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There is an increasing demand for microbial production of lactic acid (LA) as a monomer of biodegradable poly lactic acid (PLA). Both optical isomers, D-LA and L-LA, are required to produce stereocomplex PLA with improved properties. In this study, we developed Saccharomyces cerevisiae strains for efficient production of D-LA. D-LA production was achieved by expressing highly stereospecific D-lactate dehydrogenase gene (ldhA, LEUM_1756) from Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 in S. cerevisiae lacking natural LA production activity. D-LA consumption after glucose depletion was inhibited by deleting DLD1 encoding D-lactate dehydrogenase and JEN1 encoding monocarboxylate transporter. In addition, ethanol production was reduced by deleting PDC1 and ADH1 genes encoding major pyruvate decarboxylase and alcohol dehydrogenase, respectively, and glycerol production was eliminated by deleting GPD1 and GPD2 genes encoding glycerol-3-phosphate dehydrogenase. LA tolerance of the engineered D-LA-producing strain was enhanced by adaptive evolution and overexpression of HAA1 encoding a transcriptional activator involved in weak acid stress response, resulting in effective D-LA production up to 48.9 g/L without neutralization. In a flask fed-batch fermentation under neutralizing condition, our evolved strain produced 112.0 g/L D-LA with a yield of 0.80 g/g glucose and a productivity of 2.2 g/(L · h).

The conversion of carbon dioxide to formate is a fundamental step for building C1 chemical platforms. Methylobacterium extorquens AM1 was reported to show remarkable activity converting carbon dioxide into formate. Formate dehydrogenase 1 from M. extorquens AM1 (MeFDH1) was verified as the key responsible enzyme for the conversion of carbon dioxide to formate in this study. Using a 2% methanol concentration for induction, microbial harboring the recombinant MeFDH1 expressing plasmid produced the highest concentration of formate (26.6 mM within 21 hours) in electrochemical reactor. 60 μM of sodium tungstate in the culture medium was optimal for the expression of recombinant MeFDH1 and production of formate (25.7 mM within 21 hours). The recombinant MeFDH1 expressing cells showed maximum formate productivity of 2.53 mM/g-wet cell/hr, which was 2.5 times greater than that of wild type. Thus, M. extorquens AM1 was successfully engineered by expressing MeFDH1 as recombinant enzyme to elevate the production of formate from CO 2 after elucidating key responsible enzyme for the conversion of CO 2 to formate.

Systemic ischemic-reperfusion injury following cardiac arrest results in multisystem organ failure, brain injury and death. The aim of this trial is to investigate whether the combined use of cortisol, ascorbic acid (vitamin C), and thiamine during the early post-resuscitation period reduces the neurologic injury among out-of-hospital cardiac arrest (OHCA) survivors treated with targeted temperature management (TTM). This is a single-blind, multi-center, randomized, placebo-controlled trial to be conducted in nine tertiary university-affiliated hospitals in South Korea. A total of 160 OHCA survivors treated with TTM will be randomly assigned to the treatment or control groups (1:1 ratio). For the treatment group, patients will intravenously receive a combination dose of ascorbic acid (50 mg/kg, maximum single dose 3 g), thiamine (200 mg), and cortisol (100 mg) that will be mixed in three separate 50mL bags of 0.9% saline, respectively, every 12 hours for 3 days. For the placebo group, patients will receive three separate 50mL bags of 0.9% saline intravenously in the same manner. The primary outcome is the peak neuron-specific enolase level at 48-72 hours after the return of spontaneous circulation. The potential benefits of ascorbic acid, thiamine, and cortisol as neuroprotective agents have been reported in previous preclinical trials. This trial is the first clinical trial to assess the neuroprotective effectiveness of a combination of ascorbic acid, thiamine, and cortisol for OHCA survivors. ClinicalTrials.gov NCT04921189.

A reciprocal relationship between perceptual learning and functional brain changes towards perceptual learning effectiveness has been demonstrated previously; however, the underlying neural correlates remain unclear. Further, visual perceptual learning (VPL) is implicated in visual field defect (VFD) recovery following chronic stroke. We investigated resting-state functional connectivity (RSFC) in the visual cortices associated with mean total deviation (MTD) scores for VPL-induced VFD recovery in chronic stroke. Patients with VFD due to chronic ischemic stroke in the visual cortex received 24 VPL training sessions over 2 months, which is a dual discrimination task of orientation and letters. At baseline and two months later, the RSFC in the ipsilesional, interhemispheric, and contralesional visual cortices and MTD scores in the affected hemi-field were assessed. Interhemispheric visual RSFC at baseline showed the strongest correlation with MTD scores post-2-month VPL training. Notably, only the subgroup with high baseline interhemispheric visual RSFC showed significant VFD improvement following the VPL training. The interactions between the interhemispheric visual RSFC at baseline and VPL led to improvement in MTD scores and largely influenced the degree of VFD recovery. The interhemispheric visual RSFC at baseline could be a promising brain biomarker for the effectiveness of VPL-induced VFD recovery.

