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We report the high‐resolution NMR solution‐state structure of an intramolecular G‐quadruplex with a diagonal loop of ten nucleotides. The G‐quadruplex is formed by a 34‐nt DNA sequence, d[CAG3T2A2G3TATA2CT3AG4T2AG3T2], named UpsB‐Q‐1. This sequence is found within promoters of the var genes of Plasmodium falciparum, which play a key role in malaria pathogenesis and evasion of the immune system. The [3+1]‐hybrid G‐quadruplex formed under physiologically relevant conditions exhibits a unique equilibrium between two structures, both stabilized by base stacking and non‐canonical hydrogen bonding. Unique equilibrium of the two closely related 3D structures originates from a North‐South repuckering of deoxyribose moiety of residue T27 in the lateral loop. Besides the 12 guanines involved in three G‐quartets, most residues in loop regions are involved in interactions at both G‐quartet‐loop interfaces. [ABSTRACT FROM AUTHOR]

Although more than 10% of the human genome has the potential to fold into non- B DNA, the formation of non-canonical structural motifs as part of long dsDNA chains are usually considered as unfavorable from a thermodynamic point of view. However, recent experiments have confirmed that non-canonical motifs do exist and are non-randomly distributed in genomic DNA. This distribution is highly dependent not only on the DNA sequence but also on various other factors such as environmental conditions, DNA topology and the expression of specific cellular factors in different cell types. In this study, we describe a new strategy used in the preparation of DNA minicircles containing different non-canonical motifs which arise as a result of imperfect base pairing between complementary strands. The approach exploits the fact that imperfections in the pairing of complementary strands thermodynamically weaken the dsDNA structure at the expense of enhancing the formation of non-canonical motifs. In this study, a completely different concept of stable integration of a non-canonical motif into dsDNA is presented. Our approach allows the integration of various types of non-canonical motifs into the dsDNA structure such as hairpin, cruciform, G-quadruplex and i-motif forms but also combinations of these forms. Small DNA minicircles have recently become the subject of considerable interest in both fundamental research and in terms of their potential therapeutic applications. [ABSTRACT FROM AUTHOR]

DNA, a significant physiological biometric, is present in all human cells like hair, blood, and skin. This research introduces a new approach called the Deep DNA Learning Network (DDLN) for person identification based on their DNA. This novel Machine Learning model is designed to gather DNA chromosomes from an individual's parents. The model's flexibility allows it to expand or contract and has the capability to determine one or both parents of an individual using the provided chromosomes. Notably, the DDLN model offers quick training in comparison to traditional deep learning methods. The study employs two real datasets from Iraq: the Real Iraqi Dataset for Kurds (RIDK) and the Real Iraqi Dataset for Arabs (RIDA). The outcomes demonstrate that the proposed DDLN model achieves an Equal Error Rate (EER) of 0 for both datasets, indicating highly accurate performance. [ABSTRACT FROM AUTHOR]

5‐Azacytosine (5‐AC) is one of the best interesting noncanonical nucleobases due to its functionalization and structural imitation of natural bases. 5‐AC can be used as the scaffold of two important chemotherapeutic medicines, 5‐azacytidine and 2′‐deoxy‐5‐azacytidine. Furthermore, increased sensitivity to UV leads to the photochemical effects of 5‐AC also attracted attention. Yet, no study has been reported to explore the effect of glycosyl groups on the photophysical and photochemical properties of 5‐AC, which can help to reveal the photostability of related actual clinic drugs. In this study, the excited‐state dynamics of 5‐azacytidine and 2′‐deoxy‐5‐azacytidine are studied by femtosecond transient absorption and quantum‐chemical calculations while revisiting that of 5‐AC with a wider probe spectral range. It is shown that glycosyl substitution on the N1 position leads to ultrafast excited‐state relaxation within several picoseconds in both nucleosides, which is distinct compared with the 17 ps lifetime seen in 5‐AC. It is proposed that these changes are due to altering the energy level of the dark nπ* state. Moreover, our results suggest that it should be cautioned to simply replace sugar groups with methyl groups when doing a theoretical calculation study on nucleobases and their derivatives. [ABSTRACT FROM AUTHOR]

5‐Azacytosine (5‐AC) is one of the best interesting noncanonical nucleobases due to its functionalization and structural imitation of natural bases. 5‐AC can be used as the scaffold of two important chemotherapeutic medicines, 5‐azacytidine and 2′‐deoxy‐5‐azacytidine. Furthermore, increased sensitivity to UV leads to the photochemical effects of 5‐AC also attracted attention. Yet, no study has been reported to explore the effect of glycosyl groups on the photophysical and photochemical properties of 5‐AC, which can help to reveal the photostability of related actual clinic drugs. In this study, the excited‐state dynamics of 5‐azacytidine and 2′‐deoxy‐5‐azacytidine are studied by femtosecond transient absorption and quantum‐chemical calculations while revisiting that of 5‐AC with a wider probe spectral range. It is shown that glycosyl substitution on the N1 position leads to ultrafast excited‐state relaxation within several picoseconds in both nucleosides, which is distinct compared with the 17 ps lifetime seen in 5‐AC. It is proposed that these changes are due to altering the energy level of the dark nπ* state. Moreover, our results suggest that it should be cautioned to simply replace sugar groups with methyl groups when doing a theoretical calculation study on nucleobases and their derivatives. [ABSTRACT FROM AUTHOR]

