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While 8-oxo-7,8-dihydro-2′-deoxyguanosine (dOG) on DNA G-quadruplex (G4) has been studied, the influence of 8-oxo-7,8-dihydro-guanosine (rOG) lesions on telomeric repeat-containing RNA (TERRA) G4 d...

As one of the most favorable stimuli, photoactivation provides an advantageous way to manipulate biological objects. In the current study, we have successfully demonstrated the use of light activation guide RNA (gRNA) strategy for controlling CRISPR systems. By conjugating photolabile protecting groups, the CRISPR functions became minimal, but exposure of acylated gRNAs to 365 nm light triggers the removal of masking groups, leading to the rescue of CRISPR functions. Furthermore, our strategy has been successfully used to control gene editing in human cells. This proof-of-concept study therefore demonstrates the promising potential of our strategy to versatile applications in chemical biology.

Object detection and instance segmentation are two fundamental computer vision tasks. They are closely correlated but their relations have not yet been fully explored in most previous work. This paper presents RDSNet, a novel deep architecture for reciprocal object detection and instance segmentation. To reciprocate these two tasks, we design a two-stream structure to learn features on both the object level (i.e., bounding boxes) and the pixel level (i.e., instance masks) jointly. Within this structure, information from the two streams is fused alternately, namely information on the object level introduces the awareness of instance and translation variance to the pixel level, and information on the pixel level refines the localization accuracy of objects on the object level in return. Specifically, a correlation module and a cropping module are proposed to yield instance masks, as well as a mask based boundary refinement module for more accurate bounding boxes. Extensive experimental analyses and comparisons on the COCO dataset demonstrate the effectiveness and efficiency of RDSNet. The source code is available at https://github.com/wangsr126/RDSNet.

Periodontitis is a chronic inflammatory disease caused by plaque that leads to alveolar bone resorption. In the treatment of periodontitis, it is necessary to reduce the bacterial load and promote alveolar bone regeneration. In this study, zeolitic imidazolate framework-8 (ZIF-8) is used in the treatment of periodontitis, and an injectable photopolymerizable ZIF-8/gelatin methacryloyl (GelMA) composite hydrogel (GelMA-Z) is constructed. We confirm that ZIF-8 nanoparticles are successfully loaded into GelMA, which demonstrates fluidity and photopolymerizability. GelMA-Z continuously releases Zn

Siamese trackers are shown to be vulnerable to adversarial attacks recently. However, the existing attack methods craft the perturbations for each video independently, which comes at a non-negligible computational cost. In this paper, we show the existence of universal perturbations that can enable the targeted attack, e.g., forcing a tracker to follow the ground-truth trajectory with specified offsets, to be video-agnostic and free from inference in a network. Specifically, we attack a tracker by adding a universal translucent perturbation to the template image and adding a fake target, i.e., a small universal adversarial patch, into the search images adhering to the predefined trajectory, so that the tracker outputs the location and size of the fake target instead of the real target. Our approach allows perturbing a novel video to come at no additional cost except the mere addition operations – and not require gradient optimization or network inference. Experimental results on several datasets demonstrate that our approach can effectively fool the Siamese trackers in a targeted attack manner. We show that the proposed perturbations are not only universal across videos, but also generalize well across different trackers. Such perturbations are therefore doubly universal, both with respect to the data and the network architectures. Our code is available at https://github.com/lizhenbang56/SiamAttack.

MiRNA is reported as an important biomarker candidate and therapeutic target in a variety of diseases and cancers. However, ultrasensitive, straightforward, isothermal, low-cost and credible methods for the detection of miRNA from clinical specimens still remain challenges. Here, we establish an isothermal, highly sensitive and specific method for miRNA analysis based on a novel ligation-promoted hyperbranched rolling circle amplification (L-HRCA). This strategy exhibits 103-fold sensitivity enhancement compared to T4 ligase-assisted target-primer BRCA. The excellent specificity of L-HRCA allows for discriminating target miRNA from negative miRNAs. This method is applied to analyse the expression level of miR-21 in hepatocellular carcinoma. These results indicated that the L-HRCA strategy will become a promising tool to quantify miRNA in early clinical diagnostics.