The demand for establishing an effective but inexpensive method to interfere with the spread of infectious diseases has been higher than ever before, since the recent pandemic. As a follow-up study, we tested a few practically applicable lights with a safe 410nm violet light (V) with infrared (IR, 850nm) under realistic conditions to identify an optimal light for suppressing pathogens. Our results indicate that 410nm violet light is as effective as the previously tested 405nm violet light with infrared (850nm). Therefore, we focused on optimizing combined lights (3V-1IR or 2.33V-1IR) with lower power level that is below 24 Watt. Using the Multi Drug Resistant (MDR) Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) from ATCC, we confirmed that the combined 20W light effectively suppressed the survival of both MDR bacterial strains on a smooth surface at the distance of 25cm, 50cm, 1m or 2m, which mimicked the realistic living spaces. As expected, the effectiveness was inversely proportional to the exposed distance. For example, the light exposure suppressed more than 91-97% of E. coli within 1–2 hours and 96-99% of S. aureus within 2–6 hours at short distances (25 or 50cm), whereas it took 6–8 hours to reach 92-95% of E. coli and 91-99% of S. aureus suppression at 1 or 2m. In the mechanistic studies, we confirmed that the bacterial death was mediated by the enhanced level of Reactive Oxygen Species (ROS), in addition to reduced thickness of biofilm from 410nm and 850nm infrared light. Our results strongly support the possible application of using this combined 410nm with infrared light as an inexpensive and practical solution to reduce the potential pathogens, at least from bacterial origins in a variety of living spaces.

The authors provide a holistic perspective to enhance BIM working environment for more efficient smart construction settlements. An in-depth survey with 40 questionnaires was distributed to 100 professionals in construction, design, engineering, government. Although 45% of the respondents have received a certain form of BIM education, more than 94% of the respondents have answered that there should be a formal BIM education. Both design and construction experts have reported that the biggest advantage of using BIM is in its error checking ability. It can reduce design errors and increase construction ability. More than 79% of the respondents agreed upon a proper compensation for BIM implementation. The majority of opinions have revealed that there should be an increase in construction and design fees. There are a number issues for a successful BIM application: (1) guidelines and details for BIM work and delivery; (2) more standardized BIM education; and (3) a proper compensation system for BIM work. The results show that BIM professionals are ready to adopt the consequences of using BIM, but administrative and institutional preparations are not available beforehand. There should be a higher level of regulatory concern and provision of administrative solutions for successful BIM applications.

Building information modeling (BIM) has opened up many possibilities for the construction industry. However, most studies focus mainly on its overall uses and management areas. By investigating real projects that could utilize BIM in the design phases for railway construction, the authors examine the possible advantages and disadvantages in BIM implementation. To do so, the authors have selected three projects that utilized BIM implementation during the design process and three other projects with a non-BIM, traditionally designed working environment. Similar-scale projects were carefully chosen, and their differences in costs, man-hours, and labor forces were analyzed quantitatively. In addition, an in-depth interview was conducted with four BIM-designing firms to provide a more comprehensive perspective on the advantages and issues in BIM implementation. The average results showed that BIM-implemented projects spent USD 65,800 less than their counterparts and could increase productivity by about 2.9%. More importantly, the primary difference between BIM and non-BIM projects are in their man-hours. BIM-adopting projects spent 103.5 days less than non-BIM projects on average, and required three fewer professional labor forces during the entire design process.

Background Formate converted from CO2 reduction has great potential as a sustainable feedstock for biological production of biofuels and biochemicals. Nevertheless, utilization of formate for growth and chemical production by microbial species is limited due to its toxicity or the lack of a metabolic pathway. Here, we constructed a formate assimilation pathway in Escherichia coli and applied adaptive laboratory evolution to improve formate utilization as a carbon source in sugar-free conditions. Results The genes related to the tetrahydrofolate and serine cycles from Methylobacterium extorquens AM1 were overexpressed for formate assimilation, which was proved by the 13C-labeling experiments. The amino acids detected by GC/MS showed significant carbon labeling due to biomass production from formate. Then, 150 serial subcultures were performed to screen for evolved strains with improved ability to utilize formate. The genomes of evolved mutants were sequenced and the mutations were associated with formate dehydrogenation, folate metabolism, and biofilm formation. Last, 90 mg/L of ethanol production from formate was achieved using fed-batch cultivation without addition of sugars. Conclusion This work demonstrates the effectiveness of the introduction of a formate assimilation pathway, combined with adaptive laboratory evolution, to achieve the utilization of formate as a carbon source. This study suggests that the constructed E. coli could serve as a strain to exploit formate and captured CO2.

Building information modeling (BIM) is acknowledged for enhancing efficiency and collaboration in the construction industry. However, its application in the construction phase of railway projects faces challenges. This study, utilizing quantitative and qualitative analyses, explores the advantage of BIM consulting services in the railway infrastructure projects. A comparative analysis of similar-scale projects shows that BIM significantly boosts construction efficiency, yielding a 197.6% economic benefit in pilot projects. This study also delves into the BIM application environment in railway construction. Our findings provide valuable insights into BIM’s advantages and challenges, emphasizing the need for further research. The results will contribute to advancing railway infrastructure and promoting BIM’s application, aiding decision makers and practitioners in understanding its potential contributions to a more efficient and sustainable industry.