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1.
Br J Cancer ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38729997

ABSTRACT

BACKGROUND: We investigated the role of tumor cell-intrinsic PD-L1 signaling in the epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer (NSCLC) and the role of EMT as a predictive biomarker for immune checkpoint inhibitor (ICI) therapy. METHODS: PD-L1-overexpressing or PD-L1-knockdown NSCLC cells underwent RNA-seq and EMT phenotype assessment. Mouse lung cancer LLC cells were injected into nude mice. Two cohorts of patients with NSCLC undergoing ICI therapy were analyzed. RESULTS: RNA-seq showed that EMT pathways were enriched in PD-L1-high NSCLC cells. EMT was enhanced by PD-L1 in NSCLC cells, which was mediated by transforming growth factor-ß (TGFß). PD-L1 promoted the activation of p38-MAPK by binding to and inhibiting the protein phosphatase PPM1B, thereby increasing the TGFß production. Tumor growth and metastasis increased in nude mice injected with PD-L1-overexpressing LLC cells. In the ICI cohort, EMT signature was higher in patients with progressive disease than in those with responses, and EMT was significantly associated with poor survival in PD-L1-high NSCLC. In PD-L1-high NSCLC, EMT was associated with increased M2-macrophage and regulatory T-cell infiltrations and decreased cytotoxic T-cell infiltration. CONCLUSIONS: Tumor cell-intrinsic PD-L1 function contributes to NSCLC progression by promoting EMT. EMT may predict an unfavorable outcome after ICI therapy in PD-L1-high NSCLC.

2.
3D Print Addit Manuf ; 11(2): e876-e895, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38689913

ABSTRACT

As an emerging additive manufacturing technology, inkjet printing has been increasingly applied in microelectronics field. However, due to the impacting and rebounding behaviors of conductive ink droplets impinging onto flat substrates, it is challenging to fabricate conductive lines with desired quality, such as suitable line width and line thickness, and matching resistance when it is used for interconnecting multifarious electronic components if there is not a proper configuration of operating parameters. To address this research gap, this article aims to investigate the effect of process parameters on the quality of conductive lines, including the platform temperature, printing speed, number of layers, and delay time (droplet interarrival time), are selected to conduct a full factorial experiment. First, the approximate parameter ranges for ensuring the continuity of conductive lines are determined. Second, this study analyzes the interactive effect among process parameters on line quality. Third, an artificial neural network (ANN) is constructed to predict the quality of printed lines. Results show that the line width does not increase with an increased number of layers, while the line thickness shows an increasing trend. The low resistance and high aspect ratio of printed line are achieved by printing 5 layers with the platform temperature of 70°C, the delay time of 12.2 ms, and the printing speed of 1139.39 mm/min. Moreover, the ANN model can be used to predict line width and line thickness with excellent performance, except for the resistance due to the irregular line edge. This study provides a useful guide for the selection of appropriate printing parameters to realize a diverse range of quality properties for 3D printed conductive lines in integrated circuits.

3.
Ann Occup Environ Med ; 36: e11, 2024.
Article in English | MEDLINE | ID: mdl-38741681

ABSTRACT

Background: Occupational neck disability is a prevalent issue, especially among line workers, who are often exposed to elevated levels of cervical ergonomic stress. The aim of this study was to investigate the impact of neck posture and insulating stick use on neck disability in a specific occupational group in Korea. Methods: This cross-sectional study was conducted among 483 line workers in Gwangju and Jeonnam, Korea. Data were collected using the Neck Disability Index, Cervical Degenerative Index, and a structured questionnaire focusing on demographic and occupational factors. Logistic regression analysis was applied to determine the adjusted odds ratio (OR) and 95% confidence interval (CI) for neck posture and factors related to neck disability. Results: Neck disability prevalence was 17.2% among the participants. Multivariate logistic regression analysis showed that factors related to neck disability included age over 60 years (adjusted OR: 3.08; 95% CI: 1.63-5.83), depression (adjusted OR: 8.33; 95% CI: 3.85-18.00), a history of cervical trauma (adjusted OR: 2.13; 95% CI: 1.04-4.40), and radiological degenerative changes in the cervical spine (adjusted OR: 2.33; 95% CI: 1.26-4.33). In particular, the adjusted OR of neck disability among live-line workers was 2.10 (95% CI: 1.12-3.92) when compared with support workers (model 1). Other analysis models showed that use of insulating sticks for more than 10 hours per week (adjusted OR: 2.46; 95% CI: 1.32-4.61) and higher neck extension (adjusted OR: 2.98; 95% CI: 1.14-3.46) were significant work-related risk factors (model 2,3). Conclusions: Neck posture, age, depression, cervical trauma history, degenerative changes in the cervical spine, and use of insulating sticks are significant risk factors for neck disability among line workers in Korea. These findings highlight the need to improve the working environment and reduce the burden of cervical ergonomic stress among line workers.

