Aberrant upregulation of hepatic lipogenesis induced by chronic and excessive alcohol consumption is a critical driver of the progression of alcohol-associated liver disease (ALD), however, no effective approaches inhibiting lipogenesis are currently available for treating ALD patients. Moreover, little is known about whether and how nonethanol ingredients in alcoholic beverages regulate the pathogenesis of ALD. Here the discovery of a small molecule that activates the production and secretion of fibroblast growth factor 21 (FGF21) is reported.
View Article and Find Full Text PDFBenzylisoquinoline alkaloids (BIAs) are a class of natural compounds found in plants of the family, known for their diverse pharmacological activities. However, the extraction yields of BIAs from plants are limited, and the cost of chemical synthesis is prohibitively high. Recent advancements in systems metabolic engineering and genomics have made it feasible to use microbes as bioreactors for BIAs production.
View Article and Find Full Text PDFThe declining availability of cheap fossil-based resources has sparked growing interest in the sustainable biosynthesis of organic acids. l-Malic acid, a crucial four-carbon dicarboxylic acid, finds extensive applications in the food, chemical, and pharmaceutical industries. Synthetic biology and metabolic engineering have enabled the efficient microbial production of l-malic acid, albeit not in , an important industrial microorganism.
View Article and Find Full Text PDFDiacetyl is a flavor compound in wine with a low threshold (1-2 mg/L). It is produced during alcoholic fermentation (AF) and malolactic fermentation (MLF) initiated by lactic acid bacteria (LAB). Whereas, the environment after AF suppresses the normal metabolism of LAB after AF.
View Article and Find Full Text PDFBackground: Benzyl acetate is an aromatic ester with a jasmine scent. It was discovered in plants and has broad applications in food, cosmetic, and pharmaceutical industries. Its current production predominantly relies on chemical synthesis.
View Article and Find Full Text PDFAlveolar echinococcosis (AE) is a highly lethal helminth infection. Current chemotherapeutic strategies for AE primarily involve the use of benzimidazoles (BZs) such as mebendazole (MDZ) and albendazole (ABZ), which exhibit limited efficacy. In a previous study, the vaccine of recombinant Echinococcus granulosus P29 (rEgP29) showed significant immunoprotection against E.
View Article and Find Full Text PDFBackground: 2-Phenylethanol (2-PE) is one of the most widely used spices. Recently, 2-PE has also been considered a potential aviation fuel booster. However, the lack of scientific understanding of the 2-PE biosynthetic pathway and the cellular response to 2-PE cytotoxicity are the most important obstacles to the efficient biosynthesis of 2-PE.
View Article and Find Full Text PDFDuring malolactic fermentation (MLF) of vinification, the harsh L-malic acid undergoes transformation into the milder L-lactic acid, and via decarboxylation reactions it is catalyzed by malolactic enzymes in LAB. The use of bacterial malolactic starter cultures, which usually present challenges in the industry as the suboptimal conditions after alcoholic fermentation (AF), including nutrient limitations, low temperatures, acidic pH levels, elevated alcohol, and sulfur dioxide concentrations after AF, lead to "stuck" or "sluggish" MLF and spoilage of wines. has interesting oenological properties and provides a stronger aromatic intensity than in AF.
View Article and Find Full Text PDFSqualene is a highly sought-after triterpene compound in growing demand, and its production offers a promising avenue for circular economy practices. In this study, we applied metabolic engineering principles to enhance squalene production in the nonconventional yeast , using waste cooking oil as a substrate. By overexpressing key enzymes in the mevalonate pathway - specifically ERG9 encoding squalene synthase, ERG20 encoding farnesyl diphosphate synthase, and HMGR encoding hydroxy-methyl-glutaryl-CoA reductase - we achieved a yield of 779.
View Article and Find Full Text PDFThis study investigates innovative approaches to improve the quality and aroma characteristics of Muscat Hamburg wine production by substituting the conventional yeast with an efficient fermentation strain of . The typical use of in Muscat Hamburg wine often leads to uniformity and prolonged processing times, requiring subsequent malolactic fermentation to degrade excessive malic acid. The study advocates for the replacement of with a specific strain, , isolated from the fermented grains of sauce-flavor Baijiu, a Chinese spirit.
View Article and Find Full Text PDFBackground: Telehealth has emerged as a popular channel for providing outpatient services in many countries. However, the majority of telehealth systems focus on operational functions and offer only a sectional patient journey at most. Experiences with incorporating longitudinal real-world medical record data into telehealth are valuable but have not been widely shared.
View Article and Find Full Text PDFAlveolar echinococcosis is considered to be one of the most potentially lethal parasitic zoonotic diseases. However, the molecular mechanisms by which Echinococcus multilocularis interacts with hosts are poorly understood, hindering the prevention and treatment of this disease. Due to the great advantages of cell culture systems for molecular research, numerous attempts have been made to establish primary cell cultures for E.
