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1.
Clin Epigenetics ; 16(1): 92, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014432

ABSTRACT

BACKGROUND: Healthy sleep is vital for maintaining optimal mental and physical health. Accumulating evidence suggests that sleep loss and disturbances play a significant role in the biological aging process, early onset of disease, and reduced lifespan. While numerous studies have explored the association between biological aging and its drivers, only a few studies have examined its relationship with sleep quality. In this study, we investigated the associations between sleep quality and epigenetic age acceleration using whole blood samples from a cohort of 692 Korean adults. Sleep quality of each participant was assessed using the validated Pittsburgh Sleep Quality Index (PSQI), which encompassed seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction. Four epigenetic age accelerations (HorvathAgeAccel, HannumAgeAccel, PhenoAgeAccel, and GrimAgeAccel) and the pace of aging, DunedinPACE, were investigated for epigenetic aging estimates. RESULTS: Among the 692 participants (good sleepers [n = 441, 63.7%]; poor sleepers [n = 251, 36.3%]), DunedinPACE was positively correlated with PSQI scores in poor sleepers ( γ =0.18, p < 0.01). GrimAgeAccel ( ß =0.18, p = 0.02) and DunedinPACE ( ß =0.01, p < 0.01) showed a statistically significant association with PSQI scores only in poor sleepers by multiple linear regression. In addition, every one-point increase in PSQI was associated with a 15% increase in the risk of metabolic syndrome (MetS) among poor sleepers (OR = 1.15, 95% CI = 1.03-1.29, p = 0.011). In MetS components, a positive correlation was observed between PSQI score and fasting glucose ( γ = 0.19, p < 0.01). CONCLUSIONS: This study suggests that worsening sleep quality, especially in poor sleepers, is associated with accelerated epigenetic aging for GrimAgeAccel and DundinePACE with risk of metabolic syndrome. This finding could potentially serve as a promising strategy for preventing age-related diseases in the future.


Subject(s)
Aging , Epigenesis, Genetic , Metabolic Syndrome , Sleep Quality , Humans , Metabolic Syndrome/genetics , Metabolic Syndrome/epidemiology , Male , Female , Republic of Korea/epidemiology , Middle Aged , Adult , Aging/genetics , Aged
2.
Plants (Basel) ; 13(14)2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39065431

ABSTRACT

Extensive research has been conducted on the in vitro mass propagation of pear (Pyrus spp.) trees through vegetative propagation, demonstrating high efficiency in shoot multiplication across various pear species. However, the low in vitro rooting rates remain a significant barrier to the practical application and commercialization of mass propagation. This study aims to determine the favorable conditions for inducing root formation in the in vitro microshoots of Pyrus genotypes. The base of the microshoots was exposed to a high concentration (2 mg L-1) of auxins (a combination of IBA and NAA) for initial root induction at the moment when callus formation begins. The microshoots were then transferred to an R1 medium (1/2 MS with 30 g L-1 sucrose without PGRs) to promote root development. This method successfully induced rooting in three European pear varieties, one Asian pear variety, and a European-Asian hybrid, resulting in rooting rates of 66.7%, 87.2%, and 100% for the European pear (P. communis), 60% for the Asian pear (P. pyrifolia), and 83.3% for the hybrid pear (P. pyrifolia × P. communis) with an average of 25 days. In contrast, the control group (MS medium) exhibited rooting rates of 0-13.3% after 60 days of culture. These findings will enhance in vitro root induction for various pear varieties and support the mass propagation and acclimatization of pear. The in vitro root induction method developed in this study has the potential for global commercial application in pear cultivation.

