Inhaled mRNA nanoparticles dual-targeting cancer cells and macrophages in the lung for effective transfection.

Messenger RNA (mRNA)-based therapeutics are transforming the landscapes of medicine, yet targeted delivery of mRNA to specific cell types while minimizing off-target accumulation remains challenging for mRNA-mediated therapy. In this study, we report an innovative design of a cationic lipid- and hyaluronic acid-based, dual-targeted mRNA nanoformulation that can display the desirable stability and efficiently transfect the targeted proteins into lung tissues. More importantly, the optimized dual-targeted mRNA nanoparticles (NPs) can not only accumulate primarily in lung tumor cells and inflammatory macrophages after inhalation delivery but also efficiently express any desirable proteins (e.g., p53 tumor suppressor for therapy, as well as luciferase and green fluorescence protein for imaging as examples in this study) and achieve efficacious lung tissue transfection in vivo. Overall, our findings provide proof-of-principle evidence for the design and use of dual-targeted mRNA NPs in homing to specific cell types to up-regulate target proteins in lung tissues, which may hold great potential for the future development of mRNA-based inhaled medicines or vaccines in treating various lung-related diseases.

Genome-wide association of the metabolic shifts underpinning dark-induced senescence in Arabidopsis.

Dark-induced senescence provokes profound metabolic shifts to recycle nutrients and to guarantee plant survival. To date, research on these processes has largely focused on characterizing mutants deficient in individual pathways. Here, we adopted a time-resolved genome-wide association-based approach to characterize dark-induced senescence by evaluating the photochemical efficiency and content of primary and lipid metabolites at the beginning, or after 3 or 6 days in darkness. We discovered six patterns of metabolic shifts and identified 215 associations with 81 candidate genes being involved in this process. Among these associations, we validated the roles of four genes associated with glycine, galactinol, threonine, and ornithine levels. We also demonstrated the function of threonine and galactinol catabolism during dark-induced senescence. Intriguingly, we determined that the association between tyrosine contents and TYROSINE AMINOTRANSFERASE 1 influences enzyme activity of the encoded protein and transcriptional activity of the gene under normal and dark conditions, respectively. Moreover, the single-nucleotide polymorphisms affecting the expression of THREONINE ALDOLASE 1 and the amino acid transporter gene AVT1B, respectively, only underlie the variation in threonine and glycine levels in the dark. Taken together, these results allow us to present a very detailed model of the metabolic aspects of dark-induced senescence, as well as the process itself.

Beyond the standard GWAS - a guide for plant biologists.

Classic genome-wide association studies (GWAS) look for associations between individual SNPs and phenotypes of interest. With the rapid progress of high-throughput genotyping and phenotyping technologies, GWAS have become increasingly powerful for detecting genetic determinants and their molecular mechanisms underpinning natural phenotypic variation. However, GWAS frequently yield results with neither expected nor promising loci, nor any significant associations. This is often because associations between SNPs and a single phenotype are confounded, for example with the environment, other traits, or complex genetic structures. Such confounding can mask true genotype-phenotype associations, or inflate spurious associations. To address these problems, numerous methods have been developed that go beyond the standard model. Such advanced GWAS models are flexible and can offer improved statistical power for understanding the genetics underlying complex traits. Despite this advantage, these models have not been widely adopted and implemented compared to the standard GWAS approach, partly because this literature is diverse and often technical. In this review, our aim is to provide an overview of the application and the benefits of various advanced GWAS models for handling complex traits and genetic structures, targeting plant biologists who wish to carry out GWAS more effectively.

Functional analyses of TRAF6 gene in Argopecten scallops.