4.
Fitoterapia ; : 106026, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38768794

ABSTRACT

Rydingia michauxii and R. persica, respectively, known as Kase Gol and Goldar in Persian, belong to the family Lamiaceae and they are well known herbal medicine in Iran for the treatment of various diseases, particularly diabetes. This review aims to appraise the phytochemistry, ethnopharmacology, and pharmacological activities of Rydingia species growing in Iran and assess their potential in clinical applications. Besides, it critically evaluates existing literature and looks into the perspective for further research and utilization. All available scientific literature was consulted using the database searches involving Google Scholar, PubMed, and Web of Science applying the keyword Rydingia and its Syn; Otostegia. Only the search results that are associated with the Iranian species R. michauxii and R. persica are included in this review. α-pinene, carvacrol, caryophyllene oxide, diisooctyl phthalate, dillapiole, eugenol, hexadecanoic acid, and pentacosane are the major constituents of the essential oils of the Rydingia species. Additionally, these species produce bioactive flavonoids, phenolic acids, steroids, and terpenoids. Extracts and active compounds from Rydingia species have been reported to possess various pharmacological activities including antidiabetic, anti-inflammatory, antimalarial, antimicrobial, antioxidant, cytotoxic, and lipid-lowering properties. Based on the information available to date on the Iranian Rydingia species, it will be worth subjecting these species to further developmental work involving preclinical and clinical trials.

6.
Sci Rep ; 14(1): 7718, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38565556

ABSTRACT

We aimed to examine the relationship between abdominal computed tomography (CT)-based body composition data and both renal function decline and all-cause mortality in patients with non-dialysis chronic kidney disease (CKD). This retrospective study comprised non-dialysis CKD patients who underwent consecutive unenhanced abdominal CT between January 2010 and December 2011. CT-based body composition was measured using semiautomated method that included visceral fat, subcutaneous fat, skeletal muscle area and density, and abdominal aortic calcium score (AAS). Sarcopenia and myosteatosis were defined by decreased skeletal muscle index (SMI) and decreased skeletal muscle density, respectively, each with specific cutoffs. Risk factors for CKD progression and survival were identified using logistic regression and Cox proportional hazard regression models. Survival between groups based on myosteatosis and AAS was compared using the Kaplan-Meier curve. 149 patients (median age: 70 years) were included; 79 (53.0%) patients had sarcopenia and 112 (75.2%) had myosteatosis. The median AAS was 560.9 (interquartile range: 55.7-1478.3)/m2. The prognostic factors for CKD progression were myosteatosis [odds ratio (OR) = 4.31, p = 0.013] and high AAS (OR = 1.03, p = 0.001). Skeletal muscle density [hazard ratio (HR) = 0.93, p = 0.004] or myosteatosis (HR = 4.87, p = 0.032) and high AAS (HR = 1.02, p = 0.001) were independent factors for poor survival outcomes. The presence of myosteatosis and the high burden of aortic calcium were significant factors for CKD progression and survival in patients with non-dialysis CKD.


Subject(s)
Renal Insufficiency, Chronic , Sarcopenia , Humans , Aged , Sarcopenia/diagnostic imaging , Sarcopenia/etiology , Sarcopenia/pathology , Calcium , Prognosis , Retrospective Studies , Muscle, Skeletal/pathology , Tomography, X-Ray Computed , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnostic imaging , Renal Insufficiency, Chronic/pathology
7.
Nat Commun ; 15(1): 2983, 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38582860

ABSTRACT

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.


