Comparison of Statin With Ezetimibe Combination Therapy Versus Statin Monotherapy for Primary Prevention in Middle-Aged Adults.

BACKGROUND AND OBJECTIVES: Lipid lowering therapy is essential to reduce the risk of major cardiovascular events; however, limited evidence exists regarding the use of statin with ezetimibe as primary prevention strategy for middle-aged adults. We aimed to investigate the impact of single pill combination therapy on clinical outcomes in relatively healthy middle-aged patients when compared with statin monotherapy. METHODS: Using the Korean National Health Insurance Service database, a propensity score match analysis was performed for baseline characteristics of 92,156 patients categorized into combination therapy (n=46,078) and statin monotherapy (n=46,078) groups. Primary outcome was composite outcomes, including death, coronary artery disease, and ischemic stroke. And secondary outcome was all-cause death. The mean follow-up duration was 2.9±0.3 years. RESULTS: The 3-year composite outcomes of all-cause death, coronary artery disease, and ischemic stroke demonstrated no significant difference between the 2 groups (10.3% vs. 10.1%; hazard ratio (HR), 1.022; 95% confidence interval [CI], 0.980-1.064; p=0.309). Meanwhile, the 3-year all-cause death rate was lower in the combination therapy group than in the statin monotherapy group (0.2% vs. 0.4%; p<0.001), with a significant HR of 0.595 (95% CI, 0.460-0.769; p<0.001). Single pill combination therapy exhibited consistently lower mortality rates across various subgroups. CONCLUSIONS: Compared to the statin monotherapy, the combination therapy for primary prevention showed no difference in composite outcomes but may reduce mortality risk in relatively healthy middle-aged patients. However, since the study was observational, further randomized clinical trials are needed to confirm these findings.

Information Density Enhancement Using Lossy Compression in DNA Data Storage.

This study develops two deoxyribonucleic acid (DNA) lossy compression models, Models A and B, to encode grayscale images into DNA sequences, enhance information density, and enable high-fidelity image recovery. These models, distinguished by their handling of pixel domains and interpolation methods, offer a novel approach to data storage for DNA. Model A processes pixels in overlapped domains using linear interpolation (LI), whereas Model B uses non-overlapped domains with nearest-neighbor interpolation (NNI). Through a comparative analysis with Joint Photographic Experts Group (JPEG) compression, the DNA lossy compression models demonstrate competitive advantages in terms of information density and image quality restoration. The application of these models to the Modified National Institute of Standards and Technology (MNIST) dataset reveals their efficiency and the recognizability of decompressed images, which is validated by convolutional neural network (CNN) performance. In particular, Model B2, a version of Model B, emerges as an effective method for balancing high information density (surpassing over 20 times the typical densities of two bits per nucleotide) with reasonably good image quality. These findings highlight the potential of DNA-based data storage systems for high-density and efficient compression, indicating a promising future for biological data storage solutions.

Observation of Ultrahigh Photoconductivity in DNA-MoS2 Nano-Biocomposite.

A nano-biocomposite film with ultrahigh photoconductivity remains elusive and critical for bio-optoelectronic applications. A uniform, well-connected, high-concentration nanomaterial network in the biological matrix remains challenging to achieve high photoconductivity. Wafer-scale continuous nano-biocomposite film without surface deformations and cracks plays another major obstacle. Here ultrahigh photoconductivity is observed in deoxyribonucleic acid-molybdenum disulfide (DNA-MoS2) nano-biocomposite film by incorporating a high-concentration, well-percolated, and uniform MoS2 network in the ss-DNA matrix. This is achieved by utilizing DNA-MoS2 hydrogel formation, which results in crack-free, wafer-scale DNA-MoS2 nano-biocomposite films. Ultra-high photocurrent (5.5 mA at 1 V) with a record-high on/off ratio (1.3 × 106) is observed, five orders of magnitude higher than conventional biomaterials (≈101) reported so far. The incorporation of the Wely semimetal (Bismuth) as an electrical contact exhibits ultrahigh photoresponsivity (2.6 × 105 A W-1). Such high photoconductivity in DNA-MoS2 nano-biocomposite could bridge the gap between biology, electronics, and optics for innovative biomedicine, bioengineering, and neuroscience applications.

M-State and N-Color (M-N = 1-1, 2-1, and 1-2) Turing Algorithms Demonstrated via DNA Self-Assembly.

