IL-27 Gene Therapy Ameliorates IPEX Syndrome Caused by Germline Mutation of Foxp3 Gene: A Major Role for Induction of IL-10.

Inactivating mutations of Foxp3, the master regulator of regulatory T cell development and function, lead to immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome in mice and humans. IPEX is a fatal autoimmune disease, with allogeneic stem cell transplant being the only available therapy. In this study, we report that a single dose of adeno-associated virus (AAV)-IL-27 to young mice with naturally occurring Foxp3 mutation (Scurfy mice) substantially ameliorates clinical symptoms, including growth retardation and early fatality. Correspondingly, AAV-IL-27 gene therapy significantly prevented naive T cell activation, as manifested by downregulation of CD62L and upregulation of CD44, and immunopathology typical of IPEX. Because IL-27 is known to induce IL-10, a key effector molecule of regulatory T cells, we evaluated the contribution of IL-10 induction by crossing IL-10-null allele to Scurfy mice. Although IL-10 deficiency does not affect the survival of Scurfy mice, it largely abrogated the therapeutic effect of AAV-IL-27. Our study revealed a major role for IL-10 in AAV-IL-27 gene therapy and demonstrated that IPEX is amenable to gene therapy.

The first discovery of Polypedatesteraiensis (Dubois, 1987) (Rhacophoridae, Anura) in China.

Background: The genus of Polypedates Tschudi, 1838 currently comprises 25 recognised species with four of these species reported in Yunnan, China. Dubois (1987) speculated the distribution of P.teraiensis in China; however, there was no study carried out to confirm its distribution in the region. New information: We herein describe P.teraiensis as a new national record, based on a specimen collected from Yunnan border region. Phylogenetically, our sequence clustered with the sequences of recognised P.teraiensis specimens from Bangladesh, Myanmar and India. The uncorrected pairwise distances between the specimens from China and other P.teraiensis localities was small, ranging from 0.0-0.7%, based on 16S rRNA gene. Therefore, we report P.teraiensis as a new species record for China.

Autonomous Stabilization of Fock States in an Oscillator against Multiphoton Losses.

Fock states with a well-defined number of photons in an oscillator have shown a wide range of applications in quantum information science. Nonetheless, their usefulness has been marred by single and multiphoton losses due to unavoidable environment-induced dissipation. Though several dissipation engineering methods have been developed to counteract the leading single-photon-loss error, averting multiple-photon losses remains elusive. Here, we experimentally demonstrate a dissipation engineering method that autonomously stabilizes multiphoton Fock states against losses of multiple photons using a cascaded selective photon-addition operation in a superconducting quantum circuit. Through measuring the photon-number populations and Wigner tomography of the oscillator states, we observe a prolonged preservation of nonclassical Wigner negativities for the stabilized Fock states |N⟩ with N=1, 2, 3 for a duration of about 10 ms. Furthermore, the dissipation engineering method demonstrated here also facilitates the implementation of a nonunitary operation for resetting a binomially encoded logical qubit. These results highlight potential applications in error-correctable quantum information processing against multiple-photon-loss errors.

An improved Dijkstra cross-plane image encryption algorithm based on a chaotic system.

While encrypting information with color images, most encryption schemes treat color images as three different grayscale planes and encrypt each plane individually. These algorithms produce more duplicated operations and are less efficient because they do not properly account for the link between the various planes of color images. In addressing the issue, we propose a scheme that thoroughly takes into account the relationship between pixels across different planes in color images. First, we introduce a new 1D chaotic system. The performance analysis shows the system has good chaotic randomness. Next, we employ a shortest-path cross-plane scrambling algorithm that utilizes an enhanced Dijkstra algorithm. This algorithm effectively shuffles pixels randomly within each channel of a color image. To accomplish cross-plane diffusion, our approach is then integrated into the adaptive diffusion algorithm. The security analysis and simulation results demonstrate that the approach can tackle the issue of picture loss in telemedicine by encrypting color images without any loss of quality. Furthermore, the images we utilize are suitable for both standard RGB and medical images. They incorporate more secure and highly sensitive keys, robustly withstanding various typical ciphertext analysis attacks. This ensures a reliable solution for encrypting original images.

