Search

Although various marine ingredients have been exploited for the development of cosmetic products, no previous study has examined the potential of seaweed extracellular vesicles (EV) in such applications. Our results revealed that EV from Codium fragile and Sargassum fusiforme effectively decreased α-MSH-mediated melanin synthesis in MNT-1 human melanoma cells, associated with downregulation of MITF (microphthalmia-associated transcription factor), tyrosinase and TRP1 (tyrosinase-related proteins 1). The most effective inhibitory concentrations of EV were 250 μg/ml for S. fusiforme and 25 μg/ml for C. fragile, without affecting the viability of MNT-1 cells. Both EV reduced melanin synthesis in the epidermal basal layer of a three-dimensional model of human epidermis. Moreover, the application of the prototype cream containing C. fragile EV (final 5 μg/ml) yielded 1.31% improvement in skin brightness in a clinical trial. Together, these results suggest that EV from C. fragile and S. fusiforme reduce melanin synthesis and may be potential therapeutic and/or supplementary whitening agents.

We investigated the properties of Korean traditional animal glue which are associated with the use of different parts of cattle hide and extraction conditions. Both average molecular weight(Mw, Mz) and polydispersity (PDI) of the animal glue increased with extraction time, whereas only PDI decreased after 48h. There were no differences in the average molecular weight and PDI for the different cattle hide parts used, although a individual difference was observed with regard to total molecular weight. Differences in extracts over time were compared by investigating the amide regions representing the gelatien component of the animal glue. The triple helix structure of the belly skin deteriorated in a manner proportional to the extraction time, and differences were observed for each cattle hide part. The yellowness increased with the extraction time; however, the viscosity was not proportional to the average change in molecular weight. This study has some limitations because of difficulties in the quality control of cases where small amounts of glue were extracted as small differences might impact the overall results considerably. Further research exploring various extraction conditions is required to ensure the prodiction of traditional animal glue with optimum qualities.

Shikimate is a key high-demand metabolite for synthesizing valuable antiviral drugs, such as the anti-influenza drug, oseltamivir (Tamiflu®). Microbial-based strategies for shikimate production have been developed to overcome the unstable and expensive supply of shikimate derived from traditional plant extraction processes. In this study, a microbial cell factory using Corynebacterium glutamicum was designed to overproduce shikimate in a fed-batch culture system. First, the shikimate kinase gene (aroK) responsible for converting shikimate to the next step was disrupted to facilitate the accumulation of shikimate. Several genes encoding the shikimate bypass route, such as dehydroshikimate dehydratase (QsuB), pyruvate kinase (Pyk1), and quinate/shikimate dehydrogenase (QsuD), were disrupted sequentially. An artificial operon containing several shikimate pathway genes, including aroE, aroB, aroF, and aroG were overexpressed to maximize the glucose uptake and intermediate flux. The rationally designed shikimate-overproducing C. glutamicum strain grown in an optimized medium produced approximately 37.3 g/L of shikimate in 7-L fed-batch fermentation. Overall, rational cell factory design and culture process optimization for the microbial-based production of shikimate will play a key role in complementing traditional plant-derived shikimate production processes.

Background The effect of humeral component retroversion on clinical outcomes after reverse total shoulder arthroplasty (RTSA) is unclear. Intended retroversion intraoperatively may not produce the same retroversion of the humeral component postoperatively. Methods This retrospective study was conducted on consecutive patients who received RTSA using a single product with humeral lateralization at a targeted 25° of humeral retroversion from 2014 to 2019 with minimum 1-year clinical follow-up and postoperative computed tomography (CT). Forty-five patients were enrolled, and humeral component retroversion was measured three-dimensionally. Correlation and regression analyses were conducted between humeral retroversion and postoperative isometric strength and range of motion in forward flexion (FF), external rotation (ER), and internal rotation (IR). Group comparison between a ≤25° group and a >25° group was conducted as sub-analysis to verify possible confounders. Results The actual humeral retroversion was 21.7 ± 11.9°, and it was significantly correlated with postoperative FF [Pearson's correlation coefficient (PCC) = 0.464, P= .003], ER (PCC = 0.481, P = .002), and IR (PCC = 0.471, P = .002) strengths. Multivariable regression analysis showed that humeral retroversion was significantly associated with postoperative FF (Exp(B) = 0.492, P = .003), ER (Exp(B) = 0.336, P = .002), and IR (Exp(B) = 0.578, P = .002) strengths. Two groups in sub-analysis showed no significant difference in pre- or intraoperative variables other than humeral component retroversion. Some functional outcome scores including the Constant score, American Shoulder and Elbow Surgeons score, and activity scales were significantly higher in the >25° group. Conclusion Discrepancies between intraoperatively targeted humeral retroversion angle and actual postoperative angle after RTSA should be considered by operators and researchers. Increased humeral component retroversion than recommendation can yield acceptable outcomes and might be associated with higher postoperative strength, and possibly with better functional outcome after RTSA with humeral lateralization. Level of evidence Level III; Retrospective Comparative Study

