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Abstract This study explores Arctic warming's effect on Eurasia's temperature variability, notably the warm Arctic–cold Eurasia (WACE) pattern, and assesses seasonal prediction models' accuracy in capturing this phenomenon and its monthly variation. Arctic warming events are categorized into deep Arctic warming (DAW), shallow Arctic warming (SAW), warming aloft (WA), and no Arctic warming (NOAW), based on the temperatures at 2 m and 500 hPa in the Barents–Kara Sea. It is revealed that DAW events are significantly correlated with monthly cold temperature anomalies in East Asia, predominantly occurring in January–February, excluding December. This study evaluates two primary capabilities of seasonal prediction models: their proficiency in forecasting these Arctic warming events, particularly DAW, and their ability to replicate the spatial patterns associated with DAW. Some models demonstrated notable predictive skill for DAW events, with enhanced performance in January and February. Regarding spatial pattern reproduction, models showed limited alignment with the reference dataset over the Northern Hemisphere (above 25° N) in December, whereas a higher degree of concordance was observed in January–February. This indicates their capability in capturing the atmospheric circulation patterns associated with DAW, pointing to areas where model performance can be enhanced.

Abstract Type 2 diabetes (T2D) is known as one of the important risk factors for the severity and mortality of COVID-19. Here, we evaluate the impact of T2D and its genetic susceptibility on the severity and mortality of COVID-19, using 459,119 individuals in UK Biobank. Utilizing the polygenic risk scores (PRS) for T2D, we identified a significant association between T2D or T2D PRS, and COVID-19 severity. We further discovered the efficacy of vaccination and the pivotal role of T2D-related genetics in the pathogenesis of severe COVID-19. Moreover, we found that individuals with T2D or those in the high T2D PRS group had a significantly increased mortality rate. We also observed that the mortality rate for SARS-CoV-2-infected patients was approximately 2 to 7 times higher than for those not infected, depending on the time of infection. These findings emphasize the potential of T2D PRS in estimating the severity and mortality of COVID-19.

This study explores the phylogeny of Korean native black goats through analysis of their complete mitochondrial DNA. The National Institute of Animal Science has gathered genetic material on purebred goats from isolated regions such as Tongyeong, Dangjin, and Jangsu, and is actively breeding them on a national level. These populations, however, are small and exhibit high inbreeding rates, highlighting the urgent need to preserve genetic diversity. The haplotype diversity within this native group is 0.659, with 39 haplotypes identified. By contrast, including international breeds in the analysis increases the overall haplotype diversity to 0.925 with 203 haplotypes identified, highlighting the limited genetic diversity among native black goats. For phylogenetic assessment, a neighbor-joining tree and median-joining network were constructed using identified haplogroups (A, B, C, D, G, and F) from prior studies. The results pinpoint the native black goats as closely related to, but distinct from, Haplogroup A with a bootstrap value of 98, establishing them as a separate clade (A’). This supports the notion of a shared ancestry with various global populations. This research provides essential data on the origins and evolutionary history of Korean native black goats, supporting conservation and breeding efforts aimed at enhancing genetic diversity.

Genomic prediction (GP) has emerged an effective tool for addressing the many shortcomings of traditional selective breeding, thereby enhancing the selection process. In this study, we optimized GP methods using 5-fold cross-validation to estimate genome-estimated breeding values for the weight traits of olive flounder (Paralichthys olivaceus). To accomplish our goal, we determined the parentage of the target broodstock and the ability of 11 prediction models to predict the weight traits of 1.8-year-old olive flounders, which were genotyped using a 70 K single nucleotide polymorphism (SNP) array. Moreover, our optimization efforts toward the predictive ability of genomic best linear unbiased prediction (GBLUP), Bayesian B (BB), and random forest (RF) methods encompassed changes in various aspects such as fixed effects, SNP quantity, population size, and phenotypic data collected at different fish ages. Additionally, we assessed the predictive ability for the total length and body depth of fish using GBLUP, BB, and RF. Among the 11 prediction methods used in this study, the BB (0.675), Elastic Net (0.679), and RF (0.698) methods exhibited the highest predictive abilities, whereas the GBLUP (0.637) method demonstrated the lowest. Incorporating information regarding fish sex as a fixed effect substantially improved the predictive ability of GBLUP and BB. For mean models, utilizing 3000–5000 random SNP markers resulted in a higher predictive ability, similar to that obtained using 50,000 SNPs. Increasing the population size reduced the standard deviation of the predictive ability. Notably, phenotypic records from 1.8-year-old fish exhibited a significantly higher predictive ability than those from the other age groups. Furthermore, GBLUP, BB, and RF provided higher predictive abilities for length (0.655–0.852) and body depth (0.665–0.861). These findings may significantly shape future olive flounder genomic selection programs and offer valuable insights into GP in aquaculture.

