Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.

BACKGROUND: Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence. METHODS: Transcriptomic analysis was conducted using datasets of CML patients' stem cells and healthy cells. DNA damage was evaluated by fluorescent microscopy and flow cytometry. Cell death was assessed by trypan blue exclusion test, fluorescent microscopy, flow cytometry, colony formation assay, and in vivo Zebrafish xenografts. Energy metabolism was determined by measuring NAD+ and NADH levels, ATP production rate by Seahorse analyzer, and intracellular ATP content. Mitochondrial fitness was estimated by measurements of mitochondrial membrane potential, ROS, and calcium accumulation by flow cytometry, and morphology was visualized by TEM. Bioinformatic analysis, real-time qPCR, western blotting, chemical reaction prediction, and molecular docking were utilized to identify the drug target. The immunogenic potential was assessed by high mobility group box (HMGB)1 ELISA assay, luciferase-based extracellular ATP assay, ectopic calreticulin expression by flow cytometry, and validated by phagocytosis assay, and in vivo vaccination assay using syngeneic C57BL/6 mice. RESULTS: Transcriptomic analysis identified metabolic alterations and DNA repair deficiency signatures in CML patients. CML patients exhibited enrichment in immune system, DNA repair, and metabolic pathways. The gene signature associated with BRCA mutated tumors was enriched in CML datasets, suggesting a deficiency in double-strand break repair pathways. Additionally, poly(ADP-ribose) polymerase (PARP)1 was significantly upregulated in CML patients' stem cells compared to healthy counterparts. Consistent with the CML patient DNA repair signature, treatment with the methylated indolequinone MAC681 induced DNA damage, mitochondrial dysfunction, calcium homeostasis disruption, metabolic catastrophe, and necroptotic-like cell death. In parallel, MAC681 led to PARP1 degradation that was prevented by 3-aminobenzamide. MAC681-treated myeloid leukemia cells released DAMPs and demonstrated the potential to generate an immunogenic vaccine in C57BL/6 mice. MAC681 and asciminib exhibited synergistic effects in killing both imatinib-sensitive and -resistant CML, opening new therapeutic opportunities. CONCLUSIONS: Overall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.

Enhancing Si3N4 Selectivity over SiO2 in Low-RF Power NF3-O2 Reactive Ion Etching: The Effect of NO Surface Reaction.

Highly selective etching of silicon nitride (Si3N4) and silicon dioxide (SiO2) has received considerable attention from the semiconductor community owing to its precise patterning and cost efficiency. We investigated the etching selectivity of Si3N4 and SiO2 in an NF3/O2 radio-frequency glow discharge. The etch rate linearly depended on the source and bias powers, whereas the etch selectivity was affected by the power and ratio of the gas mixture. We found that the selectivity can be controlled by lowering the power with a suitable gas ratio, which affects the surface reaction during the etching process. X-ray photoelectron spectroscopy of the Si3N4 and QMS measurements support the effect of surface reaction on the selectivity change by surface oxidation and nitrogen reduction with the increasing flow of O2. We suggest that the creation of SiOxNy bonds on the surface by NO oxidation is the key mechanism to change the etch selectivity of Si3N4 over SiO2.

Identification and Molecular Docking Analysis of Angiotensin-Converting Enzyme Inhibitors from Finger Millet (Eleusine coracana).

Hypertension remains a significant global health concern, contributing significantly to cardiovascular diseases and mortality rates. The inhibition of angiotensin-converting enzyme (ACE) plays a crucial role in alleviating high blood pressure. We investigated the potential of finger millets (Eleusine coracana) as a natural remedy for hypertension by isolating and characterizing its ACE-inhibitory compound. First, we evaluated the ACE-inhibitory activity of the finger millet ethanol extract and subsequently proceeded with solvent fractionation. Among the solvent fractions, the ethyl acetate fraction exhibited the highest ACE inhibitory activity and was further fractionated. Using preparative high-performance liquid chromatography, the ethyl acetate fraction was separated into four subfractions, with fraction 2 (F2) exhibiting the highest ACE inhibitory activity. Subsequent 1 H-nuclear magnetic resonance (NMR) and 13 C-NMR analyses confirmed that the isolated compound from F2 was catechin. Furthermore, molecular docking studies indicated that catechin has the potential to act as an ACE inhibitor. These findings suggest that finger millets, particularly as a source of catechin, have the potential to be used as a natural antihypertensive.