The fast and extensive generation of patterns using specific algorithms is a major challenge in the field of DNA algorithmic self-assembly. Turing machines (TMs) are simple computable machines that execute certain algorithms using carefully designed logic gates. We investigate Turing algorithms for the generation of patterns on algorithmic lattices using specific logic gates. Logic gates can be implemented into Turing building blocks. We discuss comprehensive methods for designing Turing building blocks to demonstrate an M-state and N-color Turing machine (M-N TM). The M-state and N-color (M-N = 1-1, 2-1, and 1-2) TMs generate Turing patterns that can be fabricated via DNA algorithmic self-assembly. The M-N TMs require two-input and three-output logic gates. We designed the head, tape, and transition rule tiles to demonstrate TMs for the 1-1, 2-1, and 1-2 Turing algorithms. By analyzing the characteristics of the Turing patterns, we classified them into two classes (DL and DR for states grown diagonally to the left and right, respectively) for the 1-1 TM, three for the 2-1 TM, and nine for the 1-2 TM. Among these, six representative Turing patterns generated using rules R11-0 and R11-1 for 1-1 TM, R21-01 and R21-09 for 2-1 TM, and R12-02 and R12-08 for 1-2 TM were constructed with DNA building blocks. Turing patterns on the DNA lattices were visualized by atomic force microscopy. The Turing patterns on the DNA lattices were similar to those simulated patterns. Implementing the Turing algorithms into DNA building blocks, as demonstrated via DNA algorithmic self-assembly, can be extended to a higher order of state and color to generate more complicated patterns, compute arithmetic operations, and solve mathematical functions.

DNA lattice growth with single, double, and triple double-crossover boundaries by stepwise self-assembly.

Construction of various nanostructures with nanometre-scale precision through various DNA building blocks depends upon self-assembly, base-pair complementarity and sequence programmability. During annealing, unit tiles are formed by the complementarity of base pairs in each strand. Enhancement of growth of target lattices is expected if seed lattices (i.e. boundaries for growth of target lattices) are initially present in a test tube during annealing. Although most processes for annealing DNA nanostructures adopt a one-step high temperature method, multi-step annealing provides certain advantages such as reusability of unit tiles and tuneability of lattice formation. We can construct target lattices effectively (through multi-step annealing) and efficiently (via boundaries) by multi-step annealing and combining boundaries. Here, we construct efficient boundaries made of single, double, and triple double-crossover DNA tiles for growth of DNA lattices. Two unit double-crossover DNA tile-based lattices and copy-logic implemented algorithmic lattices were introduced to test the growth of target lattices on boundaries. We used multi-step annealing to tune the formation of DNA crystals during fabrication of DNA crystals comprised of boundaries and target lattices. The formation of target DNA lattices was visualized using atomic force microscopy (AFM). The borders between boundaries and lattices in a single crystal were clearly differentiable from AFM images. Our method provides way to construct various types of lattices in a single crystal, which might generate various patterns and enhance the information capacity in a given crystal.

Water-resistant free-standing DNA-complexed films with antioxidant and H2O2-responsive activity.

Water-insoluble DNA complexes are suitable for producing free-standing DNA films due to their low water sensitivity, which prevents their rapid degradation in aqueous environments. Here, we proposed two types of free-standing films that exhibit low dissolution rates in water: low molecular weight chitosan (LCS)-DNA films and phosphatidylcholine (PC)-cetyltrimethylammonium (CTMA)-DNA films. The structure and binding characteristics of the LCS-DNA and PC-CTMA-DNA complexes were investigated with UV-Vis spectroscopy and via the fluorescent characteristics of daunorubicin bound to them. A simple drop-casting method was then adopted for both complexes to fabricate free-standing films. An increase in antioxidant activity and water-resistance of the LCS-DNA DNA film was observed when the molar ratio of LCS to DNA was increased, but the dissolution rate of the LCS-DNA film was also dependent on the ionic strength of the dissolving solution. Fourteen days were required to dissolve the LCS-DNA film in deionized water, whereas immediate dissolution was observed in 1× phosphate-buffered saline (PBS). Deformation of the PC-CTMA-DNA film was accelerated by H2O2, such that the PC-CTMA-DNA film was degraded after 21 days of immersion in 1× PBS with H2O2. Due to the low dissolution rate in water and antioxidant activity, the free-standing LCS-DNA film should be able to store and protect embedded clinical materials, such as proteins and intercalating drugs, from moisture and enable localized delivery of treatments to designated sites. Also, the free-standing PC-CTMA-DNA film could be a biocompatible candidate for use as a membrane or sensor for detecting the levels of reactive oxygen species.