To improve the chemical regulation on the activity of cyclic dinucleotides (CDNs), we here designed a reduction-responsive dithioethanol (DTE)-based dCDN prodrug 9 (DTE-dCDN). Prodrug 9 improved the cell permeability with the intracellular levels peaking in 2 h in THP-1 cells. Under the reductive substance such as GSH or DTT, prodrug 9 could be quickly decomposed in 30 min to release the parent dCDN. In THP1-Lucia cells, prodrug 9 also retained a high bioactivity with the EC50 of 0.96 μM, which was 51-, 43-, and 3-fold more than the 2′,3′-cGAMP (EC50 = 48.6 μM), the parent compound 3′,3′-c-di-dAMP (EC50 = 41.3 μM), and ADU-S100 (EC50 = 2.9 μM). The high bioactivity of prodrug 9 was validated to be highly correlated with the activation of the STING signaling pathway. Furthermore, prodrug 9 could also improve the transcriptional expression levels of IFN-β, CXCL10, IL-6, and TNF-α in THP-1 cells. These results will be helpful to the development of chemically controllable CDN prodrugs with a high cellular permeability and potency. [ABSTRACT FROM AUTHOR]

Aims: The existence of modified ribonucleotide monophosphates embedded in genomic DNA, as a consequence of oxidative stress conditions, including 8-oxo-guanosine and ribose monophosphate abasic site (rAP), has been recently highlighted by several works and associated with oxidative stress conditions. Although human apurinic-apyrimidinic endodeoxyribonuclease 1 (APE1), a key enzyme of the base-excision repair pathway, repairs rAP sites and canonical deoxyribose monophosphate abasic sites with similar efficiency, its incision-repairing activity on 8-oxo-guanosine is very weak. The aims of this work were to: (i) identify proteins able to specifically bind 8-oxo-guanosine embedded in DNA and promote APE1 endoribonuclease activity on this lesion, and (ii) characterize the molecular and biological relevance of this interaction using human cancer cell lines. Results: By using an unbiased proteomic approach, we discovered that the AU-rich element RNA-binding protein 1 (AUF1) actively recognizes 8-oxo-guanosine and stimulates the APE1 enzymatic activity on this DNA lesion. By using orthogonal approaches, we found that: (i) the interaction between AUF1 and APE1 is modulated by H2O2-treatment; (ii) depletion of APE1 and AUF1 causes the accumulation of single- and double- strand breaks; and (iii) both proteins are involved in modulating the formation of DNA:RNA hybrids. Innovation: These results establish unexpected functions of AUF1 in modulating genome stability and improve our knowledge of APE1 biology with respect to 8-oxo-guanosine embedded in DNA. Conclusion: By showing a novel function of AUF1, our findings shed new light on the process of genome stability in mammalian cells toward oxidative stress-related damages. Antioxid. Redox Signal. 39, 411–431. [ABSTRACT FROM AUTHOR]

Photographic investigations of rising bubbles in seawater revealed that each bubble may conduct a single or bi-spiraling motion, which resemble architecture of RNA or DNA respectively. The rotational motion results from acceleration of ionic hydrates, which are separated to anionic and cationic domains at the upper and bottom curvatures of the bubble. Afterwards, rotational motion undergoes further acceleration in the bubble upper vortex, followed by deceleration at the vortex tip. During that phase, the spiraling motion cause significant friction that result in polarization of electronegative atoms of H, C, N, O and P. These may be simultaneously arranged around a whirling cationic strands and form phosphate groups, ribose and nitrogen bases equipped with H2 and H3 rotors. It is hypothesized that such hydrogen rotors may operate as generators of electrons, which may be detached from valence shells of electropositive atoms. Then, electrons may flow via nitrogen bases and deoxyribose or ribose to phosphate groups. Next, the negatively charged edges of phosphate groups may attract cationic hydrates and energize their rotational motion in the grooves, then causing also its spiraling projection outward. That may be responsible for replication of nucleotides and its arrangement along the cationic flow into RNA or DNA polymers, in the same manner as originally produced by rising bubbles. Moreover, it points that hydrogen rotors may generate energy needed for viability as well as interact with all physical and chemical fields. [ABSTRACT FROM AUTHOR]

When modified uridine derivatives are incorporated into DNA, radical species may form that cause DNA damage. This category of molecules has been proposed as radiosensitizers and is currently being researched. Here, we study electron attachment to 5-bromo-4-thiouracil (BrSU), a uracil derivative, and 5-bromo-4-thio-2′-deoxyuridine (BrSdU), with an attached deoxyribose moiety via the N-glycosidic (N1-C) bond. Quadrupole mass spectrometry was used to detect the anionic products of dissociative electron attachment (DEA), and the experimental results were supported by quantum chemical calculations performed at the M062X/aug-cc-pVTZ level of theory. Experimentally, we found that BrSU predominantly captures low-energy electrons with kinetic energies near 0 eV, though the abundance of bromine anions was rather low compared to a similar experiment with bromouracil. We suggest that, for this reaction channel, proton-transfer reactions in the transient negative ions limit the release of bromine anions. [ABSTRACT FROM AUTHOR]

We employ the Tight Binding Fishbone-Wire Model to study the electronic structure and coherent transfer of a hole (the absence of an electron created by oxidation) in all possible ideal B-DNA dimers as well as in homopolymers (one base pair repeated along the whole sequence with purine on purine). The sites considered are the base pairs and the deoxyriboses, with no backbone disorder. For the time-independent problem, we calculate the eigenspectra and the density of states. For the time-dependent problem after oxidation (i.e., the creation of a hole either at a base pair or at a deoxyribose), we calculate the mean-over-time probabilities to find the hole at each site and establish the frequency content of coherent carrier transfer by computing the Weighted Mean Frequency at each site and the Total Weighted Mean Frequency of a dimer or polymer. We also evaluate the main oscillation frequencies of the dipole moment along the macromolecule axis and the relevant amplitudes. Finally, we focus on the mean transfer rates from an initial site to all others. We study the dependence of these quantities on the number of monomers that are used to construct the polymer. Since the value of the interaction integral between base pairs and deoxyriboses is not well-established, we treat it as a variable and examine its influence on the calculated quantities. [ABSTRACT FROM AUTHOR]