3.
J Hazard Mater ; 476: 135193, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39029192

ABSTRACT

While the hazardous effects of microplastics (MPs) are increasingly reported, it remains uncertain if MPs induce inner ear dysfunction. Nonetheless, prevalence of inner ear dysfunction was observed across all age groups. In this study, we investigated whether MP polyethylene affect inner ear function in a murine model. To detect hearing loss and balance defect after polyethylene (PE) exposure, we evaluated hearing threshold levels, assessed cerebral glucose metabolism, conducted transcriptome analysis, and performed behavioral studies. C57BL/6 J mice (5-week-old) were grouped into control (n = 10) and PE-fed groups (n = 10). Mice were orally administered 100 ppm/100 µL (equivalent to 10 µg) of PE every day for 4 months. We identified the accumulation of PE in the cochlea and vestibular region. The fragmented PE in inner ear was 3.00 ± 0.38 µm in size; the administered PE concentration was 1.14 ± 1.06 mg/g. Fourier transform infrared spectrometry confirmed that the properties of the MP were identical with those of PE fed to the mice. Transcriptomic analysis showed up-regulation of PER1, NR4A3 and CEBPB at the PE exposed inner ear tissue and it was confirmed using qRT-PCR, western blotting, and immunofluorescence staining. We observed abnormalities in balance related behavior assessment in the PE group. Exposure to PE increased the hearing thresholds and decreased glucose metabolism in the bilateral lateral entorhinal cortex, right primary auditory cortex, and right secondary auditory cortex. We can conclude that PE exposure induced inner ear dysfunction such as hearing loss and balance disorder.


Subject(s)
Ear, Inner , Mice, Inbred C57BL , Microplastics , Polyethylene , Animals , Polyethylene/toxicity , Ear, Inner/drug effects , Ear, Inner/metabolism , Microplastics/toxicity , Male , Mice , Glucose/metabolism , Hearing Loss/chemically induced , Postural Balance/drug effects , Disease Models, Animal
4.
Plants (Basel) ; 13(12)2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38931087

ABSTRACT

Cryopreservation is a promising method for the long-term preservation of plant germplasm, especially for vegetatively propagated species like freesias. In this study, we investigate streamlining the cryopreservation process for 'Sunny Gold' Freesia, starting from effective in vitro initiation and proliferation using various plant growth regulator combinations. We also assess the impact of subculture on regrowth rates after cryopreservation. The shoot tips were successfully initiated in vitro after sterilization. The shoots were multiplied an average of three times in media containing N6-benzyladenine and kinetin. The regrowth rates of non-cryopreserved shoot tips excised from different subculture cycles did not differ significantly, with rates of 44% observed for plants from more than five subcultures and 47% for those from three subcultures. However, only the shoot tips excised from cultures subjected to three subculture cycles were able to recover after cryopreservation, with a regrowth rate of 31%. Our findings lay the groundwork for the development of an efficient cryopreservation protocol for freesias in the future.

5.
Clin Epigenetics ; 16(1): 60, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38685121

ABSTRACT

BACKGROUND: While multiple studies have investigated the relationship between metabolic syndrome (MetS) and its related traits (fasting glucose, triglyceride, HDL cholesterol, blood pressure, waist circumference) and DNA methylation, our understanding of the epigenetic mechanisms in MetS remains limited. Therefore, we performed an epigenome-wide meta-analysis of blood DNA methylation to identify differentially methylated probes (DMPs) and differentially methylated regions (DMRs) associated with MetS and its components using two independent cohorts comprising a total of 2,334 participants. We also investigated the specific genetic effects on DNA methylation, identified methylation quantitative trait loci (meQTLs) through genome-wide association studies and further utilized Mendelian randomization (MR) to assess how these meQTLs subsequently influence MetS status. RESULTS: We identified 40 DMPs and 27 DMRs that are significantly associated with MetS. In addition, we identified many novel DMPs and DMRs underlying inflammatory and steroid hormonal processes. The most significant associations were observed in 3 DMPs (cg19693031, cg26974062, cg02988288) and a DMR (chr1:145440444-145441553) at the TXNIP, which are involved in lipid metabolism. These CpG sites were identified as coregulators of DNA methylation in MetS, TG and FAG levels. We identified a total of 144 cis-meQTLs, out of which only 13 were found to be associated with DMPs for MetS. Among these, we confirmed the identified causal mediators of genetic effects at CpG sites cg01881899 at ABCG1 and cg00021659 at the TANK genes for MetS. CONCLUSIONS: This study observed whether specific CpGs and methylated regions act independently or are influenced by genetic effects for MetS and its components in the Korean population. These associations between the identified DNA methylation and MetS, along with its individual components, may serve as promising targets for the development of preventive interventions for MetS.


