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Direct reprogramming provides a novel breakthrough for generating functional endothelial cells (ECs) without the need for intermediate stem or progenitor states, offering a promising resource for cardiovascular research and treatment. ETV2 is a key transcription factor that has been identified as a pioneering factor for specifying endothelial lineage. Achieving precise ETV2 induction is essential for effective endothelial reprogramming, and maintaining the reprogrammed cellular phenotype relies on a specific combination of growth factors and small molecules. Thus, we hereby provide a straightforward and comprehensive protocol for generating two distinct types of reprogrammed ECs (rECs) from human dermal fibroblasts (HDFs). Early rECs demonstrate a robust neovascularization property but lack the mature EC phenotype, while late rECs exhibit phenotypical similarity to human postnatal ECs and have a neovascularization capacity similar to early rECs. Both cell types can be derived from human somatic source cells, making them suitable for personalized disease investigations, drug discovery, and disease therapy.
Subject(s)
Cell Culture Techniques , Cellular Reprogramming , Endothelial Cells , Fibroblasts , Humans , Endothelial Cells/cytology , Endothelial Cells/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism , Cell Culture Techniques/methods , Cells, Cultured , Neovascularization, Physiologic , Cell Differentiation , Transcription Factors/metabolism , Transcription Factors/genetics , Cellular Reprogramming Techniques/methodsABSTRACT
This study presents a thorough investigation of the novel application of graphene oxide (GO) modified with melamine formaldehyde to fabricate granular three-dimensional GO (3D-GO), followed by the introduction of UiO-66 doping (3D-GO/U) for high uranium (U) adsorption. The U(VI) adsorption isotherms revealed that 3D-GO/U-10 with 10 % UiO-66 incorporation exhibited an impressive adsorption capacity of 375.5 mg g-1 and remained high U(VI) sorption performance in wide pH range. The introduction of UiO-66 to 3D-GO (3D-GO/U-10) led to the deagglomeration of the UiO-66 particles. The in situ surface-enhanced-Raman-spectroscopy-analysis and density-functional-theory simulations showed the symmetric metal center site Zr-O2 on UiO-66 was discovered to exhibit the highest adsorption energy (-3.21 eV) for U(VI) species due to the electrons transfer from the oxygen atom to U(VI) drives the covalent bonding between the symmetric metal center sites Zr-O2 and U(VI) on 3D-GO/U-10. The 3D-GO/U-10 was regenerated using a 0.1 M Na2CO3/0.01 M H2O2 solution and achieved up to 89.7 % U(VI) removal in the 5th cycle. The continuous flow column experiments results revealed 3D-GO/U-10 can regenerate and maintain a U(VI) removal capacity of â¼76 % for up to 4 cycles column experiments. Therefore, 3D-GO/U-10 exhibits great potential for removing U(VI) from water bodies.
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PURPOSE: The purpose of this study was to present a new surgical technique to convert a single roll of Descemet membrane (DM) into a double roll using 2 cannulas in a balanced salt solution-filled Petri dish during DM endothelial keratoplasty. METHODS: A single DM roll stained with trypan blue was placed in a balanced salt solution-filled Petri dish. Two cannulas (28G) were introduced from opposite ends of the single roll, inserted into the roll, and slowly spread apart to change the single roll into a double roll. The DM was aspirated into the modified Jones tube and loaded, maintaining a double-roll configuration with endothelium-down orientation in a bevel-up position. The modified Jones tube with the bevel down was inserted into the recipient anterior chamber through the main wound. The modified Jones tube was rotated to the bevel-up orientation. After checking the graft orientation, the DM was inserted into the recipient anterior chamber. The double-roll DM was easily unfolded by tapping the center of the cornea using a cannula. A 28G cannula was inserted under the DM, and the anterior chamber was filled with air. RESULTS: Three months after surgery, the patient's corrected visual acuity in the right eye was 6/7.5 and the endothelial cell count was 1095/mm2. The corneal thickness was 533 µm, and the cornea was clear. CONCLUSIONS: The double-cannula maneuver mechanically changes the single roll of the donor DM to a double roll outside the recipient anterior chamber, making DM unfolding easier and minimizing the risk of upside-down apposition of the donor DM.
