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The brewing of solid vinegar is traditionally carried out in an open solid-state fermentation system, which is susceptible to environmental factors, leading to unstable flavor quality, low degree of mechanization and low labor productivity. Compared with the traditional open solid-state fermentation system, the closed solid-state fermentation system is not disturbed by external environmental factors, and allows mechanized and automated vinegar brewing, which is beneficial for stabilizing product quality, improving labor productivity, and promoting the modernization of the vinegar industry. In recent years, the closed solid-state fermentation system has been widely used in the field of vinegar brewing, which has brought significant improvement to the production efficiency of solid-state fermented vinegar. This article introduces the structure, characteristics, and regulatory measures of common closed solid-state fermentation systems. Besides, the factors affecting the fermentation performance of the closed solid-state fermentation system are summarized, the application of the closed solid-state fermentation system in vinegar brewing is briefly discussed, and an outlook on future trends in the development of an automatic and intelligent closed solid-state fermentation system is given. We hope that this review can provide a reference for the development of a new closed solid-state vinegar system in the future.

Abstract Background The integration of biotechnology into chemical manufacturing has been recognized as a key technology to build a sustainable society. However, the practical applications of biocatalytic chemical conversions are often restricted due to their complexities involving the unpredictability of product yield and the troublesome controls in fermentation processes. One of the possible strategies to overcome these limitations is to eliminate the use of living microorganisms and to use only enzymes involved in the metabolic pathway. Use of recombinant mesophiles producing thermophilic enzymes at high temperature results in denaturation of indigenous proteins and elimination of undesired side reactions; consequently, highly selective and stable biocatalytic modules can be readily prepared. By rationally combining those modules together, artificial synthetic pathways specialized for chemical manufacturing could be designed and constructed. Results A chimeric Embden-Meyerhof (EM) pathway with balanced consumption and regeneration of ATP and ADP was constructed by using nine recombinant E. coli strains overproducing either one of the seven glycolytic enzymes of Thermus thermophilus, the cofactor-independent phosphoglycerate mutase of Pyrococcus horikoshii, or the non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase of Thermococcus kodakarensis. By coupling this pathway with the Thermus malate/lactate dehydrogenase, a stoichiometric amount of lactate was produced from glucose with an overall ATP turnover number of 31. Conclusions In this study, a novel and simple technology for flexible design of a bespoke metabolic pathway was developed. The concept has been testified via a non-ATP-forming chimeric EM pathway. We designated this technology as “synthetic metabolic engineering”. Our technology is, in principle, applicable to all thermophilic enzymes as long as they can be functionally expressed in the host, and thus would be potentially applicable to the biocatalytic manufacture of any chemicals or materials on demand.

Background: Fibroblast activation protein (FAP) has gained attention as a promising molecular target with potential utility for cancer diagnosis and therapy. [68Ga]Ga-labeled FAP-targeting peptides have been successfully applied to positron emission tomography (PET) imaging of various tumor types. To meet the applicable demand for peptide-based FAP tracers with high patient throughput, we herein report the radiosynthesis, preclinical evaluation, and the first-in-human imaging of a novel [18F]F-labeled FAP-targeting peptide. Results: [18F]AlF-FAP-NUR was automatedly prepared within 45 min with a non-decay corrected radiochemical yield of 18.73 ± 4.25% (n = 3). Compared to [68Ga]Ga-FAP-2286, the [18F]F-labeled peptide demonstrated more rapid, higher levels of cellular uptake and internalization, and lower levels of cellular efflux in HT1080-FAP cells. Micro-PET imaging and biodistribution studies conducted on xenograft mice models revealed a similar distribution pattern between the two tracers. However, [18F]AlF-FAP-NUR demonstrated significantly higher tumor-specific uptake resulting in improved Tumor-Background Ratios (TBRs). In the patients, a significant accumulation of [18F]AlF-FAP-NUR was found in the primary tumor. High uptake of the tracer within the bladder indicated that its major route of excretion was through urine. Conclusions: Based on the physical imaging properties and longer half-life of [18F]F, [18F]AlF-FAP-NUR exhibited promising characteristics such as enhanced tumor-specific accumulation and elevated TBRs, which made it a viable candidate for further clinical investigation. Trial registration: www.Chictr.org.cn, ChiCTR2300076976 Retrospectively registered 25 October 2023. at, URL: https://www.chictr.org.cn/showproj.html?proj=206753. [ABSTRACT FROM AUTHOR]

Vinegar is traditionally produced by fermentation with a mixed system composed of naturally inoculated microorganisms. The complex microbial communities in the fermentation system are crucial to the formation of vinegar flavor. Studies on the microbial communities and their interactions are helpful to reveal the relationship between microorganisms and the quality of vinegar and are of great significance for targeted regulation of microorganisms in the fermentation process, productivity enhancement and vinegar quality improvement. Therefore, recent studies on the microbial diversity and the interactions among core functional microorganisms in the traditional fermentation process of vinegar are reviewed in this paper. Moreover, the positive effects of the interaction among core functional microorganisms on the flavor of vinegar are discussed. Finally, the problems existing in the current research are summarized. This review is expected to provide a reference for targeted regulation of vinegar quality.

