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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]

Purpose: Fibroblast-activated protein (FAP) is highly expressed in cancer-associated fibroblasts (CAFs) of many solid cancers, but low or absent in normal tissues. Our study aimed to develop a novel FAP-specific tracer, namely [18F]FAP-2286, and evaluated its performance in comparison with well-established agents such as [18F]FAPI-42 and [68Ga]Ga-FAP-2286 in preclinical research, as well as 2-[18F]FDG in pilot clinical study. Methods: [18F]FAP-2286 was manually synthesized in accordance with Good Manufacturing Practice (GMP). Subsequent investigations encompassed cell uptake, competitive binding affinity, internalization and efflux assays using HT-1080hFAP cell lines. PET imaging and biodistribution studies were conducted in HEK-293ThFAP, A549hFAP, HT-1080hFAP tumor-bearing mice as well as HEK-293T, A549 and HT-1080 control groups. Furthermore, clinical evaluation of [18F]FAP-2286 was performed in fifteen patients with various cancers compared to 2-[18F]FDG PET. Results: The radiolabeling yield of [18F]FAP-2286 was 30.53 ± 5.20%, with a radiochemical purity exceeding 97%. In cell assays, [18F]FAP-2286 showed specific uptake, high internalization fraction and low cellular efflux. Rapid tumor uptake and satisfactory tumor retention was observed on micro-PET imaging and cancer patients. Meanwhile, the clinical research demonstrated that [18F]FAP-2286 may represent an alternative for low glucose-metabolism malignant tumors PET imaging such as gastric cancers. Conclusion: [18F]FAP-2286 showed superior imaging quality including rapid and high target uptake and satisfactory retention in both tumor-bearing mice and cancer patients. It may emerge as a promising candidate for early or delayed phase imaging and 2-[18F]FDG non-avid cancers PET scan. [ABSTRACT FROM AUTHOR]