The effect of invertebrates like termites and beetle larvae on dead wood could be time-dependent due to changes in wood traits and invertebrate species composition over time. This study assessed changes in the impact of termites and beetle larvae on dead wood decomposition in two tree species, Pinus densiflora and Quercus acutissima, in South Korea over a 6-year period (2016–2022). Wood samples were prepared, with half of them encased in a stainless-steel mesh to prevent access by invertebrates larger than 0.26 mm. These samples were placed in three regions representative of different environments in South Korea (southern, eastern, and western). Significant variations in the mass loss of dead wood were observed based on the tree species, region, and time (p < 0.05). The mean standardized invertebrate effect, assessed with Hedges’ d and a 95% confidence interval, was 0.83 ± 2.19 for P. densiflora and 1.08 ± 2.26 for Q. acutissima. Termites were found in the southern and western regions, with the highest invertebrate effect after two years. Our results indicate that the influence of invertebrates, especially termites, on dead wood decomposition could be most significant during the initial decomposition stages, as noted in the southern region of this research.

Lysozymes are well-known antibacterial enzymes that mainly target the peptidoglycan layer of the bacterial cell wall. Animal lysozymes are mainly categorized as g-type, c-type, and i-type based on protein sequence and structural differences. In this study, c-type (AcLysC) and g-like-type (AcLysG-like) lysozymes from Amphiprion clarkii were characterized in silico via expressional and functional approaches. According to in silico analysis, open reading frames of AcLysC and AcLysG-like were 429 bp and 570 bp, respectively, encoding the corresponding polypeptide chains with 142 and 189 amino acids. Elevated expression levels of AcLysC and AcLysG-like were observed in the liver and the heart tissues, respectively, as evidenced by quantitative real-time polymerase chain reaction assays. AcLysC and AcLysG-like transcript levels were upregulated in gills, head kidney, and blood cells following experimental immune stimulation. Recombinant AcLysC exhibited potent lytic activity against Vibrio anguillarum, whereas recombinant AcLysG-like showed remarkable antibacterial activity against Vibrio harveyi and Streptococcus parauberis, which was further evidenced by scanning electron microscopic imaging of destructed bacterial cell walls. The findings of this study collectively suggest the potential roles of AcLysC and AcLysG-like in host immune defense.

Zinc oxide nanoparticles (ZnO NPs) have been widely used in various materials including sunscreens, cosmetics, over-the-counter topical skin products, and pigments. As traces of the used ZnO NPs have been found in the kidney, it is crucial to uncover their potential risks. The aim of this study is to elucidate detrimental effects of ZnO NPs and the molecular mechanism behind their renal toxicity. Cytotoxic effects were measured by MTT assay after HK2 cells were exposed to ZnO NPs for 24 h and IC50 value was determined. ROS and intracellular Zn2+ levels were detected by flow cytometry, and localization of Zn2+ and lysosome was determined by confocal microscopy. Occurrence of autophagy and detection of autophagic flux were determined by Western blot and confocal microscopy, respectively. We performed unpaired student t test for two groups, and one-way ANOVA with Tukey’s post hoc for over three groups. ZnO NPs induced cell death in human renal proximal tubule epithelial cells, HK2. Cytosolic Zn2+ caused autophagy-mediated cell death rather than apoptosis. Cytosolic Zn2+ processed in lysosome was released by TRPML1, and inhibition of TRPML1 significantly decreased autophagic flux and cell death. The findings of this study suggest that ZnO NPs strongly induce autophagy-mediated cell death in human kidney cells. Controlling TRPML1 can be potentially used to prevent the kidney from ZnO NPs-induced toxicity.