Objective This research investigated the biological role of isoprenylcysteine carboxyl methyltransferase (ICMT) in tongue squamous cell carcinoma (TSCC) progression meanwhile to explore the conceivable mechanism. Methods The mRNA and protein expression were measured using real-time PCR and Western blot. Cell proliferation, apoptosis, cycle distribution, migration and invasion were evaluated by CCK-8 assay, flow cytometry, wound-healing assay and transwell assay. The anti-tumor activity of ICMT silencing was observed in nude mice. Results Our results indicated that silencing of ICMT-mediated methylation effectively inhibited TSCC cells proliferation in vitro and reduced tumor growth in vivo. Moreover, ICMT knockdown also induced cell apoptosis and cell cycle arrest of both CAL-27 and SCC-4 cells. In addition, CAL-27 and SCC-4 cells migration and invasion were weakened by ICMT siRNA. Mechanistically, ICMT deficiency significantly decreased the K-Ras and RhoA membrane targeting localization, leading to the suppression of K-Ras- and RhoA-mediated downstream signaling in CAL-27 and SCC-4 cells. Conclusions Altogether, our findings identified a crucial role played by ICMT in the progression of TSCC and the potential mechanisms by which exerted its effects, indicating that targeting ICMT may represent a promising therapeutic strategy for TSCC. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Prokaryotes use repetitive genomic elements termed CRISPR (clustered regularly interspaced short palindromic repeats) to destroy invading genetic molecules. Although CRISPR systems have been widely used in DNA and RNA technology, certain adverse effects do occur. For example, constitutively active CRISPR systems may lead to a certain risk of off-target effects. Here, we introduce post-synthetic masking and chemical activation of guide RNA (gRNA) to controlling CRISPR systems. An RNA structure profiling probe (2-azidomethylnicotinic acid imidazolide) is used. Moreover, we accomplish conditional control of gene editing in live cells. This proof-of-concept study demonstrates promising potential of chemical activation of gRNAs as a versatile tool for chemical biology., Constituitively active CRISPR systems have the risk of adverse off-target effects. Here the authors use chemical masking and activation of gRNA to control activity.

Summary G-quadruplex (G4) is an important type of nucleic acid secondary structure. An abundance of potential G4-forming sites have been shown to exist in genomes, leading to increasing interest in this research field. G4 motifs are thought to be involved in the regulation of diverse biological processes and to interact with various protein factors. Because of their important regulatory functions, G4s could have a variety of applications, the most meaningful of which is the role of G4s as potential targets of antitumor therapies. Here, we focus on the regulatory functions of G4s in tumor-related gene regulation and the use of G4s in the design of antitumor therapies, including relatively recently reported G4-related binding proteins, regulatory mechanisms, and G4-ligand designs. We also introduce G4 probes for the identification of G4 structure formation in live cells. Finally, we describe some challenges in this field and the new G4-related research field.

The identification of hydroxylmethyl- and formylpyrimidines in genomic DNA was a landmark event in epigenetics. Numerous laboratories in related fields are investigating the biology of these and other nucleic acid modifications. However, limitations in the ability to detect and synthesize appropriate modifications are an impediment. Herein, we explored a remarkable development in the selective detection of 5-formyluracil in both single-stranded and double-stranded DNA under mild conditions. The “switch-on” specificity towards 5-formyluracil enabled a high signal-to-noise ratio in qualitatively and quantitatively detecting materials containing 5-formyluracil, which is not affected by the presence of abasic sites and 5-formylcytosine, the modified cytosine counterpart of 5-formyluracil. In summary, the innoxiousness, convenience, and cost-efficiency of the 5-formyluracil phosphoramidite synthetic routine would promote the understanding of the epigenetic role of this natural thymidine modification.