Botulism is a neuroparalytic disease caused by a neurotoxin produced by Clostridium botulinum. This study aimed to genetically characterize C. botulinum strain isolated from the first case of infant botulism in Korea reported on June 17, 2019. We isolated C. botulinum strain CB-27 from a stool sample of the patient and analyzed the toxin types and toxin gene cluster compositions of the strain using a mouse bioassay, real-time PCR, and genome sequencing. Toxin gene cluster analysis showed that strain CB-27 possesses a C. botulinum neurotoxin type A harboring an unexpressed B gene. Although the nucleotide and amino acid sequences of toxin genes as well as the toxin gene cluster arrangements in strain CB-27 were identical to those of the known strain CDC_69094, the total nucleotide sequences of the toxin gene clusters of CB-27 differed from those of CDC_69094 by 0.47%, indicating genetic diversity of toxin gene clusters of CB-27 among other previously reported C. botulinum strains. To our knowledge, this is the first description of a C. botulinum strain with two separate toxin gene clusters in Korea.

IntroductionThe transcranial approach (TCA) has historically been used to remove craniopharyngiomas. Although the extended endoscopic endonasal approach (EEA) to these tumors has been more commonly accepted in the recent two decades, there is debate over whether this approach leads to better outcomes. The goal of this systematic review and meta-analysis was to more comprehensively understand the benefits and limitations of these two approaches in craniopharyngioma resection based on comparative studies.MethodsWe conducted a systematic literature search in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations using MEDLINE, EMBASE, and the Cochrane Library. A total of 448 articles were screened. Data were extracted and analyzed using proportional meta-analysis. Eight comparative studies satisfied the inclusion criteria. The extent of resection, visual outcomes, and postoperative complications such as endocrine dysfunction and cerebrospinal fluid (CSF) leakage were compared.Results and discussionEight studies, involving 376 patients, were included. Resection by EEA led to a greater rate of gross total resection (GTR) (odds ratio [OR], 2.42; p = 0.02; seven studies) with an incidence of 61.3% vs. 50.5% and a higher likelihood of visual improvement (OR, 3.22; p < 0.0001; six studies). However, TCA resulted in a higher likelihood of visual deterioration (OR, 3.68; p = 0.002; seven studies), and was related, though not significantly, to panhypopituitarism (OR, 1.39; p = 0.34; eight studies) and diabetes insipidus (OR, 1.14; p = 0.58; seven studies). Although TCA showed significantly lower likelihoods of CSF leakage (OR, 0.26; 95% confidence interval [CI], 0.10–0.71; p = 0.008; eight studies) compared to EEA, there was no significant difference in meningitis (OR, 0.92; 95% CI, 0.20–4.25; p = 0.91; six studies) between the two approaches. When both approaches can completely resect the tumor, EEA outperforms TCA in terms of GTR rate and visual outcomes, with favorable results in complications other than CSF leakage, such as panhypopituitarism and diabetes insipidus. Although knowledge of and competence in traditional microsurgery and endoscopic surgery are essential in surgical decision-making for craniopharyngioma treatment, when both approaches are feasible, EEA is associated with favorable surgical outcomes.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021234801.

