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Jwa-Kyung Kim,1 Young Rim Song,1 Young-Jun Kwon,2 Hyung Jik Kim,1 Sung Gyun Kim,1 Young-Su Ju21Department of Internal Medicine, Kidney Research Institute, 2Department of Occupational and Environmental Medicine, Hallym University Sacred Heart Hospital, Anyang-si, South KoreaBackground: With increasing age, body fat increases and muscle mass reduces. Even people with a normal weight may have a higher percentage of body fat. The aim of this study is to investigate the association between increased body fat and renal function decline (RFD) in the general elderly population with normal or mildly impaired renal function.Method: We conducted a prospective study of 615 healthy individuals in the general Korean population aged ≥60 years who participated in two health screening check-ups separated by a 4-year period. Obesity was defined as the highest sex-specific tertiles of the percentage body fat (PBF). The main outcome was changes of estimated glomerular filtration rate (eGFR) during the 4 years. Significant RFD was defined as a decrease of eGFR over the upper quartile (≤-2.1% per year). Results: The mean age was 67.2±6.6 years. The median value of the absolute decline in the eGFR and the percent change was -3.0 mL/minute/1.73 m2 and -0.87%/year in men and -3.1 mL/minute/1.73 m2 and -0.89%/year in women, respectively. When stratified by sex-specific PBF tertiles, pronounced differences were observed in both sexes; those at the highest tertile of PBF showed the greatest decline in eGFR. Even after adjustments for traditional risk factors of RFD, PBF was independently associated with eGFR changes (ß=-0.181; P

HER2 antagonists remain the cornerstone of therapy for patients with HER2-positive breast cancer. This study introduces a novel small-molecule inhibitor of DNA methyltransferase 1 (DNMT-1), referred to as DI-1, designed to synergize with HER2 antagonists in treating HER2-positive breast cancer cells. Clinical data reveal a negative correlation between DNMT-1 expression and PTEN levels, and a positive correlation with the methylation rates of PTEN's promoter. In experiments with SKBR3 and BT474 cells, DI-1 effectively reduced the methylation of PTEN's promoter region, thereby upregulating PTEN expression. This upregulation, in turn, enhanced the cells' sensitivity to HER2 antagonists, indicating that DI-1's mechanism involves inhibiting DNMT-1's recruitment to PTEN's promoter region. Consequently, by increasing PTEN expression, DI-1 amplifies the sensitivity of HER2-positive breast cancer cells to treatment, suggesting its potential as a promising therapeutic strategy in this context., Competing Interests: Declarations Ethics approval and consent to participate The human ethics and research ethics committees of Tianjin Medical University Cancer Institute and Hospital approved the study (Approval no. bc2020176). Written informed consent was obtained from the patients for the collection and use of clinical specimens in this study and all the relevant experiments were conducted in accordance with the Declaration of Helsinki (World Health Organization). Competing interests The authors declare no competing interests. All co-authors confirm that all methods were carried out in accordance with relevant guidelines and regulations. All co-authors confirm that the informed consent was obtained from all subjects and/or their legal guardian(s)., (© 2024. The Author(s).)

Dyskalemia is a common electrolyte abnormality. Since dyskalemia can cause fatal arrhythmias and cardiac arrest in severe cases, it is crucial to monitor serum potassium (K + ) levels on time. We developed deep learning models to detect hyperkalemia (K +  ≥ 5.5 mEq/L) and hypokalemia (K +  < 3.5 mEq/L) from electrocardiograms (ECGs), which are noninvasive and can be quickly measured. The retrospective cohort study was conducted at two hospitals from 2006 to 2020. The training set, validation set, internal testing cohort, and external validation cohort comprised 310,449, 15,828, 23,849, and 130,415 ECG-K + samples, respectively. Deep learning models demonstrated high diagnostic performance in detecting hyperkalemia (AUROC 0.929, 0.912, 0.887 with sensitivity 0.926, 0.924, 0.907 and specificity 0.706, 0.676, 0.635 for 12-lead, limb-lead, lead I ECGs) and hypokalemia (AUROC 0.925, 0.896, 0.885 with sensitivity 0.912, 0.896, 0.904 and specificity 0.790, 0.734, 0.694) in the internal testing cohort. The group predicted to be positive by the hyperkalemia model showed a lower 30-day survival rate compared to the negative group (p < 0.001), supporting the clinical efficacy of the model. We also compared the importance of ECG segments (P, QRS, and T) on dyskalemia prediction of the model for interpretability. By applying these models in clinical practice, it will be possible to diagnose dyskalemia simply and quickly, thereby contributing to the improvement of patient outcomes., (© 2024. The Author(s).)

As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry., (© 2024 Wiley-VCH GmbH.)

