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The microbial community structure and diversity of Jiang-flavor Daqu (TS, WS, WM, MH and DJ) from different areas of Maotai town were analyzed by using the third-generation nanopore sequencing platform, and its physicochemical indexes and characteristic flavor substances were measured. The results showed that there were some similarities and differences between Daqu in different areas of Maotai town. In terms of microbial community structure, Bacillus, Saccharopolyspora, Weissella, Staphylococcus and Streptomyces were the common dominant bacterial genera in the five Daqu samples. Among them, Bacillus was the absolute dominant bacteria in MH and DJ. Aspergillus and Penicillium were the common dominant fungal genera, and the proportions of Lichtheimia and Saccharomycopsis in TS, WM and MH were significantly higher than those in DJ and WS. Compared with TS and WM, network correlation analysis showed that MH, DJ and WS had stronger interactions among dominant bacteria. In addition, redundancy analysis (RDA) showed that Weissella was positively correlated with esterification power, liquefaction power, saccharification power, acetic acid, ethyl acetate, ethyl lactate and n-pentanol. Lichtheimia was positively correlated with liquefaction power, saccharification power, acetic acid, isovaleric acid, 2,3-butanediol, phenylacetaldehyde and dibutyl phthalate. Saccharomycopsis was positively correlated with esterification power and ethyl acetate. Bacillus was positively correlated with 2,3,5,6-tetramethylpyrazine, propionic acid, isovaleric acid, dibutyl phthalate, 2,3-butanediol and phenacetaldehyde.

Background: Respiratory syncytial virus (RSV) causes the most common type of severe lower respiratory tract infection worldwide, and the fusion (F) protein is a target for neutralizing antibodies and vaccine development. This study aimed to investigate the immunogenicity and efficacy of an mRNA-based RSV vaccine with an F protein sequence. Methods: We designed an mRNA construct encoding a modified RSV F protein, which was further developed into an LNP-encapsulated mRNA vaccine (LVRNA007). LVRNA007 was administered to mice and cotton rats, followed by immunogenicity analysis and viral challenge studies. Protection of rodents from the viral infection was evaluated based on the presence of the virus in the lung and pathological examination of respiratory tissues. Results: LVRNA007 induced robust humoral and cellular immune responses in both mice and cotton rats, with neutralization antibody levels in the immunized animals maintained at high levels for over one year. Vaccination of LVRNA007 also protected the rodents from RSV challenge, judged by the much decreased virus titer and the pathological score in the lung tissue. In addition, no vaccine-enhanced disease (VED) phenomenon was observed with LVRNA007 vaccination. Conclusions: Based on the preclinical immunogenicity and efficacy data, LVRNA007 could be a potential promising vaccine for prophylaxis of RSV infection. [ABSTRACT FROM AUTHOR]

The remarkable success of mRNA‐based coronavirus 2019 (COVID‐19) vaccines has propelled the advancement of nanomedicine, specifically in the realm of RNA technology and nanomaterial delivery systems. Notably, significant strides have been made in the development of RNA‐based in vivo chimeric antigen receptor (CAR) therapy. In comparison to the conventional ex vivo CAR therapy, in vivo CAR therapy offers several benefits including simplified preparation, reduced costs, broad applicability and decreased potential for carcinogenic effects. This review summarises the RNA‐based CAR constructs in in vivo CAR therapy, discusses the current applications of in vivo delivery vectors and outlines the immune cells edited with CAR molecules. We aim for the conveyed messages to contribute towards the advancement of in vivo CAR application. [ABSTRACT FROM AUTHOR]

Currently, conventional immunotherapies for the treatment of non‐small cell lung cancer (NSCLC) have low response rates and benefit only a minority of patients, particularly those with advanced disease, so novel therapeutic strategies are urgent deeded. Therapeutic cancer vaccines, a form of active immunotherapy, harness potential to activate the adaptive immune system against tumor cells via antigen cross‐presentation. Cancer vaccines can establish enduring immune memory and guard against recurrences. Vaccine‐induced tumor cell death prompts antigen epitope spreading, activating functional T cells and thereby sustaining a cancer‐immunity cycle. The success of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has rendered cancer vaccines a promising avenue, especially when combined with immunotherapy or chemoradiotherapy for NSCLC. This review delves into the intricate antitumor immune mechanisms underlying therapeutic cancer vaccines, enumerates the tumor antigen spectrum of NSCLC, discusses different cancer vaccines progress and summarizes relevant clinical trials. Additionally, we analyze the combination strategies, current limitations, and future prospects of cancer vaccines in NSCLC treatment, aiming to offer fresh insights for their clinical application in managing NSCLC. Overall, cancer vaccines offer promising potential for NSCLC treatment, particularly combining with chemoradiotherapy or immunotherapy could further improve survival in advanced patients. Exploring inhaled vaccines or prophylactic vaccines represents a crucial research avenue. [ABSTRACT FROM AUTHOR]

