Efficient data reconstruction: The bottleneck of large-scale application of DNA storage.

Over the past decade, the rapid development of DNA synthesis and sequencing technologies has enabled preliminary use of DNA molecules for digital data storage, overcoming the capacity and persistence bottlenecks of silicon-based storage media. DNA storage has now been fully accomplished in the laboratory through existing biotechnology, which again demonstrates the viability of carbon-based storage media. However, the high cost and latency of data reconstruction pose challenges that hinder the practical implementation of DNA storage beyond the laboratory. In this article, we review existing advanced DNA storage methods, analyze the characteristics and performance of biotechnological approaches at various stages of data writing and reading, and discuss potential factors influencing DNA storage from the perspective of data reconstruction.

DNA-QLC: an efficient and reliable image encoding scheme for DNA storage.

BACKGROUND: DNA storage has the advantages of large capacity, long-term stability, and low power consumption relative to other storage mediums, making it a promising new storage medium for multimedia information such as images. However, DNA storage has a low coding density and weak error correction ability. RESULTS: To achieve more efficient DNA storage image reconstruction, we propose DNA-QLC (QRes-VAE and Levenshtein code (LC)), which uses the quantized ResNet VAE (QRes-VAE) model and LC for image compression and DNA sequence error correction, thus improving both the coding density and error correction ability. Experimental results show that the DNA-QLC encoding method can not only obtain DNA sequences that meet the combinatorial constraints, but also have a net information density that is 2.4 times higher than DNA Fountain. Furthermore, at a higher error rate (2%), DNA-QLC achieved image reconstruction with an SSIM value of 0.917. CONCLUSIONS: The results indicate that the DNA-QLC encoding scheme guarantees the efficiency and reliability of the DNA storage system and improves the application potential of DNA storage for multimedia information such as images.

Efficacy and safety of traditional Chinese manual therapy (Tuina) in patients with non-specific chronic low back pain: a study protocol for a randomised controlled trial.

INTRODUCTION: Non-pharmacological interventions play a crucial role in the management of non-specific chronic low back pain (NSCLBP). One prime example is Tuina, a traditional Chinese manual therapy that incorporates pressing, kneading and rubbing techniques to alleviate physical discomfort and enhance overall well-being. It serves as a widely used technique in China and other East Asian countries. However, the effectiveness and safety of Tuina for managing NSCLBP have not been substantiated through rigorous clinical research. We sought to carry out a randomised controlled trial with an open-label design, blinded assessors and parallel arms to assess the effectiveness and safety of Tuina as a treatment for NSCLBP. The trial aims to provide high-quality evidence regarding the efficacy and safety of Tuina in improving outcomes for patients with NSCLBP. METHODS AND ANALYSIS: A total of 150 patients aged 18-60 years with NSCLBP will be recruited. Participants will be randomly assigned to one of the two groups. Both groups will receive standard health education. In addition, the treatment group will receive Tuina therapy, while the control group will participate in core stability exercises. Each group will undergo a total of 18 interventions over 6 weeks, with the interventions administered three times per week. The primary outcome measure is the patient's pain intensity, assessed using the Numerical Rating Scale, at week 6 following randomisation. Secondary outcomes encompass disability (measured by the Roland-Morris Disability Questionnaire), quality of life (assessed using the EuroQoL-5 dimensions questionnaire), adverse emotions (evaluated with the Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia and Depression Anxiety Stress Scale), biomechanical outcomes, socioeconomic indicators (medication use, healthcare utilisation and absenteeism), patient satisfaction, treatment adherence and other relevant factors.The statistical analysis will follow the intention-to-treat principle. Two-way repeated measures analysis of variance will be used to compare the clinical data across different time points within both groups. ETHICS AND DISSEMINATION: The study protocol has received approval from the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (2023-1366-133-01). All study participants will be required to give written informed consent. The findings of the study will be submitted to a peer-reviewed journal for publication and presented at scientific conferences. Additionally, the participants will receive copies of the results. TRIAL REGISTRATION NUMBER: ChiCTR2300076257.