The purpose of this study was to evaluate the quantitative computed tomography (CT) volumetry and densitometry and in pediatric patients with pectus excavatum (PE). We measured pectus index (PI) and separated inspiratory and expiratory lung volumes and densities. We obtained the total lung volume (TLV) and mean lung density (MLD) during inspiration and expiration, and the ratio of end expiratory to inspiratory volume (E/I volume) and MLD (E/I density) were calculated. The difference between inspiratory and end expiratory volume (I-E volume) and MLD (I-E density) were also calculated. A total of 199 patients, including 164 PE patients and 35 controls, were included in this study. The result shows that the PE group had lower inspiratory TLV (mean, 2670.76±1364.22 ml) than the control group (3219.57±1313.87 ml; p = 0.027). In the PE group, the inspiratory (-787.21±52.27 HU vs. -804.94±63.3 HU) and expiratory MLD (-704.51±55.41 HU vs. -675.83±64.62 HU) were significantly lower than the indices obtained from the control group (p = 0.006). In addition, significantly lower values of TLV and MLD difference and higher value of TLV and MLD ratio were found in the PE group (p <0.0001). PE patients were divided into severe vs. mild groups based on the PI cutoff value of 3.5. The inspiratory MLD and TLV ratio in the severe PE group were lower than those in the mild PE group, respectively (p <0.05). In conclusion, quantitative pulmonary evaluation through CT in pediatric PE patients may provide further information in assessing the functional changes in lung parenchyma as a result of chest wall deformity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Song, Im. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Network pharmacology has emerged as a powerful tool to understand the therapeutic effects and mechanisms of natural products. However, there is a lack of comprehensive evaluations of network-based approaches for natural products on identifying therapeutic effects and key mechanisms., Purpose: We systematically explore the capabilities of network-based approaches on natural products, using Panax ginseng as a case study. P. ginseng is a widely used herb with a variety of therapeutic benefits, but its active ingredients and mechanisms of action on chronic diseases are not yet fully understood., Methods: Our study compiled and constructed a network focusing on P. ginseng by collecting and integrating data on ingredients, protein targets, and known indications. We then evaluated the performance of different network-based methods for summarizing known and unknown disease associations. The predicted results were validated in the hepatic stellate cell model., Results: We find that our multiscale interaction-based approach achieved an AUROC of 0.697 and an AUPR of 0.026, which outperforms other network-based approaches. As a case study, we further tested the ability of multiscale interactome-based approaches to identify active ingredients and their plausible mechanisms for breast cancer and liver cirrhosis. We also validated the beneficial effects of unreported and top-predicted ingredients, in cases of liver cirrhosis and gastrointestinal neoplasms., Conclusion: our study provides a promising framework to systematically explore the therapeutic effects and key mechanisms of natural products, and highlights the potential of network-based approaches in natural product research., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (© 2024 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Micro/nanomotors (MNMs) emerge as a vital candidate for biosensing due to its nano-size structure, high surface-to-area ratio, directional mobility, biocompatibility, and ease of functionalization, therefore being able to detect objects with high efficiency, precision, and selectivity. The driving mode, nanostructure, materials property, preparation technique, and biosensing applications have been thoroughly discussed in publications. To promote the MNMs-based biosensors from in vitro to in vivo, it is necessary to give a comprehensive discussion from the perspective of sensing performances enhancement. However, until now, there is few reviews dedicated to the systematic discussion on the multiple performance enhancement schemes and the current challenges of MNMs-based biosensors. Bearing it in mind and based on our research experience in this field, we summarized the enhancement methods for biosensing properties such as sensitivity, selectivity, detection time, biocompatibility, simplify system operation, and environmental availability. We hope that this review provides the readers with fundamental understanding on performance enhancement schemes for MNMs-based biosensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: A patent vascular access (VA) is a lifeline for hemodialysis (HD) patients. However, vascular access is prone to thrombosis, which, if left untreated, can lead to permanent VA loss and increased mortality. Neutrophil extracellular traps (NETs) are known to be involved in intravascular thrombosis. We evaluated the relationship between NETs and VA thrombosis and their impact on VA prognosis., Methods: A total of 189 patients with VA flow problems were enrolled. Among these, 93 patients underwent percutaneous transluminal angioplasty (PTA) for stenosis, and 96 patients underwent PTA with thrombectomy for thrombosis. Plasma nucleosome, myeloperoxidase-DNA complex, and von Willebrand factor (vWF) were measured as markers of circulating NETs and thrombosis risk, respectively. The primary outcome was permanent VA loss and the secondary outcome was recurrent thrombotic occlusion within 6 months. In addition, the presence of NETs in thrombi was evaluated by histopathological analysis., Results: Circulating nucleosome levels were closely associated with plasma vWF levels (r = 0.172, p = 0.025), and both were higher in thrombectomy cases than in PTA alone cases (nucleosome; 0.83 ± 0.70 vs. 0.35 ± 0.26, p < 0.001, vWF: 9.0 ± 7.6 vs. 7.3 ± 6.2, p = 0.038). The highest quartile of nucleosomes (Q4) was associated with an 18-fold increased rate of access thrombotic occlusion (p < 0.001). In addition, multivariate analysis showed that the rates of permanent access loss (HR 2.77, 95 % CI 1.35-5.77) and recurrent thrombosis (HR 2.35, 95 % CI 1.22-4.54) were much higher in patients with the Q4 nucleosome group than in those with Q1-3. In addition, higher neutrophil infiltration and NET expression in thrombi were also associated with poor VA prognosis., Conclusions: Higher levels of circulating NETs and the amount of NET expression in thrombi may be associated with VA thrombosis and poor VA outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent studies have highlighted the positive effects of Kaempferol (KP), including its anti-inflammatory and antioxidant properties. However, its impact on oxidative damage induced by heavy metals and pro-inflammatory mediators, such as arachidonic acid (AA), has not yet been identified. Our objective was to specifically evaluate liver damage due to AA + iron-induced oxidative stress, both in vitro and in vivo. In HepG2 cells, KP activated the AMP-activated protein kinase (AMPK), suggesting a hepatoprotective effect through AMPK inhibition, as assessed by immunoblot and FACS analysis (EC 50  = 10 μM). KP also stimulated autophagy, a degradation process that eliminates aged, damaged, and unnecessary components, via mTOR inhibition and ULK1 phosphorylation. This activation was further validated by the upregulation of autophagy-related genes (ATG5) and Beclin-1, along with the conversion of LC3BI to LC3BII. Ferroptosis, a non-apoptotic type of cell death characterized by oxidative stress from the production of reactive oxygen species (ROS) and excessive iron accumulation, was linked to the activation of autophagy, as confirmed through the protein expression of deferoxamine (DFO) and ferrostatin-1 (Fer-1), the representative ferroptosis inhibitors (positive controls). In mice, oral administration of KP demonstrated protective effects against CCl 4 -induced hepatotoxicity. In conclusion, KP provides hepatoprotective effects against oxidative stress induced by AA + iron treatment in vitro and CCl 4 treatment in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

In the 3D printing industry, photopolymerization-based 3D printing is considered to have the characteristics of high printing accuracy and mature technology. Therefore, it is of wide concern in industrial application and academic research. With the rapid development of photopolymerization-based technology, photopolymerization-based plastic waste will inevitably be produced in the process of product manufacturing and use. This kind of plastic waste is a new type of organic solid waste with an incalculable growth rate, and its impact on the environment is difficult to predict. Based on available research results, the latest research progress of sources, disposal technologies, and environmental impact of photopolymerization-based plastic waste were summarized and analyzed. The results revealed that the photopolymerization-based plastic waste was covalently crosslinked with thermosetting plastic. It had relatively higher activation energy and photo-sensitive chromogenic groups. There were some potential hazards to the environment and biosome caused by the raw material, printing process, and waste disposal process of photopolymerization-based plastic. Therefore, prospects and suggestions were proposed for the possibility of future disposal of photopolymerization-based plastic waste, in order to provide a reference for developing the photopolymerization-based 3D printing industry.

Chronic kidney disease (CKD) and Alzheimer's disease (AD) are common chronic diseases in the elderly population. Although a relationship between CKD and the occurrence of AD has been proposed, previous research results have been disputed, and further investigation is necessary to confirm this relationship. In this longitudinal follow-up study, we examined data from the Korean National Health Insurance Service-Health Screening Cohort, consisting of 15,756 individuals with CKD and 63,024 matched controls aged ≥40 years who received health check-ups between 2002 and 2019. Overlap-weighted Cox proportional hazard regression models were exploited to calculate hazard ratios (HRs) for the association between CKD and AD. During the monitoring period, individuals with CKD had a greater incidence of AD than those without CKD (15.80 versus 12.40 per 1000 person years). After accounting for various factors, CKD was significantly associated with a 1.14-fold increased likelihood of developing AD, with a 95% confidence interval ranging from 1.08 to 1.20. In subgroup analysis, this relationship persisted irrespective of age (≥70 or <70), sex, income, smoking status, alcohol consumption, place of residence, or fasting blood glucose level. Additionally, the association between CKD and AD was still evident among patients who were overweight or obese, those with normal blood pressure or cholesterol levels, and those without any other health conditions or with a CCI score of ≥2. These results suggest that CKD could increase the probability of developing AD in the Korean adult population irrespective of demographic or lifestyle conditions. This may make it challenging to predict AD in patients with CKD, emphasizing the importance of frequent AD screening and management.

Obesity is a common health problem in peritoneal dialysis (PD) patients and causes high serum ferritin levels. However, mixed results have been reported on whether serum ferritin levels affect the prognosis of PD patients. We investigated the effect of increased adiposity on ferritin levels and its association with mortality in 350 well-nourished PD patients. Body composition was measured using a portable whole-body bioimpedance spectroscope, and clinical determinants of high ferritin levels were evaluated. High ferritin levels (≥600 ng/mL) were observed in 63 (18.0%) patients. Patients with high ferritin levels had a significantly higher body fat percentage and a lower lean tissue index than patients with low or normal ferritin levels. During a median follow-up of 30 months, there were 65 deaths. Ferritin ≥ 600 ng/mL was associated with significantly higher all-cause mortality compared with 200-600 ng/mL of ferritin. Multivariate analysis showed that high ferritin levels were significantly associated with a higher percentage of body fat after adjustment for lean tissue index and volume status. High ferritin increased all-cause mortality in PD patients, and increased fat mass was an important determinant of the high ferritin. Our results support that adiposity may lead to an adverse clinical outcome in PD patients.

