Digital synthetic polymers for information storage.

Digital synthetic polymers with uniform chain lengths and defined monomer sequences have recently become intriguing alternatives to traditional silicon-based information devices or natural biomacromolecules for data storage. The structural diversity of information-containing macromolecules endows the digital synthetic polymers with higher stability and storage density but less occupied space. Through subtly designing each unit of coded structure, the information can be readily encoded into digital synthetic polymers in a more economical scheme and more decodable, opening up new avenues for molecular digital data storage with high-level security. This tutorial review summarizes recent advances in salient features of digital synthetic polymers for data storage, including encoding, decoding, editing, erasing, encrypting, and repairing. The current challenges and outlook are finally discussed to offer potential solution guidance and new perspectives for the creation of next-generation digital synthetic polymers and broaden the scope of their applicability.

Antifouling Asymmetric Block Copolymer Nanofilms via Freestanding Interfacial Polymerization for Efficient and Sustainable Water Purification.

Membrane materials that resist nonspecific or specific adsorption are urgently required in widespread applications. In water purification, inevitable membrane fouling not only limits separation performance, but also remarkably increases operation requirements, and augments extra maintenance costs and higher energy consumption. In this work, we report a freestanding interfacial polymerization (IP) fabrication strategy for in-situ creation of asymmetric block copolymer (BCP) nanofilms with antifouling properties, greatly outperforming the conventional surface post-modification approaches. The resultant asymmetric BCP nanofilms with highly-dense, highly-hydrophilic polyethylene glycol (PEG) brushes, can be readily formed via a typical IP process of a double-hydrophilic BCP composed of an antifouling PEG block and a membrane-forming multiamine block. The asymmetric BCP nanofilms have been applied for efficient and sustainable natural water purification, demonstrating extraordinary antifouling capabilities accompanied with superior separation performance far beyond commercial polyamide nanofiltration membranes. The antifouling behaviors of BCP nanofilms derived from the combined effect of the hydration layer, electrostatic repulsion and steric hindrance were further elucidated by water flux and fouling resistance in combination with all-atom molecular dynamics simulation. This work opens up a new avenue for large-scale and low-cost creation of broad-spectrum, asymmetric membrane materials with diverse functional "defect-free" surfaces in real-world applications.

Erythrocyte membrane with CLIPPKF as biomimetic nanodecoy traps merozoites and attaches to infected red blood cells to prevent Plasmodium infection.

BACKGROUND: Malaria remains a serious threat to global public health. With poor efficacies of vaccines and the emergence of drug resistance, novel strategies to control malaria are urgently needed. RESULTS: We developed erythrocyte membrane-camouflaged nanoparticles loaded with artemether based on the growth characteristics of Plasmodium. The nanoparticles could capture the merozoites to inhibit them from repeatedly infecting normal erythrocytes, owing to the interactions between merozoites and heparin-like molecules on the erythrocyte membrane. Modification with a phosphatidylserine-targeting peptide (CLIPPKF) improved the drug accumulation in infected red blood cells (iRBCs) from the externalized phosphatidylserine induced by Plasmodium infection. In Plasmodium berghei ANKA strain (pbANKA)-infected C57BL/6 mice, the nanoparticles significantly attenuated Plasmodium-induced inflammation, apoptosis, and anemia. We observed reduced weight variation and prolonged survival time in pbANKA-challenged mice, and the nanoparticles showed good biocompatibility and negligible cytotoxicity. CONCLUSION: Erythrocyte membrane-camouflaged nanoparticles loaded with artemether were shown to provide safe and effective protection against Plasmodium infection.

Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers.

Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

HA-DOPE-Modified Honokiol-Loaded Liposomes Targeted Therapy for Osteosarcoma.