Newborn hearing screening (NHS) has been covered by national health insurance since October 2018 in Korea. However, the results of the NHS are not reported due to the absence of a follow-up tracking system. This study analyzed the status and the predicted referral rates of NHS after the Korean national health insurance coverage by analyzing the National Health Insurance Service database in 2019 and 2020. The NHS coverage was 91.7% of total birth in 2019 and 92.1% in 2020. The predicted referral rate of NHS calculated by the duplicated NHS cases was 1.05% in 2019 and 0.99% in 2020. However, another predicted referral rate calculated by the number of diagnostic auditory brainstem responses (ABRs) performed was 1.44% in 2019 and 1.43% in 2020. The first NHS was performed within one day of birth for 96.5% of the babies and within three days of birth for 97%. However, diagnostic ABR was adequately performed within three months of birth for only 4.3%, while 82.3% performed the test after six months which delays appropriate intervention for hearing loss. National support such as national coordinators, follow-up tracking, and data management systems are needed for early hearing detection and intervention of newborns and infants in Korea.

Background and Objectives: The number of patients who undergo multiple operations on a knee is increasing. The objective of this study was to develop a deep learning algorithm that could detect 17 different surgical implants on plain knee radiographs. Materials and Methods: An internal dataset consisted of 5206 plain knee antero-posterior X-rays from a single, tertiary institute for model development. An external set contained 238 X-rays from another tertiary institute. A total of 17 different types of implants including total knee arthroplasty, unicompartmental knee arthroplasty, plate, and screw were labeled. The internal dataset was approximately split into a train set, a validation set, and an internal test set at a ratio of 7:1:2. You Only look Once (YOLO) was selected as the detection network. Model performances with the validation set, internal test set, and external test set were compared. Results: Total accuracy, total sensitivity, total specificity value of the validation set, internal test set, and external test set were (0.978, 0.768, 0.999), (0.953, 0.810, 0.990), and (0.956, 0.493, 0.975), respectively. Means ± standard deviations (SDs) of diagonal components of confusion matrix for these three subsets were 0.858 ± 0.242, 0.852 ± 0.182, and 0.576 ± 0.312, respectively. True positive rate of total knee arthroplasty, the most dominant class of the dataset, was higher than 0.99 with internal subsets and 0.96 with an external test set. Conclusion: Implant identification on plain knee radiographs could be automated using a deep learning technique. The detection algorithm dealt with overlapping cases while maintaining high accuracy on total knee arthroplasty. This could be applied in future research that analyzes X-ray images with deep learning, which would help prompt decision-making in clinics.

The process of designing streamlined workflows for developing microbial strains using classical methods from vast amounts of biological big data has reached its limits. With the continuous increase in the amount of biological big data, data-driven machine learning approaches are being used to overcome the limits of classical approaches for strain development. Here, machine learning-guided engineering of Deinococcus radiodurans R1 for high-yield production of lycopene was demonstrated. The multilayer perceptron models were first trained using the mRNA expression levels of the key genes along with lycopene titers and yields obtained from 17 strains. Then, the potential overexpression targets from 2,047 possible combinations were predicted by the multilayer perceptron combined with a genetic algorithm. Through the machine learning-aided fine-tuning of the predicted genes, the final-engineered LY04 strain resulted in an 8-fold increase in the lycopene production, up to 1.25 g/L from glycerol, and a 6-fold increase in the lycopene yield.

Abnormal vaginal colonisation can lead to adverse pregnancy outcomes such as preterm birth through intra-amniotic inflammation. Despite the concern, little is known about its risk factors and impact in pregnant women at high-risk for spontaneous preterm birth. Thus, we conducted this single-centre retrospective cohort study including 1381 consecutive women who were admitted to the high-risk pregnancy unit. The results of vaginal culture at admission were categorised according to the colonising organism: bacteria (Gram-negative or -positive) and genital mycoplasmas. Maternal baseline socioeconomic, and clinical characteristics, as well as pregnancy, delivery, and neonatal outcomes were compared according to the category. Maternal risk factors for Gram-negative colonisation included advanced maternal age, increased pre-pregnancy BMI, a greater number of past spontaneous abortions, earlier gestational age at admission, and IVF. Gram-positive colonisation was likewise associated with earlier gestational age at admission. Genital mycoplasmal colonisation was associated with a greater number of past induced abortions, a lower level of education completed, and a lower rate of multifetal pregnancy and IVF. The neonates from mothers with Gram-negative colonisation had a greater risk of NICU admission, proven early onset neonatal sepsis, and mortality. However, not Gram-positive bacteria or genital mycoplasma was directly associated with adverse pregnancy outcomes.