Siglec-H-/- Plasmacytoid Dendritic Cells Protect Against Acute Liver Injury by Suppressing IFN-γ/Th1 Response and Promoting IL-21+ CD4 T Cells.

BACKGROUND & AIMS: Siglec-H is a receptor specifically expressed in mouse plasmacytoid dendritic cells (pDCs), which functions as a negative regulator of interferon-α production and plays a critical role in pDC maturation to become antigen-presenting cells. The function of pDCs in autoimmune and inflammatory diseases has been reported. However, the effect of Siglec-H expression in pDCs in liver inflammation and diseases remains unclear. METHODS: Using the model of concanavalin A-induced acute liver injury (ALI), we investigated the Siglec-H/pDCs axis during ALI in BDCA2 transgenic mice and Siglec-H-/- mice. Anti-BDCA2 antibody, anti-interleukin (IL)-21R antibody, and Stat3 inhibitor were used to specifically deplete pDCs, block IL21 receptor, and inhibit Stat3 signaling, respectively. Splenocytes and purified naive CD4 T cells and bone marrow FLT3L-derived pDCs were cocultured and stimulated with phorbol myristate acetate/ionomycin and CD3/CD28 beads, respectively. RESULTS: Data showed that specific depletion of pDCs aggravated concanavalin A-induced ALI. Remarkably, alanine aminotransferase, hyaluronic acid, and proinflammatory cytokines IL6 and tumor necrosis factor-α levels were lower in the blood and liver of Siglec-H knockout mice. This was associated with attenuation of both interferon-γ/Th1 response and Stat1 signaling in the liver of Siglec-H knockout mice while intrahepatic IL21 and Stat3 signaling pathways were upregulated. Blocking IL21R or Stat3 signaling in Siglec-H knockout mice restored concanavalin A-induced ALI. Finally, we observed that the Siglec-H-null pDCs exhibited immature and immunosuppressive phenotypes (CCR9LowCD40Low), resulting in reduction of CD4 T-cell activation and promotion of IL21+CD4 T cells in the liver. CONCLUSIONS: During T-cell-mediated ALI, Siglec-H-null pDCs enhance immune tolerance and promote IL21+CD4 T cells in the liver. Targeting Siglec-H/pDC axis may provide a novel approach to modulate liver inflammation and disease.

Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models.

BACKGROUND: Acute pancreatitis (AP) encompasses a spectrum of pancreatic inflammatory conditions, ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure. Given the challenges associated with obtaining human pancreatic samples, research on AP predominantly relies on animal models. In this study, we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models. AIM: To investigate the shared molecular changes underlying the development of AP across varying severity levels. METHODS: AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide (LPS). Additionally, using Ptf1α to drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J- hM3/Ptf1α(cre) mice were administered Clozapine N-oxide to induce AP. Subsequently, we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus (GEO) database. RESULTS: Caerulein-induced AP showed severe inflammation and edema, which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis. Compared with the control group, RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model. Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway, TLR signaling pathway, and NF-κB signaling pathway, alongside elevated levels of apoptosis-related pathways, such as apoptosis, P53 pathway, and phagosome pathway. The significantly elevated genes in the TLR and NOD-like receptor signaling pathways, as well as in the apoptosis pathway, were validated through quantitative real-time PCR experiments in animal models. Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood, while TLR1, TLR7, RIPK3, and OAS2 genes exhibited marked elevation in human AP. The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP. The transgenic mouse model hM3/Ptf1α(cre) successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway, indicating that these pathways represent shared pathological processes in AP across different models. CONCLUSION: The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP, notably the MYD88 gene. Apoptosis holds a central position in the necrotic processes of AP, with TUBA1A and GADD45A genes exhibiting prominence in human AP.