Chirality, defined as “a mirror image,” is a universal geometry of biological and nonbiological forms of matter. This geometry of molecules determines how they interact during their assembly and transport. With the development of nanotechnology, many nanoparticles with chiral geometry or chiroptical activity have emerged for biomedical research. The mechanisms by which chirality originates and the corresponding synthesis methods have been discussed and developed in the past decade. Inspired by the chiral selectivity in life, a comprehensive and in-depth study of interactions between chiral nanomaterials and biological systems has far-reaching significance in biomedicine. Here, we investigated the effect of the chirality of nanoscale drug carriers, graphene quantum dots (GQDs), on their transport in tumor-like cellular spheroids. Chirality of GQDs (L/D-GQDs) was achieved by the surface modification of GQDs with L/D-cysteines. As an in-vitro tissue model for drug testing, cellular spheroids were derived from a human hepatoma cell line (i.e., HepG2 cells) using the Hanging-drop method. Our results reveal that the L-GQDs had a 1.7-fold higher apparent diffusion coefficient than the D-GQDs, indicating that the L-GQDs can enhance their transport into tumor-like cellular spheroids. Moreover, when loaded with a common chemotherapy drug, Doxorubicin (DOX), via π-π stacking, L-GQDs are more effective as nanocarriers for drug delivery into solid tumor-like tissue, resulting in 25% higher efficacy for cancerous cellular spheroids than free DOX. Overall, our studies indicated that the chirality of nanocarriers is essential for the design of drug delivery vehicles to enhance the transport of drugs in a cancerous tumor.

Background: The lysosome has emerged as a promising target for overcoming chemoresistance, owing to its role in facilitating the lysosomal sequestration of drugs. The lysosomal calcium channel TRPML1 not only influences lysosomal biogenesis but also coordinates both endocytosis and exocytosis. This study explored the modulation of cisplatin sensitivity by regulating TRPML1-mediated lysosomal exocytosis and identified the metabolomic profile altered by TRPML1 inhibition. Methods: We used four types of ovarian cancer cells: two cancer cell lines (OVCAR8 and TOV21G) and two patient-derived ovarian cancer cells. Metabolomic analyses were conducted to identify altered metabolites by TRPML1 inhibition. Results: Lysosomal exocytosis in response to cisplatin was observed in resistant cancer cells, whereas the phenomenon was absent in sensitive cancer cells. Through the pharmacological intervention of TRPML1, lysosomal exocytosis was interrupted, leading to the sensitization of resistant cancer cells to cisplatin treatment. To assess the impact of lysosomal exocytosis on chemoresistance, we conducted an untargeted metabolomic analysis on cisplatin-resistant ovarian cancer cells with TRPML1 inhibition. Among the 1446 differentially identified metabolites, we focused on 84 significant metabolites. Metabolite set analysis revealed their involvement in diverse pathways. Conclusions: These findings collectively have the potential to enhance our understanding of the interplay between lysosomal exocytosis and chemoresistance, providing valuable insights for the development of innovative therapeutic strategies.

Abstract Background Photothermal therapy (PTT) is an emerging anti-cancer therapeutic strategy that generates hyperthermia to ablate cancer cells under laser irradiation. Gold (Au) coated liposome (AL) was reported as an effective PTT agent with good biocompatibility and excretory property. However, exposed Au components on liposomes can cause instability in vivo and difficulty in further functionalization. Results Herein, we developed a theranostic dual-layered nanomaterial by adding liposomal layer to AL (LAL), followed by attaching polyethylene glycol (PEG) and radiolabeling. Functionalization with PEG improves the in vivo stability of LAL, and radioisotope labeling enables in vivo imaging of LAL. Functionalized LAL is stable in physiological conditions, and 64Cu labeled LAL (64Cu-LAL) shows a sufficient blood circulation property and an effective tumor targeting ability of 16.4%ID g−1 from in vivo positron emission tomography (PET) imaging. Also, intravenously injected LAL shows higher tumor targeting, temperature elevation in vivo, and better PTT effect in orthotopic breast cancer mouse model compared to AL. The tumor growth inhibition rate of LAL was 3.9-fold higher than AL. Conclusion Based on these high stability, in vivo imaging ability, and tumor targeting efficiency, LAL could be a promising theranostic PTT agent. Graphic Abstract