Delayed flail chest from osteomyelitis and malnutrition that emerged 3 weeks after blunt chest trauma: a case report.

We present the case of a victim of a motor vehicle accident in his late 60s who suffered from severe torso injuries. He initially presented with abdominal and chest pain, and underwent emergency laparotomy for hemoperitoneum. After surgery, the patient developed pneumonia and septicemia, which were responsive to antibiotics. The patient was treated with mechanical ventilation in the intensive care unit for approximately 10 days and experienced a severe weight loss of approximately 30%, but slowly recovered without dyspnea. Notably, on hospital day 24, he experienced sudden respiratory distress and flail motion of the chest wall in a general ward. This late presentation of flail chest was attributed to non-union at rib fracture sites, and was likely exacerbated by malnutrition and osteomyelitis. Surgical stabilization of rib fractures and excision of the infected rib were successfully performed. The findings from this case highlight the complexity of managing delayed onset of flail chest. The findings from this case suggest the importance of vigilance for late emerging complications in patients with trauma, even when initial symptoms are absent.

An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis.

The appearance of senescent cells in age-related diseases has spurred the search for compounds that can target senescent cells in tissues, termed senolytics. However, a major caveat with current senolytic screens is the use of cell lines as targets where senescence is induced in vitro, which does not necessarily reflect the identity and function of pathogenic senescent cells in vivo. Here, we developed a new pipeline leveraging a fluorescent murine reporter that allows for isolation and quantification of p16Ink4a+ cells in diseased tissues. By high-throughput screening in vitro, precision-cut lung slice (PCLS) screening ex vivo, and phenotypic screening in vivo, we identified a HSP90 inhibitor, XL888, as a potent senolytic in tissue fibrosis. XL888 treatment eliminated pathogenic p16Ink4a+ fibroblasts in a murine model of lung fibrosis and reduced fibrotic burden. Finally, XL888 preferentially targeted p16INK4a-hi human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF), and reduced p16INK4a+ fibroblasts from IPF PCLS ex vivo. This study provides proof of concept for a platform where p16INK4a+ cells are directly isolated from diseased tissues to identify compounds with in vivo and ex vivo efficacy in mice and humans, respectively, and provides a senolytic screening platform for other age-related diseases.

Effect of Sevoflurane Anesthesia on Diastolic Function: A Prospective Observational Study.

BACKGROUND: The effect of sevoflurane on left ventricular diastolic function is not well understood. We hypothesized that parameters of diastolic function may improve under sevoflurane anesthesia in patients with preexisting diastolic dysfunction compared to patients with normal diastolic function. METHODS: This observational study included 60 patients undergoing breast surgery or laparoscopic cholecystectomy. Patients were assigned to diastolic dysfunction (n = 34) or normal (n = 26) groups of septal e' < 8 or ≥ 8.0 cm/s on the first thoracic echocardiography (TTE) performed before anesthesia. During anesthesia, sevoflurane was maintained at 1 to 2 minimum alveolar concentration (MAC) to maintain the bispectral index at 40 to 50. At the end of surgery, the second TTE was performed under 0.8 to 1 MAC of sevoflurane with the patient breathing spontaneously without ventilator support. Primary end point was the percentage change (Δ) of e' on 2 TTEs (Δe'). Secondary end points were ΔE/e', Δleft atrial volume index (ΔLAVI), and Δtricuspid regurgitation maximum velocity (ΔTR Vmax). These percentage changes (Δ) were compared between diastolic dysfunction and normal groups. RESULTS: e' (Δe': 30 [6, 64] vs 0 [-18, 11]%; P < .001), mitral inflow E wave velocity (E), mitral inflow E/A ratio (E/A), and mitral E velocity deceleration time (DT) improved significantly in diastolic dysfunction group compared to normal group. LAVI decreased in diastolic dysfunction group but did not reach statistical significance between the 2 groups (ΔLAVI:-15 [-31, -3] vs -4 [-20, 10]%, P = .091). ΔE/e' was not different between the 2 groups (11 [-16, 26] vs 12 [-9, 22]%, P = .853) (all: median [interquartile range, IQR]). TR was minimal in both groups. CONCLUSIONS: In this study, echocardiographic parameters of diastolic function, including septal e', E, E/A, and DT, improved with sevoflurane anesthesia in patients with preexisting diastolic dysfunction, but remained unchanged in patients with normal diastolic function.

