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The fall armyworm (FAW), Spodoptera frugiperda is a cold-sensitive species that overwinters in temperate climates without diapause. Overwintering in insects involves rapid cold hardening (RCH), supported by trehalose (TRE), which serves as an intermediate between glycogen (GLY) and glucose (GLU). However, both GLU and TRE help maintain homeostasis under stress. TRE is hydrolyzed by the enzyme trehalase (Treh) into GLU. This study retrieved Sf-Treh1a, Sf-Treh1b, and Sf-Treh2 from the FAW transcriptome analysis. RNA interference (RNAi) targeting these three Treh genes resulted in significant downregulation of mRNA levels and altered survival rates in RNAi-treated FAW larvae following RCH treatment. High-pressure liquid chromatography (HPLC) quantification of TRE and GLU in treated groups suggests that GLU is an essential component of the hemolymph for survival adaptation to cold conditions in S. frugiperda. This study reveals limited cold adaptability of FAW, as evidenced by lower glucose concentration levels. We found that FAW requires alternative molecules, in conjunction with glucose and trehalose for freeze tolerance and survivability. Our study aims to discover the molecular mechanisms that contribute to freeze tolerance in FAW by exploring the roles of trehalose, glucose, and glycogen., (© 2024. The Author(s).)

DNA methylation is a molecular process that mediates gene-environment interactions. Epigenome-wide association studies (EWAS) using the Illumina Human Methylation BeadChip are powerful tools for quantifying the relationship between DNA methylation and phenotypes. Recently, the Illumina Methylation EPICv2 BeadChip (EPICv2) was released, which includes new features, such as duplicated probes and changed probe names. Several published algorithms have been updated to address these features in EPICv2. However, appropriate EPICv2 preprocessing and integration with previous microarray versions remain complex. Therefore, MethylCallR, an open-source R package designed to provide standard procedures for performing EWAS using Illumina methylation microarrays including EPICv2, was developed. MethylCallR can be used to control duplicated probes in EPICv2, by using pre-set data implemented in MethylCallR or new customized data. MethylCallR includes a straightforward conversion function between different types of Illumina Human Methylation BeadChips. Using MethylCallR, potential outlier sample detection and statistical power estimation were conducted and used to select meaningful probes. Publicly available data was analyzed using MethylCallR and the findings were compared to that of a previous study., (© 2024. The Author(s).)

Metastatic gastric cancer (GC) presents significant clinical challenges due to its poor prognosis and limited treatment options. To address this, we conducted a targeted protein biomarker discovery study to identify markers predictive of metastasis in advanced GC (AGC). Serum samples from 176 AGC patients (T stage 3 or higher) were analyzed using the Olink Proteomics Target panels. Patients were retrospectively categorized into nonmetastatic, metastatic, and recurrence groups, and differential protein expression was assessed. Machine learning and gene set enrichment analysis (GSEA) methods were applied to discover biomarkers and predict prognosis. Four proteins (MUC16, CAIX, 5'-NT, and CD8A) were significantly elevated in metastatic GC patients compared to the control group. Additionally, GSEA indicated that the response to interleukin-4 and hypoxia-related pathways were enriched in metastatic patients. Random forest classification and decision-tree modeling showed that MUC16 could be a predictive marker for metastasis in GC patients. Additionally, ELISA validation confirmed elevated MUC16 levels in metastatic patients. Notably, high MUC16 levels were independently associated with metastatic progression in T3 or higher GC. These findings suggest the potential of MUC16 as a clinically relevant biomarker for identifying GC patients at high risk of metastasis., (© 2024. The Author(s).)

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS., (© 2024. The Author(s).)

Severe intraventricular hemorrhage (IVH) in premature infants can lead to serious neurological complications. This retrospective cohort study used the Korean Neonatal Network (KNN) dataset to develop prediction models for severe IVH or early death in very-low-birth-weight infants (VLBWIs) using machine-learning algorithms. The study included VLBWIs registered in the KNN database. The outcome was the diagnosis of IVH Grades 3-4 or death within one week of birth. Predictors were categorized into three groups based on their observed stage during the perinatal period. The dataset was divided into derivation and validation sets at an 8:2 ratio. Models were built using Logistic Regression with Ridge Regulation (LR), Random Forest, and eXtreme Gradient Boosting (XGB). Stage 1 models, based on predictors observed before birth, exhibited similar performance. Stage 2 models, based on predictors observed up to one hour after birth, showed improved performance in all models compared to Stage 1 models. Stage 3 models, based on predictors observed up to one week after birth, showed the best performance, particularly in the XGB model. Its integration into treatment and management protocols can potentially reduce the incidence of permanent brain injury caused by IVH during the early stages of birth., (© 2024. The Author(s).)

Cardiac discomfort has been reported periodically in COVID-19-vaccinated individuals. Thus, this study aimed to evaluate the role of myocardial strains in the early assessment of the clinical presentations after COVID-19 vaccination. Totally, 121 subjects who received at least one dose of vaccine within 6 weeks underwent laboratory tests, electrocardiogram (ECG), and echocardiogram. Two-dimensional speckle tracking echocardiography (2D-STE) was implemented to analyze changes in the left ventricular myocardium. After vaccination, 66 individuals (55.4 ± 17.4 years) developed cardiac discomforts, such as chest tightness, palpitations, dyspnea, and chest pain. The ECG readings exhibited both premature ventricular contractions and premature atrial contractions (n = 24, 36.4%), while none of the individuals in the control group manifested signs of cardiac arrhythmia. All had normal serum levels of creatine phosphokinase, creatine kinase myocardial band, troponin, N-terminal pro b-type natriuretic peptide, platelets, and D-dimer. Left ventricular ejection fraction in the symptomatic group (71.41% ± 7.12%) and the control group (72.18% ± 5.11%) (p = 0.492) were normal. Use of 2D-STE presented global longitudinal strain (GLS) and global circumferential strain (GCS) was reduced in the symptomatic group (17.86% ± 3.22% and 18.37% ± 5.22%) compared to the control group (19.54% ± 2.18% and 20.73% ± 4.09%) (p = 0.001 and p = 0.028). COVID-19 vaccine-related cardiac adverse effects can be assessed early by 2D-STE. The prognostic implications of GLS and GCS enable the evaluation of subtle changes in myocardial function after vaccination., (© 2024. The Author(s).)

We aimed to determine whether Crohn's disease (CD) activity patterns assessed via a web-based symptom diary can help predict clinical outcomes in patients with newly diagnosed CD. Patients diagnosed with CD within the preceding 3 months were prospectively enrolled at four tertiary centers. All patients recorded their symptoms on a website using a smartphone at least once a week. The index outcomes were disease-related admission and surgery during follow-up. The disease activity from enrollment to outcome or last follow-up was reviewed for pattern analysis. Cox regression analysis was used to identify the predictors of disease outcomes. A total of 102 patients were enrolled. During a median follow-up period of 42 months, 25 (24.5%) and 6 (5.9%) patients required admission and surgery, respectively. Poor activity pattern was an independent predictor of disease-related hospitalization (adjusted hazard ratio [aHR], 3.96; 95% confidence interval [CI] 1.5-10.45; p = 0.005). A poor activity pattern (aHR, 19.48; 95% CI 1.86-203.95; p = 0.013) and female sex (aHR, 11.28; 95% CI 1.49-85.01; p = 0.018) were found to be independent predictors of bowel resection. CD disease activity patterns monitored through the mobile monitoring system may help predict clinical outcomes, such as disease-related hospitalization and surgery, in patients with newly diagnosed CD., (© 2024. The Author(s).)