The Earth's atmosphere plays a critical role in transporting and dispersing biological aerosols. Nevertheless, the amount of microbial biomass in suspension in the air is so low that it is extremely difficult to monitor the changes over time in these communities. Real-time genomic studies can provide a sensitive and rapid method for monitoring changes in the composition of bioaerosols. However, the low abundance of deoxyribose nucleic acid (DNA) and proteins in the atmosphere, which is of the order of the contamination produced by operators and instruments, poses a challenge for the sampling process and the analyte extraction. In this study, we designed an optimized, portable, closed bioaerosol sampler based on membrane filters using commercial off-the-shelf components, demonstrating its end-to-end operation. This sampler can operate autonomously outdoors for a prolonged time, capturing ambient bioaerosols and avoiding user contamination. We first performed a comparative analysis in a controlled environment to select the optimal active membrane filter based on its ability to capture and extract DNA. We have designed a bioaerosol chamber for this purpose and tested three commercial DNA extraction kits. The bioaerosol sampler was tested outdoors in a representative environment and run for 24 h at 150 L/min. Our methodology suggests that a 0.22-µm polyether sulfone (PES) membrane filter can recover up to 4 ng of DNA in this period, sufficient for genomic applications. This system, along with the robust extraction protocol, can be automated for continuous environmental monitoring to gain insights into the time evolution of microbial communities within the air. [ABSTRACT FROM AUTHOR]

The rapid improvements in identifying the genetic factors contributing to facial morphology have enabled the early identification of craniofacial syndromes. Similarly, this technology can be vital in forensic cases involving human identification from biological traces or human remains, especially when reference samples are not available in the deoxyribose nucleic acid (DNA) database. This review summarizes the currently used methods for predicting human phenotypes such as age, ancestry, pigmentation, and facial features based on genetic variations. To identify the facial features affected by DNA, various two-dimensional (2D)- and three-dimensional (3D)-scanning techniques and analysis tools are reviewed. A comparison between the scanning technologies is also presented in this review. Face-landmarking techniques and face-phenotyping algorithms are discussed in chronological order. Then, the latest approaches in genetic to 3D face shape analysis are emphasized. A systematic review of the current markers that passed the threshold of a genome-wide association (GWAS) of single nucleotide polymorphism (SNP)-face traits from the GWAS Catalog is also provided using the preferred reporting items for systematic reviews and meta-analyses (PRISMA), approach. Finally, the current challenges in forensic DNA phenotyping are analyzed and discussed. [ABSTRACT FROM AUTHOR]

Glycyrrhizin, a bioactive constituent of Glycyrrhiza glabra has been reported to ameliorate diabetes. Here, the effects of liposome-encapsulated glycyrrhizin on STZ-induced diabetes and associated oxidative stress were investigated. Wistar rats were grouped as control (NC, received placebo), diabetic (DC, STZ-induced), diabetic treated with free glycyrrhizin (DTG, 3 i.v. doses, 1.6 mg/0.5 ml), empty liposomes (DTl, 3 i.v. doses), and liposome-encapsulated glycyrrhizin (DTbd, 3 i.v. doses, 1.6 mg/0.5 ml). Serum glucose, insulin, intraperitoneal glucose tolerance test and glycohemoglobin were estimated. Free iron and iron-mediated oxidative stress were examined. Histological examinations of the kidney and liver were performed. Liposomal-glycyrrhizin treatment caused significant improvement of hyperglycemia (DC vs. DTbd p <.05), glucose intolerance (DC vs. DTG p <.01 and DC vs. DTbd p <.05), insulin (DC vs. DTG p <.1, DTbd vs. DC p <.05 and DTbd vs. DTG p <.1) and glycohemoglobin (DC vs. DTG p <.1 and DC vs. DTbd p <.05) levels in the DTbd group. Alleviation of free iron release (DC vs. DTbd p <.05), lipid peroxidation (DC + H2O2 vs. DTbd + H2O2p <.05), deoxyribose (DC + H2O2 vs. DTbd + H2O2, p <.05), and DNA degradation occurred in the DTbd group. The abnormalities of the kidney and liver were abolished in the DTbd group. The inhibitory effects were more pronounced compared to free glycyrrhizin. Liposome-encapsulated glycyrrhizin treatment caused inhibition of diabetic complications through its antioxidant effects and can be exploited for effective treatment of diabetes. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is the causative agent of one of the most widespread sexually transmitted diseases in the world. The adhesion of the parasite to the vaginal epithelial cells is mediated by specific proteins and by a complex glycan structure, the lipoglycan (TvLG), which covers the pathogen surface. L-rhamnose is an important component of TvLG, comprising up to 40% of the monosaccharides. Thus, the inhibition of its production could lead to a severe alteration in the TvLG structure, making the L-rhamnose biosynthetic pathway an attractive pharmacologic target. We report the identification and characterization of the first committed and limiting step of the L-rhamnose biosynthetic pathway, UDP-D-glucose 4,6-dehydratase (UGD, EC 4.2.1.76). The enzyme shows a strong preference for UDP-D-glucose compared to dTDP-D-glucose; we propose that the mechanism underlying the higher affinity for the UDP-bound substrate is mediated by the differential recognition of ribose versus the deoxyribose of the nucleotide moiety. The identification of the enzymes responsible for the following steps of the L-rhamnose pathway (epimerization and reduction) was more elusive. However, sequence analyses suggest that in T. vaginalis L-rhamnose synthesis proceeds through a mechanism different from the typical eukaryotic pathways, displaying intermediate features between the eukaryotic and prokaryotic pathways and involving separate enzymes for the epimerase and reductase activities, as observed in bacteria. Altogether, these results form the basis for a better understanding of the formation of the complex glycan structures on TvLG and the possible use of L-rhamnose biosynthetic enzymes for the development of selective inhibitors. [ABSTRACT FROM AUTHOR]

