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The present study explored university students' perceptions and attitudes toward music listening in foreign language learning, examining its perceived supportive role in their learning process. In this study, “music listening in foreign language learning” refers to the practice of incorporating music as a background accompaniment during language study. With 200 participants from various majors, findings indicated that a majority (94.5%) frequently listened to music in general, with a preference for slow ballad, fast dance, and classical music genres for language study. Of these, 142 stated that listening to music played a beneficial role in their foreign language learning, perceiving it not just as a stress-reliever but also a valuable tool enhancing language skills. A significant correlation emerged between music listening and decreased communication apprehension from the Foreign Language Classroom Anxiety Scales (FLCAS). Hierarchical regression highlighted the individual variables like gender, age, and English proficiency as influential factors in foreign language anxiety, while frequent music listening displayed a protective, inverse relationship with such anxiety. The findings suggest foreign language proficiency demands both knowledge and emotional stability, with managing anxiety through informal practices like music listening playing a critical role. This highlights the potential for further pedagogical insights and more detailed subsequent research.

Aims: Metformin improves glucose regulation through various mechanisms in the periphery. Our previous study revealed that oral intake of metformin activates several brain regions, including the hypothalamus, and directly activates hypothalamic S6 kinase in mice. In this study, we aimed to identify the direct effects of metformin on glucose regulation in the brain.Materials and methods: We investigated the role of metformin in peripheral glucose regulation by directly administering metformin intracerebroventricularly in mice. The effect of centrally administered metformin (central metformin) on peripheral glucose regulation was evaluated by oral or intraperitoneal glucose, insulin, and pyruvate tolerance tests. Hepatic gluconeogenesis and gastric emptying were assessed to elucidate the underlying mechanisms. Liver-specific and systemic sympathetic denervation were performed.Results: Central metformin improved the glycemic response to oral glucose load in mice compared to that in the control group, and worsened the response to intraperitoneal glucose load, indicating its dual role in peripheral glucose regulation. It lowered the ability of insulin to decrease serum glucose levels and worsened the glycemic response to pyruvate load relative to the control group. Furthermore, it increased the expression of hepatic G6pc and decreased the phosphorylation of STAT3, suggesting that central metformin increased hepatic glucose production. The effect was mediated by sympathetic nervous system activation. In contrast, it induced a significant delay in gastric emptying in mice, suggesting its potent role in suppressing intestinal glucose absorption.Conclusion: Central metformin improves glucose tolerance by delaying gastric emptying through the brain-gut axis, but at the same time worsens it by increasing hepatic glucose production via the brain-liver axis. However, with its ordinary intake, central metformin may effectively enhance its glucose-lowering effect through the brain-gut axis, which could surpass its effect on glucose regulation via the brain-liver axis.

Chrysophanic acid (CA) is a member of the anthraquinone family abundant in rhubarb, a widely used herb for obesity treatment in Traditional Korean Medicine. Though several studies have indicated numerous features of CA, no study has yet reported the effect of CA on obesity. In this study, we tried to identify the anti-obesity effects of CA. By using 3T3-L1 adipocytes and primary cultured brown adipocytes as in vitro models, high-fat diet (HFD)-induced obese mice, and zebrafish as in vivo models, we determined the anti-obesity effects of CA. CA reduced weight gain in HFD-induced obese mice. They also decreased lipid accumulation and the expressions of adipogenesis factors including peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in 3T3-L1 adipocytes. In addition, uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), the brown fat specific thermogenic genes, were up-regulated in brown adipocytes by CA treatment. Furthermore, when co-treated with Compound C, the AMP-activated protein kinase (AMPK) inhibitor, CA was able to restore the activation of AMPKα in both types of adipocytes, indicating the multi-controlling effect of CA was partially via the AMPKα pathway. Given all together, these results indicate that CA can ameliorate obesity by controlling the adipogenic and thermogenic pathway at the same time. On these bases we suggest the new potential of CA as an anti-obese pharmacotherapy.