Mean corpuscular volume as a prognostic factor for 30-day mortality in major trauma patients: a retrospective cohort study.

We investigated the clinical implications of the mean corpuscular volume (MCV) in patients with major trauma. This single-center retrospective review included 2021 trauma patients admitted to the intensive care unit between January 2016 and June 2020. We included 1218 patients aged [Formula: see text] 18 years with an injury severity score [Formula: see text] 16 in the final analysis. The clinical and laboratory variables were compared between macrocytosis (defined as MCV [Formula: see text] 100 fL) and non-macrocytosis groups. Cox regression analysis was performed to calculate the hazard ratios (HRs) of variables for 30-day mortality, with adjustment for other potential confounding factors. The initial mean value of MCV was 102.7 fL in the macrocytosis group (n = 199) and 93.7 fL in the non-macrocytosis group (n = 1019). The macrocytosis group showed a significantly higher proportion of initial hypotension, transfusion within 4 and 24 h, and 30-day mortality than the non-macrocytosis group. Age ([Formula: see text] 65 years), hypotension (systolic blood pressure [Formula: see text] 90 mmHg), transfusion (within 4 h), anemia (Hb < 12 g/day in women, < 13 g/day in men), and macrocytosis were significantly associated with 30-day mortality (adjusted HR = 1.4; 95% confidence interval 1.01-1.94; p = 0.046) in major trauma patients. Thus, initial macrocytosis independently predicted 30-day mortality in patients with major trauma at a Level I trauma center.

Uranyl ammonium carbonate precipitation and conversion into triuranium octaoxide.

Uranyl ammonium carbonate (AUC), with the chemical formula UO2CO3·2(NH4)2CO3, plays a crucial role in the wet conversion of uranium hexafluoride (UF6) into uranium dioxide (UO2) or triuranium octaoxide (U3O8) for nuclear fuel production, and is used in commercial and research reactors. In this study, the precipitation of AUC from uranyl fluoride (UO2F2) solution and its subsequent conversion into U3O8 powder were investigated. AUC precipitation was performed at uranium concentrations in UO2F2 solution of 80-120 gL-1, ammonium carbonate (NH4)2CO3 concentrations of 200-400 gL-1, and (NH4)2CO3 to U (C/U) ratios of 5-9. The conversion of AUC into U3O8 powder was studied and sintering of the U3O8 nuclear material derived from ammonium uranyl carbonate (ex-AUC U3O8) was conducted at temperatures of 1000-1800 °C. The kinetics of AUC precipitation from the UO2F2 solution were studied using fundamental kinetic equations, and the kinetics of AUC conversion into UO3 were examined using an isoconversion method based on the thermogravimetric analysis of AUC. The final product of U3O8 nuclear material was characterized using typical techniques, such as thermogravimetric analysis, X-ray diffraction, and scanning electron microscopy. This study provides valuable insights into the production and characterization of AUC and U3O8 nuclear materials, which are key materials in the nuclear fuel industry.

Comprehensive RNA-sequencing analysis of colorectal cancer in a Korean cohort.