Simultaneous fluorogenic switch-on detection and single-base resolution analysis of 5fC through yielding an intramolecular cyclization nucleobase has been presented., 5-Formylcytosine (5fC), which plays an important role in epigenetic functions, has received widespread attention in many related fields. Here, we demonstrate a new design for both the fluorogenic switch-on detection and single-base resolution analysis of 5fC through selectively reacting a reagent with 5fC to yield an intramolecular cyclization nucleobase. The generated product, bearing a similar benzothiazole-iminocoumarin scaffold, is highly fluorescent and enables us to qualitatively and quantitatively detect 5fC moieties in γ-irradiated calf thymus DNA. Additionally, losing the exocyclic 4-amino group in 5fC causes the incorporation of dATP through base pairing with the generated nucleobase during polymerase extension, which helped us to analyze the 5fC sites in both single- and double-stranded oligonucleotides. Our Sanger and Illumina sequencing results show great potential in single-base resolution analysis of 5fC. It is hopeful that a similar design may be used for more detection targets.

Supramolecular chemistry addresses intermolecular forces and consequently promises great flexibility and precision. Biological systems are often the inspirations for supramolecular research. The G-quadruplex (G4) belongs to one of the most important secondary structures in nucleic acids. Until recently, the supramolecular manipulation of the G4 has not been reported. The present study is the first to disclose a supramolecular switch for the reversible control of human telomere G4s. Moreover, this supramolecular switch has been successfully used to manipulate an enzymatic reaction. Using various methods, we show that cucurbit[7]uril preferably locks and encapsulates the positively charged piperidines of Razo through supramolecular interactions. They can switch the conformations of the DNA inhibitor between a flexible state and the rigid G4 and are therefore responsible for the reversible control of the thrombin activity. Thus, our findings open a promising route and exhibit potential applications in future studies of chemical biology.

Natural nucleic acid bases can form Watson–Crick (WC) or Hoogsteen (HG) base pairs. Importantly, 8-oxo-2′-deoxyguanosine (8-oxo-dG) in DNA or 8-oxo-dG 5′-triphosphate (8-oxo-dGTP) favors a syn conformation because of the steric repulsion between O8 and O4′ of the deoxyribose ring. 8-oxo-dGTP can be incorporated into DNA opposite the templating adenine (A) using HG pairing as the dominant mechanism. Both RNA and DNA can be methylated at the N6 position of A to form N6-methyladenine (m6A). It has been found that certain viral infections may trigger an increase in the production of both 8-oxo-dGTP and m6A. The current study aims to systematically explore the effects of m6A methylation on HG base pairs and the consequent nucleotide incorporation. Our thermodynamic melting study shows that the m6A·8-oxo-dG is significantly less stable than the A·8-oxo-dG base pair in the paired region of a DNA duplex. Moreover, we have used pre-steady-state kinetics to examine the incorporation of 8-oxo-dGTP opposite m6A relative to A by a variety of reverse transcriptase (RT) enzymes and DNA polymerase (DNA pol) enzymes such as the human immunodeficiency virus type 1 (HIV-1) RT and human DNA pol β. The results demonstrate that all of these enzymes incorporate 8-oxo-dGTP less efficiently opposite m6A relative to A. Considering the steric bulk of the purine–purine pair between 8-oxo-dG and A, m6A methylation may affect the HG pairing to a great extent. Hence, it will be unfavorable to incorporate 8-oxo-dGTP into the growing strand opposite m6A. Moreover, the impeded incorporation of 8-oxo-dGTP opposite m6A has been extended to determine m6A at pre-defined positions in human rRNA. Our study may provide new insights into the roles of m6A in reducing the mutagenic potential of cellular 8-oxo-dGTP.