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1-4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1-2) or a high-grade group (WHO/ISUP grade 3-4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5-18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6-17.4) in the high-grade group and 28.0 months (21.1-34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0-10.0) for the high-grade group and 10.0 months (6.8-13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135-2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient., (© 2024. The Author(s).)

Formate dehydrogenase (FDH) is critical for the conversion between formate and carbon dioxide. Despite its importance, the structural complexity of FDH and difficulties in the production of the enzyme have made elucidating its unique physicochemical properties challenging. Here, we purified recombinant Methylobacterium extorquens AM1 FDH (MeFDH1) and used cryo-electron microscopy to determine its structure. We resolved a heterodimeric MeFDH1 structure at a resolution of 2.8 Å, showing a noncanonical active site and a well-embedded Fe-S redox chain relay. In particular, the tungsten bis-molybdopterin guanine dinucleotide active site showed an open configuration with a flexible C-terminal cap domain, suggesting structural and dynamic heterogeneity in the enzyme., (© 2024. The Author(s).)

Cancer stem-like cell (CSC) is thought to be responsible for ovarian cancer recurrence. CD24 serves as a CSC marker for ovarian cancer and regulates the expression of miRNAs, which are regulators of CSC phenotypes. Therefore, CD24-regulated miRNAs may play roles in manifesting the CSC phenotypes in ovarian cancer cells. Our miRNA transcriptome analysis showed that 94 miRNAs were up or down-regulated in a CD24-high clone from an ovarian cancer patient compared to a CD24-low one. The CD24-dependent expression trend of the top 7 upregulated miRNAs (miR-199a-3p, 34c, 199a-5p, 130a, 301a, 214, 34b*) was confirmed in other 8 clones (4 clones for each group). CD24 overexpression upregulated the expression of miR-199a-3p, 34c, 199a-5p, 130a, 301a, 214, and 34b* in TOV112D (CD24-low) cells compared to the control, while CD24 knockdown downregulated the expression of miR-199a-3p, 199a-5p, 130a, 301a, and 34b* in OV90 (CD24-high) cells. miR-130a and 301a targeted CDK19, which induced a cellular quiescence-like state (increased G0/G1 phase cell population, decreased cell proliferation, decreased colony formation, and decreased RNA synthesis) and resistance to platinum-based chemotherapeutic agents. CD24 regulated the expression of miR-130a and 301a via STAT4 and YY1 phosphorylation mediated by Src and FAK. miR-130a and 301a were positively correlated in expression with CD24 in ovarian cancer patient tissues and negatively correlated with CDK19. Our results showed that CD24 expression may induce a cellular quiescence-like state and resistance to platinum-based chemotherapeutic agents in ovarian cancer via miR-130a and 301a upregulation. CD24-miR-130a/301a-CDK19 signaling axis could be a prognostic marker for or a potential therapeutic target against ovarian cancer recurrence., (© 2024. The Author(s).)

Recently, diesel engine emissions have been designated as a first-class carcinogen by the World Health Organization (WHO). As such, problems with diesel engine emissions continue to increase around the world. This study aimed to analyze the emissions (CO, NOx, PM) of agricultural tractors during farming operations in order to build a reliable national inventory of air pollutant emissions. Emission data were collected using a portable emission measurement system during actual agricultural operation. The load factor (LF) of the engine was calculated using the collected engine information, the emission factor was analyzed using the LF and the measured emission. The LF was significantly different from the current standard value of 0.48, which is used in Korea to calculate exhaust emissions. The deviation ratio of the emission factor was 0.039 ~ 56.59 compared to Tier-4 emission regulation standards. Under many conditions, the calculated emission factor was higher than the emission limit. Thus, this study provides useful information for emission inventory construction through emission calculation under actual conditions and suggests the need to realize the currently applied emission factor., (© 2024. The Author(s).)

Adaptive multicolor filters have emerged as key components for ensuring color accuracy and resolution in outdoor visual devices. However, the current state of this technology is still in its infancy and largely reliant on liquid crystal devices that require high voltage and bulky structural designs. Here, we present a multicolor nanofilter consisting of multilayered 'active' plasmonic nanocomposites, wherein metallic nanoparticles are embedded within a conductive polymer nanofilm. These nanocomposites are fabricated with a total thickness below 100 nm using a 'lithography-free' method at the wafer level, and they inherently exhibit three prominent optical modes, accompanying scattering phenomena that produce distinct dichroic reflection and transmission colors. Here, a pivotal achievement is that all these colors are electrically manipulated with an applied external voltage of less than 1 V with 3.5 s of switching speed, encompassing the entire visible spectrum. Furthermore, this electrically programmable multicolor function enables the effective and dynamic modulation of the color temperature of white light across the warm-to-cool spectrum (3250 K-6250 K). This transformative capability is exceptionally valuable for enhancing the performance of outdoor optical devices that are independent of factors such as the sun's elevation and prevailing weather conditions., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2024.)

UPF1, a novel posttranscriptional regulator, regulates the abundance of transcripts, including long noncoding RNAs (lncRNAs), and thus plays an important role in cell homeostasis. In this study, we revealed that UPF1 regulates the abundance of hepatocellular carcinoma upregulated EZH2-associated lncRNA (lncRNA-HEIH) by binding the CG-rich motif, thereby regulating hepatocellular carcinoma (HCC) tumorigenesis. UPF1-bound lncRNA-HEIH was susceptible to degradation mediated by UPF1 phosphorylation via SMG1 and SMG5. According to analysis of RNA-seq and public data on patients with liver cancer, the expression of lncRNA-HEIH increased the levels of miR-194-5p targets and was inversely correlated with miR-194-5p expression in HCC patients. Furthermore, UPF1 depletion upregulated lncRNA-HEIH, which acts as a decoy of miR-194-5p that targets GNA13, thereby promoting GNA13 expression and HCC proliferation. The UPF1/lncRNA-HEIH/miR-194-5p/GNA13 regulatory axis is suggested to play a crucial role in cell progression and may be a suitable target for HCC therapy., (© 2024. The Author(s).)

