerous tumors (p value < 0.0001) was found. The insights into the aromatic nature of purines and their stacking energies explain the role of purine stretches in DNA structure, contributing to their role in cancer progression. This research lays the groundwork for understanding the nature of purine stretches, emphasizing their importance in gene regulation and chromatin restructuring, and offers potential avenues for novel cancer therapies and insights into cancer etiology.

Direct and Indirect Effects for Radiosensitization of Gold Nanoparticles in Proton Therapy.

The radiosensitization characteristics of gold nanoparticles (GNPs) have been investigated in a single cell irradiated with monoenergetic beams of protons of various energies using TOPAS-nBio, an advanced toolkit of TOPAS. Both direct and indirect effects against single-strand breaks (SSBs) are investigated and their double-strand breaks (DSBs) have been calculated. A single spherical cell interaction with a detailed DNA structure has been modeled and simulated under different conditions such as particle sizes and concentrations of GNPs, their biodistributions and associated proton energies. The physical interaction among protons, suspension water and GNPs has been simulated using a dual physics approach, while the interaction between water radiolysis and OH radicals was considered in the chemical process to save computational time. The present simulations involve irradiating the cell geometry with a dose of 1 Gy. The range of DSBs (Gy-1 Gbp-1) obtained was 2.1 ± 0.09 to 21.74 ± 0.4 for all GNPs of sizes 6-50 nm the proton energies in the range of 5-50 MeV. Regardless of proton energy and GNP size, the calculations showed that the contribution of indirect and hybrid DSBs remains higher in all simulation types than that of direct DSBs. New simulation outcomes of the indirect DSBs illustrate a percentage increase, while we cannot get an increase in the direct and hybrid DSBs in most cases when compared with no GNPs cases. The indirect DSBs provide the highest enhancement factor of 1.89 at 30 nm GNPs in size for 30 MeV protons energy, and the direct and hybrid DSBs indicate a slight increase in enhancement. The work indicates that the use of GNPs increased indirect DNA DSBs, while hybrid DSBs show only a slight increase in enhancement, and no enhancement is shown in direct DNA DSBs. It is significant to consider other mechanisms such as DNA damage repair when investigating DNA damage.

Engineering tunable catch bonds with DNA

Unlike most adhesive bonds, biological catch bonds strengthen with increased tension. This characteristic is essential to specific receptor-ligand interactions, underpinning biological adhesion dynamics, cell communication, and mechanosensing. While artificial catch bonds have been conceived, the tunability of their catch behaviour is limited. Here, we present the fish-hook, a rationally designed DNA catch bond that can be finely adjusted to a wide range of catch behaviours. We develop models to design these DNA structures and experimentally validate different catch behaviours by single-molecule force spectroscopy. The fish-hook architecture supports a vast sequence-dependent behaviour space, making it a valuable tool for reprogramming biological interactions and engineering force-strengthening materials.

The Acid-Stimulated Self-Assembled DNA Nanonetwork for Sensitive Detection and Living Cancer Cell Imaging of MicroRNA-221.

Herein, a novel functional DNA structure, acid-stimulated self-assembly DNA nanonetwork (ASDN), was proposed for miRNA-221 sensitive detection and high-resolution living cancer cell imaging. Significantly, the self-assembly of ASDN only occurred in the acidic extracellular environment of cancer cells, which could be endocytosed by cancer cells to eliminate the interference of noncancer cells and deliver the ASDN into cancer cells. Subsequently, endogenous miRNA-221 could trigger the catalytic hairpin assembly within ASDN, resulting in the separation of the fluorophore Cy5 and the quencher BHQ2 to recover the substantial Cy5 fluorescence signals, thus achieving signal amplification for sensitive detection of miRNA-221 with a detection limit of 5.5 pM, as well as facilitating high-resolution and low-background imaging of miRNA-221 in cancer cells. In consequence, this strategy provides an innovative DNA nanonetwork to distinguish cancer cells from other cells for sensitive detection of biomarkers, offering a meaningful reference for the application of DNA nanostructure self-assembly technology in relevant fundamental research and disease diagnosis.