Storing Images in DNA via base128 Encoding.

Current DNA storage schemes lack flexibility and consistency in processing highly redundant and correlated image data, resulting in low sequence stability and image reconstruction rates. Therefore, according to the characteristics of image storage, this paper proposes storing images in DNA via base128 encoding (DNA-base128). In the data writing stage, data segmentation and probability statistics are carried out, and then, the data block frequency and constraint encoding set are associated with achieving encoding. When the image needs to be recovered, DNA-base128 completes internal error correction by threshold setting and drift comparison. Compared with representative work, the DNA-base128 encoding results show that the undesired motifs were reduced by 71.2-90.7% and that the local guanine-cytosine content variance was reduced by 3 times, indicating that DNA-base128 can store images more stably. In addition, the structural similarity index (SSIM) and multiscale structural similarity (MS-SSIM) of image reconstruction using DNA-base128 were improved by 19-102 and 6.6-20.3%, respectively. In summary, DNA-base128 provides image encoding with internal error correction and provides a potential solution for DNA image storage. The data and code are available at the GitHub repository: https://github.com/123456wk/DNA_base128.

EPO promotes the progression of rheumatoid arthritis by inducing desialylation via increasing the expression of neuraminidase 3.

OBJECTIVE: Erythropoietin (EPO) known as an erythrocyte-stimulating factor is increased in patients with rheumatoid arthritis (RA). Nevertheless, the function of EPO in the process of RA and relative mechanism needs to be further clarified. METHODS: The level of EPO in serum and synovial fluid from patients with RA and healthy controls was determined by . Collagen-induced arthritis (CIA) mice were constructed to confirm the role of EPO on RA pathogenesis. Differentially expressed genes (DEGs) of EPO-treated fibroblast-like synoviocyte (FLS) were screened by transcriptome sequencing. The transcription factor of neuraminidase 3 (NEU3) of DEGs was verified by double luciferase reporting experiment, DNA pulldown, electrophoretic mobility shift assay and chromatin immunoprecipitation-quantitative PCR (qPCR) assay. RESULTS: The overexpression of EPO was confirmed in patients with RA, which was positively associated with Disease Activity Score 28-joint count. Additionally, EPO intervention could significantly aggravate the joint destruction in CIA models. The upregulation of NEU3 was screened and verified by transcriptome sequencing and qPCR in EPO-treated FLS, and signal transducer and activator of transcription 5 was screened and verified to be the specific transcription factor of NEU3. EPO upregulates NEU3 expression via activating the Janus kinase 2 (JAK2)-STAT5 signalling pathway through its receptor EPOR, thereby to promote the desialylation through enhancing the migration and invasion ability of FLS, which is verified by JAK2 inhibitor and NEU3 inhibitor. CONCLUSION: EPO, as a proinflammatory factor, accelerates the process of RA through transcriptional upregulation of the expression of NEU3 by JAK2/STAT5 pathway.

Biomolecule-Driven Two-Factor Authentication Strategy for Access Control of Molecular Devices.

The rise of DNA nanotechnology is promoting the development of molecular security devices and marking an essential change in information security technology, to one that can resist the threats resulting from the increase in computing power, brute force attempts, and quantum computing. However, developing a secure and reliable access control strategy to guarantee the confidentiality of molecular security devices is still a challenge. Here, a biomolecule-driven two-factor authentication strategy for access control of molecular devices is developed. Importantly, the two-factor is realized by applying the specificity and nicking properties of the nicking enzyme and the programmable design of the DNA sequence, endowing it with the characteristic of a one-time password. To demonstrate the feasibility of this strategy, an access control module is designed and integrated to further construct a role-based molecular access control device. By constructing a command library composed of three commands (Ca, Cb, Ca and Cb), the authorized access of three roles in the molecular device is realized, in which the command Ca corresponds to the authorization of role A, Cb corresponds to the authorization of role B, and Ca and Cb corresponds to the authorization of role C. In this way, when users access the device, they not only need the correct factor but also need to apply for role authorization in advance to obtain secret information. This strategy provides a highly robust method for the research on access control of molecular devices and lays the foundation for research on the next generation of information security.