The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family has been reported to be involved in many immune pathways. In a previous study, we identified 5 TRAF genes, including TRAF2, 3, 4, 6, and 7, in the bay scallop (Argopecten irradians, Air) and the Peruvian scallop (Argopecten purpuratus, Apu). Since TRAF6 is a key molecular link in the TNF superfamily, we conducted a series of studies targeting the TRAF6 gene in the Air and Apu scallops as well as their hybrid progeny, Aip (Air ♀ × Apu ♂) and Api (Apu ♀ × Air ♂). Subcellular localization assay showed that the Air-, Aip-, and Api-TRAF6 were widely distributed in the cytoplasm of the human embryonic kidney cell line (HEK293T). Additionally, dual-luciferase reporter assay revealed that among TRAF3, TRAF4, and TRAF6, only the overexpression of TRAF6 significantly activated NF-κB activity in the HEK293T cells in a dose-dependent manner. These results suggest a crucial role of TRAF6 in the immune response in Argopecten scallops. To investigate the specific immune mechanism of TRAF6 in Argopecten scallops, we conducted TRAF6 knockdown using RNA interference. Transcriptomic analyses of the TRAF6 RNAi and control groups identified 1194, 2403, and 1099 differentially expressed genes (DEGs) in the Air, Aip, and Api scallops, respectively. KEGG enrichment analyses revealed that these DEGs were primarily enriched in transport and catabolism, amino acid metabolism, peroxisome, lysosome, and phagosome pathways. Expression profiles of 28 key DEGs were confirmed by qRT-PCR assays. The results of this study may provide insights into the immune mechanisms of TRAF in Argopecten scallops and ultimately benefit scallop breeding.

Metabolomic reveals the responses of sludge properties and microbial communities to high nitrite stress in denitrifying phosphorus removal systems.

Nitrite, as an electron acceptor, plays a good role in denitrifying phosphorus removal (DPR); however, high nitrite concentration has adverse affects on sludge performance. We investigated the precise mechanisms of responses of sludge to high nitrite stress, including surface characteristics, intracellular and extracellular components, microbial and metabolic responses. When the nitrite stress reached 90 mg/L, the sludge settling performance was improved, but the activated sludge was aging. FTIR and XPS analysis revealed a significant increase in the hydrophobicity of the sludge, resulting in improve settling performance. However, the intracellular carbon sources synthesis was inhibited. In addition, the components in the tightly bound extracellular polymeric substances (TB-EPS) of sludge were significantly reduced and indicated the disturb of metabolism. Notably, Exiguobacterium emerged as a new genus when face high nitrite stress that could maintaining survival in hostile environments. Moreover, metabolomic analysis demonstrated strong biological response to nitrite stress further supported above results that include the inhibited of carbohydrate and amino acid metabolism. More importantly, some lipids (PS, PA, LysoPA, LysoPC and LysoPE) were significantly upregulated that related enhanced membrane lipid remodeling. The comprehensive analyses provide novel insights into the high nitrite stress responses mechanisms in activated sludge systems.

IGF-1's protective effect on OSAS rats' learning and memory.

PURPOSE: Patients with obstructive sleep apnea syndrome (OSAS) frequently experience cognitive dysfunction, which may be connected to chronic intermittent hypoxia (CIH). Insulin-like growth factor-1 (IGF-1) is thought to be closely associated with cognitive function, but its role in cognitive impairment caused by OSAS is unclear. The purpose of this study was to investigate the potential protective effect of IGF-1 on cognitive impairment in OSAS rats. METHODS: Healthy male SD rats (n = 40) were randomly assigned into four groups: control group, CIH group, NS + CIH group, and IGF-1 + CIH group. All experimental rats except for those in the control group were exposed to intermittent hypoxic (IH) environments for 8 h per day over 28 days. Prior to daily exposure to IH, rats in the IGF-1 + CIH group received subcutaneous injections of IGF-1. The Morris water maze test was conducted on all experimental rats. Brain tissue testing methods included Enzyme-Linked Immunosorbent Assay, Hematoxylin and eosin staining, Immunohistochemistry, and Western blotting. RESULTS: The rat model of OSAS was successfully established following exposure to CIH and exhibited significant cognitive impairment. However, daily subcutaneous injections of IGF-1 partially restored the impaired cognitive function in OSAS rats. Compared with the control group, there was a significant decrease in the expression levels of IGF-1, p-IGF-IR, and SYP in the CIH group; however, these expression levels increased significantly in the IGF-I + CIH group. CONCLUSION: In OSAS rats, IGF-1 enhances learning memory; this effect may be linked to increased p-IGF-1R and SYP protein production in the hippocampus.

