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Some studies have shown that lyophilization significantly improves the stability of mRNA-LNPs and enables long-term storage at 2–8 ℃. However, there is little research on the lyophilization process of mRNA-lipid nanoparticles (LNPs). Most previous studies have used empirical lyophilization with only a single lyoprotectant, resulting in low lyophilization efficiency, often requiring 40–100 h. In the present study, an efficient lyophilization method suitable for mRNA-LNPs was designed and optimized, shortening the total length of the lyophilization process to 8–18 h, which significantly reduced energy consumption and production costs. When the mixed lyoprotectant composed of sucrose, trehalose, and mannitol was added to mRNA-LNPs, the eutectic point and collapse temperature of the system were increased. The lyophilized product had a ginger root-shaped rigid structure with large porosity, which tolerated rapid temperature increases and efficiently removed water. In addition, the lyophilized mRNA-LNPs rapidly rehydrated and had good particle size distribution, encapsulation rate, and mRNA integrity. The lyophilized mRNA-LNPs were stable at 2–8 ℃, and they did not reduce immunogenicity in vivo or in vitro. Molecular dynamics simulation was used to compare the phospholipid molecular layer with the lyoprotectant in aqueous and anhydrous environments to elucidate the mechanism of lyophilization to improve the stability of mRNA-LNPs. This efficient lyophilization platform significantly improves the accessibility of mRNA-LNPs.

The current COVID-19 epidemic has greatly accelerated the application of mRNA technology to our real world, and during this battle mRNA has proven it's unique advantages compared to traditional biopharmaceutical and vaccine technology. In order to overcome mRNA instability in human physiological environments, mRNA chemical modifications and nano delivery systems are two key factors for their in vivo applications. In this review, we would like to summarize the challenges for clinical translation of mRNA-based therapeutics, with an emphasis on recent advances in innovative materials and delivery strategies. The nano delivery systems include lipid delivery systems (lipid nanoparticles and liposomes), polymer complexes, micelles, cationic peptides and so on. The similarities and differences of lipid nanoparticles and liposomes are also discussed. In addition, this review also present the applications of mRNA to other areas than COVID-19 vaccine, such as infectious diseases, tumors, and cardiovascular disease, for which a variety of candidate vaccines or drugs have entered clinical trials. Furthermore, mRNA was found that it might be used to treat some genetic disease, overcome the immaturity of the immune system due to the small fetal size in utero, treat some neurological diseases that are difficult to be treated surgically, even be used in advancing the translation of iPSC technology et al. In short, mRNA has a wide range of applications, and its era has just begun., Graphical abstract Image 1

A series of FeOx-MnO2-CeO2 catalysts were synthesized by the surfactant-templated coprecipitation method and applied for HCHO removal. The influence of Fe/Mn/Ce molar ratio on the catalytic performance was investigated, and the FeOx-MnO2-CeO2 catalyst exhibited excellent catalytic activity, with complete HCHO conversion at low temperatures (40 °C) when the molar ratio of Fe/Mn/Ce was 2/5/5. The catalysts were characterized by N2 adsorption and desorption, XRD, H2-TPR, O2-TPD and XPS techniques to illustrate their structure–activity relationships. The result revealed that the introduction of FeOx into MnO2-CeO2 formed a strong interaction between FeOx-MnO2-CeO2, which facilitated the improved dispersion of MnO2-CeO2, subsequently increasing the surface area and aiding pore development. This promotion effect of Fe enhanced the reducibility and produced abundant surface-active oxygen. In addition, a great number of Oα is beneficial to the intermediate decomposition, whereas the existence of Ce3+ favors the formation of oxygen vacancies on the surface of the catalyst, all of which contributed to HCHO oxidation at low temperatures.

3'-Geranyl-mono-substituted chalcone Xanthoangelol (1b), a chalcone derivative, was previously reported to show selective cytotoxicity against human chronic myelogenous leukemia K562 cells with a half-maximal inhibitory concentration (IC50) of 3.98 μM. In the present study, we investigated the molecular mechanism underlying the cytotoxicity of 1b in K562 cells. Treatment with compound 1b caused K562 cells to adopt a typical apoptotic morphology. Flow cytometric analysis also confirmed the presence of an apoptotic cell population following treatment of Annexin-V-FITC and propidium iodide (PI) double-labeled K562 cells with 1b. Furthermore, we observed dissipation of the mitochondrial membrane potential, caspase-3 activation, and a reduction of the Bcl-2/Bax ratio in these cells, which suggest that the mitochondrial apoptotic pathway is induced by 1b in K562 cells. Collectively, our findings demonstrate that compound 1b notably induces mitochondrial-mediated apoptosis in K562 cells, which might have a potential anticancer activity.

Melanocortin 4 receptor (MC4R) is a key factor in regulating energy homeostasis, and null mutations occurring in the gene encoding MC4R cause severe early-onset morbid obesity in humans. Many obesity-causing mutations affecting MC4R clinically identified so far lead to failure of mutant receptors to shuttle to the plasma membrane. In this study, we show that a novel human MC4R antagonist, Ipsen 17, acted as an pharmacological chaperone of human MCR4. As tested with 12 obesity-causing human MC4R variants including S58C, E61K, N62S, I69T, P78L, C84R, G98R, T162I, R165W, W174C, C271Y, and P299H, Ipsen 17 was found to be the most universal pharmacological chaperone of MC4R reported so far because it can completely rescue nearly all mutant receptors (except P299H) with the highest potency (an EC50 value of approximately 10−8 M) and efficiency when compared with results for other tested pharmacological chaperones of MC4R including ML00253764, PBA, MTHP, PPPone, MPCI, DCPMP, and NBP described in the literature. Once restored to the plasma membrane, defective human MC4R variants responded to α-MSH stimulation with an EC50 value of approximately 10−8 M and displayed dramatically enhanced signaling ability (except for G98R) in a mutant-specific efficacy and potency profile. Taken together, these results indicate that Ipsen 17 represents a candidate for the development of a targeted treatment of severe early-onset morbid obesity caused by a large subset of inherited mutations in the human MC4R gene.

The photoelectrical characteristics of field-effect phototransistors (FEPTs) are investigated experimentally based on a graphene–PbS quantum dot (QD) hybrid. The device presented a wide spectral response range from 300 to 1400 nm because of multiple-exciton generation of PbS QDs. The photoelectrical responsivity reached up to $2\times 10^{5}\ \hbox{A/W}$ at low bias voltage ( $\sim$ 10 mV) and became more sensitive with increasing bias voltage. The transient response of the hybrid FEPTs was also measured with the relaxation times and the decay times around several seconds. Such devices exhibit great competitiveness in wide spectral response, flexible integrated circuits with low cost, large area, low energy consumption, and high responsivity.