Multidimensional Honeycomb-like DNA Nanostructures Made of C-Motifs.

Thanks to its remarkable properties of self-assembly and molecular recognition, DNA can be used in the construction of various dimensional nanostructures to serve as templates for decorating nanomaterials with nanometer-scale precision. Accordingly, this study discusses a design strategy for fabricating such multidimensional DNA nanostructures made of simple C-motifs. One-dimensional (1D) honeycomb-like tubes (1HTs) and two-dimensional (2D) honeycomb-like lattices (2HLs) were constructed using a C-motif with an arm length of 14 nucleotides (nt) at an angle of 240° along the counterclockwise direction. We designed and fabricated four different types of 1HTs and three different 2HLs. The study used atomic force microscopy to characterize the distinct topologies of the 1D and 2D DNA nanostructures (i.e., 1HTs and 2HLs, respectively). The width deviation of the 1HTs and height suppression percentage of the 2HLs were calculated and discussed. Our study can be provided to construct various dimensional DNA nanostructures easily with high efficiency.

Comparative analysis of scalp and gut microbiome in androgenetic alopecia: A Korean cross-sectional study.

Androgenetic alopecia (AGA) is a non-scarring and progressive form of hair loss occurring in both men and women. Although genetic predisposition and sex steroid hormones are the main causes, many factors remain unknown, and various extrinsic factors can negatively affect the lifespan of hair. We investigated skin-gut axis microorganisms as potential exogenous factors causing AGA, through comparative analyses of the scalp and gut microbiome in individuals with and without AGA in a Korean cohort. Using 16S rRNA gene sequencing, we characterized the scalp and gut microbiomes of 141 individuals divided into groups by sex and presence of AGA. Alpha diversity indices in the scalp microbiome were generally higher in individuals with AGA than in healthy controls. These indices showed a strong negative correlation with scalp-inhabitant bacteria (Cutibacterium and Staphylococcus), indicating that the appearance of non-inhabitant bacteria increases as hair loss progresses. No significant differences in diversity were observed between the gut microbiomes. However, bacterial functional differences, such as bile acid synthesis and bacterial invasion of epithelial cells, which are related to intestinal homeostasis, were observed. The networks of the scalp and gut microbiome were more complex and denser with higher values of the network topology statistic coefficient values (i.e., transitivity, density, and degree centrality) and more unique associations in individuals with AGA than in healthy controls. Our findings reveal a link between skin-gut microorganisms and AGA, indicating the former's potential involvement in the latter's development. Additionally, these results provide evidence for the development of cosmetics and therapeutics using microorganisms and metabolites involved in AGA.

Multi-Domains in a Single Lattice Formed by DNA Self-Assembly.

Using sequence programmability and the characteristics of self-assembly, DNA has been utilized in the construction of various nanostructures and the placement of specific patterns on lattices. Even though many complex structures and patterns formed by DNA assembly have been reported, the fabrication of multi-domain patterns in a single lattice has rarely been discussed. Multi-domains possessing specifically designed patterns in a single lattice provide the possibility to generate multiple patterns that enhance the pattern density in a given single lattice. Here, we introduce boundaries to construct double- and quadruple-domains with specific patterns in a single lattice and verify them with atomic force microscopy. ON, OFF, and ST (stripe) patterns on a lattice are made of DNA tiles with hairpins (ON), without hairpins (OFF), and alternating DNA tiles without and with hairpins (formed as a stripe, ST). For double- and quadruple-domain lattices, linear and cross boundaries were designed to fabricate two (e.g., ON and OFF, ON and ST, and OFF and ST) and four (OFF, ST, OFF, and ON) different types of patterns in single lattices, respectively. In double-domain lattices, each linear boundary is placed between two different domains. Similarly, four linear boundaries connected with a seed tile (i.e., a cross boundary) can separate four domains in a single lattice in quadruple-domain lattices. Due to the presence of boundaries, the pattern growth directions are different in each domain. The experimentally obtained multi-domain patterns agree well with our design. Lastly, we propose the possibility of the construction of a hexadomain lattice through the mapping from hexagonal to square grids converted by using an axial coordinate system. By proposing a hexadomain lattice design, we anticipate the possibility to extend to higher numbers of multi-domains in a single lattice, thereby further increasing the information density in a given lattice.