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Phlomoides umbrosa Turczaninow (PU), a traditional Korean medicinal herb, exhibits osteogenic and anti-inflammatory effects. This research explored the effect of PU extracts on hyperimmune responses within the respiratory tract using lipopolysaccharide-stimulated RAW 264.7 cells and an ovalbumin-induced hyper-responsiveness model. The inflammatory cytokines, protein expression linked to airway inflammation, antioxidant enzyme activity, histopathological observation, and expectorant activity were measured. The results revealed that PU treatment led to a concentration-dependent reduction in Th2 cytokines and the expression of nuclear factor (NF)-κB, phosphatase-tensin homolog, mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS). Simultaneously, antioxidant enzyme activity increased. Furthermore, PU exhibited substantial enhancements in lung tissue condition and expectorant activity relative to the allergic rhinitis-induced group. These findings indicate the potential of PU to mitigate airway inflammation and excessive mucus production by suppressing NF-κB, MAPK, and iNOS pathways. Consequently, PU emerges as a promising anti-inflammatory agent for respiratory tract applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01521-3.
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This study was performed to segment the urinary system as the basis for diagnosing urinary system diseases on non-contrast computed tomography (CT). This study was conducted with images obtained between January 2016 and December 2020. During the study period, non-contrast abdominopelvic CT scans of patients and diagnosed and treated with urinary stones at the emergency departments of two institutions were collected. Region of interest extraction was first performed, and urinary system segmentation was performed using a modified U-Net. Thereafter, fivefold cross-validation was performed to evaluate the robustness of the model performance. In fivefold cross-validation results of the segmentation of the urinary system, the average dice coefficient was 0.8673, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9651, 0.7172, and 0.9196, respectively. In the test dataset, the average dice coefficient of best performing model in fivefold cross validation for whole urinary system was 0.8623, and the dice coefficients for each class (kidney, ureter, and urinary bladder) were 0.9613, 0.7225, and 0.9032, respectively. The segmentation of the urinary system using the modified U-Net proposed in this study could be the basis for the detection of kidney, ureter, and urinary bladder lesions, such as stones and tumours, through machine learning.
Subject(s)
Kidney , Tomography, X-Ray Computed , Ureter , Urinary Bladder , Humans , Tomography, X-Ray Computed/methods , Urinary Bladder/diagnostic imaging , Ureter/diagnostic imaging , Kidney/diagnostic imaging , Female , Male , Middle Aged , Adult , Aged , Image Processing, Computer-Assisted/methods , Neural Networks, ComputerABSTRACT
BACKGROUND: According to international pediatric urinary tract infection (UTI) guidelines, selecting ampicillin/sulbactam or amoxicillin/clavulanate is recommended as the first-line treatment for pediatric UTI. In Korea, elevated resistance to ampicillin and ampicillin/sulbactam has resulted in the widespread use of third-generation cephalosporins for treating pediatric UTIs. This study aims to compare the efficacy of piperacillin-tazobactam (TZP) and cefotaxime (CTX) as first-line treatments in hospitalized children with UTIs. MATERIALS AND METHODS: The study, conducted at Jeju National University Hospital, retrospectively analyzed medical records of children hospitalized for febrile UTIs between 2014 and 2017. UTI diagnosis included unexplained fever, abnormal urinalysis, and the presence of significant uropathogens. Treatment responses, recurrence, and antimicrobial susceptibility were assessed. RESULTS: Out of 323 patients, 220 met the inclusion criteria. Demographics and clinical characteristics were similar between TZP and CTX groups. For children aged ≥3 months, no significant differences were found in treatment responses and recurrence. Extended-spectrum beta-lactamase (ESBL)-positive strains were associated with recurrence in those <3 months. CONCLUSION: In Korea, escalating resistance to empirical antibiotics has led to the adoption of broad-spectrum empirical treatment. TZP emerged as a viable alternative to CTX for hospitalized children aged ≥3 months with UTIs. Consideration of ESBL-positive strains and individualized approaches for those <3 months are crucial.
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Cliffs contain one of the least known plant communities, which has been overlooked in biodiversity assessments due to the inherent inaccessibility. Our study adopted the unmanned aerial vehicle (UAV) with the telephoto camera to remotely clarify floristic variability across unreachable cliffs. Studied cliffs comprised 17 coastal and 13 inland cliffs in Gageodo of South Korea, among which 9 and 5 cliffs were grazed by the introduced cliff-dwelling goats. The UAV telephotography showed 154 and 166 plant species from coastal and inland cliffs, respectively. Inland cliffs contained more vascular plant species (P < 0.001), increased proportions of fern and woody species (P < 0.05), and decreased proportion of herbaceous species (P < 0.001) than coastal cliffs. It was also found that coastal and inland cliffs differed in the species composition (P < 0.001) rather than taxonomic beta diversity (P = 0.29). Furthermore, grazed coastal cliffs featured the elevated proportions of alien and annual herb species than ungrazed coastal cliffs (P < 0.05). This suggests that coastal cliffs might not be totally immune to grazing if the introduced herbivores are able to access cliff microhabitats; therefore, such anthropogenic introduction of cliff-dwelling herbivores should be excluded to conserve the native cliff plant communities.