Humoral immunity confers protection against COVID-19. The longevity of antibody responses after receiving an inactivated vaccine in individuals with previous SARS-CoV-2 infection is unclear. Plasma samples were collected from 58 individuals with previous SARS-CoV-2 infection and 25 healthy donors (HDs) who had been vaccinated with an inactivated vaccine. The neutralizing antibodies (NAbs) and S1 domain-specific antibodies against the SARS-CoV-2 wild-type and Omicron strains and nucleoside protein (NP)-specific antibodies were measured using a chemiluminescent immunoassay. Statistical analysis was performed using clinical variables and antibodies at different timepoints after SARS-CoV-2 vaccination. NAbs targeting the wild-type or Omicron strain were detected in individuals with previous SARS-CoV-2 infection at 12 months after infection (wild-type: 81%, geometric mean (GM): 20.3 AU/mL; Omicron: 44%, GM: 9.4 AU/mL), and vaccination provided further enhancement of these antibody levels (wild-type: 98%, GM: 53.3 AU/mL; Omicron: 75%, GM: 27.8 AU/mL, at 3 months after vaccination), which were significantly higher than those in HDs receiving a third dose of inactivated vaccine (wild-type: 85%, GM: 33.6 AU/mL; Omicron: 45%, GM: 11.5 AU/mL). The level of NAbs in individuals with previous infection plateaued 6 months after vaccination, but the NAb levels in HDs declined continuously. NAb levels in individuals with previous infection at 3 months post-vaccination were strongly correlated with those at 6 months post-vaccination, and weakly correlated with those before vaccination. NAb levels declined substantially in most individuals, and the rate of antibody decay was negatively correlated with the neutrophil-to-lymphocyte ratio in the blood at discharge. These results suggest that the inactivated vaccine induced robust and durable NAb responses in individuals with previous infection up to 9 months after vaccination.

Acute and chronic liver disease are global problems with high morbidity and mortality. Bupleuri Radix (BR) is an herbal medicine that has been prescribed empirically in traditional Asian medicine to modulate liver metabolism. However, its active compounds and therapeutic mechanisms remain unclear. Here, we integrated a network-based approach and experimental validation to elucidate BR's therapeutic potential in treating oxidative liver injury. Our approach incorporated data collection and network construction utilizing bioinformatics tools, and identified active compounds and key mechanisms based on the multiscale interactome. The proposed mechanisms were validated using an in vitro oxidative stress model and an in vivo carbon tetrachloride-induced model. We found that BR ameliorated the oxidative hepatic damage by acting on multiple proteins (STAT3, TNF, and BCL2) and signaling pathways (AMPK and Hippo signaling pathways). Subsequent in vitro experiments confirmed that BR significantly inhibited oxidative stress and mitochondrial damage. We further validated the effect of BR on the AMPK and Hippo-YAP pathways; a key mechanism for the antioxidant properties of BR. We prioritized the active compounds in BR based on a multiscale interactome-based approach, and further experiments revealed that saikosaponin A was a key active compound involved in hepatocyte protection (EC 50  = 50 μM), similar to the result using metformin and 5-aminoimidazole-4-carboxamide ribonucleotide. Histochemistry and blood biochemistry established that BR significantly inhibited carbon tetrachloride-induced oxidative tissue damage in mice. Thus, BR can be used to develop novel therapeutics for oxidative liver injury. Moreover, we suggest a novel strategy to prioritize and validate the active compounds and key mechanisms of herbal medicine based on the multiscale interactome., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

We report the single-crystal growth of Mn 2 V 2 O 7 and the results of magnetic susceptibility, high-field magnetization up to 55 T and high-frequency electric spin resonance (ESR) measurements for its low-temperature α phase. Two antiferromagnetic (AFM) ordering at 17.5 K and 3 K and obvious magnetic anisotropy are observed in α -Mn 2 V 2 O 7 upon cooling. In pulsed high magnetic fields, the compound reaches the saturation magnetic moment of ∼10.5 μ B for each molecular formula at around 45 T after two undergoing AFM phase transitions at H c1 ≈ 16 T, H c2 ≈ 34.5 T for H //[11-0] and H sf1 = 2.5 T, H sf2 = 7 T for H //[001]. In these two directions, two and seven resonance modes are detected by ESR spectroscopy, respectively. The ω 1 and ω 2 modes of H //[11-0] can be well described by two-sublattice AFM resonance mode with two zero-field gaps at 94.51 GHz and 169.28 GHz, indicating a hard-axis feature. The seven modes for H //[001] are partially separated by the critical fields of H sf1 and H sf2 , displaying the two signs of spin-flop transition. The fittings of ω c1 and ω c2 modes yield zero-field gaps at 69.50 GHz and 84.73 GHz for H //[001], confirming the axis-type anisotropy. The saturated moment and gyromagnetic ratio indicate the Mn 2+ ion in α -Mn 2 V 2 O 7 is in a high spin state with orbital moment completely quenched. A quasi-one-dimensional magnetism with a zig-zag-chain spin configuration is suggested in α -Mn 2 V 2 O 7 , due to the special neighbor interactions caused by a distorted network structure with honeycomb layer., (© 2023 IOP Publishing Ltd.)

Elsholtzia fruticosa is an ornamental plant with high medicinal value. In this study, we sequenced and analyzed the complete chloroplast (cp) genome of the species. The complete cp sequence is 151,550 bp, including the large single-copy (LSC) region of 82,778 bp, the small single-copy (SSC) region of 17,492 bp, and a pair of invert repeats (IRs) regions of 25,640 bp. It encodes 132 unique genes in total, including 87 protein-coding genes, 37 transfer RNA genes (tRNAs), and eight ribosomal RNA genes (rRNAs). The comparative analysis of complete cp genomes showed that the genomic structure and gene order of E. fruticosa cps were conserved. The sequences of rps15 , rps19 , ycf1 , ycf3 , ycf15 , psbL , psaI , trnG-UCC , trnS-GCU , trnR-UCU , trnL-UAG , trnP-UG , and trnL-UAA serve as hotspots for developing the DNA barcoding of Elsholtzia species. There are 49 SSR loci in the cp genome of E. fruticosa , among which the repeat numbers of mononucleotide, dinucleotide, trinucleotide, tetranucleotide, and pentanucleotides SSR are 37, 9, 3, 0, and 0, respectively. A total of 50 repeats were detected, including 15 forward repeats, seven reverse repeats, 26 palindromic repeats, and two complementary repeats. Phylogenetic analysis based on the complete cp genome and protein-coding DNA sequences of 26 plants indicates that E. fruticosa has a dose relationship with E. splendens and E. byeonsanensis ., Competing Interests: No potential conflict of interest was reported by the authors., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Introduction: Sasang Constitutional Medicine (SCM) is a type of traditional Korean medicine where patients are classified as one of four Sasang constitution types (Sasang type) and medications consisting of medicinal herbs are prescribed according to the Sasang type. Despite the importance of personalized medicine, the operation mechanism is largely unknown. To gain a better understanding, we investigated the compound information that composes Sasang type-specific personalized herbal medicines on both multivariate and univariate levels., Methods: Five machine learning classifiers including extremely randomized trees (ERT) were trained to investigate whether the Sasang type can be explained by compound information at the multivariate level. Hierarchical clustering was conducted to determine whether compounds are processed distributedly or specifically. Taxonomic and biosynthetic analyses were conducted on these compounds. A univariate level statistical test was conducted to provide more robust Sasang type-specific compound information., Results: Using the trained ERT classifier, sixty important compounds were extracted. The sixty compounds were clustered into three groups, corresponding to each Sasang type-prominent compounds, suggesting that most compounds have specific preference for the Sasang type. Structural and biosynthetic characteristics of these Sasang type-prominent compounds were determined based on taxonomy and pathway analyses. Fourteen compounds showed statistically significant relevance with the Sasang type. Additionally, we predicted the Sasang type of unknown herbs, which were confirmed by their biological effects in functional assays., Conclusion: This study investigated the personalized herbal medicines of the SCM using compound information. This study provided information on the chemical characteristics of the compounds that are essential for classifying the Sasang type of medicinal herbs, as well as predictions regarding the Sasang type of the commonly used but unidentified medicinal herbs., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Background: Plastic cannulae have attracted increasing interest as an alternative to traditional metal needles with the aim of reducing cannulation-related complications. We investigated whether the substitution volumes during hemodiafiltration differ using these two types of needles in dialysis patients., Methods: An intervention study involving 26 hemodialysis patients was conducted in Korea between March and September in 2021. Patients first received online hemodiafiltration using traditional metal needles, and thereafter plastic cannulae were used in a stepwise protocol. Repeated-measures design and linear mixed-effect models were used to compare substitution volumes between the two needle types with the same inner diameter., Results: The mean patient age was 62.7 years, and their mean dialysis vintage was 95.2 months. Most patients (92.3%) had an arteriovenous fistula as the vascular access. The substitution volume increased as blood flow and needle size increased for both plastic cannulae and metal needles. The substitution volume was significantly higher with 17-gauge (G) plastic cannulae than with 16-G metal needles at blood flow rates of 280, 300, and 330 mL/min. Similar results were obtained for 15-G metal needles and 16-G plastic cannulae at a blood flow rate of 330 mL/min. However, the patient ratings of pain on a visual analogue scale were higher for plastic cannulae., Conclusion: Higher substitution volumes were obtained at the same prescribed blood flow rate with plastic cannulae than with metal needles during online hemodiafiltration. Plastic cannulae are an option for achieving high-volume hemodiafiltration for patients with low blood flow rates.