Subject(s)
CpG Islands , DNA Methylation , Epigenesis, Genetic , Genetic Predisposition to Disease , Genome-Wide Association Study , Metabolic Syndrome , Quantitative Trait Loci , Humans , Metabolic Syndrome/genetics , DNA Methylation/genetics , CpG Islands/genetics , Genome-Wide Association Study/methods , Republic of Korea/epidemiology , Female , Male , Middle Aged , Genetic Predisposition to Disease/genetics , Epigenesis, Genetic/genetics , Mendelian Randomization Analysis/methods , Epigenome/genetics , Adult , Aged , Carrier Proteins/genetics
6.
Polymers (Basel) ; 16(6)2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38543446

ABSTRACT

In this study, thiol-functionalized ladder-like polysesquioxanes end-capped with methyl and phenyl groups were synthesized via a simple sol-gel method and characterized through gel permeation chromatography (GPC), Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and thermogravimetric analysis (TGA). Additionally, epoxy blends of different formulations were prepared. Their structural, flame-retardant, thermal, and mechanical properties, as well as volatile organic compound (VOC) emissions, were determined using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), TGA, scanning electron microscopy (SEM), limiting oxygen index (LOI), cone calorimetry, and a VOC analyzer. Compared to epoxy blends with flame retardants containing elemental phosphorus alone, those with flame retardants containing elemental phosphorus combined with silicon and sulfur exhibited superior thermal, flame-retardant, and mechanical properties with low VOC emissions. SEM of the residual char revealed a dense and continuous morphology without holes or cracks. In particular, LOI values for the combustion of methyl and phenyl end-capped polysilsesquioxane mixtures were 32.3 and 33.7, respectively, compared to 28.4% of the LOI value for the blends containing only phosphorus compounds. The silicon-sulfur-phosphorus-containing blends displayed reduced flammability concerning the blends using a flame retardant containing only phosphorus. This reflects the cooperative effects of various flame-retardant moieties.

7.
Front Neurosci ; 18: 1340854, 2024.
Article in English | MEDLINE | ID: mdl-38410162

ABSTRACT

Introduction: Several studies have reported a significant correlation between noise-induced hearing loss and cognitive decline. However, comprehensive analyses of this relationship are rare. This study aimed to assess the influence of hearing impairment on cognitive functions by analyzing organ samples in the afferent auditory pathway of deafened mice using mRNA sequencing. Methods: We prepared 10 female 12-week-old C57BL/6N mice as the experimental and control groups in equal numbers. Mice in the experimental group were deafened with 120 dB sound pressure level (SPL) wideband noise for 2 h. Cochlea, auditory cortex, and hippocampus were obtained from all mice. After constructing cDNA libraries for the extracted RNA from the samples, we performed next-generation sequencing. Subsequently, we analyzed the results using gene ontologies (GOs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases for differentially expressed genes (DEGs) of each organ. Results: Our results revealed 102, 89, and 176 DEGs for cochlea, auditory cortex, and hippocampus, respectively. We identified 294, 203, and 211 GOs; 10, 7, and 17 KEGG pathways in the cochlea, auditory cortex, and hippocampus, respectively. In the long term (12 weeks) from noise-induced hearing loss, GOs and KEGG pathways related to apoptosis or inflammation persisted more actively in the order of hippocampus, auditory cortex, and cochlea. Discussion: This implies that the neurodegenerative effects of noise exposure persist more longer time in the central regions.