Unlocking growth potential in Halomonas bluephagenesis for enhanced PHA production with sulfate ions.

The mutant strain Halomonas bluephagenesis (TDH4A1B5P) was found to produce PHA under low-salt, non-sterile conditions, but the yield was low. To improve the yield, different nitrogen sources were tested. It was discovered that urea was the most effective nitrogen source for promoting growth during the stable stage, while ammonium sulfate was used during the logarithmic stage. The growth time of H. bluephagenesis (TDH4A1B5P) and its PHA content were significantly prolonged by the presence of sulfate ions. After 64 hr in a 5-L bioreactor supplemented with sulfate ions, the dry cell weight (DCW) of H. bluephagenesis weighed 132 g/L and had a PHA content of 82%. To promote the growth and PHA accumulation of H. bluephagenesis (TDH4A1B5P), a feeding regimen supplemented with nitrogen sources and sulfate ions with ammonium sodium sulfate was established in this study. The DCW was 124 g/L, and the PHA content accounted for 82.3% (w/w) of the DCW, resulting in a PHA yield of 101 g/L in a 30-L bioreactor using the optimized culture strategy. In conclusion, stimulating H. bluephagenesis (TDH4A1B5P) to produce PHA is a feasible and suitable strategy for all H. bluephagenesis.

Ultrahigh Lubricity between Two-Dimensional Ice and Two-Dimensional Atomic Layers.

Low temperature and high humidity conditions significantly degrade the performance of solid-state lubricants consisting of van der Waals (vdW) atomic layers, owing to the liquid water layer attached/intercalated to the vdW layers, which greatly enhances the interlayer friction. However, using low temperature in situ atomic force microscopy (AFM) and friction force microscopy (FFM), we unveil the unexpected ultralow friction between two-dimensional (2D) ice, a solid phase of water confined to the 2D space, and the 2D molybdenum disulfides (MoS2). The friction of MoS2 and 2D ice is reduced by more than 30% as compared to bare MoS2 and the rigid surface. The phase transition of liquid water into 2D ice under mechanical compression has also been observed. These new findings can be applied as novel frictionless water/ice transport technology in nanofluidic systems and promising high performance lubricants for operating in low temperature and high humidity environments.

Cyanobacterial Phycobilisome Allostery as Revealed by Quantitative Mass Spectrometry.

Phycobilisomes (PBSs) are the major photosynthetic light-harvesting complexes in cyanobacteria and red algae. PBS, a multisubunit protein complex, has two major interfaces that comprise intrinsically disordered regions (IDRs): rod-core and core-membrane. IDRs do not form regular, three-dimensional structures on their own. Their presence in the photosynthetic pigment-protein complexes portends their structural and functional importance. A recent model suggests that PB-loop, an IDR located on the PBS subunit ApcE and C-terminal extension (CTE) of the PBS subunit ApcG, forms a structural protrusion on the PBS core-membrane side, facing the thylakoid membrane. Here, the structural synergy between the rod-core region and the core-membrane region was investigated using quantitative mass spectrometry (MS). The AlphaFold-predicted CpcG-CTE structure was first modeled onto the PBS rod-core region, guided and justified by the isotopically encoded structural MS data. Quantitative cross-linking MS analysis revealed that the structural proximity of the PB-loop in ApcE and ApcG-CTE is significantly disturbed in the absence of six PBS rods, which are attached to PBS via CpcG-CTE, indicative of drastic conformational changes and decreased structural integrity. These results suggest that CpcG-rod attachment on the PBS rod-core side is essentially required for the PBS core-membrane structural assembly. The hypothesized long-range synergy between the rod-core interface (where the orange carotenoid protein also functions) and the terminal energy emitter of PBS must have important regulatory roles in PBS core assembly, light-harvesting, and excitation energy transmission. These data also lend strategies that genetic truncation of the light-harvesting antennas aimed for improved photosynthetic productivity must rely on an in-depth understanding of their global structural integrity.