View Article and Find Full Text PDFTo investigate the dynamic changes in dry matter accumulation in maize after anthesis, we established a logistic model to describe grain filling characteristics (GFC), and analyzed differences between spring and summer maize, and the influence of meteorological factors. The results showed that the logistic model accurately simulated the dynamic changes in grain growth. For spring maize, the fitted hundred-grain weight at maturity was closely related to the average grain filling rate until maturity, days of the active grain filling period, time of the maximum grain filling rate, and duration of the rapid increase in grain weight.
View Article and Find Full Text PDFThe mechanical process has a widely usage in large-scale high-temperature Daqu (HTD) enterprises, however, the quality of the mechanical HTD is gapped with the HTD by traditional process. Currently, the understanding of the mechanism behind this phenomenon is still over-constrained. To this end, the discrepancies in fermentation parameters, enzymatic characteristics, microbial assembly and succession patterns, metabolic phenotypes were compared between traditional HTD and mechanical HTD in this paper.
View Article and Find Full Text PDFAlthough the treatment of ovarian cancer has made great progress, there are still many patients who are not timely detected and given targeted therapy due to unknown pathogenesis. Recent studies have found that hsa_circ_0015326 is upregulated in ovarian cancer and is involved in the proliferation, invasion, and migration of ovarian cancer cells. However, whether hsa_circ_0015326 can be used as a new target of ovarian cancer needs further investigation.
View Article and Find Full Text PDFSenescence-associated microRNAs (SA-miRNAs) are important molecules for aging regulation. While many aging-promoting SA-miRNAs have been identified, confirmed aging-suppressive SA-miRNAs are rare, that impeded our full understanding on aging regulation. In this study, we verified that miR-708 expression is decreased in senescent cells and aged tissues and revealed that miR-708 overexpression can alleviate cellular senescence and aging performance.
View Article and Find Full Text PDFIt is well-known that the co-inoculation of Saccharomyces cerevisiae and non-Saccharomyces strains can modulate and improve the aromatic quality of wine through their multi-level interactions. However, the individual contribution of metabolic interaction (MI) and physical interaction (PI) on wine volatiles remains poorly understood. In this work, we utilized a double-compartment bioreactor to examine the aromatic effect of MI and PI by comparing the volatiles production in Torulaspora delbrueckii and Saccharomyces cerevisiae single fermentations to their mixed fermentations with or without physical separation.
View Article and Find Full Text PDFDescriptive sensory analysis, headspace solid-phase microextraction-gas chromatography-mass spectrometry, gas chromatography-flame ionization detector and multivariate statistical analysis were used to elucidate the regional dependence of sauce-flavor baijiu (SFB). Although SFB samples from different regions couldn't be clearly classified by sensory profiles, they could be clearly divided into 5 groups in principal component analysis plot based on quantitative targeted flavoromics analysis. And then, the relationship between sensory attributes and volatile compounds were investigated by network analysis.
View Article and Find Full Text PDF"Empty cup aroma" is an important characteristic and quality evaluation standard of Jiangxiang-type Baijiu (JXB). In this study, an in situ detection method for the empty cup aroma of JXB was established, and the authenticity and origin information of JXB were identified with an untargeted flavoromics strategy. The complex composition of JXB leads to slow ethanol volatilization, which is a potential method for identifying artificial JXB.
View Article and Find Full Text PDFThe role of follicular T helper (Tfh) cells in humoral response has been considered essential in recent years. Understanding how Tfh cells control complex humoral immunity is critical to developing strategies to improve the efficacy of vaccines against SARS-CoV-2 and other emerging pathogens. However, the immunologic mechanism of Tfh cells in SARS-CoV-2 receptor binding domain (RBD) vaccine strategy is limited.
View Article and Find Full Text PDFBackground: Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutation and concurrent mutations have a poor prognosis. This study aimed to examine anlotinib plus icotinib as a first-line treatment option for advanced NSCLC carrying EGFR mutation with or without concurrent mutations.
Methods: This phase 2, single-arm, multicenter trial (ClinicalTrials.
Bisabolene is a bioactive sesquiterpene with a wide range of applications in food, cosmetics, medicine, and aviation fuels. Microbial production offers a green, efficient, and sustainable alternative. In this study, we focused on improving the titers of α-bisabolene in by applying two strategies, (i) optimizing the metabolic flux of α-bisabolene biosynthetic pathway and (ii) sequestering α-bisabolene in lipid droplet, thus alleviating its inherent toxicity to host cells.
View Article and Find Full Text PDFPurpose: ASTRIS study aimed the largest to evaluate the effectiveness and safety of second- or higher-line osimertinib in patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC) in the real-world setting. Here we report the results of Chinese patients in ASTRIS study.
Methods: Adults with EGFR T790M-positive advanced NSCLC pretreated with EGFR-tyrosine kinase inhibitor (EGFR-TKI), having a WHO performance status score of 0-2 and asymptomatic, stable central nervous system (CNS) metastases were included.