There have been extensive genome sequencing studies for Escherichia coli strains, particularly for pathogenic isolates, because fast determination of pathogenic potential and/or drug resistance and their propagation routes is crucial. For laboratory E. coli strains, however, genome sequence information is limited except for several well-known strains. We determined the complete genome sequence of laboratory E. coli strain RR1 (HB101 RecA+), which has long been used as a general cloning host. A hybrid genome sequence of K-12 MG1655 and B BL21(DE3) was constructed based on the initial mapping of Illumina HiSeq reads to each reference, and iterative rounds of read mapping, variant detection, and consensus extraction were carried out. Finally, PCR and Sanger sequencing-based finishing were applied to resolve non-single nucleotide variant regions with aberrant read depths and breakpoints, most of them resulting from prophages and insertion sequence transpositions that are not present in the reference genome sequence. We found that 96.9% of the RR1 genome is derived from K-12, and identified exact crossover junctions between K-12 and B genomic fragments. However, because RR1 has experienced a series of genetic manipulations since branching from the common ancestor, it has a set of mutations different from those found in K-12 MG1655. As well as identifying all known genotypes of RR1 on the basis of genomic context, we found novel mutations. Our results extend current knowledge of the genotype of RR1 and its relatives, and provide insights into the pedigree, genomic background, and physiology of common laboratory strains. [ABSTRACT FROM AUTHOR]

Microbial adaptations often occur via genomic mutations under adverse environmental conditions. This study used Escherichia coli ΔadhE cells as a model system to investigate adaptation to anaerobic conditions, which we then compared with the adaptive mechanisms of two closely related E. coli strains, K-12 and B. In contrast to K-12 ΔadhE cells, the E. coli B ΔadhE cells exhibited significantly delayed adaptive growth under anaerobic conditions. Adaptation by the K-12 and B strains mainly employed anaerobic lactate fermentation to restore cellular growth. Several mutations were identified in the pta or pflB genes of adapted K-12 cells, but mostly in the pta gene of the B strains. However, the types of mutation in the adapted K-12 and B strains were similar. Cellular viability was affected directly by severe redox imbalance in B ΔadhE cells, which also impaired their ability to adapt to anaerobic conditions. This study demonstrates that closely related microorganisms may undergo different adaptations under the same set of adverse conditions, which might be associated with the specific metabolic characteristics of each strain. This study provides new insights into short-term microbial adaptation to stressful conditions, which may reflect dynamic microbial population changes in nature. [ABSTRACT FROM AUTHOR]

As culture history is known to affect the length of the lag phase and microbial cell growth, precultures are often grown in the same medium as the main culture for physiological adaptation and to reduce a prolonged lag time in some microbial cells. To understand the adaptation process of microbial cells during transfer from Luria–Bertani medium to minimal medium, we used the growth of Escherichia coli BL21(DE3) in succinate minimal medium as a model system. We observed that only one or two sequential transfers from minimal medium to fresh minimal medium accelerated the growth rate of BL21(DE3) cells. In addition, the number of large colonies (diameter ≥0.1 cm) on succinate agar increased with the number of transfers. Genome and transcript analyses showed that the C-to-T point mutation in large colony cells converted the inactive promoter of kgtP (known to encode α-ketoglutarate permease) to the active form, allowing efficient uptake of exogenous succinate. Moreover, we visualized the occurrence of genetically adapted cells with better fitness in real time and quantified the number of those cells in the microbial population during transfer to the same medium. Fluorescence microscopy showed the occurrence and increase of adapted mutant cells, which contain intracellular KgtP-fused green fluorescent proteins, as a result of the C-to-T mutation in the promoter of a fused kgtP–sfgfp during transfer to fresh medium. Flow cytometry revealed that the proportion of mutant cells increased from 1.75% (first transfer) to 12.16% (second transfer) and finally 70.79% (third transfer), explaining the shortened lag time and accelerated growth rate of BL21(DE3) cells during adaptation to the minimal medium. This study provides new insights into the genetic heterogeneity of microbial populations that aids microbial adaptability in new environments.