Characterization of Higher Order Structural Changes of a Thermally Stressed Monoclonal Antibody via Mass Spectrometry Footprinting and Other Biophysical Approaches.

Characterizing changes in the higher order structure (HOS) of monoclonal antibodies upon stressed conditions is critical to gaining a better understanding of the product and process. One single biophysical approach may not be best suited to assess HOS comprehensively; thus, the synergy from multiple, complementary approaches improves characterization accuracy and resolution. In this study, we employed two mass spectrometry (MS )-based footprinting techniques, namely, fast photochemical oxidation of proteins (FPOP)-MS and hydrogen-deuterium exchange (HDX)-MS, supported by dynamic light scattering (DLS), differential scanning calorimetry (DSC), circular dichroism (CD), and nuclear magnetic resonance (NMR) to study changes to the HOS of a mAb upon thermal stress. The biophysical techniques report a nuanced characterization of the HOS in which CD detects no changes to the secondary or tertiary structure, yet DLS measurements show an increase in the hydrodynamic radius. DSC indicates that the stability decreases, and chemical or conformational changes accumulate with incubation time according to NMR. Furthermore, whereas HDX-MS does not indicate HOS changes, FPOP-MS footprinting reveals conformational changes at residue resolution for some amino acids. The local phenomena observed with FPOP-MS indicate that several residues show various patterns of degradation during thermal stress: no change, an increase in solvent exposure, and a biphasic response to solvent exposure. All evidences show that FPOP-MS efficiently resolves subtle structural changes and novel degradation pathways upon thermal stress treatment at residue-level resolution.

Dynamically Stabilized Electronic Regulation and Electrochemical Reconstruction in Co and S Atomic Pair Doped Fe3 O4 for Water Oxidation.

The electronic regulation and surface reconstruction of earth-abundant electrocatalysts are essential to efficient oxygen evolution reaction (OER). Here, an inverse-spinel Co,S atomic pair codoped Fe3 O4 grown on iron foam (Co,S-Fe3 O4 /IF) is fabricated as a cost-effective electrocatalyst for OER. This strategy of Co and S atomic pair directional codoping features accelerates surface reconstruction and dynamically stabilizes electronic regulation. CoS atomic pairs doped in the Fe3 O4 crystal favor controllable surface reconstruction via sulfur leaching, forming oxygen vacancies and Co doping on the surface of reconstructed FeOOH (Co-FeOOH-Ov /IF). Before and after surface reconstruction via in situ electrochemical process, the Fe sites with octahedral field dynamically maintains an appropriate electronic structure for OER intermediates, thus exhibiting consistently excellent OER performance. The electrochemically tuned Fe-based electrodes exhibit a low overpotential of 349 mV at a current density of 1000 mA cm-2 , a slight Tafel slope of 43.3 mV dec-1 , and exceptional long-term electrolysis stability of 200 h in an alkaline medium. Density functional theory calculations illustrate the electronic regulation of Fe sites, changes in Gibbs free energies, and the breaking of the restrictive scaling relation between OER intermediates. This work provides a promising directional codoping strategy for developing precatalysts for large-scale water-splitting systems.

Targeted Protein Degradation Technology and Nanomedicine: Powerful Allies against Cancer.