8.
J Leukoc Biol ; 116(1): 118-131, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38417030

ABSTRACT

Neutrophils are rapidly recruited to sites of infection and are critical for pathogen clearance. Therapeutic use of primary neutrophils has been limited, as they have a short lifespan and are not amenable to genetic manipulation. Human induced pluripotent stem cells (iPSCs) can provide a robust source of neutrophils for infusion and are genetically tractable. However, current work has indicated that dampened intracellular signaling limits iPSC-derived neutrophil (iNeutrophil) cellular activation and antimicrobial response. Here, we show that protein tyrosine phosphatase 1B (PTP1B) inhibits intracellular signaling and dampens iNeutrophil effector function. Deletion of the PTP1B phosphatase increased PI3K and ERK signaling and was associated with increased F-actin polymerization, cell migration, and phagocytosis. In contrast, other effector functions like NETosis and reactive oxygen species production were reduced. PTP1B-deficient neutrophils were more responsive to Aspergillus fumigatus and displayed rapid recruitment and control of hyphal growth. Accordingly, depletion of PTP1B increased production of inflammatory factors including the neutrophil chemokine interleukin-8. Taken together, these findings suggest that PTP1B limits iNeutrophil motility and antimicrobial function.


Subject(s)
Cell Movement , Induced Pluripotent Stem Cells , Neutrophils , Protein Tyrosine Phosphatase, Non-Receptor Type 1 , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Protein Tyrosine Phosphatase, Non-Receptor Type 1/genetics , Neutrophils/metabolism , Neutrophils/immunology , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Aspergillus fumigatus , Phagocytosis , Phosphatidylinositol 3-Kinases/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Extracellular Traps/metabolism , Extracellular Traps/immunology , Actins/metabolism
9.
Acta Otolaryngol ; 143(8): 692-698, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37640054

ABSTRACT

BACKGROUND: The cochlea contains a robust biological clock associated with auditory function, exhibiting diurnal sensitivity to noise or ototoxicity. OBJECTIVES: We examined the relationship between disrupted circadian rhythm and altered expression of circadian clock genes in patients with sudden sensorineural hearing loss (SSNHL) and explored whether the circadian clock genes serve as prognostic biomarkers. MATERIAL AND METHODS: Twelve patients with SSNHL were enrolled study group. Twelve people with normal hearing were enrolled voluntarily for comparison. Audiological evaluation was performed to evaluate hearing thresholds. Korean version of the Pittsburgh Sleep Quality Index Questionnaire was performed to evaluate sleep quality and patterns. Circadian clock genes including for PERI, PER2, PER3, CRYI, CRY2, CLOCK, ARNTL, CSNKIE, and TIMELESS expression in blood were evaluated using real-time quantitative PCR method. RESULTS: Compared with healthy controls without hearing loss, most of the circadian clock genes were markedly downregulated, coupled with low sleep quality and disturbing patterns, in patients with SSNHL. Intriguingly, a weak correlation between hearing improvement following steroid treatment and altered levels of circadian clock genes was observed. CONCLUSIONS AND SIGNIFICANCE: This study provides an additional basis for the relevance of disrupted circadian rhythm to SSNHL and suggests a possible prognostic biomarker for SSNHL treatment.


Subject(s)
Circadian Clocks , Deafness , Hearing Loss, Sensorineural , Sleep Wake Disorders , Humans , Circadian Clocks/genetics , Hearing Loss, Sensorineural/genetics , Hearing , Sleep Wake Disorders/genetics , Sleep
10.
iScience ; 26(5): 106621, 2023 May 19.
Article in English | MEDLINE | ID: mdl-37250328

ABSTRACT

Hemogenic endothelium (HE) is the main source of blood cells in the embryo. To improve blood manufacturing from human pluripotent stem cells (hPSCs), it is essential to define the molecular determinants that enhance HE specification and promote development of the desired blood lineage from HE. Here, using SOX18-inducible hPSCs, we revealed that SOX18 forced expression at the mesodermal stage, in contrast to its homolog SOX17, has minimal effects on arterial specification of HE, expression of HOXA genes and lymphoid differentiation. However, forced expression of SOX18 in HE during endothelial-to-hematopoietic transition (EHT) greatly increases NK versus T cell lineage commitment of hematopoietic progenitors (HPs) arising from HE predominantly expanding CD34+CD43+CD235a/CD41a-CD45- multipotent HPs and altering the expression of genes related to T cell and Toll-like receptor signaling. These studies improve our understanding of lymphoid cell specification during EHT and provide a new tool for enhancing NK cell production from hPSCs for immunotherapies.