Abstract Radiotherapy is an essential step during the treatment of glioblastoma multiforme (GBM), one of the most lethal malignancies. The survival in patients with GBM was improved by the current standard of care for GBM established in 2005 but has stagnated since then. Since GBM is a radioresistant malignancy and the most of GBM recurrences occur in the radiotherapy field, increasing the effectiveness of radiotherapy using high-Z metal nanoparticles (NPs) has recently attracted attention. This review summarizes the progress in radiotherapy approaches for the current treatment of GBM, the physical and biological mechanisms of radiosensitization through high-Z metal NPs, and the results of studies on radiosensitization in the in vitro and in vivo GBM models using high-Z metal NPs to date.

Purpose: This study was conducted to analyze physical symptom-related and life-style factors affecting suicidal ideation of senior grade students in elementary school. Methods: Physical symptom-related and life-style factors were used to investigate suicidal ideation among 663 elementary school students. From February 11 to 15, 2018, data were collected using a structured questionnaire and analyzed using the x2 test, Pearson correlation analysis, and logistic regression analysis in SPSS for Windows version 22.0. Results: The factors affecting suicidal ideation were gender, family structure, economic status, academic performance, exposure to school violence during the past year, physical symptoms, drinking experience, smoking experience, sleeping time, and ramen noodle consumption. The regression analysis showed that exposure to school violence during the past year (odds ratio [OR]: 102.99, 95% confidence interval [CI]: 51.19~207.19, p=.001), number of physical symptoms (OR: 1.25, 95% CI: 1.12~1.41, p=.001), drinking experience (OR: 3.17, 95% CI: 1.66~6.06, p=.001), and game and internet usage time (OR: 2.08, 95% CI: 1.08~4.01, p=.029) affected suicidal ideation. Conclusion: This study revealed that physical symptoms and life-style significantly influenced suicidal ideation. Therefore, interventions to reduce suicidal ideation in children must focus on improving children’s physical symptoms and life-style.

Higher plants in terrestrial environments face to numerous unpredictable environmental challenges, which lead to a significant impact on plant growth and development. In particular, the climate change caused by global warming is causing drought stress and rapid desertification in agricultural fields. Many scientific advances have been achieved to solve these problems for agricultural and plant ecosystems. In this review, we handled recent advances in our understanding of the physiological changes and strategies for plants undergoing drought stress. The activation of ABA synthesis and signaling pathways by drought stress regulates root development via the formation of complicated signaling networks with auxin, cytokinin, and ethylene signaling. An abundance of intrinsic soluble sugar, especially trehalose-6-phosphate, promotes the SnRK-mediated stress-resistance mechanism. Suberin deposition in the root endodermis is a physical barrier that regulates the influx/efflux of water and nutrients through complex hormonal and metabolic networks, and suberization is essential for drought-stressed plants to survive. It is highly anticipated that this work will contribute to the reproduction and productivity improvements of drought-resistant crops in the future.

Purpose: This study aimed to evaluate the effects of an empowerment program on maternal stress, anxiety, depression and parenting confidence. Methods: A total of 44 mothers of preterm infants were assigned into an experimental or a control group (n=22 each). The experimental group received the usual nursing care and 7 sessions of an empowerment program. The control group only received the usual care. The program was implemented from June to December, 2016 in the neonatal intensive care unit of K university-affiliated hospital in Daegu, Korea. The outcome variables measured were parental stress (PSS: NICU), anxiety (STAI), depression (CES-D) and parenting confidence. Data were analyzed using t-test or repeated measures ANOVA. Results: Scores for both parental stress (t=3.07 p=.004) and depression (F=3.76, p=.26) were significantly lower in the experimental group than in the control group. However, there were no significant differences in anxiety between the groups (F=0.79, p=.505). Parenting confidence scores (F=9.05, p=.001) were significantly higher in the experimental group than in the control group. Conclusion: A maternal empowerment program can be an effective means of reducing parental stress and depression as well as enhancing parenting confidence, for mothers of preterm infants.