DNA foams constructed by freeze drying and their optoelectronic characteristics.

The distinctive properties of DNA make it a promising biomaterial to use in nanoscience and nanotechnology. In the present study, DNA foam was fabricated into multi-dimensional shapes using a freeze drying process with liquid nitrogen and 3D printed molds. The physicochemical and optoelectronic properties of the fabricated DNA foams were investigated using Fourier transform infrared (FTIR) spectrum, X-ray photoelectron spectrum (XPS), thermogravimetric analysis (TGA), ultraviolet-visible (UV-Vis) absorption spectrum, and current-voltage (I-V) characteristics to understand the changes formed in the DNA structure and their effect on properties during the fabrication of DNA foam. The FTIR and XPS analyses confirmed that nitrogen was diffusing into the DNA structure during the DNA foam fabrication. The diffused nitrogen caused a decrease in bond lengths, strong chemical bonds, compaction of DNA structure, existence of additional carbon-nitrogen bonds, and variation in the electron density of the base elements in DNA. These changes in the DNA structure of the DNA foam were reflected in their chemical, optical, and electrical properties. Furthermore, the proper utilization of DNA foams as a template for functional materials by embedding carbon nanotubes (CNTs) and thermocolor was demonstrated.

Nanomaterial-Embedded DNA Films on 2D Frames.

Recently, 3D printing has provided opportunities for designing complex structures with ease. These printed structures can serve as molds for complex materials such as DNA and cetyltrimethylammonium chloride (CTMA)-modified DNA that have easily tunable functionalities via the embedding of various nanomaterials such as ions, nanoparticles, fluorophores, and proteins. Herein, we develop a simple and efficient method for constructing DNA flat and curved films containing water-soluble/thermochromatic dyes and di/trivalent ions and CTMA-modified DNA films embedded with organic light-emitting molecules (OLEM) with the aid of 2D/3D frames made by a 3D printer. We study the Raman spectra, current, and resistance of Cu2+-doped and Tb3+-doped DNA films and the photoluminescence of OLEM-embedded CTMA-modified DNA films to better understand the optoelectric characteristics of the samples. Compared to pristine DNA, ion-doped DNA films show noticeable variation of Raman peak intensities, which might be due to the interaction between the ion and phosphate backbone of DNA and the intercalation of ions in DNA base pairs. As expected, ion-doped DNA films show an increase of current with an increase in bias voltage. Because of the presence of metallic ions, DNA films with embedded ions showed relatively larger current than pristine DNA. The photoluminescent emission peaks of CTMA-modified DNA films with OLEMRed, OLEMGreen, and OLEMBlue were obtained at the wavelengths of 610, 515, and 469 nm, respectively. Finally, CIE color coordinates produced from CTMA-modified DNA films with different OLEM color types were plotted in color space. It may be feasible to produce multilayered DNA films as well. If so, multilayered DNA films embedded with different color dyes, ions, fluorescent materials, nanoparticles, proteins, and drug molecules could be used to realize multifunctional physical devices such as energy harvesting and chemo-bio sensors in the near future.

Protein-Encoding Free-Standing RNA Hydrogel for Sub-Compartmentalized Translation.

RNA can self-fold into complex structures that can serve as major biological regulators in protein synthesis and in catalysis. Due to the abundance of structural primitives and functional diversity, RNA has been utilized for designing nature-defined goals despite its intrinsic chemical instability and lack of technologies. Here, a robust, free-standing RNA hydrogel is developed through a sequential process involving both ligation and rolling circle transcription to form RNA G-quadruplexes, capable of both catalytic activity and enhancing expression of several proteins in sub-compartmentalized, phase-separated translation environments. The observations suggest that this hydrogel will expand RNA research and impact practical RNA principles and applications.

A Genome-Wide Association Study and Machine-Learning Algorithm Analysis on the Prediction of Facial Phenotypes by Genotypes in Korean Women.