11.
Int J Urol ; 29(11): 1322-1330, 2022 11.
Article in English | MEDLINE | ID: mdl-36000794

ABSTRACT

OBJECTIVE: The NEAR trial is a single-arm phase II trial investigating the efficacy of neoadjuvant apalutamide and radical prostatectomy in the treatment of D'Amico intermediate- to high-risk prostate cancer. This publication focuses on health-related quality of life (HRQoL) during 12 weeks of neoadjuvant apalutamide treatment. METHODS: From 2017 to 2019, 30 suitable patients received neoadjuvant apalutamide 240 mg once daily for 12 weeks followed by radical prostatectomy (ClinicalTrials.gov Identifier: NCT03124433). Patient-reported quality of life outcomes was analyzed using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core Module (EORTC QLQ-C30), EORTC Quality of Life Questionnaire Prostate Module (QLQ-PR25), and Sexual Health Inventory for Men questionnaire (SHIM) at weeks 0,4,12, and 20 of the study. RESULTS: Thirty patients completed 12 weeks of apalutamide therapy and data analyzed for 29 with complete datasets. Neoadjuvant apalutamide therapy was associated with no clinically significant negative impact on patients' global health and QoL scores. Deteriorations in mean scores of functional and symptom scales of QLQ-C30 questionnaire were statistically significant (p = 0.011 and p = 0.008, respectively) but were not clinically meaningful. Patients were also affected by fatigue (p = 0.012), cognitive function (p = 0.038), reduced role functioning (p = 0.025), and lower SHIM scores (p < 0.001). Median daily step count reduced from 8228/day to 6001/day per day (p = 0.063), while BMI and body weight reduction were observed (statistically but not clinically significant). CONCLUSION: During 12 weeks of neoadjuvant apalutamide in organ-confined prostate cancer, the overall patient-reported HRQoL outcomes were maintained, but fatigue and sexual dysfunction were observed in those patients.


Subject(s)
Prostate , Prostatic Neoplasms , Male , Humans , Quality of Life , Neoadjuvant Therapy/adverse effects , Prostatectomy/adverse effects , Patient Reported Outcome Measures , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/surgery , Fatigue
12.
Methods Mol Biol ; 2429: 103-124, 2022.
Article in English | MEDLINE | ID: mdl-35507158

ABSTRACT

Endothelial-to-hematopoietic transition (EHT) is a unique morphogenic event in which flat, adherent hemogenic endothelial (HE) cells acquire round, non-adherent blood cell morphology. Investigating the mechanisms of EHT is critical for understanding the development of hematopoietic stem cells (HSCs) and the entirety of the adult immune system, and advancing technologies for manufacturing blood cells from human pluripotent stem cells (hPSCs). Here we describe a protocol to (a) generate and isolate subsets of HE from hPSCs, (b) assess EHT and hematopoietic potential of HE subsets in bulk cultures and at the single-cell level, and (c) evaluate the role of NOTCH signaling during HE specification and EHT. The generation of HE from hPSCs and EHT bulk cultures are performed in xenogen- and feeder-free system, providing the unique advantage of being able to investigate the role of individual signaling factors during EHT and the definitive lympho-myeloid cell specification from hPSCs.