Considering the recent increase in the number of colorectal cancer (CRC) cases in South Korea, we aimed to clarify the molecular characteristics of CRC unique to the Korean population. To gain insights into the complexities of CRC and promote the exchange of critical data, RNA-sequencing analysis was performed to reveal the molecular mechanisms that drive the development and progression of CRC; this analysis is critical for developing effective treatment strategies. We performed RNA-sequencing analysis of CRC and adjacent normal tissue samples from 214 Korean participants (comprising a total of 381 including 169 normal and 212 tumor samples) to investigate differential gene expression between the groups. We identified 19,575 genes expressed in CRC and normal tissues, with 3,830 differentially expressed genes (DEGs) between the groups. Functional annotation analysis revealed that the upregulated DEGs were significantly enriched in pathways related to the cell cycle, DNA replication, and IL-17, whereas the downregulated DEGs were enriched in metabolic pathways. We also analyzed the relationship between clinical information and subtypes using the Consensus Molecular Subtype (CMS) classification. Furthermore, we compared groups clustered within our dataset to CMS groups and performed additional analysis of the methylation data between DEGs and CMS groups to provide comprehensive biological insights from various perspectives. Our study provides valuable insights into the molecular mechanisms underlying CRC in Korean patients and serves as a platform for identifying potential target genes for this disease. The raw data and processed results have been deposited in a public repository for further analysis and exploration.

Impact of preserved ratio impaired spirometry on coronary artery calcium score progression: a longitudinal cohort study.

Background: Preserved ratio impaired spirometry (PRISm) is associated with increased cardiovascular disease (CVD) risk and mortality. However, a causal relationship between PRISm and CVD remains unclear. We investigated the progression of coronary artery calcium (CAC) scores based on the presence of PRISm and reduced forced vital capacity (FVC). Methods: This retrospective cohort study included 11 420 participants aged ≥40 years with forced expiratory volume in 1 s (FEV1)/FVC ≥0.7 who underwent at least two health screening examinations with coronary computed tomography scan between 2003 and 2020, and were without a history of CVD or interstitial lung disease. Participants with PRISm, defined as FEV1/FVC ≥0.7 and FEV1 <80% predicted, were further divided by low FVC (FVC <80% predicted). We estimated the 5-year progression rates of CAC by comparing participants with and without PRISm at baseline using mixed linear models. Results: Of the 11 420 participants, 8536 (75%), 811 (7%) and 2073 (18%) had normal spirometry, PRISm with normal FVC and PRISm with low FVC, respectively. During the mean (range) follow-up of 6.0 (0.5-17.2) years, the multivariable adjusted ratio of 5-year CAC progression rates comparing participants with PRISm to those with normal spirometry was 1.08 (95% CI 1.04-1.13). This rate was higher in participants with PRISm with low FVC (1.21 (95% CI 1.12-1.30)) than in those with normal FVC. Conclusion: In this longitudinal cohort study of subjects without a history of CVD, PRISm was significantly associated with CAC progression, which was more evident in the group with PRISm and low FVC.

Protective Behaviors Against COVID-19 and Related Factors in Korean Adults With Depressive Symptoms: Results From an Analysis of the 2020 Korean Community Health Survey.

OBJECTIVE: This study evaluated protective behaviors against coronavirus disease-2019 (COVID-19) and related factors in individuals with depressive symptoms. METHODS: This cross-sectional study included data from the 2020 Korean Community Health Survey. Depressive symptoms, COVID- 19 protection behaviors, and related factors were investigated in 228,485 people. Chi-square test and logistic regression analysis were used to analyze categorical variables. Statistical analysis was performed using SPSS software (version 27.0). RESULTS: In the study, 3.9% (n=8,970) had depressive symptoms. The prevalence of depressive symptoms was higher in individuals in their 19-39 years , and ≥60s than in those in their 40-59 years (p<0.001). Lower education level and household income were associated with a higher prevalence of depression (p<0.001). Among the various occupations, service workers had the highest prevalence of depressive symptoms (p<0.001). Individuals with depressive symptoms were less likely to adopt protective behaviors against COVID-19 (p<0.001) or exhibit concerns regarding death and economic damage (p<0.001) compared to individuals without depressive symptoms. Individuals with depressive symptoms were more likely to have unhealthy behaviors than those without depressive symptoms (p<0.001). Individuals with depressive symptoms considered that the COVID-19 response by the government and other organizations was inadequate (p<0.001). CONCLUSION: During the COVID-19 pandemic, individuals with depressive symptoms faced greater challenges in adopting protective behaviors. Therefore, it is crucial to develop strategies to protect people with depressive symptoms during another pandemic in the future.