Small molecule drugs are increasingly emerging as innovative and effective treatments for various diseases, with mRNA therapeutics being a notable representative. The success of COVID‐19 vaccines has underscored the transformative potential of mRNA in RNA therapeutics. Within the RNA family, there is another unique type known as circRNA. This single‐stranded closed‐loop RNA molecule offers notable advantages over mRNA, including enhanced stability and prolonged protein expression, which may significantly impact therapeutic strategies. Furthermore, circRNA plays a pivotal role in the pathogenesis of various diseases, such as cancers, autoimmune disorders, and cardiovascular diseases, making it a promising clinical intervention target. Despite these benefits, the application of circRNA in clinical settings remains underexplored. This review provides a comprehensive overview of the current state of synthetic circRNA therapeutics, focusing on its synthesis, optimization, delivery, and diverse applications. It also addresses the challenges impeding the advancement of circRNA therapeutics from bench to bedside. By summarizing these aspects, the review aims to equip researchers with insights into the ongoing developments and future directions in circRNA therapeutics. Highlighting both the progress and the existing gaps in circRNA research, this review offers valuable perspectives for advancing the field and guiding future investigations. [ABSTRACT FROM AUTHOR]

Modern, large bridges and tunnels represent important nodes in transportation arteries and have a significant impact on the development of transportation. The health and safety monitoring of these structures has always been a significant concern and is reliant on various types of sensors. Distributed acoustic sensing (DAS) with telecommunication fibers is an emerging technology in the research areas of sensing and communication. DAS provides an effective and low-cost approach for the detection of various resources and seismic activities. In this study, field experiments are elucidated, using DAS for the Hong Kong–Zhuhai–Macao Bridge, and for studying vehicle trajectories, earthquakes, and other activities. The basic signal-processing methods of filtering and normalization are adopted for analyzing the data obtained with DAS. With the proposed DAS technology, the activities on shore, vehicle trajectories on bridges and in tunnels during both day and night, and microseisms within 200 km were successfully detected. Enabled by DAS technology and mass fiber networks, more studies on sensing and communication systems for the monitoring of bridge and tunnel engineering are expected to provide future insights. [ABSTRACT FROM AUTHOR]

The article explores the impact of N1‐methylpseudouridine (m1Ψ) modification levels on mRNA protein expression, immunogenicity, and stability. The study conducted in vitro experiments with different m1Ψ modification ratios in mRNA encoding enhanced green fluorescent protein (EGFP) and found that low m1Ψ ratios increased protein expression, while high ratios decreased it. Additionally, the research suggests that m1Ψ modification reduces mRNA immunogenicity and enhances stability, with a positive correlation between modification ratio and stability. The study highlights the importance of optimizing mRNA modification strategies for various therapeutic applications. [Extracted from the article]

Bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment are among the most common morbidities affecting preterm infants. Although BPD is a predictor of poor neurodevelopmental outcomes, it is currently uncertain how BPD contributes to brain injury in preterm infants. Extracellular vesicles (EVs) are involved in interorgan communication in diverse pathological processes. ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain) is pivotal in inflammasome assembly and activation of inflammatory response. We assessed expression profiles of the alveolar macrophage (AM) markers CD11b, CD11c, and CD206 as well as ASC in EVs isolated from the plasma of preterm infants at risk for BPD at 1 week of age. We found that infants on higher fraction of inspired oxygen therapy (HO2⩾30%) had increased concentrations of AM-derived EV-ASC compared with infants on lower fraction of inspired oxygen (LO2<30%). To assess the function of these EVs, we performed adoptive transfer experiments by injecting them into the circulation of newborn mice. We discovered that mice that received EVs from infants on HO2 had increased lung inflammation, decreased alveolarization, and disrupted vascular development, the hallmarks of BPD. Importantly, these EVs crossed the blood–brain barrier, and the EVs from infants on HO2 caused inflammation, reduced cell survival, and increased cell death, with features of pyroptosis and necroptosis in the hippocampus. These results highlight a novel role for AM-derived EV-ASC in mediating the lung-to-brain cross-talk that is critical in the pathogenesis of BPD and brain injury and identify potential novel targets for preventing and treating BPD and brain injury in preterm infants. [ABSTRACT FROM AUTHOR]

This article discusses a study that explores a new strategy for constructing circular RNA (circRNA) called NeoAna, which enhances the sensitivity of non-small cell lung cancer (NSCLC) to the drug Osimertinib. The researchers successfully designed and synthesized circRNAs without scar sequences, and they observed the formation of circRNA and successful protein translation in cells. They also restored the expression of the tumor suppressor PTEN using the NeoAna system, which increased sensitivity to Osimertinib and induced apoptosis in Osimertinib-resistant cells. The researchers further demonstrated the efficacy of the NeoAna system in animal models. Overall, this study suggests that engineered circRNA can enhance the effectiveness of Osimertinib in treating NSCLC. The article also discusses the potential mechanisms of PTEN in enhancing the sensitivity of Osimertinib, a drug used to treat NSCLC. The study used RNA-seq to identify common genes between Osimertinib-resistant cells and cells with restored PTEN expression, and found that AKR1C2, a gene involved in drug resistance, was in line with the RNA-seq results. The study also explored the use of a circRNA platform called NeoAna to restore PTEN expression and overcome Osimertinib resistance, suggesting that this platform could be a promising strategy for RNA-based therapeutics. [Extracted from the article]