Subject(s)
Verrucomicrobia , beta Catenin , Male , Mice , Animals , beta Catenin/metabolism , Verrucomicrobia/metabolism , Intestines , Cadherins/metabolism , Akkermansia
8.
PLoS One ; 19(4): e0294474, 2024.
Article in English | MEDLINE | ID: mdl-38558002

ABSTRACT

The growing prevalence of antibiotic resistance has made it imperative to search for new antimicrobial compounds derived from natural products. In the present study, Brevibacillus laterosporus TSA31-5, isolated from red clay soil, was chosen as the subject for conducting additional antibacterial investigations. The fractions exhibiting the highest antibacterial activity (30% acetonitrile eluent from solid phase extraction) were purified through RP-HPLC. Notably, two compounds (A and B) displayed the most potent antibacterial activity against both Escherichia coli and Staphylococcus aureus. ESI-MS/MS spectroscopy and NMR analysis confirmed that compound A corresponds to brevicidine and compound B to brevibacillin. Particularly, brevicidine displayed notable antibacterial activity against Gram-negative bacteria, with a minimum inhibitory concentration (MIC) range of 1-8 µg/mL. On the other hand, brevibacillin exhibited robust antimicrobial effectiveness against both Gram-positive bacterial strains (MIC range of 2-4 µg/mL) and Gram-negative bacteria (MIC range of 4-64 µg/mL). Scanning electron microscopy analysis and fluorescence assays uncovered distinctive morphological alterations in bacterial cell membranes induced by brevicidine and brevibacillin. These observations imply distinct mechanisms of antibacterial activity exhibited by the peptides. Brevicidine exhibited no hemolysis or cytotoxicity up to 512 µg/mL, comparable to the negative control. This suggests its promising therapeutic potential in treating infectious diseases. Conversely, brevibacillin demonstrated elevated cytotoxicity in in vitro assays. Nonetheless, owing to its noteworthy antimicrobial activity against pathogenic bacteria, brevibacillin could still be explored as a promising antimicrobial agent.


Subject(s)
Anti-Infective Agents , Bacillus , Brevibacillus , Tandem Mass Spectrometry , Anti-Bacterial Agents/chemistry , Anti-Infective Agents/pharmacology , Gram-Positive Bacteria , Gram-Negative Bacteria , Microbial Sensitivity Tests
9.
J Chest Surg ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38650485

ABSTRACT

Background: Type A aortic dissection (AD) and intramural hematoma (IMH) are critical medical conditions. Emergency surgery is typically performed under cardiopulmonary bypass immediately after diagnosis, which involves lowering the body temperature to induce total circulatory arrest. Selection of the arterial cannulation site is a critical consideration in cardiac surgery and becomes more challenging in patients with AD. This study explored the strengths and weaknesses of different cannulation methods by comparing each cannulation strategy and analyzing the reasons for patients' outcomes, especially mortality and cerebrovascular accidents (CVAs). Methods: This retrospective study reviewed the medical records of patients who underwent surgery for type A AD or IMH between 2008 and 2023, using the moderate hypothermic circulatory arrest approach at a single center. Results: Among the 146 patients reviewed, 32 underwent antegrade cannulation via axillary, innominate artery, aortic, or transapical cannulation, while 114 underwent retrograde cannulation via the femoral artery. The analysis of surgical outcomes revealed a significant difference in the total surgical time, with 356 minutes for antegrade and 443 minutes for retrograde cannulation (p<0.001). The mean length of stay in the intensive care unit was significantly longer in the retrograde group (5±16 days) than in the antegrade group (3±5 days, p=0.013). Nevertheless, no significant difference was found between the groups in the 30-day mortality or postoperative CVA rates (p=0.2 and p=0.7, respectively). Conclusion: Surgeons should consider an appropriate cannulation strategy for each patient instead of adhering strictly to a specific approach in AD surgery.