Novel Artificial Intelligence-Based Technology to Diagnose Asthma Using Methacholine Challenge Tests.

PURPOSE: The methacholine challenge test (MCT) has high sensitivity but relatively low specificity for asthma diagnosis. This study aimed to develop and validate machine learning (ML) models to improve the diagnostic performance of MCT for asthma. METHODS: Data from 1,501 patients with asthma symptoms who underwent MCT between 2015 and 2020 were analyzed. The patients were grouped as either the training (80%, n = 1,265) and test sets (20%, n = 236) depending on the time of referral. The conventional model (provocative concentration that causes a 20% decrease in forced expiratory volume in one second [FEV1]; PC20 ≤ 16 mg/mL) was compared with the prediction models derived from five ML methods: logistic regression, support vector machine, random forest, extreme gradient boosting, and artificial neural network. The area under the receiver operator characteristic curves (AUROC) and area under the precision-recall curves (AUPRC) of each model were compared. The prediction models were further analyzed using different input combinations of FEV1, forced vital capacity (FVC), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) values obtained during MCT. RESULTS: In total, 545 patients (36.3%) were diagnosed with asthma. The AUROC of the conventional model was 0.856 (95% confidence interval [CI], 0.852-0.861), and the AUPRC was 0.759 (95% CI, 0.751-0.766). All the five ML prediction models had higher AUROC and AUPRC values than those of the conventional model, and random forest showed both highest AUROC (0.950; 95% CI, 0.948-0.952) and AUROC (0.909; 95% CI, 0.905-0.914) when FEV1, FVC, and FEF25%-75% were included as inputs. CONCLUSIONS: Artificial intelligence-based models showed excellent performance in asthma prediction compared to using PC20 ≤ 16 mg/mL. The novel technology could be used to enhance the clinical diagnosis of asthma.

Circulating lumican as a potential biomarker for osteosarcopenia in older adults.

In vitro and animal experiments demonstrated that lumican exerts anabolic effects on bone and muscle by stimulating osteoblastogenesis, suppressing osteoclastogenesis and increasing myogenesis. However, the relationship between circulating lumican and musculoskeletal phenotypes in humans remains unclear. We aimed to analyze the relationship between serum lumican levels and osteosarcopenia in older adults. Blood samples were collected from 134 participants (age: 65 years and older) who underwent comprehensive assessment of bone and muscle phenotypes. Osteoporosis and sarcopenia were diagnosed based on World Health Organization and Asian consensus guidelines, respectively. Osteosarcopenia was defined as the simultaneous presence of osteoporosis and sarcopenia. After adjusting for sex, age, and body mass index, older adults with osteosarcopenia had 20.2 % lower serum lumican levels than those without (P = 0.010). The odds ratio (OR) for osteosarcopenia per standard deviation decrease in serum lumican level was 4.17 (P = 0.003). Consistently, higher serum lumican levels were correlated with higher bone mass at all measured sites (P = 0.004 to 0.045) and higher grip strength (P = 0.023). Furthermore, participants in the lowest tertile (T1) had 7.56-fold higher OR for osteosarcopenia (P = 0.024) than those in the highest lumican tertile (T3). In conclusion, these findings clinically validate previous experimental data showing the musculoskeletal protective effects of lumican and suggest that blood lumican levels could be used as a potential biomarker to assess the risk of not only osteosarcopenia but also osteoporosis or sarcopenia in older adults.

Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers.

Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis. [BMB Reports 2024; 57(3): 161-166].

Comprehensive profiling of DNA methylation in Korean patients with colorectal cancer.