Quercetin in Osteoporosis Treatment: A Comprehensive Review of Its Mechanisms and Therapeutic Potential.

PURPOSE OF REVIEW: This review aims to provide a theoretical basis and insights for quercetin's clinical application in the prevention and treatment of osteoporosis (OP), analyzing its roles in bone formation promotion, bone resorption inhibition, anti-inflammation, antioxidant effects, and potential mechanisms. RECENT FINDINGS: OP, a prevalent bone disorder, is marked by reduced bone mineral density and impaired bone architecture, elevating the risk of fractures in patients. The primary approach to OP management is pharmacotherapy, with quercetin, a phytochemical compound, emerging as a focus of recent interest. This natural flavonoid exerts regulatory effects on bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts and promotes bone health and metabolic equilibrium via anti-inflammatory and antioxidative pathways. Although quercetin has demonstrated significant potential in regulating bone metabolism, there is a need for further high-quality clinical studies focused on medicinal quercetin.

NADPH Oxidase-Like Nanozyme for High-Efficiency Tumor Therapy Through Increasing Glutathione Consumption and Blocking Glutathione Regeneration.

To counteract the high level of reactive oxygen species (ROS) caused by rapid growth, tumor cells resist oxidative stress by accelerating the production and regeneration of intracellular glutathione (GSH). Numerous studies focus on the consumption of GSH, but the regeneration of GSH will enhance the reduction level of tumor cells to resist oxidative stress. Therefore, inhibiting the regeneration of GSH; while, consuming GSH is of great significance for breaking the redox balance of tumor cells. Herein, a simple termed MnOx-coated Au (AMO) nanoflower, as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) nanoenzyme, is reported for efficient tumor therapy. Au nanoparticles exhibit the capability to catalyze the oxidation of NADPH, hindering GSH regeneration; while, concurrently functioning as a photothermal agent. During the process of eliminating intracellular GSH, MnOx releases Mn2+ that subsequently engages in Fenton-like reactions, ultimately facilitating the implementation of chemodynamic therapy (CDT). Overall, this NOX enzyme-based nanoplatform enhances ROS generation and disrupts the state of reduction equilibrium, inducing apoptosis and ferroptosis by blocking GSH regeneration and increasing GSH consumption, thereby achieving collaborative treatments involving photothermal therapy (PTT), CDT, and catalytic therapy. This research contributes to NADPH and GSH targeted tumor therapy and showcases the potential of nanozymes.

Oxygen-Vacancy-Engineered W18 O49-x Nanobrush with a Suitable Band Structure for Highly Efficient Sonodynamic Therapy.

With the rapid development of external minimally invasive or noninvasive therapeutic modalities, ultrasound-based sonodynamic therapy (SDT) is a new alternative for treating deep tumors. However, inadequate sonosensitizer efficiency and poor biosecurity limit clinical applications. In this study, we prepared an oxygen-vacancy-engineered W18 O49-x nanobrush with a band gap of 2.79 eV for highly efficient SDT using a simple solvothermal method. The suitable band structures of the W18 O49-x nanobrush endows it with the potential to simultaneously produce singlet oxygen (1 O2 ), superoxide anions (⋅O2 - ), and hydroxyl radicals (⋅OH) under ultrasound irradiation. Additionally, abundant oxygen vacancies that serve as further charge traps that inhibit electron-hole recombination are incidentally introduced through one-step thermal reduction. Collectively, the in vitro and in vivo results demonstrate that the oxygen-vacancy-engineered W18 O49-x nanobrush delivers highly efficient reactive oxygen species (ROS) for SDT in a very biosafe manner. Overall, this study provides a new avenue for discovering and designing inorganic nanosonosensitizers with enhanced therapeutic efficiencies for use in SDT.