11.
Adv Mater ; : e2314274, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38647521

ABSTRACT

A gate stack that facilitates a high-quality interface and tight electrostatic control is crucial for realizing high-performance and low-power field-effect transistors (FETs). However, when constructing conventional metal-oxide-semiconductor structures with two-dimensional (2D) transition metal dichalcogenide channels, achieving these requirements becomes challenging due to inherent difficulties in obtaining high-quality gate dielectrics through native oxidation or film deposition. Here, a gate-dielectric-less device architecture of van der Waals Schottky gated metal-semiconductor FETs (vdW-SG MESFETs) using a molybdenum disulfide (MoS2) channel and surface-oxidized metal gates such as nickel and copper is reported. Benefiting from the strong SG coupling, these MESFETs operate at remarkably low gate voltages, <0.5 V. Notably, they also exhibit Boltzmann-limited switching behavior featured by a subthreshold swing of ≈60 mV dec-1 and negligible hysteresis. These ideal FET characteristics are attributed to the formation of a Fermi-level (EF) pinning-free gate stack at the Schottky-Mott limit. Furthermore, authors experimentally and theoretically confirm that EF depinning can be achieved by suppressing both metal-induced and disorder-induced gap states at the interface between the monolithic-oxide-gapped metal gate and the MoS2 channel. This work paves a new route for designing high-performance and energy-efficient 2D electronics.

12.
Biochemistry ; 63(9): 1067-1074, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38619104

ABSTRACT

NANOG protein levels correlate with stem cell pluripotency. NANOG concentrations fluctuate constantly with low NANOG levels leading to spontaneous cell differentiation. Previous literature implicated Pin1, a phosphorylation-dependent prolyl isomerase, as a key player in NANOG stabilization. Here, using NMR spectroscopy, we investigate the molecular interactions of Pin1 with the NANOG unstructured N-terminal domain that contains a PEST sequence with two phosphorylation sites. Phosphorylation of NANOG PEST peptides increases affinity to Pin1. By systematically increasing the amount of cis PEST conformers, we show that the peptides bind tighter to the prolyl isomerase domain (PPIase) of Pin1. Phosphorylation and cis Pro enhancement at both PEST sites lead to a 5-10-fold increase in NANOG binding to the Pin1 WW domain and PPIase domain, respectively. The cis-populated NANOG PEST peptides can be potential inhibitors for disrupting Pin1-dependent NANOG stabilization in cancer stem cells.


Subject(s)
NIMA-Interacting Peptidylprolyl Isomerase , Nanog Homeobox Protein , NIMA-Interacting Peptidylprolyl Isomerase/metabolism , NIMA-Interacting Peptidylprolyl Isomerase/chemistry , NIMA-Interacting Peptidylprolyl Isomerase/genetics , Nanog Homeobox Protein/metabolism , Nanog Homeobox Protein/genetics , Phosphorylation , Humans , Protein Stability , Protein Binding , Stereoisomerism
13.
Eur J Pharmacol ; 973: 176573, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38642669

ABSTRACT

Parkinson's disease (PD) is characterised by severe movement defects and the degeneration of dopaminergic neurones in the midbrain. The symptoms of PD can be managed with dopamine replacement therapy using L-3, 4-dihydroxyphenylalanine (L-dopa), which is the gold standard therapy for PD. However, long-term treatment with L-dopa can lead to motor complications. The central renin-angiotensin system (RAS) is associated with the development of neurodegenerative diseases in the brain. However, the role of the RAS in dopamine replacement therapy for PD remains unclear. Here, we tested the co-treatment of the angiotensin-converting enzyme inhibitor (ACEI) with L-dopa altered L-dopa-induced dyskinesia (LID) in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Perindopril, captopril, and enalapril were used as ACEIs. The co-treatment of ACEI with L-dopa significantly decreased LID development in 6-OHDA-lesioned mice. In addition, the astrocyte and microglial transcripts involving Ccl2, C3, Cd44, and Iigp1 were reduced by co-treatment with ACEI and L-dopa in the 6-OHDA-lesioned striatum. In conclusion, co-treatment with ACEIs and L-dopa, such as perindopril, captopril, and enalapril, may mitigate the severity of L-DOPA-induced dyskinesia in a mouse model of PD.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Disease Models, Animal , Dyskinesia, Drug-Induced , Levodopa , Oxidopamine , Animals , Male , Mice , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antiparkinson Agents/pharmacology , Astrocytes/drug effects , Astrocytes/metabolism , Captopril/pharmacology , Captopril/therapeutic use , Dyskinesia, Drug-Induced/drug therapy , Dyskinesia, Drug-Induced/prevention & control , Enalapril/pharmacology , Enalapril/therapeutic use , Levodopa/toxicity , Mice, Inbred C57BL , Microglia/drug effects , Microglia/metabolism , Parkinson Disease/drug therapy , Perindopril/pharmacology , Perindopril/therapeutic use
14.
Redox Biol ; 71: 103107, 2024 May.
Article in English | MEDLINE | ID: mdl-38479224