Purpose: Changes in facial appearance are affected by various intrinsic and extrinsic factors, which vary from person to person. Therefore, each person needs to determine their skin condition accurately to care for their skin accordingly. Recently, genetic identification by skin-related phenotypes has become possible using genome-wide association studies (GWAS) and machine-learning algorithms. However, because most GWAS have focused on populations with American or European skin pigmentation, large-scale GWAS are needed for Asian populations. This study aimed to evaluate the correlation of facial phenotypes with candidate single-nucleotide polymorphisms (SNPs) to predict phenotype from genotype using machine learning. Materials and Methods: A total of 749 Korean women aged 30-50 years were enrolled in this study and evaluated for five facial phenotypes (melanin, gloss, hydration, wrinkle, and elasticity). To find highly related SNPs with each phenotype, GWAS analysis was used. In addition, phenotype prediction was performed using three machine-learning algorithms (linear, ridge, and linear support vector regressions) using five-fold cross-validation. Results: Using GWAS analysis, we found 46 novel highly associated SNPs (p < 1×10-05): 3, 20, 12, 6, and 5 SNPs for melanin, gloss, hydration, wrinkle, and elasticity, respectively. On comparing the performance of each model based on phenotypes using five-fold cross-validation, the ridge regression model showed the highest accuracy (r2 = 0.6422-0.7266) in all skin traits. Therefore, the optimal solution for personal skin diagnosis using GWAS was with the ridge regression model. Conclusion: The proposed facial phenotype prediction model in this study provided the optimal solution for accurately predicting the skin condition of an individual by identifying genotype information of target characteristics and machine-learning methods. This model has potential utility for the development of customized cosmetics.

Construction and Configuration Analysis of Zelkova Serrata Lenticel-Like Patterns Generated through DNA Algorithmic Self-Assembly.

Multiple models and simulations have been proposed and performed to understand the mechanism of the various pattern formations existing in nature. However, the logical implementation of those patterns through efficient building blocks such as nanomaterials and biological molecules is rarely discussed. This study adopts a cellular automata model to generate simulation patterns (SPs) and experimental patterns (EPs) obtained from DNA lattices similar to the discrete horizontal brown-color line-like patterns on the bark of the Zelkova serrata tree, known as lenticels [observation patterns (OPs)]. SPs and EPs are generated through the implementation of six representative rules (i.e., R004, R105, R108, R110, R126, and R218) in three-input/one-output algorithmic logic gates. The EPs obtained through DNA algorithmic self-assembly are visualized by atomic force microscopy. Three different modules (A, B, and C) are introduced to analyze the similarities between the SPs, EPs, and OPs of Zelkova serrata lenticels. Each module has unique configurations with specific orientations allowing the calculation of the deviation of the SPs and the EPs with respect to the OPs within each module. The findings show that both the SP and the EP generated under R105 and R126 and analyzed with module B provide a higher similarity of Zelkova serrata lenticel-like patterns than the other four rules. This study provides a perspective regarding the use of DNA algorithmic self-assembly for the construction of various complex natural patterns.

Interaction of Prion Peptides with DNA Structures.

Prion protein aggregation is known to be modulated by macromolecules including nucleic acids. To clarify the role of nucleic acids in PrP pathology, we investigated the interaction between nucleic acids and the prion peptide (PrP)-a synthetic prion protein model peptide resembling a portion of the human prion protein in structure and function spanning amino acid residues 106-126. We used synthetic DNA lattices and natural DNA duplexes extracted from salmon (sDNA) bound with PrP and studied their interaction using distinct physical measurements. The formation of DNA lattices with PrP was visualized by atomic force microscopy (AFM) to investigate the influence of the PrP. PrP inhibited the growth of the double-crossover (DX) lattices significantly compared to the control peptide (CoP). We also conducted optical measurements such as ultraviolet-visible (UV-Vis), circular dichroism (CD), and Fourier transform infrared (FTIR) spectroscopies to validate the interaction between PrP and DNA immediately (D0) and after a 30-day incubation (D30) period. UV-Vis spectra showed variation in the absorbance intensities, specific for the binding of CoP and PrP to DNA. The CD analysis revealed the presence of various secondary structures, such as α-helices and ß-sheets, in PrP- and PrP-bound sDNA complexes. The PrP-sDNA interaction was confirmed using FTIR by the change and shift of the absorption peak intensity and the alteration of PrP secondary structures in the presence of DNA. The cytotoxic effects of the PrP-bound sDNA complexes were assessed by a cytotoxicity assay in human neuroblastoma cells in culture. It confirmed that PrP with sDNA was less cytotoxic than CoP. This study provides new applications for DNA molecules by investigating their effect in complex with aggregated proteins. Our study unequivocally showed the beneficial effect of the interaction between DNA and the pathological prion protein. It therefore provides valuable information to exploit this effect in the development of potential therapeutics. Moreover, our work might serve as a basis for further studies investigating the role of DNA interactions with other amyloidogenic proteins.