Biotinylated o-phenylenediamine directly tethered to naphthalimide can both enrich and fluorogenically label 5-formyluracil in DNA under physiological conditions., Recently, the detection of natural thymine modified 5-formyluracil has attracted widespread attention. Herein, we introduce a new insight into designing reagents for both the selective biotin enrichment and fluorogenic labelling of 5-formyluracil in DNA. Biotinylated o-phenylenediamine directly tethered to naphthalimide can switch on 5-formyluracil, under physiological conditions, which can then be used in cell imaging after exposure to γ-irradiation. In addition, its labelling property caused the polymerase extension to stop in the 5-formyluracil site, which gave us more information than the fluorescence did itself. The idea of detecting 5-formyluracil might be used in the synthesis of other modified diaminofluoresceins.

The epigenetic modification of nucleic acids represents one of the most significant areas of study in the field of nucleic acids because it makes gene regulation more complex and heredity more complicated, thus indicating its profound impact on aspects of heredity, growth, and diseases. The recent characterization of epigenetic modifications of DNA and RNA using chemical labelling strategies has promoted the discovery of these modifications, and the newly developed single-base or single-cell resolution mapping strategies have enabled large-scale epigenetic studies in eukaryotes. Due to these technological breakthroughs, several new epigenetic marks have been discovered that have greatly extended the scope and impact of epigenetic modifications in nucleic acids over the past few years. Because epigenetics is reversible and susceptible to environmental factors, it could potentially be a promising direction for clinical medicine research. In this review, we have comprehensively discussed how these epigenetic marks are involved in disease, including the pathogenesis, prevention, diagnosis and treatment of disease. These findings have revealed that the epigenetic modification of nucleic acids has considerable significance in various areas from methodology to clinical medicine and even in biomedical applications.

In the present study, our bioinformatics analysis first reveals the existence of a conserved guanine-rich sequence within the Zaire ebolavirus L gene. Using various methods, we show that this sequence tends to fold into G-quadruplex RNA. TMPyP4 treatment evidently inhibits L gene expression at the RNA level. Moreover, the mini-replicon assay demonstrates that TMPyP4 effectively inhibits the artificial Zaire ebolavirus mini-genome and is a more potent inhibitor than ribavirin. Although TMPyP4 treatment reduced the replication of the mutant mini-genome when G-quadruplex formation was abolished in the L gene, its inhibitory effect was significantly alleviated compared with wild-type. Our findings thus provide the first evidence that G-quadruplex RNA is present in a negative-sense RNA virus. Finally, G-quadruplex RNA stabilization may represent a new therapeutic strategy against Ebola virus disease.

In this study, a resorufin derivative RTP-1, which is a novel fluorescent “turn-on” probe for sensitive detection of hydrazine within 30 min, is designed and synthesized. The selective deprotection of the ester group of the probe by hydrazine led to a prominent enhancement of fluorescent intensity, as well as a remarkable color change from colorless to pink, which could be distinguished by naked eye. The fluorescence enhancement showed decent linear relationship with hydrazine concentration ranging from 0 to 50 μmol/L, with a detection limit of 0.84 μmol/L. The specificity of RTP-1 for hydrazine to a number of metal ions, anions and amines is satisfactory. The sensing mechanism of RTP-1 and hydrazine was evaluated by HPLC, ESI mass spectrometry and density functional theory (DFT). Moreover, we have utilized this fluorescent probe for imaging hydrazine in living cells, and the fluorescence was clearly observed when the cells were incubated with hydrazine (100 μmol/L) for 30 min.