ABSTRACT

Fibroblast growth factor 23 (FGF23) is a member of endocrine FGF family, along with FGF15/19 and FGF21. Recent reports showed that under pathological conditions, liver produces FGF23, although the role of hepatic FGF23 remains nebulous. Here, we investigated the role of hepatic FGF23 in alcoholic liver disease (ALD) and delineated the underlying molecular mechanism. FGF23 expression was compared in livers from alcoholic hepatitis patients and healthy controls. The role of FGF23 was examined in hepatocyte-specific knock-out (LKO) mice of cannabinoid receptor type 1 (CB1R), estrogen related receptor γ (ERRγ), or FGF23. Animals were fed with an alcohol-containing liquid diet alone or in combination with ERRγ inverse agonist. FGF23 is mainly expressed in hepatocytes in the human liver, and it is upregulated in ALD patients. In mice, chronic alcohol feeding leads to liver damage and induced FGF23 in liver, but not in other organs. FGF23 is transcriptionally regulated by ERRγ in response to alcohol-mediated activation of the CB1R. Alcohol induced upregulation of hepatic FGF23 and plasma FGF23 levels is lost in ERRγ-LKO mice, and an inverse agonist mediated inhibition of ERRγ transactivation significantly improved alcoholic liver damage. Moreover, hepatic CYP2E1 induction in response to alcohol is FGF23 dependent. In line, FGF23-LKO mice display decreased hepatic CYP2E1 expression and improved ALD through reduced hepatocyte apoptosis and oxidative stress. We recognized CBIR-ERRγ-FGF23 axis in facilitating ALD pathology through hepatic CYP2E1 induction. Thus, we propose FGF23 as a potential therapeutic target to treat ALD.


Subject(s)
Cytochrome P-450 CYP2E1 , Liver Diseases, Alcoholic , Animals , Humans , Mice , Cytochrome P-450 CYP2E1/genetics , Cytochrome P-450 CYP2E1/metabolism , Drug Inverse Agonism , Ethanol/pharmacology , Hepatocytes/metabolism , Liver/metabolism , Liver Diseases, Alcoholic/metabolism , Oxidative Stress
15.
Korean J Radiol ; 25(4): 351-362, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38528693