Subject(s)
Hemangioblasts , Pluripotent Stem Cells , Cell Differentiation , Hematopoiesis , Hematopoietic Stem Cells , Humans
13.
Genes Genomics ; 44(5): 629-636, 2022 05.
Article in English | MEDLINE | ID: mdl-35384631

ABSTRACT

BACKGROUND: Metabolic syndrome (MetS) is a group of very common human conditions promoting strong understand the impact of rare variants, beyond exome-wide association studies, to potentially discover causative variants, across different ethnic populations. OBJECTIVE: We performed transethnic, exome-wide MetS association studies on MetS in men. METHODS: We analyzed genotype data of 5302 European subjects (2658 cases and 2644 controls), in the discovery stage of the European METabolic Syndrome In Men study, generated from exome chips, and 2481 subjects (714 cases and 1767 controls), in the replication stage, across 6 independent cohorts of 5 ancestries (T2D-GENES consortium), using whole-exome sequencing. We therefore evaluated gene-level and variant-level associations, of rare variants for MetS, using logistic regression (LR) and multivariate analyses (MulA). RESULTS: Gene-based association found the gene for the cholesteryl ester transfer protein (CETP) (from MulA, p value = 4.67 × 10-9; from LR, p value = 0.009) to well associate with MetS. At two missense variants, from 8 rare variants in CETP, Ala390Pro (rs5880) (from MulA, p value = 1.28 × 10-7; from LR, p value = 1.34 × 10-4) and Arg468Gln (rs1800777) (from MulA, p value = 2.40 × 10-5; from LR, p value = 1.49 × 10-3) significantly associated with MetS across five ancestries. CONCLUSIONS: Our findings highlight novel rare variants of genes that confer MetS susceptibility, in Europeans, that are shared with diverse populations, emphasizing an opportunity to further understand the biological target or genes that underlie MetS, across populations.


Subject(s)
Exome , Metabolic Syndrome , Exome/genetics , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Male , Metabolic Syndrome/genetics , Exome Sequencing
14.
Nat Cancer ; 3(3): 337-354, 2022 03.
Article in English | MEDLINE | ID: mdl-35256819

ABSTRACT

Costimulatory receptors such as glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) play key roles in regulating the effector functions of T cells. In human clinical trials, however, GITR agonist antibodies have shown limited therapeutic effect, which may be due to suboptimal receptor clustering-mediated signaling. To overcome this potential limitation, a rational protein engineering approach is needed to optimize GITR agonist-based immunotherapies. Here we show a bispecific molecule consisting of an anti-PD-1 antibody fused with a multimeric GITR ligand (GITR-L) that induces PD-1-dependent and FcγR-independent GITR clustering, resulting in enhanced activation, proliferation and memory differentiation of primed antigen-specific GITR+PD-1+ T cells. The anti-PD-1-GITR-L bispecific is a PD-1-directed GITR-L construct that demonstrated dose-dependent, immunologically driven tumor growth inhibition in syngeneic, genetically engineered and xenograft humanized mouse tumor models, with a dose-dependent correlation between target saturation and Ki67 and TIGIT upregulation on memory T cells. Anti-PD-1-GITR-L thus represents a bispecific approach to directing GITR agonism for cancer immunotherapy.


Subject(s)
Neoplasms , Programmed Cell Death 1 Receptor , Animals , Cluster Analysis , Disease Models, Animal , Glucocorticoid-Induced TNFR-Related Protein/agonists , Humans , Immunotherapy/methods , Mice , Neoplasms/drug therapy , Receptors, Tumor Necrosis Factor/agonists , T-Lymphocytes
16.
Prostate Cancer Prostatic Dis ; 25(4): 741-748, 2022 04.
Article in English | MEDLINE | ID: mdl-35091711