As a common heavy metal contaminant, Cd2+ has adverse effects on food safety and consumer health. It is very important for human health to realize highly sensitive Cd2+ detection methods. The self-powered sensing system based on enzyme biofuel cells (EBFCs) does not need an external power supply, which can simplify the experimental equipment and has great application value in portable detection. Thus, the biosensor is innovatively integrated into the screen-printed electrode to construct a new type of portable sensor suitable for on-site and real-time Cd2+ detection. Hybridization chain reaction (HCR) combined with the Cd2+-dependent deoxyribose (DNAzyme) signal amplification strategy is used to enhance the detection sensitivity while specifically recognizing the Cd2+. Moreover, the self-powered sensor combines with smartphones to realize quantitative Cd2+ detection without other instruments and has the characteristic of Effectively improving the hazard detection technology is essential to ensure food safety. Portability, simplicity, and speed are suitable for real-time Cd2+ detection in the field. The dual mechanism and three quantitative modes combining colorimetric and two electrical signals output modes are adopted to realize the visualization and accurate detection. A series of research results confirm that this strategy is of great significance to strengthen the development of intelligent Cd2+ technology, expand the application of self-powered sensing technology, and improve the safety detection system. • Plug and play self-powered chip facilitates precision heavy metal detection. • Dual mechanism and three quantitative mode for quantitative analysis. • High sensitive detection chip can be used for Cd detection in tea samples. [ABSTRACT FROM AUTHOR]

We study transitions in intrinsically disordered regions (IDRs) upon complex formation, utilizing X-ray-solved structural dataset of protein-DNA and protein-RNA complexes, along with their available unbound protein forms. The identified IDRs are categorized into three classes: Disordered-to-Ordered (D-O), Disordered-to-Partial Ordered (D-PO) and Disordered-to-Disordered (D-D) after comparing them in unbound and complex forms. In the D-O class, IDRs form secondary structures like coils, helices, and strands upon binding to nucleic acids. Though a majority of these IDRs are present at the surface of the complexes, a significant number of IDRs are also observed at the interfaces and are involved in polar interactions. The hydrogen bonds made by the interface IDRs (B_IDRs) with phosphates and bases of nucleic acids are comparatively more than those formed with sugars. B_IDRs form more H-bonds with the ribose in protein-RNA than with the deoxyribose in protein-DNA. Among the B_IDRs, Arg and Lys prefer to interact with the major and minor grooves of DNA and RNA, respectively. Ser, however, prefers the minor groove in both the nucleic acids. Interestingly, we report 61 and 48 IDRs in 31 protein-DNA and 22 protein-RNA complexes, respectively, suggesting nucleic acid binding to proteins may also result in ordered-to-disordered transitions. [ABSTRACT FROM AUTHOR]

A smart deoxyribose nucleic acid nanogel coated polydopamine nanosphere hybrid was designed for chemo-photothermal therapy of cancer. The nanohybrid showed good colloid stability, narrow size distribution, high drug loading, good biocompatibility, and high photothermal conversion efficiency, and could release the drug on desired tumor sites. [ABSTRACT FROM AUTHOR]

Heavy charged particles induce severe damage in DNA, which is a radiobiological advantage when treating radioresistant tumors. However, these particles can also induce cancer in humans exposed to them, such as astronauts in space missions. This damage can be directly induced by the radiation or indirectly by the attack of free radicals mainly produced by water radiolysis. We previously studied the impact of a proton on a DNA base pair, using the Time Dependent-Density Functional Theory (TD-DFT). In this work, we go a step further and study the attack of the OH· radical on the Guanine nucleotide to unveil how this molecule subsequently dissociates. The OH· attack on the H1′, H2′, H3′, and H5′ atoms in the guanine was investigated using the Ehrenfest dynamics within the TD-DFT framework. In all cases, the hydrogen abstraction succeeded, and the subsequent base pair dissociation was observed. The DNA dissociates in three major fragments: the phosphate group, the deoxyribose sugar, and the nitrogenous base, with slight differences, no matter which hydrogen atom was attacked. Hydrogen abstraction occurs at about 6 fs, and the nucleotide dissociation at about 100 fs, which agrees with our previous result for the direct proton impact on the DNA. These calculations may be a reference for adjusting reactive force fields so that more complex DNA structures can be studied using classical molecular dynamics, including both direct and indirect DNA damage. [ABSTRACT FROM AUTHOR]

DNA hydrogels have attracted increasing attention owing to their excellent permeability and high mechanical strength, together with thixotropy, versatile programmability and good biocompatibility. However, the moderate biostability and immune stimulation of DNA have arisen as big concerns for future potential clinical applications. Herein, we report the self‐assembly of a novel l‐DNA hydrogel, which inherited the extraordinary physical properties of a d‐DNA hydrogel. With the mirror‐isomer deoxyribose, this hydrogel exhibited improved biostability, withstanding fetal bovine serum (FBS) for at least 1 month without evident decay of its mechanical properties. The low inflammatory response of the l‐DNA hydrogel has been verified both in vitro and in vivo. Hence, this l‐DNA hydrogel with outstanding biostability and biocompatibility can be anticipated to serve as an ideal 3D cell‐culture matrix and implanted bio‐scaffold for long‐term biomedical applications. [ABSTRACT FROM AUTHOR]