Upper airway collapse can be effectively dealt with positive airway pressure (PAP), and patient adherence is considered as a major determining factor for success of PAP therapy. This study was performed to determine the potential factors affecting the adherence to PAP in patients with OSA by using polysomnography (PSG) parameters recorded for diagnosis of OSA. The data of 158 patients between December 2018 and July 2021 were collected. They were prescribed with PAP and used the device during the adaptation period for 90 days. They were categorized into adherent and non-adherent group according to the criteria of good adherence as use of PAP ≥ 4 h per night on 70% of nights. Demographic, clinical characteristics, and PSG results were reviewed. Among 158 patients engaged in PAP therapy, 121 patients (76.6%) met the criteria of good adherence. No significant differences were found in good adherence rate regarding demographic and clinical characteristics. None of the polysomnographic factors showed significant differences between adherent and non-adherent groups. However, the percentage of sleep time on back in the adherent group was significantly higher than non-adherent group (p = 0.041). The cut-off value was determined to be 41.45% (95% confidence interval 0.43 to 0.79) by receiver operating characteristic curve analysis and the odds ratio was calculated as 2.97. Only the percentage of sleep time on back appeared to be polysomnographic predictor for identifying good adherence to PAP therapy in OSA patients. However, the conclusions may be limited in generalization due to the small sample size., (© 2023. The Author(s).)

Obesity is considered a high-risk disease and a global epidemic, and the number of obese patients is rising at an alarming rate worldwide. High-fat diet-induced dysbiosis of the intestinal microbiota is considered an essential factor related to obesity. Bariatric surgery induces a sharp decrease in fat content and effectively improves the metabolism of obese individuals. Herein, we aimed to investigate the effects of a high-fat diet-induced obesity and the alterations in gastric and intestinal microbiota resulting from sleeve gastrectomy on clinical outcomes. We performed 16S sequencing of gastric and fecal samples obtained from rats in three treatment groups: normal chow diet, high-fat diet (HFD), and sleeve gastrectomy after HDF for 14 weeks. The area under the curve of fasting glucose and the levels of leptin and low-density lipoproteins were significantly different between groups. Microbial taxa that were highly correlated with several clinical parameters were identified for each group. Glyoxylate and dicarboxylate, taurine and hypotaurine, butanoate, nitrogen, and pyrimidine metabolism and aminoacyl-transfer ribonucleic acid biosynthesis were affected by bariatric surgery and were significantly associated with changes in the composition of gastric and fecal microbiomes. Connectivity and co-occurrence were higher in fecal samples than in gastric tissues. Our results elucidated the positive effects of sleeve gastrectomy in obesity and shed light on changes in the microbiomes of gastric and fecal samples., (© 2023. The Author(s).)

Genetic, environment, and behaviour factors have a role in causing sudden cardiac arrest (SCA). We aimed to determine the strength of the association between various risk factors and SCA incidence. We conducted a multicentre case-control study at 17 hospitals in Korea from September 2017 to December 2020. The cases included out-of-hospital cardiac arrest aged 19-79 years with presumed cardiac aetiology. Community-based controls were recruited at a 1:1 ratio after matching for age, sex, and urban residence level. Multivariable conditional logistic regression analysis was conducted. Among the 1016 cases and 1731 controls, 948 cases and 948 controls were analysed. A parental history of SCA, low educational level, own heart disease, current smoking, and non-regular exercise were associated with SCA incidence (Adjusted odds ratio [95% confidence interval]: 2.51 [1.48-4.28] for parental history of SCA, 1.37 [1.38-2.25] for low edication level, 3.77 [2.38-5.90] for non-coronary artery heart disease, 4.47 [2.84-7.03] for coronary artery disease, 1.39 [1.08-1.79] for current smoking, and 4.06 [3.29-5.02] for non-regular exercise). Various risk factors related to genetics, environment, and behaviour were independently associated with the incidence of SCA. Establishing individualised SCA prevention strategies in addition to general prevention strategies is warranted., (© 2023. The Author(s).)

The USP19 deubiquitinase is found in a locus associated with Parkinson's Disease (PD), interacts with chaperonins, and promotes secretion of α-synuclein (α-syn) through the misfolding-associated protein secretion (MAPS) pathway. Since these processes might modulate the processing of α-syn aggregates in PD, we inactivated USP19 (KO) in mice expressing the A53T mutation of α-syn and in whom α-syn preformed fibrils (PFF) had been injected in the striatum. Compared to WT, KO brains showed decreased accumulation of phospho-synuclein (pSyn) positive aggregates. This improvement was associated with less activation of microglia and improved performance in a tail-suspension test. Exposure of primary neurons from WT and KO mice to PFF in vitro also led to decreased accumulation of pSyn aggregates. KO did not affect uptake of PFF nor propagation of aggregates in the cultured neurons. We conclude that USP19 instead modulates intracellular dynamics of aggregates. At an early time following PFF injection when the number of pSyn-positive neurons were similar in WT and KO brains, the KO neurons contained less aggregates. KO brain aggregates stained more intensely with anti-ubiquitin antibodies. Immunoprecipitation of soluble proteins from WT and KO brains with antibodies to pSyn showed higher levels of ubiquitinated oligomeric species in the KO samples. We propose that the improved pathology in USP19 KO brains may arise from decreased formation or enhanced clearance of the more ubiquitinated aggregates and/or enhanced disassembly towards more soluble oligomeric species. USP19 inhibition may represent a novel therapeutic approach that targets the intracellular dynamics of α-syn complexes., (© 2023. The Author(s).)

Advancements in minimally invasive surgery has led to the development of several surgical instruments, including the ArtiSential®. This new instrument provides a greater range of motion and improved dexterity to laparoscopic procedures, making it an alternative option to traditional straight instruments, and the Da Vinci robot system. The purpose of this study is to compare the postoperative outcomes of a prospective cohort of patients who underwent laparoscopic gastrectomy using articulating instruments with those of a historical cohort of patients who underwent the same procedure using straight instruments. The study was designed as a prospective observational cohort study matched to a retrospective historical cohort using propensity score matching. The primary outcome was the rate of early complications within 90 days of surgery. Other outcomes included the operation time, estimated blood loss, time to first flatus, time to first soft fluid diet, hospital stay, and mortality. After propensity score matching, 41 patients were enrolled in both groups. The mean age was 62.4 ± 12.3 years in the conventional group and 63.5 ± 9.6 years in the artisential group (p = 0.647). Mean operative time was significantly shorter in the artisential group compared to the conventional group (136.1 min vs. 163.9 min, p = 0.032). The time to first soft fluid diet was also significantly shorter in the artisential group (2.2 days vs. 2.8 days, p = 0.030), but there was no significant difference in the time to first flatus and overall hospital stay. The incidence of early complications was lower in the artisential group, but the difference was not significant (24.4% vs 7.3%, p = 0.070). There was no mortality in either group. The use of articulating instruments for laparoscopic gastrectomy did not increase postoperative morbidity compared to straight laparoscopic instruments. The use of articulating instruments may be associated with faster bowel recovery and less early complications., (© 2023. Springer Nature Limited.)