Fatty acid esters of hydroxyl fatty acids (FAHFAs) are a new family of endogenous lipids that exert anti-inflammatory action. Among the various FAHFA isomers, the dietary source of oleic acid-hydroxy stearic acid (OAHSA) and its anti-inflammatory functions are poorly understood. This study investigated the composition of OAHSA isomers in dietary oils and the impact of 12-OAHSA on obesity-induced inflammation. Liquid chromatography with tandem mass spectrometry analysis revealed that various dietary oils, including fish oil, corn oil, palm oil, soybean oil, and olive oil, present a wide variation in OAHSA profiles and amounts. The highest amounts of total OAHSAs are present in olive oil including 12-OAHSA. Compared to vehicle-treated obese mice, administration of 12-OAHSA significantly improved glucose homeostasis, independent of body weight. 12-OAHSA-treated mice displayed significantly reduced accumulation of CD11c + adipose tissue macrophages, and CD4 + /CD8 + adipose tissue T lymphocytes. Concomitantly, the expression of pro-inflammatory cytokine genes and the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway were significantly decreased in the 12-OAHSA-treated adipose tissue, while the expression of the anti-inflammatory gene Il10 was markedly increased. Moreover, in vitro cell culture experiments showed that 12-OAHSA significantly inhibited the lipopolysaccharides-induced inflammatory response in macrophages by suppressing the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway. Collectively, these results indicated that 12-OAHSA, as a component of olive oil, mitigates obesity-induced insulin resistance by regulating AT inflammation. Therefore, 12-OAHSA could be used as a novel nutritional intervention against obesity-associated metabolic dysregulation., (Copyright © 2022. Published by Elsevier Inc.)

Background: Sarcopenia is a prevalent complication in patients with chronic kidney disease and is associated with poor quality of life, morbidity, and mortality. Several candidate biomarkers have been evaluated for this condition. This study assessed the serum cystatin C to creatinine (serum cystatin C/Cr) ratio as a potential biomarker for sarcopenia in patients with non-dialysis-dependent chronic kidney disease., Methods: This study enrolled 517 outpatients. Muscle mass (lean tissue index) was measured using a bioimpedance spectroscopic device, and muscle strength (handgrip strength) was also measured. Sarcopenia was defined as a combination of low muscle strength and low muscle mass., Results: Sarcopenia was observed in 25.5% of patients, and the mean serum cystatin C/Cr ratio was significantly higher in patients with sarcopenia than in those without it (1.14 ± 0.26 vs. 1.01 ± 0.27, p &lt; 0.001). The prevalence of sarcopenia and low lean tissue index increased as the cystatin C/Cr ratio increased. The negative predictive value of the cystatin C/Cr ratio for sarcopenia or low lean tissue index was ≥80%. Multivariate analyses revealed that when the serum cystatin C/Cr ratio increased by 1, the risk of sarcopenia, low lean tissue index, and low handgrip strength increased by 4.6-, 7.2-, and 2.6-fold, respectively (p = 0.003, p &lt; 0.001, and p = 0.048). The association was maximized in patients with an estimated glomerular filtration rate of &lt;30 mL/min/1.73 m2., Conclusion: Calculating the serum cystatin C/Cr ratio could be helpful for detecting and managing sarcopenia in patients with chronic kidney disease.

Physicochemical changes in fermented alcoholic beverages are significantly related to microbial community development during fermentation. Due to its unusually long fermentation, Gayangju , a traditional Korean house rice wine fermented with nuruk as the traditional starter, gives rise to a strong yeast community and, therefore, a high ethanol concentration and different flavors. However, no detailed analysis has been examined. Changes in microbial community structure during Gayangju fermentation were examined using both culture-dependent and culture-independent methods. During fermentation, Saccharomyces cerevisiae and Saccharomycopsis fibuligera were dominant during all stages of the fermentation. In contrast, Candida parapsilosis , Hanseniaspora guilliermondii , Pichia anomala , Malassezia cuniculi and P. fermentans were identified as minor. P. anomala appeared after the second brewing and then remained constant. Among the 19 compounds identified in this study as order-active compounds, 2-methyl-1-butanol (isoamyl alcohol) was the major compound that increased during the long fermentation stage. Most of the odor-active compounds such as 2,3-butanediol, 3-methyl-1-butanol, ethyl tetradecanoate, ethyl decanoate, ethyl dodecanoate, butanoic acid, 3-methylbutanoic acid (isovaleric acid), 2-methylbutanoic acid, 2-methyl-1-propanol, ethyl acetate, ethyl caprylate, 2-phenylethanol, and 3-methylbutyl acetate increased as the fermentation progressed during 68 days of fermentation, which showed significant differences in the concentrations of odor-active compounds of commercially fermented makgeolli .

Background: Dulaglutide is associated with improved cardiovascular and kidney outcomes and can be a good therapeutic option for patients with type 2 diabetes with chronic kidney disease (CKD). In this study, the effects of dulaglutide on glucose-lowering efficacy and changes in renal function were analyzed., Methods: This retrospective study involved 197 patients with type 2 diabetes with mild-to-severe CKD treated with dulaglutide for at least 3 months between January 2017 and December 2020 at two tertiary hospitals in Korea. Changes in the creatinine-based estimated glomerular filtration rate (eGFR) and HbA1c were compared before and after the use of dulaglutide in each patient., Results: The number of patients and mean eGFR (mL/min/1.73 m2) in CKD 2, 3a, 3b, and 4 were 94 (75.0 ± 8.5), 46 (54.8 ± 6.3), 31 (38.8 ± 4.4), and 26 (22.5 ± 5.4), respectively. Mean HbA1c level and body mass index (BMI) at the initiation of dulaglutide were 8.9% ± 1.4% and 29.1 ± 3.6 kg/m2, the median duration of the use of dulaglutide was 16 months. The use of dulaglutide was associated with a mean decrease in HbA1c by 0.9% ± 1.5% and the glucose-lowering efficacy was similar across all stages of CKD. Also, it was associated with a reduced decline in the eGFR; the mean eGFR change after the use of dulaglutide was -0.76 mL/min/1.73 m2 per year, whereas it was -2.41 mL/min/1.73 m2 before use (paired t-test, P = 0.003). The difference was more pronounced in patients with an eGFR < 60 mL/min/1.73 m2. Subgroup analysis showed that the renal protective effect was better in patients with proteinuria, age ≤ 65 years, and HbA1c < 9.0%, but showed no association with BMI., Conclusions: The use of dulaglutide provided adequate glycemic control irrespective of CKD stage and was associated with a reduced decline in the eGFR in the CKD population., Competing Interests: The authors have declared that no competing interests exist.