Mycoplasma hominis is an opportunistic urogenital pathogen in vertebrates. It is a nonglycolytic species that produces energy via arginine degradation. Among genital mycoplasmas, M. hominis is the most commonly reported to play a role in systemic infections and can persist in the host for a long time. However, it is unclear how M. hominis proceeds under arginine limitation. The recent metabolic reconstruction of M. hominis has demonstrated its ability to catabolize deoxyribose phosphate to produce ATP. In this study, we cultivatedM. hominis on two different energy sources (arginine and thymidine) and demonstrated the differences in growth rate, antibiotic sensitivity, and biofilm formation. Using label-free quantitative proteomics, we compared the proteome of M. hominis under these conditions. A total of 466 proteins were identified from M. hominis, representing approximately 85% of the predicted proteome, while the levels of 94 proteins changed significantly. As expected, we observed changes in the levels of metabolic enzymes. The energy source strongly affects the synthesis of enzymes related to RNA modifications and ribosome assembly. The translocation of lipoproteins and other membrane-associated proteins was also impaired. Our study, the first global characterization of the proteomic switching of M. hominis in arginine-deficiency media, illustrates energy source-dependent control of pathogenicity factors and can help to determine the mechanisms underlying the interaction between the growth rate and fitness of genome-reduced bacteria. [ABSTRACT FROM AUTHOR]

The current study was designed to assess five species of the genus Phaseolus for phenolic content, flavonoid content, and antioxidant ability. The antioxidant capacity of the sample extracts was assessed using different antioxidant models such as ferric reducing antioxidant power (FRAP), DPPH free radical scavenging, phosphomolybdenum reducing power, ferrous ion chelating activity, hydrogen peroxide radical scavenging, hydroxyl radical scavenging, deoxyribose degradation, and ß-carotene bleaching assays. The results obtained discovered that the concentration of phenolics and flavonoids in the studied species ranged from 1.11 to 4.01mg TAE/g plant material and 0.11 to 1.16 mg QE/g plant material. The antioxidant activity of the extracts varied in a wide range in the different antioxidant assays depending on the genotype as well as the polarity of the solvents used to obtain the extracts. Ethanolic and aqueous extracts exhibited the maximum amount of phenolics and flavonoids among the solvents. The species studied exhibited a significant range of phenolics, flavonoids, and antioxidant capacity. Hence, the present investigation can provide a new direction by utilizing Phaseolus species to formulate cost-effective, eco-friendly, and valueadded therapeutic products. [ABSTRACT FROM AUTHOR]

Nonheme iron- and a-ketoglutarate (αKG)-dependent halogenases (NHFeHals), which catalyze the regio- and stereoselective halogenation of the unactivated C (sp3)-H bonds, exhibit tremendous potential in the challenging asymmetric halogenation. AdeV from Actinomadura sp. ATCC 39365 is the first identified carrier protein-free NHFeHal that catalyzes the chlorination of nucleotide 2'-deoxyadenosine-59-monophosphate (2'-dAMP) to afford 2'-chloro-2'-deoxyadenosine-5'-monophosphate. Here, we determined the complex crystal structures of AdeV/FeII/Cl and AdeV/FeII/Cl/αKG at resolutions of 1.76 and 1.74 Å, respectively. AdeV possesses a typical β-sandwich topology with H194, H252, αKG, chloride, and one water molecule coordinating FeII in the active site. Molecular docking, mutagenesis, and biochemical analyses reveal that the hydrophobic interactions and hydrogen bond network between the substrate-binding pocket and the adenine, deoxyribose, and phosphate moieties of 2'-dAMP are essential for substrate recognition. Residues H111, R177, and H192 might play important roles in the second-sphere interactions that control reaction partitioning. This study provides valuable insights into the catalytic selectivity of AdeV and will facilitate the rational engineering of AdeV and other NHFeHals for synthesis of halogenated nucleotides. [ABSTRACT FROM AUTHOR]

R-loops are ubiquitous, dynamic nucleic-acid structures that play fundamental roles in DNA replication and repair, chromatin and transcription regulation, as well as telomere maintenance. The DNA-RNA hybrid–specific S9.6 monoclonal antibody is widely used to map R-loops. Here, we report crystal structures of a S9.6 antigen-binding fragment (Fab) free and bound to a 13-bp hybrid duplex. We demonstrate that S9.6 exhibits robust selectivity in binding hybrids over double-stranded (ds) RNA and in categorically rejecting dsDNA. S9.6 asymmetrically recognizes a compact epitope of two consecutive RNA nucleotides via their 2′-hydroxyl groups and six consecutive DNA nucleotides via their backbone phosphate and deoxyribose groups. Recognition is mediated principally by aromatic and basic residues of the S9.6 heavy chain, which closely track the curvature of the hybrid minor groove. These findings reveal the molecular basis for S9.6 recognition of R-loops, detail its binding specificity, identify a new hybrid-recognition strategy, and provide a framework for S9.6 protein engineering. The S9.6 monoclonal antibody is widely used to map R-loops genome wide. Here, Bou-Nader et al., define the nucleic acid-binding specificity of S9.6 and report its crystal structures free and bound to a hybrid, which reveal the asymmetric recognition of the RNA and DNA strands and its A-form conformation. [ABSTRACT FROM AUTHOR]