DBTRG: De Bruijn Trim rotation graph encoding for reliable DNA storage.

DNA is a high-density, long-term stable, and scalable storage medium that can meet the increased demands on storage media resulting from the exponential growth of data. The existing DNA storage encoding schemes tend to achieve high-density storage but do not fully consider the local and global stability of DNA sequences and the read and write accuracy of the stored information. To address these problems, this article presents a graph-based De Bruijn Trim Rotation Graph (DBTRG) encoding scheme. Through XOR between the proposed dynamic binary sequence and the original binary sequence, k-mers can be divided into the De Bruijn Trim graph, and the stored information can be compressed according to the overlapping relationship. The simulated experimental results show that DBTRG ensures base balance and diversity, reduces the likelihood of undesired motifs, and improves the stability of DNA storage and data recovery. Furthermore, the maintenance of an encoding rate of 1.92 while storing 510 KB images and the introduction of novel approaches and concepts for DNA storage encoding methods are achieved.

DUHI: Dynamically updated hash index clustering method for DNA storage.

The exponential growth of global data leads to the problem of insufficient data storage capacity. DNA storage can be an ideal storage method due to its high storage density and long storage time. However, the DNA storage process is subject to unavoidable errors that can lead to increased cluster redundancy during data reading, which in turn affects the accuracy of the data reads. This paper proposes a dynamically updated hash index (DUHI) clustering method for DNA storage, which clusters sequences by constructing a dynamic core index set and using hash lookup. The proposed clustering method is analyzed in terms of overall reliability evaluation and visualization evaluation. The results show that the DUHI clustering method can reduce the redundancy of more than 10% of the sequences within the cluster and increase the reconstruction rate of the sequences to more than 99%. Therefore, our method solves the high redundancy problem after DNA sequence clustering, improves the accuracy of data reading, and promotes the development of DNA storage.

High Net Information Density DNA Data Storage by the MOPE Encoding Algorithm.

DNA has recently been recognized as an attractive storage medium due to its high reliability, capacity, and durability. However, encoding algorithms that simply map binary data to DNA sequences have the disadvantages of low net information density and high synthesis cost. Therefore, this paper proposes an efficient, feasible, and highly robust encoding algorithm called MOPE (Modified Barnacles Mating Optimizer and Payload Encoding). The Modified Barnacles Mating Optimizer (MBMO) algorithm is used to construct the non-payload coding set, and the Payload Encoding (PE) algorithm is used to encode the payload. The results show that the lower bound of the non-payload coding set constructed by the MBMO algorithm is 3%-18% higher than the optimal result of previous work, and theoretical analysis shows that the designed PE algorithm has a net information density of 1.90 bits/nt, which is close to the ideal information capacity of 2 bits per nucleotide. The proposed MOPE encoding algorithm with high net information density and satisfying constraints can not only effectively reduce the cost of DNA synthesis and sequencing but also reduce the occurrence of errors during DNA storage.

RBS: A Rotational Coding Based on Blocking Strategy for DNA Storage.

The data volume of global information has grown exponentially in recent years, but the development of silicon-based memory has entered a bottleneck period. Deoxyribonucleic acid (DNA) storage is drawing attention owing to its advantages of high storage density, long storage time, and easy maintenance. However, the base utilization and information density of existing DNA storage methods are insufficient. Therefore, this study proposes a rotational coding based on blocking strategy (RBS) for encoding digital information such as text and images in DNA data storage. This strategy satisfies multiple constraints and produces low error rates in synthesis and sequencing. To illustrate the superiority of the proposed strategy, it was compared and analyzed with existing strategies in terms of entropy value change, free energy size, and Hamming distance. The experimental results show that the proposed strategy has higher information storage density and better coding quality in DNA storage, so it will improve the efficiency, practicality, and stability of DNA storage.