Targeted protein degradation (TPD) is an emerging therapeutic strategy with the potential of targeting undruggable pathogenic proteins. After the first proof-of-concept proteolysis-targeting chimeric (PROTAC) molecule was reported, the TPD field has entered a new era. In addition to PROTAC, numerous novel TPD strategies have emerged to expand the degradation landscape. However, their physicochemical properties and uncontrolled off-target side effects have limited their therapeutic efficacy, raising concerns regarding TPD delivery system. The combination of TPD and nanotechnology offers great promise in improving safety and therapeutic efficacy. This review provides an overview of novel TPD technologies, discusses their clinical applications, and highlights the trends and perspectives in TPD nanomedicine.

High-Throughput CRISPR/Cas9 Mutagenesis Streamlines Trait Gene Identification in Maize.

Maize (Zea mays) is one of the most important crops in the world. However, few agronomically important maize genes have been cloned and used for trait improvement, due to its complex genome and genetic architecture. Here, we integrated multiplexed CRISPR/Cas9-based high-throughput targeted mutagenesis with genetic mapping and genomic approaches to successfully target 743 candidate genes corresponding to traits relevant for agronomy and nutrition. After low-cost barcode-based deep sequencing, 412 edited sequences covering 118 genes were precisely identified from individuals showing clear phenotypic changes. The profiles of the associated gene-editing events were similar to those identified in human cell lines and consequently are predictable using an existing algorithm originally designed for human studies. We observed unexpected but frequent homology-directed repair through endogenous templates that was likely caused by spatial contact between distinct chromosomes. Based on the characterization and interpretation of gene function from several examples, we demonstrate that the integration of forward and reverse genetics via a targeted mutagenesis library promises rapid validation of important agronomic genes for crops with complex genomes. Beyond specific findings, this study also guides further optimization of high-throughput CRISPR experiments in plants.

Tumor-derived exosomal linc00881 induces lung fibroblast activation and promotes osteosarcoma lung migration.

Osteosarcoma (OS) commonly metastasizes to the lung, yet the underlying molecular mechanisms remain poorly understood. Exosomes play a crucial role in tumor migration, including OS lung migration. However, the underlying mechanism by which exosome-derived long non-coding RNAs (lncRNAs) contribute to lung migration in osteosarcoma (OS) remains unclear. This study presents a newly discovered lncRNA, linc00881, derived from OS exosomes. Our study shows that linc00881 promotes the migration of OS cells to the lung and induces the conversion of normal lung fibroblasts into cancer-associated fibroblasts (CAFs). Subsequently, we found that exosomal linc00881 secreted by OS cells can regulate the expression of matrix metalloproteinase 2 (MMP2) in HFL-1 cells by sponging miR-29c-3p, thereby activating the NF-κB signaling in lung fibroblasts. Finally, we discovered that pro-inflammatory cytokines, namely IL-1ß, IL-6, and IL-8, were secreted through the linc00881/miR-29c-3p/MMP2 axis. These results suggest that OS-derived exosomes can mediate the intercellular crosstalk between OS cells and lung fibroblasts, ultimately impacting OS lung migration. Our study provides a potential target for the treatment of OS lung migration.

Potential roles of IFI44 genes in high resistance to Vibrio in hybrids of Argopecten scallops.