Iron deficiency (ID) in very preterm infants born at 28-32 weeks of gestational age (GA) can lower mental and motor test scores. This study aimed to determine whether the rapid growth of very preterm infants might be associated with ID. Among 134 very preterm born between January 2014 and December 2020 at Jeonbuk National University Hospital and discharged home, 93 were included in this study. Rapid BMI increase (RBI) was defined as a z-score difference of > 1 standard deviation between birth and 8 months. ID occurred in 23 of 93 (24.7%) infants at 8 months of corrected age (CA). ID was more common in the RBI group (50%) than in the non-RBI group (18.7%). In the multivariate logistic regression corrected for GA, infants small for gestational age (SGA) (odds ratio [OR] 6.06, 95% confidence interval [CI] 1.34-30.21) and RBI by z-score (OR 4.26, 95% CI 1.28-14.65) were identified as independent risk factors for ID at 8 months of CA. Conclusively, both SGA and RBI in the early life of very preterm were risk factors for ID at 8 months of CA., (© 2023. Springer Nature Limited.)

Methylation patterns in cell-free DNA (cfDNA) have emerged as a promising genomic feature for detecting the presence of cancer and determining its origin. The purpose of this study was to evaluate the diagnostic performance of methylation-sensitive restriction enzyme digestion followed by sequencing (MRE-Seq) using cfDNA, and to investigate the cancer signal origin (CSO) of the cancer using a deep neural network (DNN) analyses for liquid biopsy of colorectal and lung cancer. We developed a selective MRE-Seq method with DNN learning-based prediction model using demethylated-sequence-depth patterns from 63,266 CpG sites using SacII enzyme digestion. A total of 191 patients with stage I-IV cancers (95 lung cancers and 96 colorectal cancers) and 126 noncancer participants were enrolled in this study. Our study showed an area under the receiver operating characteristic curve (AUC) of 0.978 with a sensitivity of 78.1% for colorectal cancer, and an AUC of 0.956 with a sensitivity of 66.3% for lung cancer, both at a specificity of 99.2%. For colorectal cancer, sensitivities for stages I-IV ranged from 76.2 to 83.3% while for lung cancer, sensitivities for stages I-IV ranged from 44.4 to 78.9%, both again at a specificity of 99.2%. The CSO model's true-positive rates were 94.4% and 89.9% for colorectal and lung cancers, respectively. The MRE-Seq was found to be a useful method for detecting global hypomethylation patterns in liquid biopsy samples and accurately diagnosing colorectal and lung cancers, as well as determining CSO of the cancer using DNN analysis.Trial registration: This trial was registered at ClinicalTrials.gov (registration number: NCT04253509) for lung cancer on 5 February 2020, https://clinicaltrials.gov/ct2/show/NCT04253509 . Colorectal cancer samples were retrospectively registered at CRIS (Clinical Research Information Service, registration number: KCT0008037) on 23 December 2022, https://cris.nih.go.kr , https://who.init/ictrp . Healthy control samples were retrospectively registered., (© 2023. Springer Nature Limited.)

Mitochondria, ubiquitous double-membrane-bound organelles, regulate energy production, support cellular activities, harbor metabolic pathways, and, paradoxically, mediate cell fate. Evidence has shown mitochondria as points of convergence for diverse cell death-inducing pathways that trigger the various mechanisms underlying apoptotic and nonapoptotic programmed cell death. Thus, dysfunctional cellular pathways eventually lead or contribute to various age-related diseases, such as neurodegenerative, cardiovascular and metabolic diseases. Thus, mitochondrion-associated programmed cell death-based treatments show great therapeutic potential, providing novel insights in clinical trials. This review discusses mitochondrial quality control networks with activity triggered by stimuli and that maintain cellular homeostasis via mitohormesis, the mitochondrial unfolded protein response, and mitophagy. The review also presents details on various forms of mitochondria-associated programmed cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, parthanatos, and paraptosis, and highlights their involvement in age-related disease pathogenesis, collectively suggesting therapeutic directions for further research., (© 2023. The Author(s).)

This study aimed to investigate the residual characteristics of pesticides drifted by unmanned aerial spray according to buffer strip, windbreak, and morphological characteristics of non-target crops, suggest prevention for drift reduction, and finally conduct a risk analysis on pesticides exceeding the maximum residue limit (MRL) or uniform level (0.01 mg/kg) of the positive list system (PLS). Non-target crops were collected around the aerial sprayed area (paddy rice) in Boryeong, Seocheon, and Pyeongtaek after UAV spray. When pesticides were detected in more than three samples, Duncan's multiple range test was performed. In cases where pesticides were detected in only two samples, an independent sample t-test was conducted (p < 0.05). The drift rate of pesticides tends to decrease by up to 100% as the buffer distance from aerial sprayed area increases or when a windbreak, such as maize, is present between two locations. Thus, the reduction of drifted pesticides could be effective if both factors were applied near the UAV spray area. Moreover, the residue of drifted pesticides was found to be the highest in leafy vegetables such as perilla leaves or leaf and stem vegetables such as Welsh onion, followed by fruit vegetables and cucurbits, owing to the morphological characteristics of crops. Therefore, selecting pulse or cereal such as soybean or maize as a farm product near the UAV spray area can be considered to minimize the drift. For pesticides that exceed the MRL or PLS uniform level, %acceptable dietary intake is 0-0.81% with no risk. Additionally, employing pesticides approved for both paddy rice and farm products in UAV spraying can effectively minimize instances where MRL or PLS are exceeded. Therefore, this study aims to provide farmers with effective guidelines for mitigating drift. Furthermore, we strive to promote stable and uninterrupted food production while facilitating the utilization of agricultural technologies such as UAV spraying to address labor shortages and ensure sustainable food security., (© 2023. The Author(s).)

Transient receptor potential vanilloid member 3 (TRPV3) is an ion channel that plays a critical role in temperature sensing in skin. There have been active studies on how TRPV3, which is also known as one of the temperature-sensitive transient receptor potential (thermoTRP) channels, responds to temperature. However, the previous studies were mostly based on TRPV3 originating from mice or rats. Here, we focus on human TRPV3 (hTRPV3) and show that which domain of hTRPV3 undergoes conformational changes as temperature increases by Förster resonance energy transfer (FRET) assay. During the heat-induced activation of hTRPV3, the linker domain close to C-terminus, that is, the C-terminal domain shows a largest structural change whereas there is little change in the ankyrin repeat domain (ARD). Interestingly, the activation of hTRPV3 by an agonist shows structural change patterns that are completely different from those observed during activation by heat; we observe structural changes in ARD and S2-S3 linker after ligand stimulation whereas relatively little change is observed when stimulated by heat. Our results provide insight into the thermal activation of hTRPV3 channel., (© 2023. The Author(s).)