Background: The role of high-flow arteriovenous fistula (AVF) in cardiovascular morbidity in hemodialysis (HD) patients is very likely under-recognized. We assessed the relationship between high access flow (Qa) and myocardial fibrosis in HD patients., Methods: Myocardial fibrosis was assessed by native T1 relaxation times on non-contrast cardiac magnetic resonance imaging and a potential marker of fibrosis. Serum levels of galectin-3, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and monocyte chemoattractant protein 1 (MCP-1) were measured in 101 HD patients who underwent regular monitoring of AVF Qa. A high-flow AVF was defined as a Qa >2 L/min., Results: Hemodialysis patients showed significantly higher galectin-3 value and increased T1 relaxation time compared to healthy volunteers, suggesting increased myocardial fibrosis in uremic cardiomyopathy. In HD patients, 20 (19.8%) had a Qa > 2L/min, and they had significantly higher cardiac output, cardiac index, left ventricular mass, and increased T1 times than those with a Qa ≤ 2 L/min. Also, serum galectin-3 and NT-proBNP levels were much higher in the high Qa group, indicating a close relationship between the high Qa, increased myocardial fibrosis, and the risk of heart failure (HF) in HD patients. It is interesting that a higher AVF Qa for myocardial fibrosis was independent of several traditional cardiovascular risk factors as well as serum levels of NT-proBNP and MCP-1., Conclusions: A supra-physiologically high Qa can be related to myocardial fibrosis and increased risk of HF in HD patients. Regular Qa monitoring could allow early detection of a high-flow AVF that could arise cardiac complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Choi, Lee, An, Song, Kim, Lee and Kim.)

Non-small-cell lung carcinoma (NSCLC) is the most common kind of lung cancer, which is also the largest cause of cancer-linked deaths globally. A lack of effective prognostic biomarkers contributes to the poor prognosis of NSCLC. For better patient outcomes, NSCLC diagnosing, prognostic, and predictive biomarkers are critically needed. A component of the chromatin-modulatory complex that dampens gene expression, ING2 (inhibitor of growth family member 2), has been linked to cellular mechanisms that enhance tumor repression. Nevertheless, its role in human NSCLC is unclear. Herein, we observed that ING2 downregulation in NSCLC tissues correlates with poor NSCLC prognosis. Functional analysis illustrated that ING2 dampened growth, infiltration along with metastasis and blocked apoptosis of NSCLC cells in vitro, as well as in vivo. The mechanism might be implicated in the EMT (epithelial-mesenchymal transition) process. Mechanistically, we found that ING2 silencing suppresses the expressions of Wilms tumor 1-associated protein (WTAP) and that WTAP expression negatively correlates with ING2 expression. Moreover, rescue experiments illustrated that WTAP overexpression partially counteracts the effect of ING2 silencing on proliferation. Finally, we found that elevated WTAP levels correlate with poor NSCLC prognosis. These results highlight the prognostic and therapeutic potential of ING2-WTAP in NSCLC., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Natural products and medicinal herbs have been used to treat various human diseases by regulating cellular functions and metabolic pathways. Angelica gigas NAKAI (AG) helps regulate pathological processes in some medical fields, including gastroenterology, gynecology, and neuropsychiatry. Although some papers have reported its diverse indications, the effects of AG against arachidonic acid (AA)+ iron and carbon tetrachloride (CCl 4 ) have not been reported. In HepG2 cells, AA+ iron induced cellular apoptosis and mitochondrial damage, as assessed by mitochondrial membrane permeability (MMP) and the expression of apoptosis-related proteins. On the other hand, AG markedly inhibited these detrimental phenomena and reactive oxygen species (ROS) production induced by AA+ iron. AG activated the liver kinase B1 (LKB1)-dependent AMP-activated protein kinase (AMPK), which affected oxidative stress in the cells. Moreover, AG also regulated the expression of yes-associated protein (YAP) signaling as mediated by the AMPK pathways. In mice, an oral treatment of AG protected against liver toxicity induced by CCl 4 , as indicated by the plasma and histochemical parameters. Among the compounds in AG, decursin had antioxidant activity and affected the AMPK pathway. In conclusion, AG has antioxidant effects in vivo and in vitro, indicating that natural products such as AG could be potential candidate for the nutraceuticals to treat various disorders by regulating mitochondrial dysfunction and cellular metabolic pathways.

Liver cancer has relatively few early symptoms and is usually diagnosed in the advanced stage. Sorafenib is the only first-line anticancer drug approved by the Food and Drug Administration (FDA) for advanced HCC; however, its use is limited due to resistance. Therefore, the development of new drugs is essential to achieving customized treatment. Many studies have suggested that Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) is associated with metastasis and cancer formation and progression in various cancers. In the present study, YAP was overexpressed in various patient-derived hepatocarcinoma (HCC) tissues. In addition, this study examined whether evodiamine (which has anticancer effects) can inhibit YAP and, if so, modulate HCC. Evodiamine significantly reduced both the YAP level and cell growth of HCC in a dose-dependent manner. Biochemical analysis indicated mitochondria dysfunction-mediated apoptosis to be the cause of the reduction in HCC cell growth by evodiamine. YAP was overexpressed in metastatic HCC tissues as well when compared to primary HCC tissues. Migration and invasion analysis showed that evodiamine has anti-metastatic ability on Hep3B and Huh-7 cells and reduces the level of vimentin, an EMT marker. In conclusion, YAP is a critical target in HCC therapy, and evodiamine can be an effective HCC anticancer drug by reducing the YAP level.

Background: Anti-heparin/platelet factor 4 (PF4) antibodies may trigger severe thrombotic complications in hemodialysis (HD) patients. Tetrameric PF4 has a high affinity for extracellular DNA, which is a key component of neutrophil extracellular traps (NETs); therefore, the interactions between anti-heparin/PF4 antibodies and NETs can contribute to prothrombotic events., Methods: Anti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay and an optical density > 1.8 was regarded as clinically significant. We additionally measured serum nucleosome levels as representative markers of NETs, and the contributions of anti-heparin/PF4 and increased serum nucleosome levels to the primary functional patency loss of vascular access was assessed., Results: The frequency of anti-heparin/PF4 antibodies was significantly higher in incident HD patients compared to prevalent HD patients (23.6% vs. 7.7%). Serum nucleosome levels, as well as the white blood cell counts, neutrophil counts, and high- sensitivity C-reactive protein levels, were significantly higher in anti-heparin/PF4 antibody-positive patients compared to the control. Platelet counts tended to be lower in the patients with anti-heparin/PF4 of >1.8 than in the controls. Relative risk calculations showed that the presence of anti-heparin/PF4 antibodies increased the risk of primary functional patency failure by 4.28-fold, and this risk increased further with higher nucleosome levels. Furthermore, in the anti-heparin/PF4 antibody-positive group, the time to first vascular intervention was much shorter, and the risk of repeated intervention was higher, compared to the controls., Conclusion: In incident HD patients, the presence of anti-heparin/PF4 antibodies was associated with increased NET formation; this could be a strong predictor of vascular access complications.

Acute kidney injury (AKI) is a common condition in critically ill patients, and may contribute to significant medical, social, and economic consequences, including death. Although there have been advances in medical technology, including continuous renal replacement therapy (CRRT), the mortality rate of AKI is high, and there is no fundamental treatment that can reverse disease progression. The decision to implement CRRT is often subjective and based primarily on the clinician's judgment without consistent and concrete guidelines or protocols regarding when to initiate and discontinue CRRT and how to manage complications. Recently, several randomized controlled trials addressing the initiation of renal replacement therapy in critically ill patients with AKI have been completed, but clinical application of the findings is limited by the heterogeneity of the objectives and research designs. In this review, the advantages and disadvantages of CRRT initiation, clinical guideline recommendations, and the results of currently published clinical trials and meta-analyses are summarized to guide patient care and identify future research priorities.