Vibrio bacteria are often fatal to aquatic organisms and selection of Vibrio-resistant strains is warranted for aquaculture animals. In this study, we found that hybrids between bay scallops and Peruvian scallops exhibited significantly higher resistance to Vibrio challenge, but little is available on its mechanism. Interferon induced protein 44 (IFI44), a member of the type I interferon (IFN) family, plays an important role in the IFN immune response in invertebrates, which may also participate in the resistance to Vibrio in scallops. To explore the roles of IFI44 genes in the resistance to Vibrio, they were identified and characterized in the bay scallop (designated as AiIFI44), the Peruvian scallop (designated as ApIFI44), and their reciprocal hybrids (designated as AipIFI44 and ApiIFI44, respectively). Their open reading frame (ORF) sequences were all 1434 bp, encoding 477 amino acids, but with large variations among the four genes. The AipIFI44 and ApiIFI44 exhibited higher similarity with ApIFI44 than with AiIFI44. All four genes have a TLDc structural domain with significant variations in sequences among them. Predicted differences in conformation and posttranslational modifications may lead to altered protein activity. We further demonstrated that the AiIFI44, AipIFI44 and ApiIFI44 expressed in all the tested tissues, with the highest expression in the gills and hepatopancreas. In response to Vibrio anguillarum challenge, the profile of mRNA expression of IFI44 gene differed among the bay scallops and the two hybrids. In the bay scallops, it increased at 6 h but dramatically decreased after 12-48 h. However, the mRNA expression of both AipIFI44 and ApiIFI44 decreased at 6 h but continuously increased thereafter and reached the highest value at 48 h. The results in the present study suggest the immune responds of IFI44 in scallops and it may be related to the higher resistance to Vibrio bacterial in hybrids.

Characterization of TRAF genes and their responses to Vibrio anguillarum challenge in Argopecten scallops.

The tumor necrosis factor receptor-related factor (TRAF) family has been reported to be involved in many immune pathways, such as TNFR, TLR, NLR, and RLR in animals. However, little is known about the roles of TRAF genes in the innate immune of Argopecten scallops. In this study, we first identified five TRAF genes, including TRAF2, TRAF3, TRAF4, TRAF6 and TRAF7, but not TRAF1 and TRAF5, from both the bay scallop A. irradians (Air) and the Peruvian scallop A. purpuratus (Apu). The phylogenetic analysis showed that the TRAF genes in Argopecten scallops (AiTRAF) belong to the branch of molluscan TRAF family, which lacks TRAF1 and TRAF5. Since TRAF6 is a key bridge factor in the tumor necrosis factor superfamily and plays an important role in innate and adaptive immunity, we cloned the ORFs of the TRAF6 gene in both A. irradians and A. purpuratus, as well as in two reciprocal hybrids (Aip for the hybrid Air × Apu and Api for the hybrid Apu × Air). Differences in conformational and post-translational modification resulted from the variation in amino acid sequences may cause differences in activity among them. Analysis of conserved motifs and protein structural domains revealed that AiTRAF contains typical structural domains similar to those of other mollusks and has the same conserved motifs. Tissue expression of TRAF in Argopecten scallops challenged by Vibrio anguillarum was examined by qRT-PCR. The results showed that AiTRAF were higher in gill and hepatopancreas. When challenged by Vibrio anguillarum, the expression of AiTRAF was significantly increased compared with the control group, indicating that AiTRAF may play an important role in the immunity of scallops. In addition, the expression of TRAF was higher in Api and Aip than in Air when challenged by Vibrio anguillarum, suggesting that TRAF may have contributed to the high resistance of Api and Aip to Vibrio anguillarum. The results of this study may provide new insights into the evolution and function of TRAF genes in bivalves and ultimately benefit scallop breeding.

A survey of Transformer applications for histopathological image analysis: New developments and future directions.

Transformers have been widely used in many computer vision challenges and have shown the capability of producing better results than convolutional neural networks (CNNs). Taking advantage of capturing long-range contextual information and learning more complex relations in the image data, Transformers have been used and applied to histopathological image processing tasks. In this survey, we make an effort to present a thorough analysis of the uses of Transformers in histopathological image analysis, covering several topics, from the newly built Transformer models to unresolved challenges. To be more precise, we first begin by outlining the fundamental principles of the attention mechanism included in Transformer models and other key frameworks. Second, we analyze Transformer-based applications in the histopathological imaging domain and provide a thorough evaluation of more than 100 research publications across different downstream tasks to cover the most recent innovations, including survival analysis and prediction, segmentation, classification, detection, and representation. Within this survey work, we also compare the performance of CNN-based techniques to Transformers based on recently published papers, highlight major challenges, and provide interesting future research directions. Despite the outstanding performance of the Transformer-based architectures in a number of papers reviewed in this survey, we anticipate that further improvements and exploration of Transformers in the histopathological imaging domain are still required in the future. We hope that this survey paper will give readers in this field of study a thorough understanding of Transformer-based techniques in histopathological image analysis, and an up-to-date paper list summary will be provided at https://github.com/S-domain/Survey-Paper .