Alterations in DNA methylation play an important pathophysiological role in the development and progression of colorectal cancer. We comprehensively profiled DNA methylation alterations in 165 Korean patients with colorectal cancer (CRC), and conducted an in-depth investigation of cancer-specific methylation patterns. Our analysis of the tumor samples revealed a significant presence of hypomethylated probes, primarily within the gene body regions; few hypermethylated sites were observed, which were mostly enriched in promoter-like and CpG island regions. The CpG Island Methylator PhenotypeHigh (CIMP-H) exhibited notable enrichment of microsatellite instability-high (MSI-H). Additionally, our findings indicated a significant correlation between methylation of the MLH1 gene and MSI-H status. Furthermore, we found that the CIMP-H had a higher tendency to affect the right-side of the colon tissues and was slightly more prevalent among older patients. Through our methylome profile analysis, we successfully verified the thylation patterns and clinical characteristics of Korean patients with CRC. This valuable dataset lays a strong foundation for exploring novel molecular insights and potential therapeutic targets for the treatment of CRC. [BMB Reports 2024; 57(2): 110-115].

Evaluation of Factors Affecting Illumination Intensity in Lightwand Endotracheal Intubation.

BACKGROUND/AIM: A lightwand is a stylet with a light bulb at its tip that can be used to guide intubation by confirming the illumination through the anterior neck. We aimed to determine the factors affecting the illumination intensity during lightwand endotracheal intubation. PATIENTS AND METHODS: We retrospectively collected data from 180 patients who underwent lightwand endotracheal intubation. We recorded illumination intensity on a 5-point scale. The patients were categorized into weak (score <3) and bright (score ≥3) groups based on the illumination intensity scale score. RESULTS: A total of 176 patients were analyzed, of whom 125 (71.1%) were enrolled in the bright group, and 51 (29.0%) were enrolled in the weak group. Multivariable logistic regression analysis revealed that an increased body mass index (BMI) and mask ventilation grade were associated with light intensity. For mask ventilation, moderate vs. easy (p=0.010) and difficult vs. easy (p=0.008) were associated with the weak group. Receiver operating characteristic curve analysis showed that BMI ≥24.6 kg/m2 was correlated with the weak group. CONCLUSION: BMI ≥24.6 kg/m2 or mask ventilation grade above moderate indicates increased odds of weak illumination intensity in lightwand intubation. Pre-intubation examination of these factors helps increase the chances of successful intubation.

Licochalcone C Inhibits the Growth of Human Colorectal Cancer HCT116 Cells Resistant to Oxaliplatin.

Licochalcone C (LCC; PubChem CID:9840805), a chalcone compound originating from the root of Glycyrrhiza inflata, has shown anticancer activity against skin cancer, esophageal squamous cell carcinoma, and oral squamous cell carcinoma. However, the therapeutic potential of LCC in treating colorectal cancer (CRC) and its underlying molecular mechanisms remain unclear. Chemotherapy for CRC is challenging because of the development of drug resistance. In this study, we examined the antiproliferative activity of LCC in human colorectal carcinoma HCT116 cells, oxaliplatin (Ox) sensitive and Ox-resistant HCT116 cells (HCT116-OxR). LCC significantly and selectively inhibited the growth of HCT116 and HCT116-OxR cells. An in vitro kinase assay showed that LCC inhibited the kinase activities of EGFR and AKT. Molecular docking simulations using AutoDock Vina indicated that LCC could be in ATP-binding pockets. Decreased phosphorylation of EGFR and AKT was observed in the LCC-treated cells. In addition, LCC induced cell cycle arrest by modulating the expression of cell cycle regulators p21, p27, cyclin B1, and cdc2. LCC treatment induced ROS generation in CRC cells, and the ROS induction was accompanied by the phosphorylation of JNK and p38 kinases. Moreover, LCC dysregulated mitochondrial membrane potential (MMP), and the disruption of MMP resulted in the release of cytochrome c into the cytoplasm and activation of caspases to execute apoptosis. Overall, LCC showed anticancer activity against both Ox-sensitive and Ox-resistant CRC cells by targeting EGFR and AKT, inducing ROS generation and disrupting MMP. Thus, LCC may be potential therapeutic agents for the treatment of Ox-resistant CRC cells.

Successful endovascular treatment of an obstruction following the surgical repair of a traumatic portal vein injury: a case report.