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). Endothelial cell (EC) dysfunction is a key CKD-specific risk factor; however, the mechanisms by which uremia harms the endothelium are still unclear. We report a role for excessive neutrophil extracellular trap (NET) formation induced by uremic serum on EC injury. Level of plasma nucleosome and myeloperoxidase-DNA, established in vivo markers of NETs, as well as intracellular adhesion molecule (ICAM)-1 were measured in hemodialysis (HD) patients and healthy volunteers (HV) and their prognostic role evaluated. For in vitro studies, HV-derived neutrophils and differentiated HL-60 cells by retinoic acid were used to determine the effect of uremic serum-induced NETs on human umbilical vein EC (HUVEC). The level of in vivo NETs was significantly higher in incident HD patients compared to HV, and these markers were strongly associated with ICAM-1. Specifically, nucleosome and ICAM-1 levels were independent predictors of a composite endpoint, all-cause mortality, or vascular access failure. In vitro, HD-derived uremic serum significantly increased NET formation both in dHL-60 and isolated neutrophils compared to control serum, and these NETs decreased EC viability and induced their apoptosis. In addition, the level of ICAM-1, E-selectin and von Willebrand factor in HUVEC supernatant was significantly increased by uremic serum-induced NETs compared to control serum-induced NETs. Dysregulated neutrophil activities in the uremic milieu may play a key role in vascular inflammatory responses. The high mortality and CVD rates in ESRD may be explained in part by excessive NET formation leading to EC damage and dysfunction., (© 2021. The Author(s).)

Most epidemiologic studies assessing the relationship between chronic kidney disease (CKD) and sarcopenia have been performed in dialysis patients. This study aimed to evaluate the relationship between estimated glomerular filtration rate (eGFR), proteinuria, and sarcopenia in patients with non-dialysis-dependent CKD. A total of 892 outpatients who did not show any rapid changes in renal function were enrolled in this observational cohort study. We measured the muscle mass using bioimpedance analysis and handgrip strength (HGS), and sarcopenia was defined as low HGS and low muscle mass. Sarcopenia was found in 28.1% of the patients and its prevalence decreased as the body mass index (BMI) increased; however, in patients with BMI ≥ 23 kg/m 2 , the prevalence did not increase with BMI. As eGFR decreased, the lean tissue index and HGS significantly decreased. However, the eGFR did not affect the fat tissue index. The risk of sarcopenia increased approximately 1.6 times in patients with eGFR < 45 mL/min/1.73 m 2 . However, proteinuria was not associated with sarcopenia. With a decrease in eGFR, the lean muscle mass and muscle strength decreased, and the prevalence of sarcopenia increased. In patients with late stage 3 CKD, further assessment of body composition and screening for sarcopenia may be needed., (© 2021. The Author(s).)

This study aimed to determine the probiotic potential of Pediococcus acidilactici M76 (PA-M76) for lactic acid fermentation of black raspberry extract (BRE). PA-M76 showed outstanding probiotic properties with high tolerance in acidic GIT environments, broad antimicrobial activity, and high adhesion capability in the intestinal tract of Caenorhabditis elegans . PA-M76 treatment resulted in significant increases of pro-inflammatory cytokine mRNA expression in macrophages, indicating that PA-M76 elicits an effective immune response. When PA-M76 was used for lactic acid fermentation of BRE, an EPS yield of 1.62 g/L was obtained under optimal conditions. Lactic acid fermentation of BRE by PA-M76 did not significantly affect the total anthocyanin and flavonoid content, except for a significant increase in total polyphenol content compared to non-fermented BRE (NfBRE). However, fBRE exhibited increased DPPH radical scavenging activity, linoleic acid peroxidation inhibition rate, and ABTS scavenging activity of fBRE compared to NfBRE. Among the 28 compounds identified in the GC-MS analysis, esters were present as the major groups. The total concentration of volatile compounds was higher in fBRE than that in NfBRE. However, the undesirable flavor of terpenes decreased. PA-M76 might be useful for preparing functionally enhanced fermented beverages with a higher antioxidant activity of EPS and enhanced flavors.

Nucleic acid aptamers, broad-spectrum target-specific single-stranded oligonucleotides, serve as molecules in targeted therapy, targeted delivery and disease diagnosis for the treatment of tumor or microbial infection and clinical detection. Due to the existence of components in the use of traditional Chinese medicine(TCM), the target is difficult to concentrate and the specificity of treatment is poor. The effective components of TCM are toxic components, so a highly sensitive detection method is urgently needed to reduce the toxicity problem at the same time. The combined application of TCM and modern medical treatment strategy are difficult and cannot improve the therapeutic effect. Aptamers, advantageous in biosensors, aptamer-nanoparticles for targeted drug delivery, and aptamer-siRNA chimeras, are expected to connect Chinese medicinals with nanotechnology, diagnostic technology and combined therapies. We summarized the preparation, screening, and modification techniques of nucleic acid aptamers and the biomedical applications and advantages in therapy, targeting, and diagnosis, aiming at providing a reference for the in-depth research and development in TCM.

Pseudomonas syringae pv. actinidiae (Psa) is a Gram-negative bacterium that causes bacterial canker disease in kiwifruit. Copper or antibiotics have been used in orchards to control this disease, but the recent emergence of antibiotic-resistant Psa has called for the development of a new control agent. We previously reported that the bacteriophage (or phage) PPPL-1 showed antibacterial activity for both biovar 2 and 3 of Psa. To investigate the possibility of PPPL-1 to control bacterial canker in kiwifruit, we further tested the efficacy of PPPL-1 and its phage cocktail with two other phages on suppressing disease development under greenhouse conditions using 6 weeks old kiwifruit plants. Our results showed that the disease control efficacy of PPPL-1 treatment was statistically similar to those of phage cocktail treatment or Agrimycin TM , which contains streptomycin and oxytetracycline antibiotics as active ingredients. Moreover, PPPL-1 could successfully kill streptomycin-resistant Psa isolates, of which the treatment of Buramycin TM carrying only streptomycin as an active ingredient had no effect in vitro. The phage PPPL-1 was further characterized, and stability assays showed that the phage was stable in the field soil and at low temperature of 0 ± 2 °C. In addition, the phage could be scaled up quickly up to 10 10 pfu/mL at 12 h later from initial multiplicity of infection of 0.000005. Our results indicate that PPPL-1 phage is a useful candidate as a biocontrol agent and could be a tool to control the bacterial canker in kiwifruit by Psa infection in the field conditions.

Competing Interests: There are no financial or other issues that might lead to conflict of interest.

Pectobacterium odoriferum has recently emerged as a widely infective and destructive pathogen causing soft-rot disease in various vegetables. Bacteriophage phiPccP-1 isolated from Pyeongchang, South Korea, showed lytic activity against P. odoriferum Pco14 and two other Pectobacterium species. The transmission electron microscopy and genome phylograms revealed that phiPccP-1 belongs to the Unyawovirus genus, Studiervirinae subfamily of the Autographivirinae family. Genome comparison showed that its 40,487 bp double-stranded DNA genome shares significant similarity with Pectobacterium phage DU&#95;PP&#95;II with the identity reaching 98% of the genome. The phiPccP-1 application significantly inhibited the development of soft-rot disease in the mature leaves of the harvested Kimchi cabbage up to 48 h after Pco14 inoculation compared to the untreated leaves, suggesting that phiPccP-1 can protect Kimchi cabbage from soft-rot disease after harvest. Remarkably, bioassays with phiPccP-1 in Kimchi cabbage seedlings grown in the growth chamber successfully demonstrated its prophylactic and therapeutic potential in the control of bacterial soft-rot disease in Kimchi cabbage. These results indicate that bacteriophage phiPccP-1 can be used as a potential biological agent for controlling soft rot disease in Kimchi cabbage.