Purpose: Osteosarcoma (OS) is the most common bone cancer with a high risk of metastasis, high growth rate, and poor prognosis. Honokiol (HNK) is a general ingredient of traditional Chinese medicine, with a potential anti-tumor effect. However, HNK is insoluble in water and lacks drug targeting, which limits its clinical application. To improve the OS therapeutic effect of HNK, we used HNK-loaded liposomes modified with hyaluronic acid-phospholipid conjugates (HA-DOPE) to treat OS based on the HA interaction with CD44. Methods: The HNK-loaded liposomes were prepared via thin-film hydration and sonication. HA-DOPE was used to combine the HNK-loaded liposomes (HA-DOPE@Lips/HNK) via sonication and co-extrusion. HA-DOPE@Lips/HNK were characterized with respect to size, zeta potential, polymer dispersity index (PDI), and stability, and transmission electron microscopy was performed. Cellular uptake, cell viability, cell apoptosis, cell cycle, and mitochondrial activity were utilized to evaluate the antitumor effect in vitro. The biodistribution, xenograft tumor growth inhibition, and safety of HA-DOPE@Lips/HNK were evaluated in 143B OS xenograft mice in vivo. Results: The particle size, PDI, and zeta potential of HA-DOPE@Lips/HNK were 146.20±0.26 nm, 0.20±0.01, and -38.45±0.98 mV, respectively. The encapsulation rate and drug loading were 80.14±0.32% and 3.78±0.09%, respectively. HA-DOPE@Lips/HNK could inhibit cell proliferation, cause apoptosis, block the cell cycle and disrupt mitochondrial activity. HA-DOPE@Lips/HNK specially delivered the drug into the tumor and inhibited tumor growth, and showed no obvious toxicity to normal tissues. Conclusion: HA-DOPE@Lips/HNK could deliver HNK into the tumor site and had a good antitumor ability in vitro and in vivo. In addition, HA-DOPE@Lips/HNK increased the antitumor effects of HNK. Thus, it provides a promising nanocarrier to improve drug delivery in OS therapy.

Reproductive and Developmental Toxicity Assessment of Human Umbilical Cord Mesenchymal Stem Cells in Rats.

Objective: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown very attractive potential in clinical applications for the treatment of various diseases. However, the data about the reproductive and developmental toxicity of hUC-MSCs remains insufficient. Thus, we assessed the potential effects of intravenous injection of hUC-MSCs on reproduction and development in Sprague-Dawley rats. Methods: In the fertility and early embryonic development study, hUC-MSCs were administered at dose levels of 0, 6.0 × 106, 8.5 × 106, and 1.2 × 107/kg to male and female rats during the pre-mating, mating and gestation period. In the embryo-fetal development study, the pregnant female rats received 0, 6.0 × 106, 1.2 × 107, and 2.4 × 107/kg of hUC-MSCs from gestation days (GD) 6-15. Assessments made included mortality, clinical observations, body weight, food consumption, fertility parameters of male and female, litter, and fetus parameters, etc. Results: No hUC-MSCs-related toxicity was observed on the fertility of male and female rats, and no teratogenic effect on fetuses. hUC-MSCs at 1.2 × 107/kg caused a mildly decrease in body weight gain of male rats, transient listlessness, tachypnea, and hematuria symptoms in pregnant female rats. Death was observed in part of the pregnant females at a dose of 2.4 × 107/kg, which could be due to pulmonary embolism. Conclusion: Based on the results of the studies, the no-observed-adverse-effect levels (NOAELs) are 8.5 × 106/kg for fertility and early embryonic development, 1.2 × 107/kg for maternal toxicity and 2.4 × 107/kg for embryo-fetal development in rats intravenous injected with hUC-MSCs, which are equivalent to 8.5-fold, 12-fold, and 24-fold respectively of its clinical dosage in humans. These findings may provide a rational basis for human health risk assessment of hUC-MSCs.

Genome-scale transcriptional analysis reveals key genes associated with the development of type II diabetes in mice.

Diabetes mellitus is one of the primary diseases that pose a threat to human health. The focus of the present study is type II diabetes (T2D), which is caused by obesity and is the most prevalent type of diabetes. However, genome-scale transcriptional analysis of diabetic liver in the development process of T2D is yet to be further elucidated. Microassays were performed on liver tissue samples from three-, six- and nine-week-old db/db mice with diabetes and db/m mice to investigate differentially expressed mRNA. Based on the results of genome-scale transcriptional analysis, five genes were screened in the present study: chromobox 8 (CBX8), de-etiolated homolog 1 and damage specific DNA binding protein 1 associated 1 (DDA1), Phosphoinositide-3-kinase regulatory subunit 6 (PIK3R6), WD repeat domain 41 (WDR41) and Glycine Amidinotransferase (GATM). At three weeks of age, no significant differences in levels or ratios of expression were observed. However, at six and nine weeks, expression of CBX8, DDA1, PIK3R6 and WDR41 was significantly upregulated (P<0.05) in the db/db model group compared with the control group, whereas GATM expression was significantly downregulated (P<0.05). These results suggest that T2D-related differential expression of genes becomes more marked with age, which was confirmed via reverse transcription-quantitative polymerase chain reaction. Genome-scale transcriptional analysis in diabetic mice provided a novel insight into the molecular. events associated with the role of mRNAs in T2D development, with specific emphasis upon CBX8, DDA1, PIK3R6, GATM and WDR41. The results of the present study may provide rationale for the investigation of the target genes of these mRNAs in future studies.