GCNSA: DNA storage encoding with a graph convolutional network and self-attention.

DNA Encoding, as a key step in DNA storage, plays an important role in reading and writing accuracy and the storage error rate. However, currently, the encoding efficiency is not high enough and the encoding speed is not fast enough, which limits the performance of DNA storage systems. In this work, a DNA storage encoding system with a graph convolutional network and self-attention (GCNSA) is proposed. The experimental results show that DNA storage code constructed by GCNSA increases by 14.4% on average under the basic constraints, and by 5%-40% under other constraints. The increase of DNA storage codes effectively improves the storage density of 0.7-2.2% in the DNA storage system. The GCNSA predicted more DNA storage codes in less time while ensuring the quality of codes, which lays a foundation for higher read and write efficiency in DNA storage.

A DNA Finite-State Machine Based on the Programmable Allosteric Strategy of DNAzyme.

Living organisms can produce corresponding functions by responding to external and internal stimuli, and this irritability plays a pivotal role in nature. Inspired by such natural temporal responses, the development and design of nanodevices with the ability to process time-related information could facilitate the development of molecular information processing systems. Here, we proposed a DNA finite-state machine that can dynamically respond to sequential stimuli signals. To build this state machine, a programmable allosteric strategy of DNAzyme was developed. This strategy performs the programmable control of DNAzyme conformation using a reconfigurable DNA hairpin. Based on this strategy, we first implemented a finite-state machine with two states. Through the modular design of the strategy, we further realized the finite-state machine with five states. The DNA finite-state machine endows molecular information systems with the ability of reversible logic control and order detection, which can be extended to more complex DNA computing and nanomachines to promote the development of dynamic nanotechnology.

Active Self-Assembly of Ladder-Shaped DNA Carrier for Drug Delivery.

With the advent of nanotechnology, DNA molecules have been transformed from solely genetic information carriers to multifunctional materials, showing a tremendous potential for drug delivery and disease diagnosis. In drug delivery systems, DNA is used as a building material to construct drug carriers through a variety of DNA self-assembly methods, which can integrate multiple functions to complete in vivo and in situ tasks. In this study, ladder-shaped drug carriers are developed for drug delivery on the basis of a DNA nanoladder. We first demonstrate the overall structure of the nanoladder, in which a nick is added into each rung of the nanoladder to endow the nanoladder with the ability to incorporate a drug loading site. The structure is designed to counteract the decrement of stability caused by the nick and investigated in different conditions to gain insight into the properties of the nicked DNA nanoladders. As a proof of concept, we fix the biotin in every other nick as a loading site and assemble the protein (streptavidin) on the loading site to demonstrate the feasibility of the drug-carrying function. The protein can be fixed stably and can be extended to different biological and chemical drugs by altering the drug loading site. We believe this design approach will be a novel addition to the toolbox of DNA nanotechnology, and it will be useful for versatile applications such as in bioimaging, biosensing, and targeted therapy.

Synthesis of Fibrous Phosphorus Micropillar Arrays with Pyro-Phototronic Effects.

The bottom-up preparation of two-dimensional material micro-nano structures at scale facilitates the realisation of integrated applications in optoelectronic devices. Fibrous Phosphorus (FP), an allotrope of black phosphorus (BP), is one of the most promising candidate materials in the field of optoelectronics with its unique crystal structure and properties.[1] However, to date, there are no bottom-up micro-nano structure preparation methods for crystalline phosphorus allotropes.[1c, 2] Herein, we present the bottom-up preparation of fibrous phosphorus micropillar (FP-MP) arrays via a low-pressure gas-phase transport (LP-CVT) method that controls the directional phase transition from amorphous red phosphorus (ARP) to FP. In addition, self-powered photodetectors (PD) of FP-MP arrays with pyro-phototronic effects achieved detection beyond the band gap limit. Our results provide a new approach for bottom-up preparation of other crystalline allotropes of phosphorus.