Heavy metals remediation through bio-solidification: Potential application in environmental geotechnics.

Heavy metals are pervasive pollutants found in water, soil, and solid wastes. Bio-solidification offers an environmentally friendly approach to immobilize heavy metal ions using two types of bacteria: urease-producing bacteria (UPB) and phosphatase-producing bacteria (PPB). UPB, exemplified by Sporosarcina pasteurii, secretes urease to hydrolyze urea and generate CO32- ions, while PPB, like Bacillus subtilis, produces alkaline phosphatase to hydrolyze organophosphate monoester (ROP) and produce PO43- ions. These ions react with heavy metal ions, effectively reducing their concentration by forming insoluble carbonate or phosphate precipitates. The success of bio-solidification is influenced by various factors, including substrate concentration, temperature, pH, and bacterial density. Optimal operational conditions can significantly enhance the remediation performance of heavy metals. UPB and PPB hold great potential for remediating heavy metal pollution in diverse contaminated areas such as tailings ponds, electroplating sewage, and garbage incineration plants. In conclusion, harnessing the power of these microbial methods can provide effective solutions for remediating heavy metal-induced pollution across a range of environmental conditions.

Minimally invasive nanomedicine: nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging.

Traditional treatments such as chemotherapy and surgery usually cause severe side effects and excruciating pain. The emergence of nanomedicines and minimally invasive therapies (MITs) has brought hope to patients with malignant diseases. Especially, minimally invasive nanomedicines (MINs), which combine the advantages of nanomedicines and MITs, can effectively target pathological cells/tissues/organs to improve the bioavailability of drugs, minimize side effects and achieve painless treatment with a small incision or no incision, thereby acquiring good therapeutic effects. In this review, we provide a comprehensive review of the research status and challenges of MINs, which generally refers to the medical applications of nanotechnology in photo-/ultrasound-/radiation-/magnetism-mediated therapy and imaging. Additionally, we also discuss their combined application in various fields including cancers, cardiovascular diseases, tissue engineering, neuro-functional diseases, and infectious diseases. The prospects, and potential bench-to-bedside translation of MINs are also presented in this review. We expect that this review can inspire the broad interest for a wide range of readers working in the fields of interdisciplinary subjects including (but not limited to) chemistry, nanomedicine, bioengineering, nanotechnology, materials science, pharmacology, and biomedicine.

Emerging mRNA technologies: delivery strategies and biomedical applications.

The great success achieved by the two highly-effective messenger RNA (mRNA) vaccines during the COVID-19 pandemic highlights the great potential of mRNA technology. Through the evolution of mRNA technology, chemistry has played an important role from mRNA modification to the synthesis of mRNA delivery platforms, which allows various applications of mRNA to be achieved both in vitro and in vivo. In this tutorial review, we provide a summary and discussion on the significant progress of emerging mRNA technologies, as well as the underlying chemical designs and principles. Various nanoparticle (NP)-based delivery strategies including protein-mRNA complex, lipid-based carriers, polymer-based carriers, and hybrid carriers for the efficient delivery of mRNA molecules are presented. Furthermore, typical mRNA delivery platforms for various biomedical applications (e.g., functional protein expression, vaccines, cancer immunotherapy, and genome editing) are highlighted. Finally, our insights into the challenges and future development towards clinical translation of these mRNA technologies are provided.