Introduction: This study was conducted to analyze the effectiveness of a custom-made Doppler ultrasound (DUS) flow simulator, vascular phantom, and Doppler test fluid in the training of dialysis staff in flow volume (FV) measurements for arteriovenous (AV) access in hemodialysis (HD) patients., Methods: A DUS flow simulator was constructed using a continuous renal replacement therapy machine. Vascular phantoms were constructed using a rubber enema tube and keyboard cleaning gel. The Doppler test fluid consisted of freeze-dried instant coffee granules and 0.9% saline. This easy and affordable simulator was used to train 12 dialysis staff members, with no previous experience in DUS FV measurement. After a 3-day lecture course, the staff members performed DUS analyses on the AV access of HD patients. Thereafter, they underwent a 3-day training course using the simulator and then performed the DUS analyses of the AV access again. Each staff member assessed the FV 3 times, and the mean values of the measurements pretraining and posttraining were analyzed using paired t tests., Results: The difference in the mean value of FV measurements and the reference value decreased from 131.6 mL/min to 62.5 mL/min (95% confidence interval = 30.0-108.0, P = 0.002), and the standard deviation of the FV measurements decreased from 96.9 mL/min to 47.0 mL/min (95% confidence interval = 7.9-91.8, P = 0.023) after DUS training with the simulator., Conclusions: The accuracy and reproducibility of FV measurements markedly improved after training with the simulator; it may be helpful for medical practitioners involved in AV access for HD treatment., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Society for Simulation in Healthcare.)

Background and Objects: We hypothesized that plastic cannulae with 17-gauge inner needle compared to 16-gauge metal needles can have stable dynamic venous and arterial pressure maintaining prescribed blood flow safely during a hemodialysis treatment., Design, Setting, Participants, and Measurements: A single-center, prospective, randomized, open-label clinical trial was conducted involving 16 incident hemodialysis patients who had arteriovenous graft placed as their first arteriovenous access. Subjects were randomized to metal needle group (n = 8) versus plastic cannula group (n = 8). We measured serial dynamic pre-pump arterial and venous pressure under five different blood pump flow rates (150, 200, 250, 300, and 350 mL/min)., Results: The mean age of patients was 67.6 ± 8.5 (range: 51-81) years, and six patients (37.5%) were male. Patients with plastic cannula showed less negative arterial pre-pump pressures and lower venous pressures than those with metal needles at all prescribed blood flow rates, and the difference was statistically significant (P < 0.001)., Conclusion: The plastic cannula had more stable arterial and venous pressures at prescribed blood pump flow rates than those pressures of the metal needle in incident patients with arteriovenous graft during hemodialysis.

Introduction: Successful cannulation of an arteriovenous fistula (AVF) is important in patients starting hemodialysis (HD). Metal needles have been used for decades, but the usefulness of plastic cannulae has recently been demonstrated as a new technique., Methods: This was a prospective, randomized, open-label study of incident HD patients. Eligible patients were randomized into 2 groups in a 1:1 ratio (n = 45/group). Maturation of the AVF was confirmed using Doppler ultrasound prior to first needling, and 2 well-trained nurses implemented the AVF cannulation. The primary endpoint was the initial cannulation failure rate, defined as the failure of successful completion of 3 consecutive dialysis sessions. The secondary endpoints were time for hemostasis at the end of HD, degree of patients' pain, degree of cannulation difficulty felt by the nursing staffs, and achieving optimal HD adequacy., Results: The mean elapsed time from AVF creation to the first cannulation was 48.1 ± 16.7 days. A total of 17 cases of cannulation failure occurred, and the failure risk tended to be higher in the metal needle group than the plastic cannula group (hazard ratio 2.6, 95% confidence interval 0.95-7.41) after adjusting for age, gender, comorbidities, and AVF location. The overall incidence of vessel injury was higher and time for hemostasis was significantly longer in the metal group than the plastic group. The use of plastic cannula was associated with a better HD adequacy compared to a metal needle. However, the patients' pain score (p = 0.004) and nursing staff's cannulation difficulty score (p = 0.084) were higher in the plastic group, emphasizing the great importance of practice using plastic cannulae., Conclusion: The vascular outcomes of plastic cannulae were much favorable compared to metal needles in incident HD patients. The use of plastic cannulae could be a new and innovative way to improve the quality of dialysis., (© 2021 S. Karger AG, Basel.)

Background & Aims: Peritoneal dialysis (PD) is associated with a number of adverse body compositional changes, including fat gain and muscle wasting. Whether body compositional changes are associated with the long-term prognosis is uncertain. The purpose of this study was to analyze the effects of longitudinal changes in body composition on all-cause mortality in PD patients., Methods: PD patients were subjected to bioimpedance spectroscopy (BIS) and handgrip strength (HGS) at baseline and after 2 years. Among 160 patients, 131 patients were tested with a repeat BIS and HGS. Lean tissue index (LTI) loss and fat tissue index (FTI) gain were defined as a 10% decline in LTI and a 10% gain in FTI, respectively after 2 years., Results: The prevalence of sarcopenia at baseline was 13.8%. After 2 years, LTI loss and FTI gain were observed in 40 (30.5%) and 58 (44.3%) patients, respectively. Baseline clinical factors did not predict longitudinal body compositional changes, and there was a negative association between changes in the LTI and FTI (r = -0.574, p < 0.001). Low LTI and low HGS at baseline were significant predictors of all-cause mortality after adjusting for demographic and biochemical parameters, but not when cardiovascular factors were included in the multivariate analysis. However, LTI loss and FTI gain were independent risk factors for all-cause mortality after adjusting for demographic, biochemical, and cardiovascular parameters., Conclusions: In PD patients, longitudinal changes in LTI and FTI were more strongly associated with all-cause mortality than single values in LTI and FTI., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier Ltd.)

Background: The long-term prognosis of Henoch-Schönlein purpura (HSP) depends on the severity of renal involvement, and crescent formation is considered an important risk factor for poor prognosis of Henoch-Schönlein purpura nephritis (HSPN). The objective of this study was to evaluate factors affecting crescent formation in children with HSPN., Methods: Demographic factors, clinical characteristics, and laboratory data of children with HSPN with or without crescents were retrospectively analyzed. Univariate and multivariate logistic regression analyses were used to determine the risk factors of crescent formation in HSPN., Results: A total of 191 children with HSPN were enrolled in the study. There were 107 (56%) males and 84 (44%) females, with a median age of 7 years (range: 2 years-15 years). International Study of Kidney Disease in Children (ISKDC) grading was used to divide subjects into two groups: those without glomerular crescent formation (ISKDC grades I-II, n = 146 cases) and those with glomerular crescent formation (ISKDC grades III-V, n = 45 cases). Logistic regression analysis showed that higher urinary white blood cell (WBC) count (OR = 3.300; 95% CI, 1.119-9.739; P = 0.0306) and higher urinary microalbumin/creatinine ratio (ACR) (OR = 25.053; 95% CI, 1.354-463.708; P = 0.0305) were independent risk factors for the formation of crescents in HSPN. The area under the receiver operating characteristic curve of urinary WBC and ACR were 0.753 and 0.698 respectively, with the Hosmer and Lemeshow goodness-of-fit test (P = 0.0669, P > 0.05)., Conclusion: These results suggest that higher urinary WBC count and ACR should be strictly monitored for children with HSPN. Adequate clinical intervention for these risk factors may limit or prevent renal crescent formation.