Effect of traditional Chinese manual therapy on alleviating pain and dysfunction of lumbar disc herniation: a randomized controlled pilot study.

OBJECTIVE: To investigate the effect of traditional Chinese manual therapy (TCMT) in alleviating pain and dysfunction in patients with lumbar disc herniation (LDH). METHODS: Sixty-six patients with LDH were recruited as the study cohort and randomly assigned to an observation group and a control group. The patients in the observation group underwent TCMT, whereas those in the control group underwent conventional lumbar traction (LT). The observed indexes comprised primary index, which referred to clinical efficacy, and secondary indexes, which include Simplified McGill Pain Questionnaire, Oswestry Disability Index (ODI), range of motion (ROM) of the lumbar spine, difference in muscle tone (MT) and pressure pain threshold (PPT) of the bilateral erector spinae, and serum inflammatory factor levels. RESULTS: The total effective rate was significantly higher in the observation group than in the control group (96.67% vs. 66.67%, P < 0.001). Compared with the control group after treatment, patients in the observation group had significantly lower ODI, pain rating index, visual analog scale and present pain intensity scores (all P < 0.05), and had significantly smaller differences in MT and PPT of the bilateral erector spinae (both P < 0.001), but had remarkably greater ROM of the lumbar spine (P < 0.001). In addition, interleukin (IL)-6, IL-8, and interferon-γ concentrations in the observation group were significantly lower than those in the control group after treatment (all P < 0.05). CONCLUSION: TCMT has positive effects on alleviating pain and improving dysfunction of patients with LDH and helps in reducing serum inflammatory factor levels.

FMG: An observable DNA storage coding method based on frequency matrix game graphs.

Using complex biomolecules for storage is a new carbon-based storage method. For example, DNA has the potential to be a good method for archival long-term data storage. Reasonable and efficient coding is the first and most important step in DNA storage. However, current coding methods, such as altruism algorithm, have the problem of low coding efficiency and high complexity, and coding constraints and sets make it difficult to see the coding results visually. In this study, a new DNA storage coding method based on frequency matrix game graph (FMG) is proposed to generate DNA storage coding satisfying combinatorial constraints. Compared with the randomness of the heuristic algorithm that satisfies the constraints, the coding method based on the FMG is deterministic and can clearly explain the coding process. In addition, the constraints and coding results have observable characteristics and are better than the previously published results for the size of the coding set. For example, when length of the code n = 10, hamming distance d = 4, the results obtained by proposed approach combining chaos game and graph are 24% better than the previous results. The proposed coding scheme successfully constructs high-quality coding sets with less complexity, which effectively promotes the development of carbon-based storage coding.

Complex dynamics of hair bundle of auditory nervous system (II): forced oscillations related to two cases of steady state.

The forced oscillations of hair bundle of inner hair cells of auditory nervous system evoked by external force from steady state are related to the fast adaption of hair cells, which are very important for auditory amplification. In the present paper, comprehensive and deep understandings to nonlinear dynamics of forced oscillations are acquired in four aspects. Firstly, the complex dynamics underlying the twitch (fast recoil of displacement X which is fast variable) induced from Case-1 and Case-2 steady states by external pulse force are obtained. With help of vector fields and nullclines, the phase trajectory of forced oscillations is identified to be an evolution process between two equilibrium points corresponding to zero force and pulse force, respectively, and then the twitch is obtained as the behavior running along the nonlinear part of X-nullcline. Especially, twitch observed in experiment are classified into 6 types, which are induced by negative change of force, negative and positive changes of force, and positive change of force, respectively, and further build relationships to three subcases of Case-2 steady state with N-shaped X-nullcline (equilibrium point locates on the left, middle, and right branches of X-nullcline, respectively). Secondly, the experimental observation of fatigue of twitch induced by continual two pulse forces, i.e. the reduced amplitude of the latter twitch when interval between two forces is short, is also explained as a nonlinear behavior beginning from an initial value different from that of the former one. Thirdly, the experimental observation of transition between sustained oscillations and steady state induced by pulse force can be simulated for Case-1 steady state with Z-shaped X-nullcline instead of Case-2, due to that there exists bifurcations with respect to external force for Case-1 while no bifurcations for Case-2. Last, the threshold phenomenon induced by simple pulse stimulation exists for Case-1 steady state rather than Case-2, due to that the upper and lower branches of Z-shaped X-nullcline close to the middle branch exhibit coexisting behaviors of variable X while N-shaped X-nullcline does not. The nonlinear dynamics of forced oscillations are helpful for explanations to the complex experimental observations, which presents potential measures to modulate the functions of twitch such as the fast adaption.