ABSTRACT

OBJECTIVE: To measure inter-reader agreement and identify associated factors in interpreting complete response (CR) on magnetic resonance imaging (MRI) following chemoradiotherapy (CRT) for rectal cancer. MATERIALS AND METHODS: This retrospective study involved 10 readers from seven hospitals with experience of 80-10210 cases, and 149 patients who underwent surgery after CRT for rectal cancer. Using MRI-based tumor regression grading (mrTRG) and methods employed in daily practice, the readers independently assessed mrTRG, CR on T2-weighted images (T2WI) denoted as mrCRT2W, and CR on all images including diffusion-weighted images (DWI) denoted as mrCRoverall. The readers described their interpretation patterns and how they utilized DWI. Inter-reader agreement was measured using multi-rater kappa, and associated factors were analyzed using multivariable regression. Correlation between sensitivity and specificity of each reader was analyzed using Spearman coefficient. RESULTS: The mrCRT2W and mrCRoverall rates varied widely among the readers, ranging 18.8%-40.3% and 18.1%-34.9%, respectively. Nine readers used DWI as a supplement sequence, which modified interpretations on T2WI in 2.7% of cases (36/1341 [149 patients × 9 readers]) and mostly (33/36) changed mrCRT2W to non-mrCRoverall. The kappa values for mrTRG, mrCRT2W, and mrCRoverall were 0.56 (95% confidence interval: 0.49, 0.62), 0.55 (0.52, 0.57), and 0.54 (0.51, 0.57), respectively. No use of rectal gel, larger initial tumor size, and higher initial cT stage exhibited significant association with a higher inter-reader agreement for assessing mrCRoverall (P ≤ 0.042). Strong negative correlations were observed between the sensitivity and specificity of individual readers (coefficient, -0.718 to -0.963; P ≤ 0.019). CONCLUSION: Inter-reader agreement was moderate for assessing CR on post-CRT MRI. Readers' varying standards on MRI interpretation (i.e., threshold effect), along with the use of rectal gel, initial tumor size, and initial cT stage, were significant factors associated with inter-reader agreement.


Subject(s)
Magnetic Resonance Imaging , Rectal Neoplasms , Humans , Retrospective Studies , Magnetic Resonance Imaging/methods , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Chemoradiotherapy , Sensitivity and Specificity , Pathologic Complete Response , Diffusion Magnetic Resonance Imaging/methods
16.
Inorg Chem ; 63(11): 4989-4996, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38440851

ABSTRACT

The triple bond in N2 is significantly stronger than the double bond in O2, meaning that synthesizing nitrogen-rich nitrides typically requires activated nitrogen precursors, such as ammonia, plasma-cracked atomic nitrogen, or high-pressure N2. Here, we report a synthesis of nitrogen-rich nitrides under ambient pressure and atmosphere. Using Na2MoO4 and dicyandiamide precursors, we synthesized nitrogen-rich γ-Mo2N3 in an alumina crucible under an ambient atmosphere, heated in a box furnace between 500 and 600 °C. Byproducts of this metathesis reaction include volatile gases and solid Na(OCN), which can be washed away with water. X-ray diffraction and neutron diffraction showed Mo2N3 with a rock salt structure having cation vacancies, with no oxygen incorporation, in contrast to the more common nitrogen-poor rock salt Mo2N with anion vacancies. Moreover, an increase in temperature to 700 °C resulted in molybdenum oxynitride, Mo0.84N0.72O0.27. This work illustrates the potential for dicyandiamide as an ambient-temperature metathesis precursor for an increased effective nitrogen chemical potential under ambient conditions. The classical experimental setting often used for solid-state oxide synthesis, therefore, has the potential to expand the nitride chemistry.

17.
Genes Genomics ; 46(4): 511-518, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38457096

ABSTRACT

BACKGROUND: Human endogenous retrovirus (HERV)-K is a type of retrovirus that is present in the human genome, and its expression is usually silenced in healthy tissues. The precise mechanism by which HERV-K env influences cancer stemness is not fully understood, but it has been suggested that HERV-K env may activate various signaling pathways that promote stemness traits in cancer cells. OBJECTIVE: To establish the connection between HERV-K env expression and cancer stemness in ovarian cancer cells, we carried out correlation analyses between HERV-K env and the cancer stem cell (CSC) marker known as the cluster of differentiation 133 (CD133) gene in SKOV3 ovarian cancer cells. METHOD: To perform correlation analysis between HERV-K env and CSCs, ovarian cancer cells were cultured in a medium designed for cancer stem cell induction. The expression of HERV-K env and CD133 genes was verified using quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analyses. Additionally, the expression of stemness-related markers, such as OCT-4 and Nanog, was also confirmed using RT-qPCR. RESULTS: In the stem cell induction medium, the number of tumorsphere-type SKOV3 cells increased, and the expression of CD133 and HERV-K env genes was up-regulated. Additionally, other stemness-related markers like OCT-4 and Nanog also exhibited increased expression when cultured in the cancer stem cell induction medium. However, when HERV-K env knockout (KO) SKOV3 cells were cultured in the same cancer stem cell induction medium, there was a significant decrease in the number of tumorsphere-type cells compared to mock SKOV3 cells subjected to the same conditions. Furthermore, the expression of CD133, Nanog, and OCT-4 did not show a significant increase in HERV-K env KO SKOV3 cells compared to mock SKOV3 cells cultured in the same cancer stem cell induction medium. CONCLUSION: These findings indicate that the expression of HERV-K env increased in SKOV3 cells when cultured in cancer stem cell induction media, and cancer stem cell induction was inhibited by KO of HERV-K env in SKOV3 cells. These results suggest a strong association between HERV-K env and stemness in SKOV3 ovarian cancer cells.