Elucidation of obstructive sleep apnoea related blood pressure surge using a novel continuous beat-to-beat blood pressure monitoring system.

BACKGROUND: Obstructive sleep apnoea (OSA) episode related blood pressure (BP) surge may mediate the association of OSA with cardiovascular disease. However, BP is not measured during a clinical sleep study. METHOD: We tested the feasibility of incorporating the Caretaker physiological monitor, which utilizes a novel continuous beat-to-beat (b-b) BP monitoring technology, into polysomnography (PSG) and aimed to characterize BP surges related to obstructive respiratory events. B-b BP was concurrently collected and merged with PSG data on a posthoc basis. We compared BP surge between mean respiratory (apnoea, hypopnea and desaturation-alone events) and nonrespiratory events (spontaneous or leg movement-related arousals). We examined the association of the degree of oxygen desaturation with BP surge in a given respiratory event combining all events. A total of 17 consecutive patients (12 men, mean 52 years old, nine diagnostic and eight split-night PSGs) undergoing clinically indicated PSG were included after excluding one patient with poor signal quality due to excessive movement. RESULTS: Caretaker was well tolerated. Mean respiratory BP surge ranged from 5 to 19 mmHg [Median (IQR) = 13.9 (9.5--16.2)]. Mean BP surge between the respiratory and nonrespiratory events was similar [13.8 (4.5) vs. 14.9 (5.3) mmHg, P = 0.13]. Accounting for the count distribution of desaturation/BP surge data pair events, there was a linear correlation between the degree of oxygen desaturation and BP surge (R = 0.57, P < 0.001). In eight patients undergoing split-night sleep studies, the number of BP surge events (≥10 mmHg/h) decreased during continuous positive airway pressure in all but one patient. CONCLUSION: We demonstrated highly variable OSA-related BP surge patterns using the Caretaker's b-b BP monitoring technology that has the potential to be integrated into sleep studies.

Fibres and films made from DNA and CTMA-modified DNA embedded with gold nanorods and organic light-emitting materials.

The scaffolding of deoxyribonucleic acid (DNA) makes DNA molecules effective templates for hosting various types of nanomaterials. Recently, electrospun fibres formed by a variety of polymers have begun to see use in a number of applications, such as filtration in energy applications, insulation in thermodynamics and protein scaffolding in biomedicine. In this study, we constructed electrospun fibres and thin films made of DNA and cetyltrimethylammonium chloride (CTMA)-modified DNA (CDNA) embedded with dyes, organic light-emitting materials (OLEMs), and gold nanorods (GNRs). These materials provide significant advantages, including selectivity of dimensionality, solubility in organic and inorganic solvents, and functionality enhancement. In addition, coaxial fibres made of CDNA were constructed to demonstrate the feasibility of constructing relatively complex fibres with an electrospinner. To determine the basic physical characteristics of the fibres and thin films containing GNRs and OLEMs, we conducted current measurements, photoluminescence (PL) measurements, X-ray photoelectron spectroscopy (XPS), and ultraviolet-visible (UV-Vis) spectroscopy. The currents in DNA and CDNA were found to exhibit Ohmic behaviour, while the PL emission could be controlled by OLEMs. In addition, the XPS provided the chemical configuration of samples, and the UV-Vis spectra revealed the plasmon resonance of GNR. Due to their simple fabrication and enhanced functionality, these DNA and CDNA fibres and thin films could be used in various devices (e.g., filters or blocking layers) and sensors (e.g., gas detectors and bio sensors) in a number of industries.

Demonstration of elementary functions via DNA algorithmic self-assembly.

Target-oriented cellular automata with computation are the primary challenge in the field of DNA algorithmic self-assembly in connection with specific rules. We investigate the feasibility of using the principle of cellular automata for mathematical subjects by using specific logic gates that can be implemented into DNA building blocks. Here, we connect the following five representative elementary functions: (i) enumeration of multiples of 2, 3, and 4 (demonstrated via R094, R062, and R190 in 3-input/1-output logic rules); (ii) the remainder of 0 and 1 (R132); (iii) powers of 2 (R129); (iv) ceiling function for n/2 and n/4 (R152 and R144); and (v) analogous pattern of annihilation (R184) to DNA algorithmic patterns formed by specific rules. After designing the abstract building blocks and simulating the generation of algorithmic lattices, we conducted an experiment as follows: designing of DNA tiles with specific sticky ends, construction of DNA lattices via a two-step annealing method, and verification of expected algorithmic patterns on a given DNA lattice using an atomic force microscope (AFM). We observed representative patterns, such as horizontal and diagonal stripes and embedded triangles, on the given algorithmic lattices. The average error rates of individual rules are in the range of 8.8% (R184) to 11.9% (R062), and the average error rate for all the rules was 10.6%. Interpretation of elementary functions demonstrated through DNA algorithmic patterns could be extended to more complicated functions, which may lead to new insights for achieving the final answers of functions with experimentally obtained patterns.