N 6-Methyladenine (m6A) is the most abundant internal modification on mammalian mRNA. Very recently, m6A has been reported as a potentially important ‘epigenetic’ mark in eukaryotes. Until now, site-specific detection of m6A is technically very challenging. Here, we first reveal that m6A significantly hinders DNA- and RNA-directed DNA synthesis. Systematic investigations of 5′-triphosphates of a variety of 5-substituted 2′-deoxyuridine analogs in primer extension have been performed. In the current study, a quantitative analysis of m6A in the RNA or DNA context has been achieved, using Bst DNA polymerase catalyzed primer extension. Molecular dynamics study predicted that m6A in template tends to enter into and be restrained in the MGR region of Bst DNA polymerase, reducing conformational flexibility of the DNA backbone. More importantly, a site-specific determination of m6A in human ribosomal RNA (rRNA) with high accuracy has been afforded. Through a cumulative analysis of methylation alterations, we first reveal that significantly cancer-related changes in human rRNA methylation were present in patients with hepatocellular carcinoma.

Herein, we report two distinct G-quadruplex conformations of the same G-rich oligonucleotide, regulated by a small molecule. This is the first report in which both right- and left-handed G-quadruplex conformations have been obtained from the same sequence. We discriminated these two distinct conformations and investigated their kinetics and thermodynamics.

The ability to detect and quantify microRNA (miRNA) could greatly facilitate the comprehension of miRNA-mediated biological process and related disease in more detail. We developed, for the first time, a convenient and efficient strategy for miRNA detection based on direct molecular recognition between initially quenched DNA probes and miRNA targets. The loop region of dual labeled DNA probe with hairpin shape was complementary to target miRNA, which could induce a corresponding conformational switch, a DNA:RNA hybrid duplex was formed with a single-strand DNA overhang, which could be recognized and degraded by various exonucleases, including Exonuclease I (Exo I) and T4 DNA polymerase. Fluorescence enhancement was generated by the degradation, which occurred in the 3′–5′ direction. This method represented a reliable way to distinguish different miRNAs with high homology, such as different members of the miR-200 family. Furthermore, multiplexed miRNAs detection could be achieved with our developed approach. More importantly, this proposed method can distinguish the expression level of miR-21 in human liver tissues between liver cancer tissues and normal tissues. This exonucleation-based fluorescence enhancement strategy holds great promise for further applications in early miRNA-related disease diagnosis and prognosis.

Even a single Gly substitution in the triple helix domain of collagen leads to pathological conditions while natural interruptions are suggested to play important functional roles. Two peptides-one mimicking a pathological Gly-Ser substitution (ERSEQ) and the other one modeling a similar natural interruption sequence (DRSER)-are designed to facilitate the comparison for elucidating the molecular basis of their different biological roles. CD and NMR investigation of peptide ERSEQ indicates a reduction of the thermal stability and disruption of hydrogen bonding at the Ser mutation site, providing a structural basis of the OI disease resulting from the Gly-Ser mutation in the highly charged RGE environment. Both CD and NMR real-time folding results indicate that peptide ERSEQ displays a comparatively slower folding rate than peptide DRSER, suggesting that the Gly-Ser mutation may lead to a larger interference in folding than the natural interruption in a similar RSE context. Our studies suggest that unlike the rigid GPO environment, the abundant R(K)GE(D) motif may provide a more flexible sequence environment that better accommodates mutations as well as interruptions, while the electrostatic interactions contribute to its stability. These results shed insight into the molecular features of the highly charged motif and may aid the design of collagen biomimetic peptides containing important biological sites.

CRISPR (clustered regularly interspaced short palindromic repeats) systems have been established as valuable genome‐editing tools. Controlling CRISPR systems has high biological significance and this field has garnered intense interest. There is a considerable need for simple approaches with no need for protein engineering. The CRISPR systems usually require a guide RNA (gRNA) moiety to recruit and direct the nuclease complexes. In this respect, the ninhydrin (1,2,3‐indantrione monohydrate) seems to have considerable potential, as yet unexploited, for modifying gRNA. In this study, ninhydrin chemistry is explored for reversible postsynthetic modification of gRNA molecules. It is further shown that ninhydrin chemistry is efficient in modulating two important CRISPR systems. Thus, ninhydrin chemistry exhibits potential applications in future chemical biology studies., In this study, ninhydrin chemistry is explored for reversible modification of guide RNA molecules. It is further shown that ninhydrin chemistry is useful in modulating two important clustered regularly interspaced short palindromic repeats systems. Thus, ninhydrin chemistry exhibits potential applications in future chemical biology studies.