Genome-editing CRISPR/Cas9 technology has led to the development of artificial transcriptional repressors, also known as CRISPR interference (CRISPRi). The deactivated Cas9 (dCas9) protein guided by crRNA can specifically bind to target DNA sequences, including promoters and operators, without DNA cleavage. Protospacer adjacent motif (PAM) sequence dependence may be disadvantageous in the design of target-specific CRISPRi, as the PAM sequence is essential for DNA cleavage by the CRISPR/Cas9 system. We constructed a chromosomally integrated dCas9 system (ΔaraBAD:dcas9) in Escherichia coli under the control of the L-arabinose-inducible PBAD promoter. Plasmids carrying various crRNAs with target sequences specific for the gal promoter (−10 region), and the galETK structural genes in the gal operon, were transformed into dCas9-expressing E. coli. Cellular growth and/or galactose metabolic rates were monitored in the presence or absence of gratuitous L-arabinose. D-galactose consumption and cell growth rates were partially retarded by targeting transcriptional elongation but were fully inhibited by targeting transcriptional initiation. Moreover, RT-qPCR analysis showed that CRISPRi with several modified PAM sequences can repress the transcription of target DNAs. These results indicate that cellular metabolic rates and cell growth can be controlled by targeting structural genes or regulatory regions using CRISPRi; also, a loose PAM sequence dependence can expand the DNA targets of CRISPRi.

The sugar phosphotransferase system (PTS) is an essential energy-saving mechanism, particularly under anaerobic conditions. Since the PTS consumes equimolar phosphoenolpyruvate to phosphorylate each molecule of internalized glucose in the process of pyruvate generation, its absence can adversely affect the mixed acid fermentation profile and cell growth under anaerobic conditions. In this study, we report that the ΔptsG mutant cells of Escherichia coli K-12 strain exhibited inefficient glucose utilization, produced a significant amount of succinate, and exhibited a low growth rate. However, cells adapted soon after and started to grow rapidly in the same batch culture. As a result, the adapted ΔptsG cells showed the same mixed acid fermentation profiles as the wild-type cells, which was attributed to the mutation of the mlc gene, a repressor of the D-mannose PTS, another transporter for D-glucose. Similar adaptations were observed in the cells with ΔptsGΔmanX and the cells with ΔptsI that resulted in the production of a substantial amount of succinate and fast growth rate. The genome sequencing showed the presence of null mutations in the exuR gene, which encodes a modulator of exuT-encoded non-PTS sugar transporter, in adapted ΔptsGΔmanX and ΔptsI strains. Results from the RT-qPCR analysis and genetic test confirmed that the enhanced expression of ExuT, a non-PTS sugar transporter, was responsible for the uptake of D-glucose, increased succinate production, and fast growth of adapted cells. In conclusion, our study showed that the regulatory network of sugar transporters can be modulated by short-term adaptation and that downstream metabolic flux could be significantly determined by the choice of sugar transporters.

Objective: Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy of radiotherapy (RT), especially combined with immune checkpoint inhibitors (ICIs), for this rare melanoma subtype remains unknown. We investigated the reciprocal effect of RT and ICI on mucosal melanoma patients.Materials and Methods: We identified 23 patients with 31 tumors who were treated with RT between July 2008 and February 2017. All patients received RT for primary or metastatic gross tumor mass with a median dose of 4 Gy per fraction (range 1.8–12 Gy). Eleven patients (14 lesions) were treated with RT alone, whereas 12 (17 lesions) were administered pembrolizumab combined with RT (ICI+RT group). The local control (LC) and adverse event (AE) rates were compared between the groups. Eight patients with metastatic mucosal melanoma treated with ICI alone during the same study period were included as a comparison group.Results: The median follow-up period was 17.4 (range 3.7–95.2) months. The target lesion control rate at 1-year was significantly higher in the ICI+RT group than in the RT-alone group or ICI-alone group (94.1% vs. 57.1% vs. 25%; P < 0.05). No abscopal effect was observed in our cohort. Treatment-related AEs were not significantly increased in the combined treatment group compared with the RT-alone group (P > 0.05). No grade ≥3 AEs occurred in the ICI+RT group.Conclusions: Besides RT acting as an immune adjuvant, ICI might have a radiosensitizing effect and may increase LC without severe toxicity. We have initiated a phase II study to determine the effects of RT in patients with melanoma undergoing anti-PD1 (NCT04017897).