Few literatures discussed the relationship of glycemic control and body mass index (BMI) with the risk of pyogenic liver abscess. We conducted a population-based cohort study using participants of a community-based health screening program in Taiwan from 2005 to 2008 (n = 125,865). Information on fasting plasma glucose (FPG), BMI, and other potential risk factors of liver abscess were collected at baseline. Incidence of pyogenic liver abscess was ascertained using inpatient records from the National Health Insurance database. During a median 8.6 years of followed up, 192 incident cases of pyogenic liver abscess were reported. The incidence rate of pyogenic liver abscess was 70.2 and 14.7 per 100,000 in the diabetic and non-diabetic population respectively. In multivariable Cox regression analysis, the adjusted hazard ratio (HR) was 2.18 (95% confidence interval (CI) 1.22-3.90) in patients with diabetes with good glycemic control (FPG ≤ 130 mg/dl) and 3.34 (95% CI 2.37-4.72) in those with poor glycemic control (FPG > 130 mg/dl), when compared with non-diabetics. In the dose-response analysis, the risk of liver abscess increased monotonically with increasing FPG. After adjusting for diabetes and other comorbidities, overweight (25 ≤ BMI < 30) (adjusted HR: 1.43, 95% CI 1.05-1.95) and obese (BMI ≥ 30) (adjusted HR: 1.75, 95% CI 1.09-2.81) populations had a higher risk of liver abscess when compared to people with normal weight. Diabetes, especially poorly controlled disease, and high BMI were associated with higher risk of pyogenic liver abscess. Improving glycemic control and weight reduction may reduce the risk of developing pyogenic liver abscess., (© 2023. The Author(s).)

Identifying the cerebral arterial branches is essential for undertaking a computational approach to cerebrovascular imaging. However, the complexity and inter-individual differences involved in this process have not been thoroughly studied. We used machine learning to examine the anatomical profile of the cerebral arterial tree. The method is less sensitive to inter-subject and cohort-wise anatomical variations and exhibits robust performance with an unprecedented in-depth vessel range. We applied machine learning algorithms to disease-free healthy control subjects (n = 42), patients with stroke with intracranial atherosclerosis (ICAS) (n = 46), and patients with stroke mixed with the existing controls (n = 69). We trained and tested 70% and 30% of each study cohort, respectively, incorporating spatial coordinates and geometric vessel feature vectors. Cerebral arterial images were analyzed based on the 'segmentation-stacking' method using magnetic resonance angiography. We precisely classified the cerebral arteries across the exhaustive scope of vessel components using advanced geometric characterization, redefinition of vessel unit conception, and post-processing algorithms. We verified that the neural network ensemble, with multiple joint models as the combined predictor, classified all vessel component types independent of inter-subject variations in cerebral arterial anatomy. The validity of the categorization performance of the model was tested, considering the control, ICAS, and control-blended stroke cohorts, using the area under the receiver operating characteristic (ROC) curve and precision-recall curve. The classification accuracy rarely fell outside each image's 90-99% scope, independent of cohort-dependent cerebrovascular structural variations. The classification ensemble was calibrated with high overall area rates under the ROC curve of 0.99-1.00 [0.97-1.00] in the test set across various study cohorts. Identifying an all-inclusive range of vessel components across controls, ICAS, and stroke patients, the accuracy rates of the prediction were: internal carotid arteries, 91-100%; middle cerebral arteries, 82-98%; anterior cerebral arteries, 88-100%; posterior cerebral arteries, 87-100%; and collections of superior, anterior inferior, and posterior inferior cerebellar arteries, 90-99% in the chunk-level classification. Using a voting algorithm on the queued classified vessel factors and anatomically post-processing the automatically classified results intensified quantitative prediction performance. We employed stochastic clustering and deep neural network ensembles. Ma-chine intelligence-assisted prediction of vessel structure allowed us to personalize quantitative predictions of various types of cerebral arterial structures, contributing to precise and efficient decisions regarding the cerebrovascular disease., (© 2023. The Author(s).)

Endoscopic tattooing with India ink is a popular method for identifying colonic lesions during minimally invasive surgery because it is highly challenging to localize lesions during laparoscopy. However, there is a perceived unmet need for the injection of India ink and carbon particle suspension due to various complications and inconstant durability during the perioperative period. In this study, carbon black-containing self-healing adhesive alginate/polyvinyl alcohol composite hydrogels were synthesized as endoscopic tattooing inks. Alginate (Alg) conjugated with phenylboronic acid (PBA) groups in the backbone was crosslinked with polyvinyl alcohol (PVA) because of the dynamic bonds between the phenylboronic acid in alginate and the cis-diol groups of PVA. The carbon black-incorporated Alg-PBA/PVA hydrogels exhibited self-healing and re-shapable properties, indicating that improved intraoperative localization could be achieved. In addition, the adhesive tattooing hydrogels were stably immobilized on the target regions in the intraperitoneal spaces. These carbon black-containing self-healing adhesive hydrogels are expected to be useful in various surgical procedures, including endoscopic tattooing., (© 2023. The Author(s).)

Based on the pharmaceutical potentials of coumarins, which have antitumor activity, we synthesized new coumarin derivatives and evaluated their biological activities. The new coumarin derivatives were chemically synthesized from 4-hydroxycoumarin, and their structures were confirmed by nuclear magnetic resonance data. Ten of the synthesized compounds were investigated for antimetastatic activity against lung carcinoma cells. Several of the tested compounds showed good to mild inhibitory effects on lung cancer cell motility. There were no cytotoxic effects related to the use of these compounds. 4-Hydroxycoumarin derivatives, 4h and 4i, elicited the significant inhibitory effect on lung cancer cell motility by suppressing expression of the epithelial-mesenchymal transition markers N-cadherin, Snail, and Twist., (© 2022. The Author(s).)

Three-dimensionally structured silicon (Si)-carbon (C) nanocomposites have great potential as anodes in lithium-ion batteries (LIBs). Here, we report a Nitrogen-doped graphene/carbon-encapsulated Si nanoparticle/carbon nanofiber composite (NG/C@Si/CNF) prepared by methods of surface modification, electrostatic self-assembly, cross-linking with heat treatment, and further carbonization as a potential high-performance anode for LIBs. The N-doped C matrix wrapped around Si nanoparticles improved the electrical conductivity of the composites and buffered the volume change of Si nanoparticles during lithiation/delithiation. Uniformly dispersed CNF in composites acted as conductive networks for the fast transport of ions and electrons. The entire tightly connected organic material of NG/C@Si and CNF prevented the crushing and shedding of particles and maintained the integrity of the electrode structure. The NG/C@Si/CNF composite exhibited better rate capability and cycling performance compared with the other electrode materials. After 100 cycles, the electrode maintained a high reversible specific capacity of 1371.4 mAh/g., (© 2022. The Author(s).)

Peritumoral cerebral edema is reported to be a side effect that can occur after stereotactic radiosurgery. We aimed to determine whether intratumoral necrosis (ITN) is a risk factor for peritumoral edema (PTE) when gamma knife radiosurgery (GKRS) is performed in patients with meningioma. In addition, we propose the concept of pseudoprogression: a temporary volume expansion that can occur after GKRS in the natural course of meningioma with ITN. This retrospective study included 127 patients who underwent GKRS for convexity meningioma between January 2019 and December 2020. Risk factors for PTE and ITN were investigated using logistic regression analysis. Analysis of variance was used to determine whether changes in tumor volume were statistically significant. After GKRS, ITN was observed in 34 (26.8%) patients, and PTE was observed in 10 (7.9%) patients. When postoperative ITN occurred after GKRS, the incidence of postoperative PTE was 18.970-fold (p = 0.009) greater. When a 70% dose volume ≥ 1 cc was used, the possibility of ITN was 5.892-fold (p < 0.001) higher. On average, meningiomas with ITN increased in volume by 128.5% at 6 months after GKRS and then decreased to 94.6% at 12 months. When performing GKRS in meningioma, a 70% dose volume ≥ 1 cc is a risk factor for ITN. At 6 months after GKRS, meningiomas with ITN may experience a transient volume expansion and PTE, which are characteristics of pseudoprogression. These characteristics typically improve at 12 months following GKRS., (© 2022. The Author(s).)