As a left‐handed helical structure, Z‐DNA is biologically active and it may be correlated with transcription and genome stability. Until recently, it remained a significant challenge to control the B/Z‐DNA transition under physiological conditions. The current study represents the first to reversibly control B/Z‐DNA transition using cucurbit[7]uril‐based supramolecular approach. It is demonstrated that cucurbit[7]uril can encapsulate the central butanediamine moiety [HN(CH2)4NH] and reverses Z‐DNA caused by spermine back to B‐DNA. The subsequent treatment with 1‐adamantanamine disassembles the cucurbit[7]uril/spermine complex and readily induces reconversion of B‐ into Z‐DNA. The DNA conformational change is unequivocally demonstrated using different independent methods. Direct evidence for supramolecular interactions involved in DNA conformational changes is further provided. These findings can therefore open a new route to control DNA helical structure in a reversible way.

Methods based on fluorescent “turn-on” sensors have been developed for methylglyoxal (MGO) detection, but the two-photon one is hardly ever reported. In this study, a naphthalimide derivative PDN-1, which is a novel two-photon fluorescent “turn-on” probe for rapid and sensitive detection of methylglyoxal, is designed and synthesized. Under physiological conditions, the probe showed minimal background emission, whereas, after interacting with MGO, it exhibited significant fluorescence enhancement (33-fold) through the inhibition of the photoinduced electron transfer (PET) effect. The fluorescence enhancement showed a decent linear relationship with the MGO concentration ranging from 0 to 10 μM, with a detection limit of 77 nM. The mechanism of the PDN-1–MGO reaction was evaluated by 1H, 13C NMR spectroscopy and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The specificity of PDN-1 for MGO to other aldehydes, ions, peroxide and nitric oxide is satisfactory. Imaging MGO in living cells by PDN-1 is also accomplished with high sensitivity and low cytotoxicity.

G-triplex has recently been identified as a new secondary structure in G-rich sequences. However, its functions and biological roles remain largely unknown. This study first developed two kinds of Amplex Red oxidases, which were based on relatively new G-triplex structure and a common G-quadruplex one. A collection of DNA binding assays including circular dichroism (CD) spectroscopy, a CD melting assay, and a UV titration study were used to determine the G-triplex structure of G3 oligomer. The low intrinsic oxidative activity of hemin was significantly enhanced using G-triplex or G-quadruplex. Only one key guanine deletion from the G3 oligomer or G4 one could result in a much decreased Amplex Red oxidation activity. To the best of our knowledge, this is the first case reporting direct use of air as the oxidant for fluorescence generation based on DNAzyme strategies. Further mechanism studies demonstrated an involvement of on-site H2O2 generation from O2 and water and a following oxidation of Amplex Red to resorufin, causing a fluorescence enhancement. Furthermore, the newly developed oxidases have been effectively used in microRNA detection, using only one biotin-labeled probe and one small-molecule substrate. The conjugation of a target DNA to the G-triplex- or G-quadruplex-forming sequence enabled one to produce G-triplex or G-quadruplex by endonuclease in the presence of a slight amount of miRNA and amplify the signal of fluorescence from the oxidation of Amplex Red. Our findings of novel Amplex Red oxidases could potentially be used in a wide range of applications.