Purpose: In this study factors affecting quality of life in mothers who have children with precocious puberty were identified. Methods: The participants were 102 mothers of children with precocious puberty. From September 12 to September 30, 2016, data were collected using a structured questionnaire and analyzed using SPSS/WIN 22.0. Results: Regression analysis showed that the model’s explanatory power was 45%(F=28.71, p

Background/Aims Transient elastography (TE) has been proposed as a promising noninvasive alternative to hepatic venous pressure gradient (HVPG) for detecting portal hypertension (PH). However, previous studies have yielded conflicting results. We gathered evidence from literature on the clinical usefulness of TE versus HVPG for assessing PH. Methods We conducted a systematic review by searching databases for relevant literature evaluating the clinical usefulness of non-invasive TE for assessing PH in patients with cirrhosis. A literature search in Ovid Medline, EMBASE and the Cochrane Library was performed for all studies published prior to December 30, 2015. Results Eight studies (1,356 patients) met our inclusion criteria. For the detection of PH (HVPG ≥6 mmHg), the summary sensitivity and specificity were 0.88 (95% confidence interval [CI] 0.86-0.90) and 0.74 (95% CI 0.67-0.81), respectively. Regarding clinically significant PH (HVPG ≥10 mmHg), the summary sensitivity and specificity were 0.85 (95% CI 0.63-0.97) and 0.71 (95% CI 0.50-0.93), respectively. The overall correlation estimate of TE and HVPG was large (0.75, 95% CI: 0.65; 0.82, P

Background/AimsWe identified reports in the literature regarding the diagnostic accuracy of hepatic vein arrival time (HVAT) measured by contrast-enhanced ultrasonography (CEUS) to assess hepatic fibrosis in cirrhosis.Methods : The Ovid MEDLINE, Embase, and Cochrane databases were searched for all studies published up to 23 July 2015 that evaluated liver status using CEUS and liver biopsy (LB). The QUADAS-II (quality assessment of diagnostic accuracy studies-II) was applied to assess the internal validity of the diagnostic studies. Selected studies were subjected to a meta-analysis with MetaDisc 1.4 and RevMan 5.3.Results : A total of 12 studies including 844 patients with chronic liver disease met our inclusion criteria. The overall summary sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of the HVAT measured by CEUS for the detection of cirrhosis compared to LB were 0.83 (95% confidence interval [CI], 0.77 to 0.89), 0.75 (95% CI, 0.69 to 0.79), 3.45 (95% CI, 1.60 to 7.43), and 0.28 (95% CI, 0.10 to 0.74), respectively. The summary diagnostic odds ratio (random effects model) was 15.23 (95% CI, 3.07 to 75.47), the summary receiver operator characteristics area under the curve was 0.74 (standard error [SE]=0.14), and the index Q was 0.69 (SE=0.11).Conclusion : sBased on a systematic review, the measurement of HVAT by CEUS exhibited an increased accuracy and correlation for the detection of cirrhosis.

Introduction. The soluble urokinase-type plasminogen activator receptor (suPAR) has been found to be elevated in primary focal segmental glomerulosclerosis (pFSGS). However, its usefulness as a biomarker for FSGS remains controversial. We conducted a meta-analysis aiming at investigating the significance of suPAR in diagnosing pFSGS. Methods. Electronic databases (PubMed and EMBASE) were searched to identify studies comparing suPAR levels in FSGS patients and controls, from the earliest available date to May 1, 2018. A random-effects model with standardized mean difference (SMD) was used for meta-analyses. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Results. A total of 187 articles were screened, and the final analysis included 13 articles. In comparison to healthy controls, serum suPAR levels were significantly increased in pFSGS patients (SMD, 1.07, 95% confidence interval (CI) 0.65 to 1.48; participants=814; studies=9, I2=85%). Higher suPAR levels were also found in patients with pFSGS compared to those with minimal change disease (SMD 0.53, 95% CI 0.22 to 0.84). Of note, such a difference was not found in pediatric groups (SMD 0.42, 95% CI -0.13 to 0.96) while it was more evidently noted in adult patients (SMD 1.32, 95% CI 0.90 to 1.74). Serum suPAR levels did not differ between pFSGS patients in remission compared to those in active proteinuric state (SMD 0.29, 95% CI -0.30 to 0.88). Comparison with membranous nephropathy and IgA nephropathy showed no significant difference. Conclusions. Our meta-analysis demonstrated that, in comparison to both healthy controls and controls with minimal change disease, suPAR levels were significantly higher in adult patients with pFSGS. suPAR levels did not differ between pFSGS patients during the initial period of diagnosis and those in remission.