Catechin is an extensively investigated plant flavan-3-ol with a beneficial impact on human health that is often associated with antioxidant activities and iron coordination complex formation. The aim of this study was to explore these properties with FeII and FeIII using a combination of nanoelectrospray-mass spectrometry, differential pulse voltammetry, site-specific deoxyribose degradation assay, FeII autoxidation assay, and brine shrimp mortality assay. Catechin primarily favored coordination complex formation with Fe ions of the stoichiometry catechin:Fe in the ratio of 1:1 or 2:1. In the detected Fe–catechin coordination complexes, FeII prevailed. Differential pulse voltammetry, the site-specific deoxyribose degradation, and FeII autoxidation assays proved that coordination complex formation affected catechin's antioxidant effects. In situ formed Fe–catechin coordination complexes showed no toxic activities in the brine shrimp mortality assay. In summary, catechin has properties for the possible treatment of pathological processes associated with ageing and degeneration, such as Alzheimer's and Parkinson's diseases. [ABSTRACT FROM AUTHOR]

This scoping review aims to perform a brief but comprehensive assessment of existing peer‐reviewed literature and determine whether raising nicotinamide adenine dinucleotide can prevent or promote tumorigenesis. The examination of extensive peer‐reviewed data regarding the synthesis of nicotinamide adenine dinucleotide has been performed with a focus on nuclear dynamics and the deoxyribose nucleic acid repair pathway. Various enzymatic protective functions have been identified from nicotinamide adenine dinucleotide levels, as well as the threat role that is also explored. Nicotinamide adenine dinucleotide precursors and sirtuin‐activating compounds are becoming ubiquitous in the commercial market. Further research into whether elevating levels of nicotinamide adenine dinucleotide or overexpression of sirtuins can increase the potential for neoplasm or other age‐related pathophysiology is warranted due to the high energy requirements of certain diseases such as cancer. [ABSTRACT FROM AUTHOR]

Daphne gnidium L. (Thymelaeaceae) has been used in the Mediterranean basin to treat skin diseases, rheumatism and toothache .Objective: the aim of this study was to evaluate the biological activities of butanol extract from the D. gnidium leaves. Methods: A quantitative analysis by high-performance liquid chromatography with a diode array detector (HPLC-DAD) was performed. The antioxidant activities were evaluated by using three different assays: 2,2-diphenyl-l-picrylhydrazyl assay (DPPH assay), deoxyribose degradation assay and Cellular Antioxidant Activity (CAA) assay. The butanol extract was investigated for anti-inflammatory and analgesic activities in animal models. In addition, its effect on the production of NO and lysosomal activity in vivo was assessed. Results: The HPLC-DAD analysis showed the presence of daphnetin. The butanol extract had a remarkable antioxidant activity in the different systems tested. Furthermore, it has an anti-inflammatory effect by inhibiting the xyleneinduced ear edema and reduced the number of abdominal constrictions in mice indicating analgesic effect. It also was found to inhibit (NO) production and lysosomal activity in vivo. Conclusion: These findings support the daphne use in traditional medicine for its analgesic and anti-inflammatory activities. Further investigations to elucidate its mechanism of action are required. [ABSTRACT FROM AUTHOR]

Prolonged ultraviolet exposure results in the formation of cyclobutane pyrimidine dimers (CPDs) in RNA. Consequently, prebiotic photolesion repair mechanisms should have played an important role in the maintenance of the structural integrity of primitive nucleic acids. 2,6-Diaminopurine is a prebiotic nucleobase that repairs CPDs with high efficiency when incorporated into polymers. We investigate the electronic deactivation pathways of 2,6-diaminopurine-2'-deoxyribose and 9-methyl-2,6-diaminopurine in acetonitrile and aqueous solution to shed light on the photophysical and excited state properties of the 2,6-diaminopurine chromophore. Evidence is presented that both are photostable compounds exhibiting similar deactivation mechanisms upon the population of the S 1 (ππ* L a ) state at 290 nm. The mechanism involves deactivation through the C2- and C6-reaction coordinates and >99% of the excited state population decays through nonradiative pathways involving two conical intersections with the ground state. The radiative and nonradiative lifetimes are longer in aqueous solution compared to acetonitrile. While τ 1 is similar in both derivatives, τ 2 is ca. 1.5-fold longer in 2,6-diaminopurine-2'-deoxyribose due to a more efficient trapping in the S 1 (ππ* L a ) minimum. Therefore, 2,6-diaminopurine could have accumulated in significant quantities during prebiotic times to be incorporated into non-canonical RNA and play a significant role in its photoprotection., (© 2023 The Authors. Photochemistry and Photobiology published by Wiley Periodicals LLC on behalf of American Society for Photobiology.)

5-Azacytosine (5-AC) is one of the best interesting noncanonical nucleobases due to its functionalization and structural imitation of natural bases. 5-AC can be used as the scaffold of two important chemotherapeutic medicines, 5-azacytidine and 2'-deoxy-5-azacytidine. Furthermore, increased sensitivity to UV leads to the photochemical effects of 5-AC also attracted attention. Yet, no study has been reported to explore the effect of glycosyl groups on the photophysical and photochemical properties of 5-AC, which can help to reveal the photostability of related actual clinic drugs. In this study, the excited-state dynamics of 5-azacytidine and 2'-deoxy-5-azacytidine are studied by femtosecond transient absorption and quantum-chemical calculations while revisiting that of 5-AC with a wider probe spectral range. It is shown that glycosyl substitution on the N1 position leads to ultrafast excited-state relaxation within several picoseconds in both nucleosides, which is distinct compared with the 17 ps lifetime seen in 5-AC. It is proposed that these changes are due to altering the energy level of the dark nπ* state. Moreover, our results suggest that it should be cautioned to simply replace sugar groups with methyl groups when doing a theoretical calculation study on nucleobases and their derivatives., (© 2022 American Society for Photobiology.)