Subject(s)
Endogenous Retroviruses , Ovarian Neoplasms , Humans , Female , Endogenous Retroviruses/genetics , Genes, env , Ovarian Neoplasms/metabolism , Neoplastic Stem Cells/metabolism
19.
ACS Appl Mater Interfaces ; 16(12): 14822-14831, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38481126

ABSTRACT

As the applications of lithium-ion batteries (LIBs) have expanded, battery safety has emerged as a major concern because of the thermal runaway of LIBs arising from the use of flammable liquid electrolytes (LEs). Gel polymer electrolytes (GPEs) have been considered as potential candidates to replace LEs and improve the thermal safety of LIBs. In our study, a chemically cross-linked nonflammable GPE was synthesized and used in an LIB. A cross-linking agent, spirocyclic pentaerythritol diphosphate perfluorinated ether acrylate, comprising a phosphorus moiety and a fluoroether chain, was designed and synthesized to prepare a nonflammable cross-linked GPE. The obtained GPE effectively suppressed the deleterious reactions of the LE and imparted nonflammable characteristics. The pouch-type graphite/LiNi0.6Co0.2Mn0.2O2 cell with a nonflammable GPE delivered an initial discharge capacity of 146.7 mAh g-1 with a capacity retention of 71.1% after 300 cycles at 0.5 C and 55 °C. Moreover, the chemically cross-linked GPE exhibited excellent dimensional and thermal stability, which allowed for the safer operation of LIBs even under harsh conditions. This work provides guidelines for designing nonflammable electrolyte systems for advanced LIBs with high safety, enhanced thermal stability, and good cycling characteristics at elevated temperatures.

20.
J Chest Surg ; 57(3): 281-288, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38472119

ABSTRACT

Background: Venoarterial extracorporeal membrane oxygenation (ECMO) is a key treatment method used with patients in cardiac arrest who do not respond to medical treatment. A critical step in initiating therapy is the insertion of ECMO cannulas. Peripheral ECMO cannulation methods have been preferred for extracorporeal cardiopulmonary resuscitation (ECPR). Methods: Patients who underwent ECPR at Daegu Catholic University Medical Center between January 2017 and May 2023 were included in this study. We analyzed the impact of 2 different peripheral cannulation strategies (surgical cutdown vs. percutaneous cannulation) on various factors, including survival rate. Results: Among the 99 patients included in this study, 66 underwent surgical cutdown, and 33 underwent percutaneous insertion. The survival to discharge rates were 36.4% for the surgical cutdown group and 30.3% for the percutaneous group (p=0.708). The ECMO insertion times were 21.3 minutes for the surgical cutdown group and 10.3 minutes for the percutaneous group (p<0.001). The factors associated with overall mortality included a shorter low-flow time (hazard ratio [HR], 1.045; 95% confidence interval [CI], 1.019-1.071; p=0.001) and whether return of spontaneous circulation was achieved (HR, 0.317; 95% CI, 0.127-0.787; p=0.013). Low-flow time was defined as the time from the start of cardiopulmonary resuscitation to the completion of ECMO cannula insertion. Conclusion: No statistically significant difference in in-hospital mortality was observed between the surgical and percutaneous groups. However, regardless of the chosen cannulation strategy, reducing ECMO cannulation time was beneficial, as a shorter low-flow time was associated with significant benefits in terms of survival.

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