Crizotinib is a clinically approved tyrosine kinase inhibitor for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EML4-ALK fusion. Crizotinib was originally developed as an inhibitor of MET (HGF receptor), which is involved in the metastatic cascade. However, little is known about whether crizotinib inhibits tumor metastasis in NSCLC cells. In this study, we found that crizotinib suppressed TGFβ signaling by blocking Smad phosphorylation in an ALK/MET/RON/ROS1-independent manner in NSCLC cells. Molecular docking and in vitro enzyme activity assays showed that crizotinib directly inhibited the kinase activity of TGFβ receptor I through a competitive inhibition mode. Cell tracking, scratch wound, and transwell migration assays showed that crizotinib simultaneously inhibited TGFβ- and HGF-mediated NSCLC cell migration and invasion. In addition, in vivo bioluminescence imaging analysis showed that crizotinib suppressed the metastatic capacity of NSCLC cells. Our results demonstrate that crizotinib attenuates cancer metastasis by inhibiting TGFβ signaling in NSCLC cells. Therefore, our findings will help to advance our understanding of the anticancer action of crizotinib and provide insight into future clinical investigations., (© 2022. The Author(s).)

Strict and repeated lockdowns have caused public fatigue regarding policy compliance and had a large impact on several countries' economies. We aimed to evaluate the effectiveness of a soft lockdown policy and the strategy of active community screening for controlling COVID-19 in Taiwan. We used village-based daily confirmed COVID-19 statistics in Taipei City and New Taipei City, between May 2, 2021, and July 17, 2021. The temporal Gi* statistic was used to compute the spatiotemporal hotspots. Simple linear regression was used to evaluate the trend of the epidemic, positivity rate from community screening, and mobility changes in COVID-19 cases and incidence before and after a level three alert in both cities. We used a Bayesian hierarchical zero-inflated Poisson model to estimate the daily infection risk. The cities accounted for 11,403 (81.17%) of 14,048 locally confirmed cases. The mean effective reproduction number (Re) surged before the level three alert and peaked on May 16, 2021, the day after the level three alert in Taipei City (Re = 3.66) and New Taipei City (Re = 3.37). Mobility reduction and a lower positive rate were positively associated with a lower number of cases and incidence. In the spatiotemporal view, seven major districts were identified with a radial spreading pattern from one hard-hit district. Villages with a higher inflow degree centrality among people aged ≥ 60 years, having confirmed cases, specific land-use types, and with a higher aging index had higher infection risks than other villages. Early soft lockdown policy and detection of infected patients showed an effective strategy to control COVID-19 in Taiwan., (© 2022. The Author(s).)

Iris ruthenica Ker Gawl. and I. uniflora Pall. ex Link, which are rare and endangered species in Korea, possess considerable horticultural and medicinal value among Korean irises. However, discrimination of the species is hindered by extensive morphological similarity. Thus, the aim of the present study was to identify discriminating features by comparing the species' complete plastid genome (i.e., plastome) sequences and micromorphological features, including leaf margins, stomatal complex distribution (hypostomatic vs. amphistomatic leaves), anther stomata density, and tepal epidermal cell patterns. Plastome comparison revealed slightly divergent regions within intergenic spacer regions, and the most variable sequences, which were distributed in non-coding regions, could be used as molecular markers for the discrimination of I. ruthenica and I. uniflora. Phylogenetic analysis of the Iris species revealed that I. ruthenica and I. uniflora formed a well-supported clade. The comparison of plastomes and micromorphological features performed in this study provides useful information for elucidating taxonomic, phylogenetic, and evolutionary relationships in Iridaceae. Further studies, including those based on molecular cytogenetic approaches using species specific markers, will offer insights into species delimitation of the two closely related Iris species., (© 2022. The Author(s).)

The advantages of laparoscopic resection over open surgery in the treatment of gastric gastrointestinal stromal tumor (GIST) are not conclusive. This study aimed to evaluate the postoperative and oncologic outcome of laparoscopic resection for gastric GIST, compared to open surgery. We retrospectively reviewed the prospectively collected database of 1019 patients with gastric GIST after surgical resection at 13 Korean and 2 Japanese institutions. The surgical and oncologic outcomes were compared between laparoscopic and open group, through 1:1 propensity score matching (PSM). The laparoscopic group (N = 318) had a lower rate of overall complications (3.5% vs. 7.9%, P = 0.024) and wound complications (0.6% vs. 3.1%, P = 0.037), shorter hospitalization days (6.68 ± 4.99 vs. 8.79 ± 6.50, P < 0.001) than the open group (N = 318). The superiority of the laparoscopic approach was also demonstrated in patients with tumors larger than 5 cm, and at unfavorable locations. The recurrence-free survival was not different between the two groups, regardless of tumor size, locational favorableness, and risk classifications. Cox regression analysis revealed that tumor size larger than 5 cm, higher mitotic count, R1 resection, and tumor rupture during surgery were independent risk factors for recurrence. Laparoscopic surgery provides lower rates of complications and shorter hospitalizations for patients with gastric GIST than open surgery., (© 2022. The Author(s).)

Laparoscopic sleeve gastrectomy is the most frequently performed surgical intervention in patients with morbid obesity. Single-port sleeve gastrectomy (SPSG) and reduced-port sleeve gastrectomy (RPSG) are increasingly reported in the literature. This study compared the short-term outcomes of SPSG, RPSG, and conventional laparoscopic sleeve gastrectomy (CLSG). This is a single-center retrospective study of 238 morbidly obese patients, of whom 148 (62.2%) patients completed follow-up one year after surgery. Propensity score matching was performed on factors influencing the choice of approach, and fifty patients from the SPSG + RPSG and CLSG groups were successfully matched. The groups were comparable in postoperative weight loss, morbidity, pain, and resolution of obesity-related comorbidities. The percentage of excess weight loss after one year was 90.0% in the SPSG + RPSG group and 75.2% in the CLSG group (P < 0.001). Complication rates showed no significant difference. The CLSG group was superior in dyslipidemia remission (17 [37.0%] vs. 28 [63.6%], P = 0.018) in the total cohort; however, this difference disappeared after matching. Our results suggest that single-port and reduced-port approaches could be alternative choices for selected patients. As our study was limited by its retrospective nature and potential selection bias, further studies are necessary to set standardized guidelines for SPSG., (© 2021. The Author(s).)