Near-Infrared Light-Triggered Thermoresponsive Pyroptosis System for Synergistic Tumor Immunotherapy.

Pyroptosis, as an inflammatory cell death, has been widely applied in tumor therapy, but its systemic adverse reactions caused by nonspecific activation still seriously hinder its application. Herein, a near-infrared (NIR) light-triggered thermoresponsive pyroptosis strategy is designed for on-demand initiation of pyroptosis and synergistic tumor immunotherapy. Specifically, glucose oxidase (GOx) loaded and heat-sensitive material p(OEOMA-co-MEMA) (PCM) modified mesoporous Pt nanoparticles (abbreviated as PCM Pt/GOx) are prepared as the mild-temperature triggered pyroptosis inducer. Pt nanoparticles can not only serve as nanozyme with catalase-like activity to promote GOx catalytic reaction, but also act as photothermal agent to achieve mild-temperature photothermal therapy (PTT) and thermoresponsive GOx release on-demand under the irradiation of NIR light, thereby activating and promoting pyroptosis. In vitro and in vivo experiments prove that NIR light-triggered thermoresponsive pyroptosis system exhibits excellent antitumor immunity activity as well as significantly inhibits tumor growth. The precise control of pyroptosis by NIR light as well as pyroptosis cooperated with mild-temperature PTT for synergistically attenuated tumor immunotherapy are reported for the first time. This work provides a new method to initiate pyroptosis on demand, which is of great significance for spatiotemporally controllable pyroptosis and immunotherapy.

Effects of Skeleton Structure of Mesoporous Silica Nanoadjuvants on Cancer Immunotherapy.

Mesoporous silica nanoparticles (MSNs) have been widely praised as nanoadjuvants in vaccine/tumor immunotherapy thanks to their excellent biocompatibility, easy-to-modify surface, adjustable particle size, and remarkable immuno-enhancing activity. However, the application of MSNs is still greatly limited by some severe challenges including the unclear and complicated relationships of structure and immune effect. Herein, three commonly used MSNs with different skeletons including MSN with tetrasulfide bonds (TMSN), MSN containing ethoxy framework (EMSN), and pure -Si-O-Si- framework of MSN (MSN) are comprehensively compared to study the impact of chemical construction on immune effect. The results fully demonstrate that the three MSNs have great promise in improving cellular immunity for tumor immunotherapy. Moreover, the TMSN performs better than the other two MSNs in antigen loading, cellular uptake, reactive oxygen species (ROS) generation, lymph node targeting, immune activation, and therapeutic efficiency. The findings provide a new paradigm for revealing the structure-function relationship of mesoporous silica nanoadjuvants, paving the way for their future clinical application.

A phase 2 trial of CD24Fc for prevention of graft-versus-host disease.

ABSTRACT: Patients who undergo human leukocyte antigen-matched unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (HSCT) with myeloablative conditioning for hematologic malignancies often develop acute graft-versus-host disease (GVHD) despite standard calcineurin inhibitor-based prophylaxis in combination with methotrexate. This trial evaluated a novel human CD24 fusion protein (CD24Fc/MK-7110) that selectively targets and mitigates inflammation due to damage-associated molecular patterns underlying acute GVHD while preserving protective immunity after myeloablative conditioning. This phase 2a, multicenter study evaluated the pharmacokinetics, safety, and efficacy of CD24Fc in combination with tacrolimus and methotrexate in preventing acute GVHD in adults undergoing MUD HSCT for hematologic malignancies. A double-blind, placebo-controlled, dose-escalation phase to identify a recommended dose was followed by an open-label expansion phase with matched controls to further evaluate the efficacy and safety of CD24Fc in preventing acute GVHD. A multidose regimen of CD24Fc produced sustained drug exposure with similar safety outcomes when compared with single-dose regimens. Grade 3 to 4 acute GVHD-free survival at day 180 was 96.2% (95% confidence interval [CI], 75.7-99.4) in the CD24Fc expansion cohort (CD24Fc multidose), compared with 73.6% (95% CI, 63.2-81.4) in matched controls (hazard ratio, 0.1 [95% CI, 0.0-0.6]; log-rank test, P = .03). No participants in the CD24Fc escalation or expansion phases experienced dose-limiting toxicities (DLTs). The multidose regimen of CD24Fc was well tolerated with no DLTs and was associated with high rates of severe acute GVHD-free survival after myeloablative MUD HSCT. This trial was registered at ClinicalTrials.gov as #NCT02663622.

CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment.

Germline CTLA-4 deficiency causes severe autoimmune diseases characterized by dysregulation of Foxp3+ Tregs, hyper-activation of effector memory T cells, and variable forms autoimmune cytopenia including gradual loss of B cells. Cancer patients with severe immune-related adverse events (irAE) after receiving anti-CTLA-4/PD-1 combination immunotherapy also have markedly reduced peripheral B cells. The immunological basis for B cell loss remains unexplained. Here, we probe the decline of B cells in human CTLA-4 knock-in mice by using anti-human CTLA-4 antibody Ipilimumab conjugated to a drug payload emtansine (Anti-CTLA-4 ADC). The anti-CTLA-4 ADC-treated mice have T cell hyper-proliferation and their differentiation into effector cells which results in B cell depletion. B cell depletion is mediated by both CD4 and CD8 T cells and at least partially rescued by anti-TNF-alpha antibody. These data revealed an unexpected antagonism between T and B cells and the importance of regulatory T cells in preserving B cells.

Sodium Citrate Nanoparticles Induce Dual-Path Pyroptosis for Enhanced Antitumor Immunotherapy through Synergistic Ion Overload and Metabolic Disturbance.

Metabolic reprogramming, as one of the characteristics of cancer, is associated with tumorigenesis, growth, or migration, and the modulation of metabolic pathways has emerged as a novel approach for cancer therapy. However, the conventional metabolism-mediated apoptosis process in tumor cells exhibits limited immunogenicity and inadequate activation of antitumor immunity. Herein, phospholipid-coated sodium citrate nanoparticles (PSCT NPs) are successfully prepared, which dissolve in tumor cells and then release significant amounts of citrate ions and Na+ ions. Massive quantities of ions lead to increased intracellular osmotic pressure, which activates the caspase-1/gasdermin D (GSDMD) mediated pyroptosis pathway. Simultaneously, citrate induces activation of the caspase-8/gasdermin C (GSDMC) pathway. The combined action of these two pathways synergistically causes intense pyroptosis, exhibiting remarkable antitumor immune responses and tumor growth inhibition. This discovery provides new insight into the potential of nanomaterials in modulating metabolism and altering cell death patterns to enhance antitumor immunotherapy.

Genetic and pharmaceutical targeting of HIF1α allows combo-immunotherapy to boost graft vs. leukemia without exacerbation graft vs. host disease.

Despite potential impact on the graft vs. leukemia (GVL) effect, immunotherapy targeting CTLA-4 and/or PD-1 has not been successfully combined with bone marrow transplant (BMT) because it exacerbates graft vs. host disease (GVHD). Here, using models of GVHD and leukemia, we demonstrate that targeting hypoxia-inducible factor 1α (HIF1α) via pharmacological or genetic approaches reduces GVHD by inducing PDL1 expression on host tissue while selectively inhibiting PDL1 in leukemia cells to enhance the GVL effect. More importantly, combination of HIF1α inhibition with anti-CTLA-4 antibodies allows simultaneous inhibition of both PDL1 and CTLA-4 checkpoints to achieve better outcomes in models of mouse and human BMT-leukemia settings. These findings provide an approach to enhance the curative effect of BMT for leukemia and broaden the impact of cancer immunotherapy.

Metal Halide Single Crystals RbCdCl3:Sn2+ and Rb3SnCl7 with Blue and White Emission Obtained via a Hydrothermal Process.