Subject(s)
Biodiversity , Plants , Animals , Republic of Korea , Islands , Unmanned Aerial Devices , Herbivory , Goats , EcosystemABSTRACT
Hepatitis B Virus (HBV) infection significantly elevates the risk of hepatocellular carcinoma (HCC), with the HBV X protein (HBx) playing a crucial role in cancer progression. Sorafenib, the primary therapy for advanced HCC, shows limited effectiveness in HBV-infected patients due to HBx-related resistance. Numerous studies have explored combination therapies to overcome this resistance. Sodium diethyldithiocarbamate (DDC), known for its anticancer effects and its inhibition of superoxide dismutase 1 (SOD1), is hypothesized to counteract sorafenib (SF) resistance in HBV-positive HCCs. Our research demonstrates that combining DDC with SF significantly reduces HBx and SOD1 expressions in HBV-positive HCC cells and human tissues. This combination therapy disrupts the PI3K/Akt/mTOR signalling pathway and promotes apoptosis by increasing reactive oxygen species (ROS) levels. These cellular changes lead to reduced tumour viability and enhanced sensitivity to SF, as evidenced by the synergistic suppression of tumour growth in xenograft models. Additionally, DDC-mediated suppression of SOD1 further enhances SF sensitivity in HBV-positive HCC cells and xenografted animals, thereby inhibiting cancer progression more effectively. These findings suggest that the DDC-SF combination could serve as a promising strategy for overcoming SF resistance in HBV-related HCC, potentially optimizing therapy outcomes.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B virus , Liver Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Reactive Oxygen Species , Signal Transduction , Sorafenib , Superoxide Dismutase-1 , TOR Serine-Threonine Kinases , Sorafenib/pharmacology , Sorafenib/therapeutic use , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/virology , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/virology , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Reactive Oxygen Species/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Superoxide Dismutase-1/metabolism , Superoxide Dismutase-1/genetics , Animals , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/drug effects , Mice , Hepatitis B virus/drug effects , Cell Line, Tumor , Xenograft Model Antitumor Assays , Apoptosis/drug effects , Hepatitis B/complications , Hepatitis B/drug therapy , Hepatitis B/virology , Ditiocarb/pharmacology , Drug Resistance, Neoplasm/drug effects , Mice, Nude , Cell Proliferation/drug effects , Trans-Activators , Viral Regulatory and Accessory ProteinsABSTRACT
OBJECTIVE: Although diabetes is one of the leading causes of death among Korean Americans, the levels and predictors of diabetes knowledge in this group have not been sufficiently reported. This study aimed to (1) describe the level of diabetes knowledge of Korean immigrant women in the U.S. and (2) examine whether there is an interaction effect between social support and education on diabetes knowledge. DESIGN: This study conducted a cross-sectional survey design. The sample included 227 Korean immigrant women living in the southeast region of the U.S. The fourteen items of the Diabetes Knowledge Test were used to assess the diabetes knowledge level of Korean American women. A multiple linear regression analysis was conducted to examine the interaction effect between social support and education on diabetes knowledge. RESULTS: Only 6% of the participants presented a good diabetes knowledge level, 12.5% had a poor level, and the majority (81.5%) had a moderate level. We found a significant interaction effect between social support and education on diabetes knowledge. The highest diabetes knowledge was observed when individuals with a lower education level had higher social support. CONCLUSION: Future health practices and policies may focus on increasing knowledge among Korean American women with lower education levels and lower social support. Implementing peer-led initiatives can enhance diabetes knowledge and encourage better self-care practices within the community.
