Fucosylated human milk oligosaccharides are valuable targets for microbial biomanufacturing. Here we engineered the probiotic Escherichia coli Nissle 1917 as a versatile chassis for synthesizing both 2′-fucosyllactose and 3-fucosyllactose. We implemented lactose preservation and blocked colanic acid precursor consumption while reinforcing the de novo GDP-L-fucose pathway. This core module was coupled with either WbgL or FutM2 to drive terminal fucosylation. Initial screening yielded a 2′-fucosyllactose titer of approximately 1.21 g/L. Integrating an additional chromosomal wbgL cassette increased the titer to approximately 1.58 g/L, whereas subsequent genomic modifications did not further improve the 2′-FL titer. Cultivation with 30 g/L glycerol and 5 g/L yeast extract significantly improved productivity, enabling the strain to produce approximately 7.71 g/L of 2′-fucosyllactose in shake-flask cultures. Conversely, the FutM2 strain produced 0.38 g/L 3-fucosyllactose without yeast extract and nutrient supplementation unexpectedly suppressed product accumulation despite promoting biomass formation. The work provides a probiotic-chassis proof of concept and identifies product-module physiology as a priority for further engineering.
The success of COVID-19 mRNA vaccines has established mRNA as a powerful therapeutic platform. Key advantages of mRNA drugs include transient expression, rapid scalability, and universal protein-encoding capability. This review focuses on the application of mRNA therapies across a broad spectrum of diseases, including cancer, infectious diseases, genetic disorders, autoimmune diseases, and cardiovascular conditions. It systematically summarizes the latest progress in mRNA drug development, covering three major therapeutic paradigms: mRNA vaccines, protein replacement therapy, and mRNA-based gene editing. Emerging approaches, such as artificial intelligence tools for mRNA therapeutic design and advanced delivery systems, are also discussed. By integrating foundational mechanisms, engineering strategies, and translational examples, this review provides a comprehensive overview of the current landscape and future directions of mRNA-based therapeutics.
This study investigated the evolution of particle migration and solution seepage caused by clay mineral swelling during the leaching of weathered crust elution-deposited rare earth ore. Column leaching experiments, high-resolution X-ray computed tomography (CT), and Avizo-based seepage simulations were conducted using a composite lixiviant consisting of composite diethylenetriamine-acetate lixiviant (CDETA) (0.2 mol/L ammonium acetate and 1.0 wt% diethylenetriamine). The pore structure, particle migration, seepage velocity, and pore pressure were systematically analyzed before and after leaching. Results showed that fine particles migrated downward under seepage forces. Consequently, in the upper layer, the average pore count increased from 13,362 (raw ore) to 19,160 (leached ore), and the overall average porosity of the ore body rose from 13.04% to 19.78%. The number of pore throats in the leached ore decreased from 19,387 to 16,502 due to particle blockage. The average seepage velocity dropped from 3.50 × 10−6 m/s to 1.90 × 10−6 m/s. Pore pressure was higher in the upper layer (3859–4128 Pa) than in the lower layer (3517–3824 Pa). These changes weakened the internal pore connectivity of the ore body and intensified the local pressure gradient, which are important triggers for clay swelling and landslide hazards. This study reveals the coupling mechanism among particle migration, swelling, and seepage. The findings provide a theoretical basis for optimizing lixiviant injection, inhibiting particle migration, and ensuring mine safety.
The rapid advancement of aerospace and transportation technologies toward weight reduction and harsh thermal environments has imposed a stringent demand for Al alloys that can sustain excellent performance at 200–400 °C. Heat-resistant Al alloys have thus garnered strategic significance as a premier class of lightweight structural materials for elevated-temperature applications. This review critically assesses the current state of heat-resistant Al alloys from the perspectives of strengthening strategies and processing technologies. Three representative strengthening strategies have been summarized, including multi-element microalloying, incorporation of nanoparticles, and formation of nano-eutectic skeleton. Meanwhile, a systematic comparative analysis has been conducted on microstructural regulations and mechanical properties of alloys manufactured by permanent mold casting (PMC), powder metallurgy (PM), and laser powder bed fusion (LPBF), with particular emphasis on the processing-structure-property correlations unique to each route. On this basis, the principal technical bottlenecks currently constraining the further advancement of high-performance heat-resistant Al alloys have been identified and critically discussed, thereby outlining prospective research directions to overcome these limitations.
Despite the high prevalence of hypovitaminosis D among athletes and the proposed role of vitamin D in musculoskeletal health and performance, data on vitamin D status in soccer referees and its relationship with body composition and performance remain scarce. This cross-sectional study evaluated 25(OH)D concentrations and their associations with the sun exposure index (SEI), body composition, and performance in a sample of 21 male referees (30.6 ± 3.4 years) from the Brazilian Football Confederation. Serum 25(OH)D concentration was assessed from blood samples, SEI by questionnaire, body fat percentage (BF%), fat free mass, and bone mineral density (BMD) by dual-energy X-ray absorptiometry, calcium and carbohydrate intake by 24-h recall, and performance by the repeated sprint ability (RSA) test. Associations were examined using linear regression analysis adjusted for (1) age, (2) fat free mass, and (3) carbohydrate or calcium intake. 76% presented serum 25(OH)D concentrations < 30 ng/mL. 25(OH)D was positively associated with SEI (β = 1.17; p = 0.04, Cohen’s f2 = 0.19), whereas no significant associations were observed with BMD, BF% or RSA, even after adjustments. There is a high prevalence of hypovitaminosis D among the soccer referees evaluated. Although 25(OH)D was not significantly associated with body composition or performance, its positive association with SEI reinforces the importance of sun exposure.