Until now, effective blue light-emitting materials are essentially needed for the creation of white light and precise color renderings in real-world applications, but the efficiency of blue light-emitting materials has lagged far behind. Here, we present a hydrothermal method to synthesize tin-based metal halide single crystals (RbCdCl3:Sn2+ and Rb3SnCl7). Two single crystal materials with different shapes and phases can simultaneously be synthesized in the same stoichiometric ratio. Rb3SnCl7 has a bulk shape, while RbCdCl3:Sn2+ has a needle shape. The deep blue emission (436 nm) of RbCdCl3:Sn2+ can be obtained under the optimal excitation wavelength irradiation. However, pure blue emission (460 nm) to white light can be obtained by changing the excitation wavelength in Rb3SnCl7. The refinement spectra of the electronic structures of RbCdCl3:Sn2+ and Rb3SnCl7 are investigated by density functional theory. It is concluded that the difference in the distribution of Cl energy states leads to the existence of Cl local defect states, which is the reason for the rich luminescence of the two single crystals. These findings provide a path for realizing single-phase broadband white-emitting materials.

Sodium Bicarbonate Nanoparticles for Amplified Cancer Immunotherapy by Inducing Pyroptosis and Regulating Lactic Acid Metabolism.

Although immunotherapy has a broad clinical application prospect, it is still hindered by low immune responses and immunosuppressive tumor microenvironment. Herein, a simple and drug-free inorganic nanomaterial, alkalescent sodium bicarbonate nanoparticles (NaHCO3 NPs), is prepared via a fast microemulsion method for amplified cancer immunotherapy. The obtained alkalescent NaHCO3 regulates lactic acid metabolism through acid-base neutralization so as to reverse the mildly acidic immunosuppressive tumor environment. Additionally, it can further release high amounts of Na+ ions inside tumor cells and induce a surge in intracellular osmolarity, and thus activate the pyroptosis pathway and immunogenic cell death (ICD), release damage-associated molecular patterns (DAMPs) and inflammatory factors, and improve immune responses. Collectively, NaHCO3 NPs observably inhibit primary/distal tumor growth and tumor metastasis through acid neutralization remitted immunosuppression and pyroptosis induced immune activation, showing an enhanced antitumor immunity efficiency. This work provides a new paradigm for lactic acid metabolism and pyroptosis mediated tumor treatment, which has a potential for application in clinical tumor immunotherapy.

A novel aptamer-based small RNA delivery platform and its application to cancer therapy.

Major challenges such as nuclease degradation, rapid renal clearance, non-specific delivery, poor cellular uptake and inflammatory response have limited the clinical application of small RNA-mediated gene silencing. To overcome these challenges, we designed a novel targeting small RNA delivery platform comprising of three oligonucleotides: (1) a guide RNA sequence, (2) part of a passenger sequence linked to a DNA aptamer via a PEG linker, and (3) another passenger sequence conjugated to cholesterol, which assemble through complementary base pair annealing. Remarkably, in the presence of magnesium, this molecule self-assembled into a nanoparticle with a hydrophobic cholesterol core, hydrophilic RNA oligonucleotide shell and PEG-linked DNA aptamer flare. The nanoparticles conferred protection to the RNA oligonucleotides against nuclease degradation, which increased bioavailability, and reduced systemic inflammatory responses. The aptamer allowed targeted delivery of RNA therapeutics through cell-specific surface markers, and once inside the cell, the nanoparticles induced lysosomal leakage that released the RNA oligonucleotides into the cytosol to achieve gene silencing. We created a c-Kit-targeting miR-26a delivery particle that specifically accumulated in c-Kit+ breast cancer, significantly increased T cell recruitment, and inhibited tumor growth. Regression of large established tumors were achieved when the nanoparticle was used in combination with anti-CTLA-4 monoclonal antibody.

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.