Background and Objectives: Transcriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation., Materials and Methods: To focus on prostate epithelial cell-relevant heterogeneity, we defined 1,629 genes expressed by prostate epithelial cells by analyzing publicly available bulk and single- cell RNA sequencing data. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. Serum markers PSA and PAP was analyzed to predict response to docetaxel chemotherapy in metastatic setting., Results: We identified two luminal subtypes and two aggressive variant subtypes of PCa: luminal A (Adipogenic/AR-active/PSA-high) (30.0%); luminal S (Secretory/PAP-high) (26.0%); AVPC-I (Immune-infiltrative) (14.7%), AVPC-M (Myc-active) (4.2%), and mixed (25.0%). AVPC-I and AVPC-M subtypes predicted to be resistant to ARI and have low PSA per tumor burden. Luminal A and AVPC-M predicted to be resistant to docetaxel and have high PSA/PAP Ratio. Metastatic PCa patients with high PSA/PAP ratio (>20) had significantly shorter progression-free survival than those with low ratio (≤20) following docetaxel chemotherapy., Conclusion: We propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents., (© 2021. The Author(s).)

Exposure to cigarette smoke (CS) is a factor that could delay or worsen the recovery of otitis media (OM) by causing inflammatory swelling of the Eustachian tube (ET). However, despite the suggested relationship, little is known about the association between OM and CS. Therefore, we aimed to evaluate the effects of CS on the development, progression, and recovery of OM, as well as the histological and molecular changes caused by CS exposure, by using a rat model of OM infected with non-typeable Haemophilus influenzae (NTHi). Eighty Sprague-Dawley rats with normal middle ears (MEs) were divided into four groups (n = 20 rats/group): control, CS, OM, and CS + OM. The CS and CS + OM groups were exposed to CS for 2 weeks. The inflammatory reaction to NTHi was more intense and lasted longer in the CS + OM group than in the other groups. Goblet cell proliferation and mucus secretion in the ET were more significant in the CS and CS + OM groups than in the other groups. These findings suggested that because CS directly affects the ET and ME mucosa, bacterial OM can become more severe and may resolve more slowly in the presence of CS exposure rather than in its absence., (© 2021. The Author(s).)

Gut microbiota is very important for energy metabolism and regulation, which in turn affect the health and physiological functions of the host, and provide energy required for exercise. Supplementation with probiotics may be one of the ways to change the gut microbiota. In recent years, many studies have shown that probiotic supplementation can effectively improve sports performance. In this study, we screened Lactobacillus plantarum (PL-02), a probiotic of human-origin, from the intestines of 2008 Olympic women's 48 kg weightlifting gold medalist and explored the role of PL-02 in improved exercise endurance performance, reduced fatigue biochemical parameters, and changes in body composition. Male Institute of Cancer Research (ICR) mice were assigned to 0, 2.05 × 10 9 , 4.10 × 10 9 and 1.03 × 10 10  CFU/kg/day groups and were fed by oral gavage once daily for 4 weeks. The results showed that 4 weeks of PL-02 supplementation could significantly increase muscle mass, muscle strength and endurance performance, and hepatic and muscular glycogen storage. Furthermore, PL-02 could significantly decrease lactate, blood urea nitrogen (BUN), ammonia, and creatine kinase (CK) levels after exercise (p < 0.05). We believe that PL-02 can be used as a supplement to improve exercise performance and for its anti-fatigue effect., (© 2021. The Author(s).)

Tenebrio molitor larva (mealworms) has recently attracted attention as a protein source for food and feed. The larva is generally fed with wheat bran, which can be possibly contaminated with glyphosate. To establish food safe standards, a rugged and effective analytical method for glyphosate, aminomethylphosphonic acid, glufosinate, and their metabolites including 3-methylphosphinico-propionic acid, and N-acetyl glufosinate, in mealworms was optimized using liquid chromatography tandem mass spectrometry. An anionic polar pesticide column was used due to its high suitability for glyphosate. Acidified water and acetonitrile were used to extract the target compounds without contribution from various fatty and pigment interferences derived from brownish insects. Seven different clean-up procedures ((1) 50 mg C18 (2) 20 mg C18/Z-sep (3) PRiME hydrophilic-lipophilic balance (HLB) cartridge (4) 75 mg Z-sep, (5) 75 mg Z-sep+, (6) EMR-lipid cartridge, and (7) 50 mg ENVI-Carb) were compared. Due to its simplicity and cost-effectiveness, PRiME HLB was selected for clean-up. The recoveries of the target compounds were ranged from 86 to 96% with < 20% relative standard deviations. Therefore, this simple and effective method can be applied for the two pesticides and their metabolites in other edible insects or high-fat matrices., (© 2021. The Author(s).)

Caspase-8-cleaved Bid (cBid) associates with mitochondria and promotes the activation of BAX, leading to mitochondria outer membrane permeabilization (MOMP) and apoptosis. However, current structural models of cBid are largely based on studies using membrane vesicles and detergent micelles. Here we employ spin-label ESR and site-directed PEGylation methods to identify conformations of cBid at real mitochondrial membranes, revealing stepwise mechanisms in the activation process. Upon the binding of cBid to mitochondria, its structure is reorganized to expose the BH3 domain while leaving the structural integrity only slightly altered. The mitochondria-bound cBid is in association with Mtch2 and it remains in the primed state until interacting with BAX. The interaction subsequently triggers the fragmentation of cBid, causes large conformational changes, and promotes BAX-mediated MOMP. Our results reveal structural differences of cBid between mitochondria and other lipid-like environments and, moreover, highlight the role of the membrane binding in modifying cBid structure and assisting the inactive-to-active transition in function.

This study evaluated whether early pulmonary hypertension (PH) in extremely preterm infants (EPIs) at 22-27 weeks of gestation detected clinically with echocardiography at 4-7 postnatal days (PND) is a risk factor for death before 36 weeks post-menstrual age (PMA) or late PH in moderate or severe (m/s) bronchopulmonary dysplasia (BPD) (BPD-PH). We analyzed risk factors for death before 36 weeks PMA or BPD-PH. Among 247 EPIs enrolled, 74 (30.0%) had early PH. Twenty-one (28.4%) infants with early PH and 18 (10.4%) without early PH died before 36 weeks PMA; 14 (18.9%) infants with early PH and 9 (5.2%) without early PH had BPD-PH at 36-38 weeks PMA. Multivariate analysis revealed that early PH (adjusted odds ratio, 6.55; 95% confidence interval, 3.10-13.82, P < 0.05), clinical chorioamnionitis (2.50; 1.18-5.31), intraventricular hemorrhage (grade 3-4) (3.43; 1.26-9.37), and late sepsis (6.76; 3.20-14.28) independently increased the risk of development of death before 36 weeks PMA or BPD-PH. Subgroup analysis among m/s BPD patients revealed that early PH (4.50; 1.61-12.58) and prolonged invasive ventilator care (> 28 days) (4.91; 1.02-23.68) increased the risk for late PH independently. In conclusion, EPIs with early PH at 4-7 PND should be monitored for BPD-associated late PH development.