Existence of G-quadruplex DNA in vivo always attract widespread interest in the field of biology and biological chemistry. We reported our findings for the existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy. Probes for selective G-quadruplex cross-linking was designed and synthesized that show high selectivity for G-quadruplex cross-linking. Further biological studies demonstrated its good inhibition activity against murine melanoma cells. To further investigate if G-quadruplex DNA was formed in vivo and as the target, a derivative was synthesized and pull-down process toward chromosome DNAs combined with circular dichroism and high throughput deep sequencing were performed. Several simulated intracellular conditions, including X. laevis oocytes, Ficoll 70 and PEG, was used to investigate the compound's pure cross-linking ability upon preformed G-quadruplex. Thus, as a potent G-quadruplex cross-linking agent, our strategy provided both valuable evidence of G-quadruplex structures in vivo and intense potential in anti-cancer therapy.

We have first demonstrated the distinctive effects of three newly reported epigenetic modifications, including 5hmC, 5fC, and 5caC, on B-Z transition of CpG dinucleotide DNAs. We have performed detailed assays and compared their effects. We further studied the regulation of B-Z transition of CpG dinucleotide dodecamers by alternating oxidation and alternating reduction.

To surmount the challenges of the locus determination and accurate quantification of 5-methyl-2'-deoxycytidine ((5Me)dC) in DNA fragments that contain multiple (5Me)dC residues, we designed and synthesized two N-halogeno-N-sodiobenzenesulfonamide reagents that provide a new chemical method for probing (5Me)dC in DNA sequences. When the strategy we provided was combined with β-glucosyltransferase, (5Me)dC could be distinguished from 5-hydroxymethyl-2'-deoxycytidine ((5hm)dC) and deoxycytidine (dC) through the introduction of a glucose moiety to the hydroxyl group of (5hm)dC.

This paper reviews the latest research progress of the nucleic acid probes based on small molecules. The related nucleic acid structures include quadruplex nucleic acids (including G-quadruplex and i-motif), triple-stranded nucleic acid structures, left-handed DNA helix structures, as well as irregular nucleic acid structures (bulge structures and loop structures). The related small molecules includ transition metal complexes, the macrocyclic conjugated compounds, cyclic peptides, and oligosaccharide antibiotics.

A conserved guanine-rich sequence could be a new target for anti–hepatitis C virus drug development., G-quadruplex (G4) is one of the most important secondary structures in nucleic acids. Until recently, G4 RNAs have not been reported in any ribovirus, such as the hepatitis C virus. Our bioinformatics analysis reveals highly conserved guanine-rich consensus sequences within the core gene of hepatitis C despite the high genetic variability of this ribovirus; we further show using various methods that such consensus sequences can fold into unimolecular G4 RNA structures, both in vitro and under physiological conditions. Furthermore, we provide direct evidences that small molecules specifically targeting G4 can stabilize this structure to reduce RNA replication and inhibit protein translation of intracellular hepatitis C. Ultimately, the stabilization of G4 RNA in the genome of hepatitis C represents a promising new strategy for anti–hepatitis C drug development.

The fine control of enzyme activity is essential for the regulation of many important cellular and organismal functions. The light-regulation of proteins serves as an important method for the spatiotemporal control over the production and degradation of an enzyme product. This area is of intense interest for researchers. To the best of our knowledge, the use of small molecules as light-triggered molecular switches to reversibly control enzyme activity at the protein level has not yet been studied. In the present study, we demonstrate the light-controlled reversible regulation of the enzyme using a small-molecule-triggered switch, which is based on molecular recognition between an azobenzene derivative and telomere DNA. This molecule interconverts between the trans and cis states under alternate 365 nm UV and visible light irradiation, which consequently triggers the compaction and extension of telomere DNA. We further provide direct evidence for this structural switch using a circular dichroism study. Furthermore, our strategy has been successfully used to effectively control blood clotting in human plasma.

A label-free and biocompatible pH sensor system based on the aggregation-caused quenching (ACQ) probe has been reported herein. The DNA i-motif, a kind of pH-triggered structure, affects the aggregation of PTCDI derivatives by structural switch that would provide significant fluorescence signals responding to the different pH values. Our method not only shows sensitive and reversible response to pH changes, but also could expand the detection range by allosteric control of the DNA i-motif.