Traumatic portal vein injury is rare, but the associated mortality rate ranges from 50% to 70%. The management of this injury is difficult and remains controversial. In this case report, we describe the successful endovascular treatment of an obstruction that developed following the surgical repair of a traumatic portal vein injury. A man in his mid-40s who had been injured in a car accident presented to our trauma center with abdominal pain, abdominal distension, and open wounds over both knees. Emergency laparotomy revealed a longitudinal rupture from the upper border of the pancreas to the mid-portion of the portal vein; his hemorrhage was successfully controlled surgically. However, postoperative abdominal computed tomography imaging revealed portal vein obstruction. One week after admission to the intensive care unit, an endovascular stent was successfully inserted into the patient's portal vein via a percutaneous transhepatic approach. The associated injuries, including the distal common bile duct obstruction, were successfully managed by choledochojejunostomy. The patient's postoperative recovery was uneventful. Thus, endovascular stent placement is an effective and safe means of treating an obstruction following the surgical repair of a traumatic portal vein injury.

Effect of Electron-Beam Irradiation on Functional Compounds and Biological Activities in Peanut Shells.

Peanut shells, rich in antioxidants, remain underutilized due to limited research. The present study investigated the changes in the functional compound content and skin aging-related enzyme inhibitory activities of peanut shells by electron-beam treatment with different sample states and irradiation doses. In addition, phenolic compounds in the peanut shells were identified and quantified using ultra-performance liquid chromatography with ion mobility mass spectrometry-quadrupole time-of-flight and high-performance liquid chromatography with a photodiode array detector, respectively. Total phenolic compound content in solid treatment gradually increased from 110.31 to 189.03 mg gallic acid equivalent/g as the irradiation dose increased. Additionally, electron-beam irradiation significantly increased 5,7-dihydroxychrome, eriodictyol, and luteolin content in the solid treatment compared to the control. However, liquid treatment was less effective in terms of functional compound content compared to the solid treatment. The enhanced functional compound content in the solid treatment clearly augmented the antioxidant activity of the peanut shells irradiated with an electron-beam. Similarly, electron-beam irradiation substantially increased collagenase and elastase inhibitory activities in the solid treatment. Mutagenicity assay confirmed the stability of toxicity associated with the electron-beam irradiation. In conclusion, electron-beam-irradiated peanut shells could serve as an important by-product with potential applications in functional cosmetic materials.

Novel nomogram for predicting paradoxical chest wall movement in patients with flail segment of traumatic rib fracture: a retrospective cohort study.

Flail chest is a severe injury to the chest wall and is related to adverse outcomes. A flail chest is classified as the physiologic, paradoxical motion of a chest wall or flail segment of rib fracture (RFX). We hypothesized that patients with paradoxical chest wall movement would present different clinical features from patients with a flail segment. This retrospective observational study included patients with blunt chest trauma who visited our level 1 trauma center between January 2019 and October 2022 and were diagnosed with one or more flail segments by computed tomography. The primary outcome of our study was a clinically diagnosed visible, paradoxical chest wall motion. We used the least absolute shrinkage and selection operator (LASSO) logistic regression model to minimize overfitting. After a feature selection using the LASSO regression model, we constructed a multivariable logistic regression (MLR) model and nomogram. A total of five risk factors were selected in the LASSO model and applied to the multivariable logistic regression model. Of these, four risk factors were statistically significant: the total number of RFX (adjusted OR [aOR], 1.28; 95% confidence interval [CI], 1.09-1.49; p = 0.002), number of segmental RFX including Grade III fractures (aOR, 1.78; 95% CI, 1.14-2.79; p = 0.012), laterally located primary fracture lines (aOR, 4.00; 95% CI, 1.69-9.43; p = 0.002), and anterior-lateral flail segments (aOR, 4.20; 95% CI, 1.60-10.99; p = 0.004). We constructed a nomogram to predict the personalized probability of the flail motion. A novel nomogram was developed in patients with flail segments of traumatic RFX to predict paradoxical chest wall motion. The number of RFX, Grade III segmental RFX, and the location of the RFX were significant risk factors.