ABSTRACT

OBJECTIVE: Treatment efficacy of androgen deprivation therapy with radical prostatectomy for intermediate- to high-risk prostate cancer is less well-studied. The NEAR trial is a single-arm, phase II investigation of neoadjuvant apalutamide monotherapy and radical prostatectomy (RP) in the treatment of D'Amico intermediate- and high-risk prostate cancer (NCT03124433). MATERIALS AND METHODS: Patients with histologically-proven, D'Amico intermediate- to high-risk prostate adenocarcinoma received apalutamide 240 mg once-daily for 12 weeks followed by RP + /-lymphadenectomy. Primary outcome was pathological complete response (pCR) rate. Secondary outcomes included rate of biochemical response (defined by PSA < 0.03 ng/mL at week 24 from starting apalutamide without subsequent PSA relapse), treatment-related adverse events, and RP complication rates. Correlative biomarker analyses were performed to examine for molecular predictors of treatment responses. RESULTS: From 2017 to 2019, 30 patients were recruited, of which 20 and 10 were high and intermediate risk, respectively; 25 completed treatment as per-protocol. We did not observe any pCR on trial; median reduction of cancer burden was 41.7% (IQR: 33.3%-60.0%). 18 out of 25 patients were classified as having a biochemical response (4 did not achieve PSA of <0.03 ng/mL at week 24 and 3 developed PSA relapse subsequently). Dry skin (N = 16; 53.3%), fatigue (N = 10; 33.3%) and skin rash (N = 9; 30.0%) were the most common adverse events, and there was no major peri-operative complication. We observed an association between tumours of low androgen receptor activity and PAM50 basal status with biochemical non-responders, albeit these molecular phenotypes were not associated with pathological response. CONCLUSIONS: A 12-week course of neoadjuvant apalutamide prior to RP did not meet the primary endpoint of pCR in this trial. Tumours with low androgen receptor activity or of the PAM50 basal subtype may have a reduced response to apalutamide.


Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Male , Humans , Prostate/pathology , Neoadjuvant Therapy/methods , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Androgen Antagonists/therapeutic use , Receptors, Androgen , Neoplasm Recurrence, Local/surgery , Prostatectomy/methods
17.
ACS Appl Mater Interfaces ; 14(1): 1270-1279, 2022 Jan 12.
Article in English | MEDLINE | ID: mdl-34979804

ABSTRACT

Charge carrier transport and corresponding thermoelectric properties are often affected by several parameters, necessitating a thorough comparative study for a profound understanding of the detailed conduction mechanism. Here, as a model system, we compare the electronic transport properties of two layered semiconductors, Sb2Si2Te6 and Bi2Si2Te6. Both materials have similar grain sizes and morphologies, yet their conduction characteristics are significantly different. We found that phase boundary scattering can be one of the main factors for Bi2Si2Te6 to experience significant charge carrier scattering, whereas Sb2Si2Te6 is relatively unaffected by the phenomenon. Furthermore, extensive point defect scattering in Sb2Si2Te6 significantly reduces its lattice thermal conductivity and results in high zT values across a broad temperature range. These findings provide novel insights into electron transport within these materials and should lead to strategies for further improving their thermoelectric performance.

18.
Article in English | WPRIM (Western Pacific) | ID: wpr-926242

ABSTRACT

This study was undertaken to investigate the association between maternal nutrition knowledge, dietary attitudes, and behaviors related to sugar intake and sugar intake reduction in preschool children. Eighty-three children aged 5 to 6 years attending kindergartens in Hongseong and their mothers participated in this study from October 2020 to February 2021. The average age of the mothers was 38.7 years, and 53.0% of the children were male. As child age increased, nutrition knowledge of sugar intake reduction increased, but no relation was found between age and, dietary behavior and preference related to sugar intake reduction. For children whose mothers perceived that their child’s sugar preference was high, the behavioral score of sugar intake reduction was low. The more mothers allowed their children to eat sweet food; the higher was their child’s preference for sweet food, which was also significantly associated with an increased risk of high sugar intake. When mothers were provided education that encouraged reducing children’s sugar intakes, knowledge about reducing sugar intake in children was significantly increased. The study emphasizes the importance of the roles of mothers and primary caregivers regarding reducing the sugar intakes of preschool children.