Nelumbo nucifera, more commonly known as the Indian lotus, is an important plant that has been incorporated into traditional herbal remedies along the years. Even today, lotus leaves are considered reservoirs for bioactive compounds that can be used as nutritional supplements to treat various human diseases. However, despite the wide ranging biological activities of lotus polysaccharides, limited information is available regarding the anti-osteoporotic effects of these substances. The aim of this study was to investigate the beneficial effects of pectinase-assisted extractable polysaccharides from lotus leaves (LLEP) on estrogen deficiency-induced bone loss and osteoclast differentiation in bone marrow-derived macrophages. We found that LLEP markedly inhibited receptor activator of the nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner. It also revoked RANKL-induced activation of osteoclastogenic signals such as the expression of key transcription factors (i.e., c-Fos and nuclear factor of activated T cells cytoplasmic 1), resulting in a decrement in osteoclast-specific marker gene expressions. Microcomputed tomography and morphometric analysis revealed that a four-week oral administration of LLEP notably decreased trabecular bone loss. Taken together, our results suggest that LLEP can mitigate estrogen deficiency-induced bone loss by suppressing osteoclastogenesis, which makes it an excellent candidate for combating osteoporosis., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020. Published by Elsevier B.V.)

Erwinia pyrifoliae is a Gram-negative bacterial plant pathogen that causes black shoot blight in apple and pear. Although earlier studies reported the genome comparison of Erwinia species, E. pyrifoliae strains for such analysis were isolated in 1996. In 2014, the strain E. pyrifoliae EpK1/15 was newly isolated in the apple tree showing black shoot blight in South Korea. This study aimed to better understand the similarities and differences caused by natural variations at the genomic level between newly isolated E. pyrifoliae EpK1/15 and the strain Ep1/96, which were isolated almost 20 years apart. Several comparative genomic analyses were conducted, and Clusters of Orthologous Groups of proteins (COG) database was used to classify functional annotation for each strain. E. pyrifoliae EpK1/15 had similarities with the Ep1/96 strain in stress-related genes, Tn3 transposase of insertion sequences, type III secretion systems, and small RNAs. The most remarkable difference to emerge from this comparison was that although the draft genome of E. pyrifoliae EpK1/15 was almost conserved, Epk1/15 strain had at least three sorts of structural variations in functional annotation according to COG database; chromosome inversion, translocation, and duplication. These results indicate that E. pyrifoliae species has gone natural variations within almost 20 years at the genomic level, and we can trace their similarities and differences with comparative genomic analysis., (© The Korean Society of Plant Pathology.)

We sought to investigate the effect of extracts from Rosa gallica petals (RPE) on skin whitening and anti-wrinkle activity. Tyrosinase activity was attenuated by RPE treatment, concomitant with the reduction of melanin accumulation in human B16F10 melanoma. Treatment of the facial skin of volunteers in a clinical trial with an RPE-containing formulation enhanced skin brightness (L* value) significantly. The underlying mechanism responsible was determined to be associated with mitogen-activated protein kinase (MAPK) activation. In addition, RPE exhibited anti-wrinkle formation activity of human dermal fibroblasts by suppressing matrix metalloproteinase (MMP)-1 level. In vivo study, RPE also inhibited solar ultraviolet-stimulated MMP-1 level by c-Jun regulation. Overall, our findings indicate that RPE evokes skin whitening and anti-wrinkle formation activity by regulating intracellular signaling, supporting its utility as an ingredient for skin whitening and anti-wrinkle cosmetic products.

Background: Increased oxidative stress in end-stage renal disease is regarded as one of the important mechanisms in the atherosclerosis and muscle wasting. However, studies examining the clinical significance of oxidative stress by direct measurement of these markers and its association with volume status and sarcopenia are limited., Methods: A follow-up cross-sectional study was performed in stable hemodialysis (HD) patients and serum protein carbonyl levels were measured as a biomarker of oxidative stress. Additionally, multi-frequency body composition analysis, handgrip strength (HGS) and nutritional assessments were performed at baseline., Results: Eighty-eight patients undergoing HD were included and 30 (34.1%) patients died during a mean follow-up of 5.2 years. The mean patient age was 60.6 ± 13.5 years, and the mean HD duration was 50.8 ± 41.3 months. In total, 16 patients (18.2%) were overhydrated, 49 (55.7%) had low HGS and 36 (40.9%) had low muscle mass. Serum protein carbonyl levels were associated with serum levels of albumin, prealbumin and transferrin, hydration status and low HGS. Overhydration (odds ratio [OR] 7.01, 95% CI 1.77-27.79, p = 0.006), prealbumin (OR 0.91, 95% CI 0.83-0.99, p = 0.030), subjective global assessment (OR 3.52, 95% CI 1.08-11.46, p = 0.037) and sarcopenia (OR 3.41, 95% CI 1.02-11.32, p = 0.046) were significantly related to increased serum protein carbonyl levels. Multivariate analysis showed that the serum levels of protein carbonyl (Hazard ratio [HR] 2.37, 95% CI 1.02-5.55, p = 0.036), albumin (HR 0.17, 95% CI 0.06-0.46, p = 0.003), prealbumin (HR 0.86, 95% CI 0.80-0.92, p = 0.001), overhydration (HR 2.31, 95% CI 1.26-8.71, p = 0.015) and sarcopenia (HR 2.72, 95% CI 1.11-6.63, p = 0.028) were independent determinants of all-cause mortality., Conclusions: Serum protein carbonyl was significantly associated with overhydration, nutritional status and sarcopenia, and could be a new predictor of mortality in patients undergoing HD.

Polysaccharides isolated from various plants are considered precious bioactive materials owing to their potent biological activities. Previously, we prepared a polysaccharide fraction (BLE0) isolated from young barley leaves ( Hordeum vulgare L.), demonstrating its anti-osteoporotic and immunostimulatory activities. However, data regarding BLE0 toxicity is lacking. To establish its safety, in vitro genotoxicity (chromosomal aberration and bacterial reverse mutation assays) and acute oral toxicity assays were conducted. In the in vitro genotoxicity assays, bacterial reverse mutation and chromosomal aberration assays showed that BLE0 possessed no mutagenicity or clastogenicity. Furthermore, the median lethal dose (LD 50 ) of BLE0 was higher than 5000 mg/kg in female and male Sprague-Dawley (SD) rats and no adverse effects were observed in terms of mortality and abnormal changes in clinical signs (body weight and necropsy). Based on these results, BLE0 was found to be safe with regards to genotoxicity under our test conditions, demonstrating no acute oral toxicity up to 5000 mg/kg in SD rats.

Lotus leaf polysaccharides were extracted by enzyme-assisted extraction using α-amylase (LLEP-A), cellulose (LLEP-C), pectinase (LLEP-P) or protease (LLEP-PR). Their physicochemical properties and immunostimulatory activities were compared with those of hot-water extracted polysaccharides (LLWP). HPAEC-PDA and HPSEC-RI profiles indicated that variations in their molecular weight patterns and chemical compositions. Moreover, their effects on proliferation, phagocytic activity, and cytokine production in macrophages could be ordered as LLEP-P > LLEP-C > LLEP-A > LLWP > LLEP-PR, suggesting that LLEP-P by pectinase-assisted extraction was the most potent enhancer of macrophage activation. LLEP-P was further purified by gel filtration, and the main fraction (LLEP-P-І) was obtained to elucidate the structural and functional properties. LLEP-P-І (14.63 × 10 3  g/mol) mainly consisted of rhamnose, arabinose, galactose, and galacturonic acid at molar percentages of 15.5:15.8:20.1:32.8. FT-IR spectra indicated the predominant acidic and esterified form, suggesting the pectic-like structure. Above all, LLEP-P-І exerted greater stimulation effects on NO and cytokines production and the phagocytic activity in macrophages. Transcriptome analysis also demonstrated that LLEP-P and LLEP-P-І could upregulate macrophage immune response genes, including cytokines, chemokines, and interferon via TLR and JAK-STAT signaling. Thus, these results suggest that pectinase application is most suitable to obtain immunostimulatory polysaccharides from lotus leaves., Competing Interests: Declaration of competing interest None., (Copyright © 2020. Published by Elsevier B.V.)