RNA-based gene therapy has been widely used for various diseases, and extensive studies have proved that suitable delivery routes greatly help the development of RNA therapeutics. Identifying a safe and effective delivery system is key to realizing RNA therapeutics' clinical translation. Inhalation is a non-invasive pulmonary delivery modality that can enhance the retention of therapeutic agents in the lungs with negligible toxicity, thereby improving patient compliance. Inhaled RNA therapeutics are increasingly becoming an area of focus for researchers; however, only several clinical trials have explored inhaled delivery of RNA for pulmonary diseases. This review presents an overview of recent advances in inhaled delivery systems for RNA therapeutics, including viral and nonviral systems, highlighting state of the art regarding inhalation in the messenger RNA (mRNA) field. We also summarize the applications of mRNA inhalants in infectious and other lung diseases. Simultaneously, the research progresses on small interfering RNAs (siRNAs), antisense oligonucleotides (ASOs), and different types of RNA are also discussed to provide new strategies for developing RNA inhalation therapy. Finally, we clarify the challenges inhaled RNA-based therapeutics face before their widespread adoption and provide insights to help advance this exciting field to the bedside.

Early diagnosis and intervention is an important way to delay the progress of Alzheimer′s disease (AD).Compared with cerebrospinal fluid, blood sampling is not invasive and easy to be obtained in clinic practice.In this study, the serum samples of 9 controls, 10 AD and 12 mild cognitive dysfunction (MCI) patients were analyzed and compared through one by one analysis to screen potential markers for AD diagnosis.The experimental results showed that VGFYESDVMGR of α-2-macroglobulin peptide was closely related to the late stage of AD disease, and the large amount degradation of apolipoprotein C-Ⅲ, histone H1.2 and histone H1.4 was significantly related to early stages of AD progression.The characteristics of serum peptidome were different for the early and late AD, and these four proteins may be used as potential biomarkers of AD disease.In addition, the obvious ladder sequence characteristic was observed for apolipoprotein C-Ⅲ and histone H1, which could partly explain why the peptides distribution in different samples was somewhat contingent.On the contrary, the distribution at protein level was more stable.Finally, it was confirmed that the peptides of proteins such as fibrinogen α-chain, thymosin β-4 and patchy proteins were the dominant peptides in all serum samples.Overall, this study showed that the method of using serum peptidomics to diagnose AD was possible.The results may provide evidence and references for the large-scale clinical validation of AD.

A novel probe (DNSBN) towards biothiols on the basis of 4-hydroxynaphthalimide as fluorophores and 2, 4-dinitrobenzenesulfonyloxy group as specific recognition site was designed and synthesized.The result of absorption and fluorescence spectral analyses indicated that the probe had high sensitivity and selectivity towards cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), and the detection was not affected by other 17 kinds of natural amino acids.Meanwhile, it was confirmed that DNSBN was a ratiometric probe through the fluorescence titration experiment, and the fluorescent intensity at 555 nm had a high linear relationship with biothiols concentration in the range of 0-20 μmol/L.The detection limits (3σ) of Cys, Hcy and GSH were 25.9, 92.0 and 77.9 nmol/L, respectively.The absorption, emission and mass spectra indicated that biothiols could be engaged in nucleophilic substitution reaction with 2,4-dinitrobenzenesulfonate, which induced the sulfonic esters decomposed.With the departure of receptor unit, the d-PeT progress (donor-excited photoinduced electron transfer) was blocked with an obvious colorimetric and fluorescence change.Finally, HeLa cell imaging experiments verified that DNSBN had good biocompatibility and could be used to detect exogenous biothiols.