TripDesign: A DNA Triplex Design Approach Based on Interaction Forces.

A DNA triplex has the advantages of improved nanostructure stability and pH environment responsiveness compared with single-stranded and double-stranded nucleic acids. However, sequence stability and low design efficiency hinder the application of DNA triplexes. Therefore, a DNA triplex design approach (TripDesign) based on interaction forces is proposed. First, we present the stacking force constraint, torsional stress constraint, and G-quadruplex motif constraint and then use an improved memetic algorithm to design triplex sequences under combinatorial constraints. Finally, to quantify the process of triplex formation, we also explore the minimum length of the triplex-forming oligos (TFOs) required to form the triplex and the factors that produce depletion in cyclic pH-jump experiments. The experimental results show that the sequences produced by TripDesign have high stability and reversibility, and the proposed approach achieves efficient and automatic sequence design. In addition, this study characterizes multiple basic parameters of DNA triplex formation and promotes the wider application of DNA triplexes in nanotechnology.

Connective tissue growth factor-targeting DNA aptamer suppresses pannus formation as diagnostics and therapeutics for rheumatoid arthritis.

Connective tissue growth factor (CTGF) has been recently acknowledged as an ideal biomarker in the early disease course, participating in the pathogenesis of pannus formation in rheumatoid arthritis (RA). However, existing approaches for the detection of or antagonist targeting CTGF are either lacking or unsatisfactory in the diagnosis and treatment of RA. To address this, we synthesized and screened high-affinity single-stranded DNA aptamers targeting CTGF through a protein-based SELEX procedure. The structurally optimized variant AptW2-1-39-PEG was characterized thoroughly for its high-affinity (KD 7.86 nM), sensitivity (minimum protein binding concentration, 2 ng), specificity (negative binding to other biomarkers of RA), and stability (viability-maintaining duration in human serum, 48 h) properties using various biochemical and biophysical assays. Importantly, we showed the antiproliferative and antiangiogenic activities of the aptamers obtained using functional experiments and further verified the therapeutic effect of the aptamers on joint injury and inflammatory response in collagen-induced arthritis (CIA) mice, thus advancing this study into actual therapeutic application. Furthermore, we revealed that the binding within AptW2-1-39-PEG/CTGF was mediated by the thrombospondin 1 (TSP1) domain of CTGF using robust bioinformatics tools together with immunofluorescence. In conclusion, our results revealed a novel aptamer that holds promise as an additive or alternative approach for CTGF-targeting diagnostics and therapeutics for RA.

Adaptive coding for DNA storage with high storage density and low coverage.

The rapid development of information technology has generated substantial data, which urgently requires new storage media and storage methods. DNA, as a storage medium with high density, high durability, and ultra-long storage time characteristics, is promising as a potential solution. However, DNA storage is still in its infancy and suffers from low space utilization of DNA strands, high read coverage, and poor coding coupling. Therefore, in this work, an adaptive coding DNA storage system is proposed to use different coding schemes for different coding region locations, and the method of adaptively generating coding constraint thresholds is used to optimize at the system level to ensure the efficient operation of each link. Images, videos, and PDF files of size 698 KB were stored in DNA using adaptive coding algorithms. The data were sequenced and losslessly decoded into raw data. Compared with previous work, the DNA storage system implemented by adaptive coding proposed in this paper has high storage density and low read coverage, which promotes the development of carbon-based storage systems.