The purpose of this study is to investigate strategies for peripherally inserted central catheter (PICC) placement in patients with venous steno-occlusive lesion (VSOL). We performed a retrospective cohort study in adults with central or peripheral VSOL who underwent PICC placement procedures from January 2015 to December 2018. Four different strategies [selecting alternative pathway/over the wire (SAP/OTW), percutaneous transluminal angioplasty (PTA), re-puncture in ipsilateral arm (RIA), and catheter placement in the contralateral arm (CICA)] were analyzed and we compared the clinical outcomes by strategy and compared the strategy between central and peripheral VSOLs. During 4 years, 258 PICC procedures performed in patients with VSOLs, 100 PICC were included in the analysis. The overall technical success rate of initial attempt with SAP/OTW was 32.2%. As a second-line technique, PTA was most frequently used in both central (100%) and peripheral (68.2%) VSOL groups. The clinical success rates within 2 months of SAP/OTW, PTA, RIA, CICA were 55.2%, 43.2%, 14.3%, and 33.3%, respectively (P = 0.24). In conclusion, when the SAP/OTW failed, the PTA can be preferred as a second-line technique for both central and peripheral VSOLs. When guidewire passage fails, the operator could adopt the RIA or CICA technique as an alternative method.

The management of vestibular schwannoma (VS) with residual tumor following incomplete resection remains controversial and little is known regarding postoperative tumor volume changes. The behavior of residual tumors was analyzed for 111 patients who underwent surgery for newly diagnosed VS between September 2006 and July 2017. The postoperative tumor volume changes were assessed during a mean follow-up of 69 months (range 36-147 months). Fifty-three patients underwent imaging surveillance following incomplete resection. There was no residual tumor growth in 44 patients (83%). A significant regression of residual tumor volume was noted in the no growth group at postoperative 1 year (p = 0.028), 2 years (p = 0.012), but not from 3 years onwards. Significant predictors of regrowth were immediate postoperative tumor volume ≥ 0.7 cm 3 (HR 10.5, p = 0.020) and residual tumor location other than the internal auditory canal (IAC) (HR 6.2, p = 0.026). The mean time to regrowth was 33 months (range 5-127 months). The 2-, 5-, and 10-year regrowth-free survival rates were 90.6%, 86.8%, and 83%, respectively. In conclusion, significant residual tumor regression could occur within 2 years for a VS with an immediate postoperative tumor volume less than 0.7 cm 3 or residual tumor in IAC.

Clival chordoma is a rare disease with high recurrence rates even after a combination of surgical resection and radiotherapy. Apparent diffusion coefficient (ADC) has been used to evaluate aggressive features of chordoma, but its utility for clival chordoma has not been explored specifically. In this study, the utility of preoperative ADC values was analyzed for predicting tumor progression and recurrence in patients with clival chordoma. Between 2012 and 2019, a total of 30 operated cases were analyzed with available preoperative ADC data. Receiver operating characteristic (ROC) analysis was used to obtain ADC cutoff values for predicting tumor aggressiveness. The mean and minimum ADC values were significantly lower in the aggressive tumor group than in the stable tumor group (both P < 0.001). ROC analysis showed that a mean cutoff ADC value of 1198 × 10 -6 mm 2 /s and minimum ADC value of 895.5 × 10 -6 mm 2 /s could be used to predict aggressive features of clival chordoma. Subtotal resection, partial resection, and mean and minimum ADC values that were lower than cutoff values were negative predictors of overall survival and progression-free survival. In conclusion, mean and minimum ADC values could be useful in predicting aggressiveness of clival chordoma.

Among the three isoforms encoded by Rtn4, Nogo-A has been intensely investigated as a central nervous system inhibitor. Although Nogo-A expression is increased in muscles of patients with amyotrophic lateral sclerosis, its role in muscle homeostasis and regeneration is not well elucidated. In this study, we discovered a significant increase in Nogo-A expression in various muscle-related pathological conditions. Nogo -/- mice displayed dystrophic muscle structure, dysregulated muscle regeneration following injury, and altered gene expression involving lipid storage and muscle cell differentiation. We hypothesized that increased Nogo-A levels might regulate muscle regeneration. Differentiating myoblasts exhibited Nogo-A upregulation and silencing Nogo-A abrogated myoblast differentiation. Nogo-A interacted with filamin-C, suggesting a role for Nogo-A in cytoskeletal arrangement during myogenesis. In conclusion, Nogo-A maintains muscle homeostasis and integrity, and pathologically altered Nogo-A expression mediates muscle regeneration, suggesting Nogo-A as a novel target for the treatment of myopathies in clinical settings.

The expression of aminoglycoside-modifying enzymes represents a survival strategy of antibiotic-resistant bacteria. Aminoglycoside 2'-N-acetyltransferase [AAC(2')] neutralizes aminoglycoside drugs by acetylation of their 2' amino groups in an acetyl coenzyme A (CoA)-dependent manner. To understand the structural features and molecular mechanism underlying AAC(2') activity, we overexpressed, purified, and crystallized AAC(2') from Mycolicibacterium smegmatis [AAC(2')-Id] and determined the crystal structures of its apo-form and ternary complexes with CoA and four different aminoglycosides (gentamicin, sisomicin, neomycin, and paromomycin). These AAC(2')-Id structures unraveled the binding modes of different aminoglycosides, explaining the broad substrate specificity of the enzyme. Comparative structural analysis showed that the α4-helix and β8-β9 loop region undergo major conformational changes upon CoA and substrate binding. Additionally, structural comparison between the present paromomycin-bound AAC(2')-Id structure and the previously reported paromomycin-bound AAC(6')-Ib and 30S ribosome structures revealed the structural features of paromomycin that are responsible for its antibiotic activity and AAC binding. Taken together, these results provide useful information for designing AAC(2') inhibitors and for the chemical modification of aminoglycosides.

There are no clear guidelines on the compatibility between endoclips that remain in the gastrointestinal (GI) tract and magnetic resonance imaging (MRI). The purpose of this study was to investigate the effect of 3T (T) MRI on endoclips placed in excised pig tissues. Two types of endoclips were assessed: Olympus EZ (HX-610-135L) and QuickClip Pro (HZ-202LR). We assessed tissue damage or perforation and detachment of endoclips under 3T MRI magnetic field. We also evaluated the magnitude of force required to detach the endoclips from the porcine tissue. We measured the magnetic force acting on the Olympus EZ clips. QuickClip Pro clips were used as a control in this study. There was no tissue damage and no detachment of the endoclips (Olympus EZ and QuickClip Pro) during 3T MRI. The force required to detach the Olympus EZ clips ranged from 0.9 to 3.0 N. The translational magnetic force acting on the endoclips was 3.18 × 10 -3  N. Ex vivo experiments showed that the magnetic field generated by 3 MRI did not cause tissue damage or perforation and did not detach the endoclips. Olympus EZ clips and QuickClip Pro clips in the GI tract appear to be safe during 3T MRI.

Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70-0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55-0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66-0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68-0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57-0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40-0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48-0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization.

Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients' blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.