Configuration Analysis of a Lizard Skin-like Pattern Formed by DNA Self-Assembly.

Nature manifests diverse and complicated patterns through efficient physical, chemical, and biological processes. One of the approaches to generate complex patterns, as well as simple patterns, is the use of the cellular automata algorithm. However, there are certain limitations to produce such patterns experimentally due to the difficulty of finding candidate programmable building blocks. Here, we demonstrated the feasibility of generating an ocellated lizard skin-like pattern by simulation considering the probabilistic occurrence of cells and constructed the simulation results on DNA lattices via bottom-up self-assembly. To understand the similarity between the simulated pattern (SP) and the observed pattern (OP) of lizard skin, a unique configuration scheme (unit configuration was composed of 7 cells) was conceived. SPs were generated through a computer with a controlling population of gray and black cells in a given pattern. Experimental patterns (EPs) on DNA lattices, consisting of double-crossover (DX) tiles without and with protruding hairpins, were fabricated and verified through atomic force microscopy (AFM). For analyzing the similarity of the patterns, we introduced deviation of the average configuration occurrence for SP and EP with respect to OP, i.e., σα(SO) and σα(EO). The configuration and deviation provide characteristic information of patterns. We recognized that the minimum values of <σα(SO)> and <σα(EO)> occurred when 50% (55%) of black cells in given SPs (DX tiles with hairpins in given EPs) appeared to be most similar to the OP. Our study provides a novel platform for the applicability of DNA molecules to systematically demonstrate other naturally existing complex patterns or processes with ease.

Central blood pressure lowering effect of telmisartan-rosuvastatin single-pill combination in hypertensive patients combined with dyslipidemia: A pilot study.

This multicenter, phase 4, Prospective Randomized Open, Blinded End-point (PROBE) study aimed to evaluate safety and efficacy of telmisartan/rosuvastatin single-pill combination (SPC) therapy on lowering central blood pressure (BP) compared with telmisartan monotherapy in hypertensive patients with dyslipidemia in Korea. Study was terminated earlier than planned due to COVID-19 pandemic, thus should be considered as a pilot study. Among 125 patients who met the inclusion criteria of hypertension and dyslipidemia (defined as 10-year Atherosclerotic Cardiovascular Disease risk score over 5%), 80 patients went through 4-week single-group run-in period with telmisartan 40-80 mg, then randomized to telmisartan 80 mg + rosuvastatin (10 or 20 mg) SPC group or telmisartan 80 mg monotherapy group. The central/brachial BP, brachial-ankle pulse wave velocity (baPWV), and augmentation index (AIx) were assessed at baseline and 16 weeks later. Mean brachial SBP changed from 135.80 ± 14.22 mmHg to 130.69 ± 13.23 mmHg in telmisartan/rosuvastatin group and from 134.37 ± 12.50 mmHg to 133.75 ± 12.30 mmHg in telmisartan monotherapy group without significant difference (between-group difference p = .149). Mean central SBP were reduced significantly in the telmisartan/rosuvastatin group with change from 126.72 ± 14.44 mmHg to 121.56 ± 14.56 mmHg while telmisartan monotherapy group showed no significant change (between-group difference p = .028). BaPWV changed from 1672.57 ± 371.72 m/s to 1591.75 ± 272.16 m/s in telmisartan/rosuvastatin group and from 1542.85 ± 263.70 m/s to 1586.12 ± 297.45 m/s in telmisartan group with no significance (between-group difference p = .078). Change of AIx had no significant difference (between-group difference p = .314). Both groups showed excellent compliance rate of 96.9 ± 4.5% with no significant difference in adverse rate. Telmisartan/rosuvastatin SPC therapy was more effective in lowering central BP compared with the telmisartan monotherapy. The results of this study showed benefit of additive statin therapy in hypertensive patients combined with dyslipidemia.