19.
Nutrients ; 13(7)2021 Jul 16.
Article in English | MEDLINE | ID: mdl-34371949

ABSTRACT

Homocysteine (Hcy) is well known to be increased in the metabolic syndrome (MetS) incidence. However, it remains unclear whether the relationship is causal or not. Recently, Mendelian Randomization (MR) has been popularly used to assess the causal influence. In this study, we adopted MR to investigate the causal influence of Hcy on MetS in adults using three independent cohorts. We considered one-sample MR and two-sample MR. We analyzed one-sample MR in 5902 individuals (2090 MetS cases and 3812 controls) from the KARE and two-sample MR from the HEXA (676 cases and 3017 controls) and CAVAS (1052 cases and 764 controls) datasets to evaluate whether genetically increased Hcy level influences the risk of MetS. In observation studies, the odds of MetS increased with higher Hcy concentrations (odds ratio (OR) 1.17, 95%CI 1.12-1.22, p < 0.01). One-sample MR was performed using two-stage least-squares regression, with an MTHFR C677T and weighted Hcy generic risk score as an instrument. Two-sample MR was performed with five genetic variants (rs12567136, rs1801133, rs2336377, rs1624230, and rs1836883) by GWAS data as the instrumental variables. For sensitivity analysis, weighted median and MR-Egger regression were used. Using one-sample MR, we found an increased risk of MetS (OR 2.07 per 1-SD Hcy increase). Two-sample MR supported that increased Hcy was significantly associated with increased MetS risk by using the inverse variance weighted (IVW) method (beta 0.723, SE 0.119, and p < 0.001), the weighted median regression method (beta 0.734, SE 0.097, and p < 0.001), and the MR-Egger method (beta 2.073, SE 0.843, and p = 0.014) in meta-analysis. The MR-Egger slope showed no evidence of pleiotropic effects (intercept -0.097, p = 0.107). In conclusion, this study represented the MR approach and elucidates the significant relationship between Hcy and the risk of MetS in the Korean population.


Subject(s)
Genetic Predisposition to Disease , Homocysteine/blood , Metabolic Syndrome/genetics , Aged , Female , Humans , Male , Mendelian Randomization Analysis , Metabolic Syndrome/blood , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Odds Ratio , Polymorphism, Single Nucleotide
20.
Ultrason Sonochem ; 73: 105545, 2021 May.
Article in English | MEDLINE | ID: mdl-33836371

ABSTRACT

Lacquer sap has received much attention as a traditional natural resin because it is a renewable and eco-friendly biopolymer resource unlike artificial coating materials. However, strict drying conditions and long drying times of lacquer sap should be modified to expand its applications. This study presents the first attempt to investigate the effect of different amplitudes of ultrasonic waves on the lacquer sap composed of water-in-oil (W/O) emulsion droplets and the mechanical properties of the resultant film by solvent evaporation. Acoustically induced cavitation via batch ultrasonication facilitates the generation of submicron-sized W/O emulsion. The drying time of sonicated lacquer sap was noticeably shortened as the amplitude of acoustic power increased. Interestingly, the transparency of the film cast from lacquer sap consisting of the smallest emulsion droplets increased significantly, weakening the degree of colour change from caramel-like yellow to dark brown as polymerisation progressed. These are attributed to the effective and frequent contact of laccase enzyme with urushiol at the increased interfacial area of nano-emulsified W/O droplets pulverised by ultrasonic waves. The quinone radical-generation in the interface layer and its transfer to the urushiol oil phase through water-insoluble glycoprotein emulsifier are greatly promoted, resulting in highly cross-linked, dense three-dimensional polymer networks, which also increased the lacquer film hardness after drying. As the emulsion droplet size decreased, the mutual interaction between the catechol moiety of urushiol and the substrates increased, resulting in improved adhesion. The nano-emulsification of the lacquer sap by ultrasonic waves can be used in a simple, effective, and eco-friendly way to shorten the drying time and improve the film characteristics of natural resins. This approach could pave the way for its wide range of applications in industrial fields, taking into account green and sustainable chemistry.

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