This study investigated the impact of seasonal environmental factors on microorganisms and flavor compounds during acetic acid fermentation (AAF) of Zhenjiang aromatic vinegar (ZAV). Environmental factors were monitored throughout the fermentation process, which spanned multiple seasons. Methods such as headspace solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), high performance liquid chromatography (HPLC), and high-throughput sequencing were employed to examine how these environmental factors influenced the flavor profile and microbial community of ZAV. The findings suggested that ZAV brewed in autumn had the strongest flavor and sweetness. The key microorganisms responsible for the flavor of ZAV included Lactobacillus acetotolerans , Lactobacillus plantarum , Lactobacillus reuteri , Lactobacillus fermentum , Acetobacter pasteurianus . Moreover, correlation analysis showed that room temperature had a significant impact on the composition of the microbial community, along with other key seasonal environmental factors like total acid, pH, reducing sugar, and humidity. These results provide a theoretical foundation for regulating core microorganisms and environmental factors during fermentation, enhancing ZAV quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ye, Yu, Liu, Zhu, Yu, Liu, Wang and Wang.)

Introduction: Baloxavir Marboxil is a per oral small-molecule antiviral for the treatment of influenza. While the efficacy and safety of Baloxavir Marboxil have been thoroughly characterized across an extensive clinical trial, studies on the effectiveness of Baloxavir Marboxil in a real-world setting are still scarce., Methods: We conducted an ambispective, observational, multi-center study that enrolled uncomplicated in-fluenza outpatients treated with Baloxavir Marboxil or Oseltamivir in East China. The primary endpoint was time from treatment to alleviation of all influenza symptoms (TTAIS). The secondary endpoints included time from treatment to alleviation of fever (TTAF) and household transmission during the duration of influenza., Results: A total of 509 patients were enrolled. The median TTAIS in the Baloxavir Marboxil group and the Oseltamivir group was 28.0  h (IQR, 20.0 to 50.0) and 48.0  h (IQR, 30.0 to 67.0), respectively. The median TTAF in the Baloxavir Marboxil group and the Oseltamivir group was 18  h (IQR, 10.0-24.0) and 30.0  h (IQR, 19.0-48.0). In the COX multivariable analysis, Baloxavir Marboxil reduced the duration of influenza symptoms (HR  =  1.36 [95%CI:1.12-1.64], p =  0.002) and the duration of fever (HR  =  1.93 [95%CI:1.48-2.52], p  < 0.001) compared to Oseltamivir. When antiviral drugs were given within 12-48  h after symptom onset, the Baloxavir Marboxil group had a significantly shorter TTAIS compared to the Oseltamivir group. There was no significant difference in the rate of adverse events between the two group ( p  = 0.555)., Discussion: Baloxavir Marboxil was superior to Oseltamivir in alleviating influenza symptoms in outpatients with uncomplicated influenza. Our findings suggested that compared to Oseltamivir, Baloxavir Marboxil might be more appropriate for patients with influenza 12- 48 h after symptom onset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cai, Wang, Ye, Lu, Tan, Li, Lin, Qian, Lu, Wan, Wang, Ai, Pu, Qu and Wang.)

Background: Biodiesel production from marine microalgae has received much attention as microalgae can be cultivated on non-arable land without the use of potable water, and with the additional benefits of mitigating CO2 emissions and yielding biomass. However, there is still a lack of effective operational strategies to promote lipid accumulation in marine microalgae, which are suitable for making biodiesel since they are mainly composed of saturated and monounsaturated fatty acids. Moreover, the regulatory mechanisms involved in lipid biosynthesis in microalgae under environmental stress are not well understood., Results: In this work, the combined effects of salinity and nitrogen depletion stresses on lipid accumulation of a newly isolated marine microalga, Chlamydomonas sp. JSC4, were explored. Metabolic intermediates were profiled over time to observe transient changes during the lipid accumulation triggered by the combination of the two stresses. An innovative cultivation strategy (denoted salinity-gradient operation) was also employed to markedly improve the lipid accumulation and lipid quality of the microalga, which attained an optimal lipid productivity of 223.2 mg L(-1) d(-1) and a lipid content of 59.4% per dry cell weight. This performance is significantly higher than reported in most related studies., Conclusions: This work demonstrated the synergistic integration of biological and engineering technologies to develop a simple and effective strategy for the enhancement of oil production in marine microalgae.