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OBJECTIVES: This study aimed to predict blood pressure during CPR using chest compression waveform information obtained from a CPR feedback device. METHODS: Quantitative data including chest compression waveforms from a CPR feedback device and the blood pressure measured by arterial cannulation in patients with cardiac arrest during CPR were used. Forty-one features to predict blood pressure were selected from chest compression waveform and demographic characteristics with neighborhood component analysis algorithm. Optimized Gaussian process regression was used as a machine learning algorithm. RESULTS: A total of 14,619 datasets from 19 patients with cardiac arrest (mean age: 66 ± 13 years, 14 men) were used in the analysis. The model could predict blood pressure with high precision and low bias for almost the whole range of systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP). The correlation coefficients (r) between the predicted and actual values were 0.954 (95% confidence interval: 0.951-0.957, p < 0.001) for SBP, 0.926 (95% confidence interval: 0.921-0.931, p < 0.001) for DBP, and 0.958 (95% confidence interval: 0.955-0.961, p < 0.001) for MBP, which all indicated a very good agreement. CONCLUSIONS: Blood pressure generated by chest compressions can be predicted with high accuracy by a machine learning method using chest compression waveform information obtained from a CPR feedback device and the patient's demographic characteristics. Real-time provision of the predicted blood pressure can be used to monitor the quality and efficacy of CPR.
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The growing need for lithium-ion batteries, fueled by the widespread use of electric vehicles (EVs) and portable electronic devices, requires high energy density and safety. The cathode material Li1-x(NiyCozMn1-y-z)O2 (NCM) shows promise, but attaining high efficiency necessitates optimization of both composition and manufacturing methods. Polycrystalline LiNiCoMnO2 powders were synthesized and assessed in this investigation using a polyvinyl alcohol (PVA) solution method. The study examined different synthesis conditions, such as the PVA to metal ions ratio and the molecular weight of PVA, to assess their influence on powder characteristics. Electrochemical analysis indicated that cathode materials synthesized with a relatively high quantity of PVA with a molecular weight of 98,000 exhibited the highest discharge capacity of 170.34 mAh/g and a high lithium-ion diffusion coefficient of 1.19 × 10-9 cm2/s. Moreover, decreasing the PVA content, irrespective of its molecular weight, led to the production of powders with reduced surface areas and increased pore sizes. The adjustments of PVA during synthesis resulted in pre-sintering observed during the synthesis process, which had an impact on the long-term stability of batteries. The electrodes produced from the synthesized powders had a positive impact on the insertion and extraction of Li+ ions, thereby improving the electrochemical performance of the batteries. This study reveals that cathode materials synthesized with a high quantity of PVA with a molecular weight of 98,000 exhibited the highest discharge capacity of 170.34 mAh/g and a high lithium-ion diffusion coefficient of 1.19 × 10-9 cm2/s. The findings underscore the significance of optimizing methods for synthesizing PVA-based materials to enhance the electrochemical properties of NCM cathode materials, contributing to the advancement of lithium-ion battery technology. The findings underscore the significance of optimizing methods for synthesizing PVA-based materials and their influence on the electrochemical properties of NCM cathode materials. This contributes to the continuous progress in lithium-ion battery technology.
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Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of chemotherapy, and effective treatments for CIPN are still lacking. For this reason, there is a growing interest in complementary and alternative medicine as a potential source of nonsurgical treatments for CIPN symptoms alongside pregabalin. One such option being explored is Chuna manual therapy (CMT), a traditional Korean manual therapy. Methods: This study compares the effectiveness and safety of using only pregabalin (PG) as a conventional method of treating breast and colorectal cancer patients with CIPN symptoms with a combination of both PG and electroacupuncture (EA) or CMT, while also assessing the feasibility of future large-scale clinical studies. Due to the COVID-19 pandemic, only 74 CIPN patients were recruited to this study. Twenty-five were assigned to the PG group, 26 to the PG + EA group, and 22 to the PG + CMT group for a five-week treatment and a four-week follow-up study. Results: For the primary outcome, we evaluated the mean differences in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) compared to the baseline at week 5 (visit 4). Although we found that the PG + CMT group showed the biggest difference (-16.64 [95% CI: -25.16, -8.11]) compared to the PG group (-8.60 [95% CI: -14.93, -2.27]) and the PG + EA group (-6.73 [95% CI: -12.34, -1.13]), this finding lacked statistical significance (p = 0.2075). In terms of safety, two patients in the PG + CMT group reported side effects: one bruise and one headache. Conclusions: The low attrition and high adherence rates of all the groups, and the similar rates of side effects among them, support the feasibility of larger-scale follow-up studies.