Sarcopenia is a common syndrome in chronic diseases such as liver cirrhosis. The association between sarcopenia and outcomes, such as complications and survival has recently been described in various patient groups. However, study results remain inconclusive. Therefore, the aim of this study was to systematically review the impact of sarcopenia on outcome in patients with cirrhosis.We conducted a systematic review (SR) and meta-analysis (MA) on the impact of sarcopenia on outcome in liver cirrhosis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Of the 312 studies identified, 20 were eligible according to our inclusion criteria. Most of the studies used CT to diagnose sarcopenia. Two studies used bioelectrical impedance analysis (BIA), 10 studies used skeletal muscle index (SMI) and 8 studies used total psoas muscle area (TPA). Seven studies included Asian participants and the remaining 13 studies included Western participants. The prevalence rate of sarcopenia among participants was mean 48.1%, and appeared more among men with a rate of 61.6% whereas the rate was 36% for women. With respect to clinical outcomes, patients with sarcopenia had poorer survival rates and an increased risk of complications such as infection compared to those without sarcopenia. According to the analysis of race subgroup, Asians had a HR 2.45 (95% confidence interval (CI) = 1.44-4.16, P = 0.001) of mortality whereas Westerners had a HR 1.45 (95% CI = 1.002-2.09, P

A systematic review (SR) is a research methodology that involves a comprehensive search for and analysis of relevant studies on a specific topic. A strict and objective research process is conducted that comprises a systematic and comprehensive literature search in accordance with predetermined inclusion/exclusion criteria, and an assessment of the risk of bias of the selected literature. SRs require a multidisciplinary approach that necessitates cooperation with clinical experts, methodologists, other experts, and statisticians. A meta-analysis (MA) is a statistical method of quantitatively synthesizing data, where possible, from the primary literature selected for the SR. Review articles differ from SRs in that they lack a systematic methodology such as a literature search, selection of studies according to strict criteria, assessment of risk bias, and synthesis of the study results. The importance of evidence-based medicine (EBM) in the decision-making for public policy has recently been increasing thanks to the realization that it should be based on scientific research data. SRs and MAs are essential for EBM strategy and evidence-based clinical practice guidelines. This review addresses the current trends in SRs and MAs in the field of hepatology via a search of recently published articles in the Cochrane Library and Ovid-MEDLINE.

Background/AimsWe compared the cirrhosis-prediction accuracy of an ultrasonographic scoring system (USSS) combining six representative sonographic indices with that of liver stiffness measurement (LSM) by transient elastography, and prospectively investigated the correlation between the USSS score and LSM in predicting cirrhosis.MethodsTwo hundred and thirty patients with chronic liver diseases (187 men, 43 women; age, 50.4±9.5 y, mean±SD) were enrolled in this prospective study. The USSS produces a combined score for nodularity of the liver surface and edge, parenchyma echogenicity, presence of right-lobe atrophy, spleen size, splenic vein diameter, and abnormality of the hepatic vein waveform. The correlations of the USSS score and LSM with that of a pathological liver biopsy (METAVIR scoring system: F0-F4) were evaluated.ResultsThe mean USSS score and LSM were 7.2 and 38.0 kPa, respectively, in patients with histologically overt cirrhosis (F4, P=0.017) and 4.3 and 22.1 kPa in patients with fibrotic change without overt cirrhosis (F0-F3) (P=0.025). The areas under the receiver operating characteristic (ROC) curves of the USSS score and LSM for F4 patients were 0.849 and 0.729, respectively. On the basis of ROC curves, criteria of USSS ≥6: LSM ≥17.4 had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 89.2%:77.6%, 69.4%:61.4%, 86.5%:83.7%, 74.6%:51.9% and 0.83:0.73, respectively, in predicting F4.ConclusionsThe results indicate that this USSS has comparable efficacy to LSM in the diagnosis of cirrhosis.