Cadmium (Cd) is a ubiquitous environmental pollutant with an exceptionally long biological half-life. The liver is a major organ for Cd metabolism, but the toxicity of Cd is unclear. This study sought to determine whether blood Cd (BCd) level (representing recent exposure [months] to Cd) was associated with liver function in Korean adults, both cross-sectionally and longitudinally. The baseline cross-sectional study involved 2,086 adults (male: 908, female: 1,178) in 2010−2011, and 503 of them (male: 207, female: 296) were followed up in 2014−2015. BCd was measured by graphite-furnace atomic absorption spectrometry, and liver function indices (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and γ-glutamyltransferase [GGT]) were determined. Liver damage was defined as an abnormal elevation of more than one liver function index. The geometric mean of BCd (1.07 µg/L) was higher in females than in males (1.16 vs. 0.96 µg/L). Liver function indices increased significantly in a dose-dependent manner according to the BCd levels, except for ALT in males, and were higher in males than in females. BCd level was also associated with the risk of liver damage in both sexes. No significant changes in BCd were observed between baseline and follow-up. The liver function indices in 2014−2015 were comparable to those in 2010−2011 in males, while ALT and GGT were significantly increased in 2014−2015 compared to 2010−2011 in females with relatively high BCd. These findings suggest that even a low level of environmental Cd exposure, short- and long-term, may affect liver function, and females appear more susceptible than males.

Lack of social activities is known to negatively impact cognitive functioning and increase risk of cognitive impairment, including dementia, among older adults.Coronavirus disease 2019 (COVID-19) stay-at-home orders implemented in the U.S. early during the pandemic were not found to negatively affect cognitive functioning of older adults.There may have been no severe, unintended consequences of the COVID-19 stay-at-home orders in terms of their impact on cognitive functioning and risk of dementia among older adults, lending further support to use of such orders.

Enhanced sampling methodologies modifying underlying Hamiltonians can be used for the systems with a rugged potential energy surface that makes it hard to observe convergence using conventional unbiased molecular dynamics (MD) simulations. We present CHARMM-GUI Enhanced Sampler, a web-based tool to prepare various enhanced sampling simulations inputs with user-selected collective variables (CVs). Enhanced Sampler provides inputs for the following nine methods: accelerated MD, Gaussian accelerated MD, conformational flooding, metadynamics, adaptive biasing force, steered MD, temperature replica exchange MD, replica exchange solute tempering 2, and replica exchange umbrella sampling for the method-implemented MD packages including AMBER, CHARMM, GENESIS, GROMACS, NAMD, and OpenMM. Users only need to select a group of atoms via intuitive web-implementation in order to define commonly used nine CVs of interest: center of mass based distance, angle, dihedral, root-mean-square-distance, radius of gyration, distance projected on axis, two types of angles projected on axis, and coordination numbers. The enhanced sampling methods are tested with several biological systems to illustrate their efficiency over conventional MD. Enhanced Sampler with carefully optimized system-dependent parameters will help users to get meaningful results from their enhanced sampling simulations.

We have developed efficient techniques to solve the first-time problems of Brownian motion. Based on a time-scale separation of recrossings, we show that Eyring's transmission coefficient ($\kappa$) equals to the one ($\kappa_\mathrm{V}$) corresponding to an absorbing boundary consistent with the transition state theory, which is greater than the one ($\kappa_\mathrm{K}$) derived by Kramers. We also propose methods for reaction rate determination by analyzing short-time trajectories from the barrier maximum, and discuss the relation to the reactive flux method and the significance of reaction coordinates., Comment: 6 pages, 5 figures