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Monascus species are capable of producing various active metabolites, including monacolin K (MK) and pigments. Studies have shown that the overexpression of the mok I gene from the MK synthesis gene cluster in Monascus species can significantly increase MK production; however, the molecular mechanism has not yet been fully elucidated. Therefore, this study focused on the mok I gene of Monascus pilosus to construct overexpression strains of the mok I gene, resulting in high-yield MK production. Sixteen positive transformants were obtained, seven of which produced 9.63% to 41.39% more MK than the original strain, with no citrinin detected in any of the transformants. The qRT-PCR results revealed that the expression levels of mok I in the transformed strains TI-13, TI-24, and TI-25 increased by more than 50% compared to the original strain at various fermentation times, with the highest increase being 10.9-fold. Furthermore, multi-omics techniques were used to analyze the molecular mechanisms underlying enhanced MK production in transformed strains. The results indicated that mok I overexpression may enhance MK synthesis in M. pilosus by regulating the expression of key genes (such as MAO, HPD, ACX, and PLC) and the synthesis levels of key metabolites (such as delta-tocopherol and alpha-linolenic acid) in pathways linked to the biosynthesis of cofactors, the biosynthesis of unsaturated fatty acids, tyrosine metabolism, ubiquinone and other terpenoid-quinone biosynthesis, alpha-linolenic acid metabolism, and glycerophospholipid metabolism. These findings provide a theoretical basis for further study of the metabolic regulation of MK in Monascus species and for effectively enhancing their MK production. [ABSTRACT FROM AUTHOR]

Background: Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA). Methods: This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors. Results: Of 957 participants (median age 68 (interquartile range, 59–75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors (vs lowest tertile, medium tertile OR 0.39, 95% CI [0.17–0.91], top tertile OR 0.33, 95% CI [0.13–0.84], overall p = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13–0.63], p = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH. Conclusions: This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed. [ABSTRACT FROM AUTHOR]

In Asia, Monascus has been used in food fermentation for nearly a thousand years. It has attracted increasing attention in recent years due to its ability to produce a variety of important active substances such as monacolin K (MK) and pigments. MK is an effective drug widely used for lowering human blood cholesterol that functions by inhibiting the rate-limiting enzyme in cholesterol biosynthesis. Monascus strains, fermentation methods and fermentation conditions have significant effects on MK yield, and much research has been undertaken to obtain higher MK yields. In this paper, the research progress of Monascus strain breeding for high MK yield, medium optimization for MK production during Monascus fermentation, and optimization of fermentation process conditions are fully reviewed. This provides reference for future research on Monascus fermentation and industrial production for high-yield MK production.

For the dynamic takeout delivery vehicle routing problem, which faces fluctuating order demand and time-varying speeds, this study presents a novel approach. We analyze the time distribution of takeout orders and apply a Receding Horizon Control (RHC) strategy to convert the dynamic challenge into a static one. The driving speed of delivery vehicles on different roads at different times is determined based on the subdivision criteria of the urban road network and a traffic congestion measurement method. We propose a dynamic takeout delivery vehicle routing optimization model and a time-varying subdivision road network is established to minimize the total delivery cost. We validated the model through simulation examples. The optimization results show that the total distribution cost is reduced after considering the time-varying subdivision road network, with the penalty cost decreasing by 39%. It is evident that considering the subdivision of the road network can enhance order delivery efficiency and optimize the overall dining experience. The sensitivity analysis of various parameters reveals that the delivery platform must appropriately determine the time domain and allocate the number of delivery personnel based on order scale to avoid escalating delivery costs. These findings provide theoretical guidance for vehicle routing planning in the context of delivery platforms. [ABSTRACT FROM AUTHOR]

Wangping Coal Mine, whose industrial heritage is of great value, was one of the eight coal mines in Beijing. A large number of field surveys and analysis of the abandoned industrial facilities of Wangping Coal Mine were carried out in this paper. From the perspective of protecting industrial heritage culture and sustainable development, this paper studies the ideas and strategies for reusing the abandoned facilities of the Wangping Coal Mine. In order to protect its industrial heritage as much as possible, it is suggested to reuse the industrial square of Wangping Coal Mine as a community park.