To improve the chemical regulation on the activity of cyclic dinucleotides (CDNs), we here designed a reduction-responsive dithioethanol (DTE)-based dCDN prodrug 9 (DTE-dCDN). Prodrug 9 improved the cell permeability with the intracellular levels peaking in 2 h in THP-1 cells. Under the reductive substance such as GSH or DTT, prodrug 9 could be quickly decomposed in 30 min to release the parent dCDN. In THP1-Lucia cells, prodrug 9 also retained a high bioactivity with the EC 50 of 0.96 μM, which was 51-, 43-, and 3-fold more than the 2',3'-cGAMP (EC 50 = 48.6 μM), the parent compound 3',3'-c-di-dAMP (EC 50 = 41.3 μM), and ADU-S100 (EC 50 = 2.9 μM). The high bioactivity of prodrug 9 was validated to be highly correlated with the activation of the STING signaling pathway. Furthermore, prodrug 9 could also improve the transcriptional expression levels of IFN-β , CXCL10 , IL-6, and TNF-α in THP-1 cells. These results will be helpful to the development of chemically controllable CDN prodrugs with a high cellular permeability and potency.

Rapid identification of DNA oxidative damage sites is of great significance for disease diagnosis. In this work, electric field-regulated click reaction surface-enhanced Raman spectroscopy (e-Click-SERS) was developed aiming at the rapid and specific analysis of furfural, the biomarker of oxidative damage to the 5-carbon site of DNA deoxyribose. In e-Click-SERS, cysteamine-modified porous Ag filaments (cys@p-Ag) were prepared and used as electrodes, amine-aldehyde click reaction sites, and SERS substrates. Cysteamine was controlled as an "end-on" conformation by setting the voltage of cys@p-Ag at -0.1 V, which ensures its activity in participating in the amine-aldehyde click reaction during the detection of furfural. Benefiting from this, the proposed e-Click-SERS method was found to be sensitive, rapid-responding, and interference-resistant in analyzing furfural from plasma. The method detection limits of furfural were 5 ng mL -1 in plasma, and the whole "extraction and detection" procedure was completed within 30 min with satisfactory recovery. Interference from 13 kinds of common plasma metabolites was investigated and found to not interfere with the analysis, according to the exclusive adaptation of the amine-aldehyde click reaction. Notably, the e-Click-SERS technique allows in situ analysis of biological samples, which offers great potential to be a point-of-care testing tool for detecting DNA oxidative damage.

Radioresistance remains the major obstacle to the failure of radiotherapy for ESCC. SOCS6 was first reported in our previous study to enhance the radiosensitivity of ESCC. Recent studies have shown that various materials were applied as radiosensitizer. Nevertheless, these radiosensitizer still suffer from inadequate tumor uptake of radiosensitizers and radiation sickness. The aim of our study was to generate a tumor targeted virus-inspired hollow mesoporous manganese-bismuth (vHMMn-Bi-PEG) loaded with SOCS6 plasmid and to explore the effect for radiosensitization and safety in vitro and in vivo. We hypothesize that SOCS6@vHMMn-Bi-PEG could enhance ESCC radiosensitivity The vHMMn-Bi-PEG were obtained by the traditional hard template synthesis. SEM and TEM were analyzed for the characterization of vHMMn-Bi-PEG. The expression of SOCS6 were detected by RT-PCR and western blot. MTT was detected cell cytotoxicity. Flow cytometry was used to detect the cellular uptake of SOCS6@vHMMn-Bi-PEG. Colony formation and γ-H2AX foci were assessed the radiosensitization effect of the SOCS6@vHMMn-Bi-PEG. The effect of SOCS6@vHMMn-Bi-PEG on radiosensitization and biosafety were analyzed by subcutaneous xenograft models in vivo. By using SEM observation, the vHMMn-Bi-PEG exhibited the rough surface morphology, which was similar to the spike on the surface of natural virus. Subsequently, TEM results exhibited that the building blocks of the interpenetrated ultrasmall MnO 2 /Bi 2 O 3 nanoparticles were constructed to form the bimetallic oxide shells. RT-PCR and western blot results revealed that pCDNA3.1-SOCS6 were successfully loaded into the vHMMn-Bi-PEG. After incubation with vHMMn-Bi-PEG or SOCS6@vHMMn-Bi-PEG, the cell survival rates of TE-10 were greater than 90%, indicating their excellent biocompatibility. Besides, flow cytometry results confirmed that SOCS6@ vHMMn-Bi-PEG could be easily taken up by TE-10 cells. Colony formation results revealed that SOCS6@vHMMn-Bi-PEG (8.90%) was significantly lower than that in the control group (21.90%) and pCDNA3.1-SOCS6 group (18.32%). Moreover, a significantly stronger fluorescence density of γ-H 2 AX foci was found in the SOCS6@vHMMn-Bi-PEG + X-ray than that in the control and pCDNA3.1-SOCS6 + X-ray, indicating the effective DNA breakage induced by the vHMMn -Bi-PEG nano-system. Finally, in vivo results found that SOCS6@vHMMn-Bi-PEG with X-ray exhibited a stronger inhibitory effect on tumor growth compared with the pCDNA3.1-SOCS6 + X-ray and vHMMn-Bi-PEG + X-ray group, indicating that SOCS6@ vHMMn-Bi-PEG has the potential to significantly enhance radiosensitivity. We successfully constructed a novel biomimetic-gene-loaded nano-system SOCS6@vHMMn-Bi-PEG as a radio-sensitizer. Moreover, SOCS6@vHMMn-Bi-PEG exhibited superior antitumor performance of ESCC without systemic toxicity. [ABSTRACT FROM AUTHOR]

The article discusses gene regulatory elements play a crucial role in the pattern formation of butterfly wings. Topics include development of morphological patterns and structures in organisms is the result of transcription factors and epigenetic regulation in different cells and tissues; Transcription factors, which are proteins that bind to DNA at sites called cis-regulatory elements (CREs), can turn gene expression on or off.

We numerically calculated doubly differential and integrated cross sections for electron elastic scattering on molecules composing the deoxyribonucleic acid (DNA), namely, the sugar 2-deoxyribose ( C 5 H 10 O 4) and its analogue 1,3-dihydroxytetrahydrofuran ( C 4 H 8 O 3) as well as molecules containing the phosphate group such as deoxyribose monophosphate (C 5 H 11 O 7 P) and THFA monophosphate ( C 5 H 11 O 5 P). The model of independent atoms (IAM), taking into account the different potentials at short and long ranges as well as the effects of multiple-scattering terms, is here used. Then doubly differential cross sections are calculated for various impact energies (50, 80, 100, 300, 500, 800 and 1000 eV) and the integrated ones for energy ranging from 20 eV to 100 keV. The obtained results are compared and discussed with the available data for molecules similar to deoxyribose such as THF and THFA. Good agreements are generally found particularly in shape, while small discrepancies are observed in terms of amplitude that may be explained by the effect of the potentials used in the current approach. [Display omitted] • DCSs and ICSs of electrons scattered by biomolecules constituting DNA are provided using corrected-IAM method. • The short-range and long-range potential effects on DCSs and ICSs are highlighted • DCSs and ICSs obtained (20 eV- 100 keV) are in good agreement with available results. [ABSTRACT FROM AUTHOR]

[Display omitted] • A set of A-analogues are derived by the fluorophore replacement and ring-expansion based on the natural adenine. • The efficient fluorescence quenching is observed upon pairing with complementary 8-oxoG. • The fluorescence quenching is ascribed to ESPT induced intermolecular charge transfer character. The 8-oxo-7,8-dihydro-2′-deoxyguanine (8-oxoG) is the representative damaged nucleoside that may increase the risk of developing diseases. Accordingly, the selective detection of 8-oxoG in DNA with minimal disturbance to the native structure is important to have an in-depth understanding of the formation mechanism and becomes an attractive tool for genomic research. To identify the DNA adduct in real-time efficiently, a series of quasi-intrinsic optical probes are performed based on the natural adenine, which has preference to form a stable base pair with 8-oxoG in the syn conformation. The calculations revealed that the A-analogues in solution could bring red-shifted absorption spectra and bright photoluminescence arisen from the additional π-conjugation by means of fluorophore modification and the ring expansion. Especially, A1 possesses large Stokes shifts and the highest fluorescence intensity in emission, which is proposed as the biosensor to monitor the optical changes in the presence and absence of the considered 8-oxoG. It is found that the fluorescence is insensitive to base pairing with thymine, while the excited state intermolecular proton transfer (ESPT) induced efficient fluorescence quenching is observed upon pairing with the 8-oxoG. To evaluate the direct usefulness of the bright adenine analogues in biological environment, we further examined the influences of linking deoxyribose on the absorption and emission, which are consistent with the experimental data. [ABSTRACT FROM AUTHOR]

Cancer immunotherapy is a powerful weapon in the fight against cancers. Cyclic dinucleotides (CDNs) have demonstrated the great potential by evoking the immune system to fight cancers. There are still a lot of unmet needs for highly active CDNs in clinical applications due to low cell permeation and serum stability. Here we reported S -acylthioalkyl ester (SATE)-based prodrugs of deoxyribose cyclic dinucleotides (dCDNs) with three different types of internucleotide linkages (3′,3′: 11a ; 2′,3′: 11b ; 2′,2′: 11c). The parent dCDNs could be efficiently released from SATE-dCDNs by cellular esterases. Compared to 2′,3′-cGAMP and ADU-S100, 11a exhibited much higher potency of activating STING pathway and higher serum stability. In a CT26-Luc tumor-bearing animal model, 11a showed the efficient antitumor activity in eliminating the established tumor and induced significant increase of mRNA expression of IFN-β and other related inflammatory cytokines. Hence, SATE-dCDN prodrugs demonstrated their benefits in promoting cell penetration, improving serum stability, and thus enhancing bioactivity, suggesting their potential application as immunotherapy in a variety of malignancies. [Display omitted] • Three SATE-dCDN prodrugs (11a , 11b , and 11c) were designed as STING agonists. • 11a was identified as a highly potent STING agonist with an EC 50 value of 5.2 nM. • 11a could suppress tumor growth in the CT26-Luc tumor-bearing mouse model. • 11a and 11b led to significant cytokine induction. [ABSTRACT FROM AUTHOR]

RNase H acts as a key effector in gene knockdown by antisense oligonucleotides (ASOs). Although various chemical modifications have been developed to regulate RNase H-mediated cleavage, precise control is yet to be achieved. In this study, we tried to address the question of whether the interaction of phosphate groups or deoxyriboses is more important in the recognition of DNA/RNA duplex by RNase H. To answer this question, we investigated the effect of methylene group insertion at the 5'-upstream or 3'-downstream phosphorothioate groups on RNase H-mediated cleavage. By inserting a methylene group at the 5'-upside or 3'-downside, the distance between phosphates or deoxyriboses could be changed in a different pattern. Maximum suppression of the cleavage reaction was observed when a methylene group was inserted at the 5'-phosphate group of the nucleoside which is known to distinguish ribose and deoxyribose via stacking of the W221 residue in RNase H. This effect was observed in a different sequence as well as mismatched duplexes, suggesting the interaction of deoxyribose rings with RNase H is more important than that of phosphate groups. Our results will contribute to the designing of further molecular modifications that improve the selectivity of RNase H-mediated cleavage reactions which allows for the development of allele-specific ASOs.