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Background: In patients with esophageal squamous cell carcinoma (ESCC), accurately predicting a pathologic complete response (pCR) to preoperative chemoradiotherapy (PCRT) has the potential to enable an active surveillance strategy without esophagectomy. We aimed to establish a reliable multiparameter nomogram model that combines tumor characteristics, imaging modalities, and hematologic markers to predict pCR in patients with ESCC who underwent PCRT and esophagectomy. Methods: We retrospectively reviewed the medical records of 457 patients with ESCC who received PCRT followed by esophagectomy between January 2005 and October 2020. The nomogram model was developed using logistic regression analysis with a training cohort and externally validated with a validation cohort. Results: In the training and validation cohorts, 44.2% (126/285) and 48.3% (83/172) of patients, respectively, achieved pCR after PCRT. The 5-year rates of overall survival, progression-free survival, and freedom from local progression in the training cohort were 51.6%, 48.5%, and 77.6%, respectively. The parameters included in the nomogram were histologic grade, clinical N stage, maximum standardized uptake value on positron emission tomography, and post-PCRT biopsy. Hematologic markers were significantly associated with survival outcomes but not with pCR. The area under the receiver operating characteristic curve of the nomogram was 0.717, 0.704, and 0.707 for the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusion: Our nomogram model based on four parameters obtained from standard clinical practice demonstrated good performance in both the training and validation cohorts and could be useful to aid clinical decision-making to determine whether surgery or active surveillance strategy should be pursued.
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BACKGROUND: Human mesenchymal stem cells originating from umbilical cord matrix are a promising therapeutic resource, and their differentiated cells are spotlighted as a tissue regeneration treatment. However, there are limitations to the medical use of differentiated cells from human umbilical cord matrix-mesenchymal stem cells (hUCM-MSCs), such as efficient differentiation methods. METHODS: To effectively differentiate hUCM-MSCs into hepatocyte-like cells (HLCs), we used the ROCK inhibitor, fasudil, which is known to induce endoderm formation, and gelatin, which provides extracellular matrix to the differentiated cells. To estimate a differentiation efficiency of early stage according to combination of gelatin and fasudil, transcription analysis was conducted. Moreover, to demonstrate that organelle states affect differentiation, we performed transcription, tomographic, and mitochondrial function analysis at each stage of hepatic differentiation. Finally, we evaluated hepatocyte function based on the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4 in mature HLCs. RESULTS: Fasudil induced endoderm-related genes (GATA4, SOX17, and FOXA2) in hUCM-MSCs, and it also induced lipid droplets (LDs) inside the differentiated cells. However, the excessive induction of LDs caused by fasudil inhibited mitochondrial function and prevented differentiation into hepatoblasts. To prevent the excessive LDs formation, we used gelatin as a coating material. When hUCM-MSCs were induced into hepatoblasts with fasudil on high-viscosity (1%) gelatin-coated dishes, hepatoblast-related genes (AFP and HNF4A) showed significant upregulation on high-viscosity gelatin-coated dishes compared to those treated with low-viscosity (0.1%) gelatin. Moreover, other germline cell fates, such as ectoderm and mesoderm, were repressed under these conditions. In addition, LDs abundance was also reduced, whereas mitochondrial function was increased. On the other hand, unlike early stage of the differentiation, low viscosity gelatin was more effective in generating mature HLCs. In this condition, the accumulation of LDs was inhibited in the cells, and mitochondria were activated. Consequently, HLCs originated from hUCM-MSCs were genetically and functionally more matured in low-viscosity gelatin. CONCLUSIONS: This study demonstrated an effective method for differentiating hUCM-MSCs into hepatic cells using fasudil and gelatin of varying viscosities. Moreover, we suggest that efficient hepatic differentiation and the function of hepatic cells differentiated from hUCM-MSCs depend not only on genetic changes but also on the regulation of organelle states.
Subject(s)
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine , Cell Differentiation , Gelatin , Hepatocytes , Mesenchymal Stem Cells , Umbilical Cord , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Cell Differentiation/drug effects , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/pharmacology , Gelatin/chemistry , Gelatin/pharmacology , Hepatocytes/metabolism , Hepatocytes/drug effects , Hepatocytes/cytology , Umbilical Cord/cytology , Viscosity , Cells, Cultured , Mitochondria/metabolism , Mitochondria/drug effectsABSTRACT
BACKGROUND: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aß) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aß and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aß and tau deposition. METHODS: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET. RESULTS: No associations were found between either thyroid hormones or TSH and Aß and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aß on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aß deposition was not significant, whereas the interaction between fT3 and Aß deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aß and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aß on tau deposition. CONCLUSION: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aß and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aß-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.
Subject(s)
Amyloid beta-Peptides , Positron-Emission Tomography , Thyroid Hormones , tau Proteins , Humans , Male , Female , Aged , tau Proteins/blood , tau Proteins/metabolism , Cross-Sectional Studies , Thyroid Hormones/blood , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/blood , Middle Aged , Aged, 80 and over , Brain/diagnostic imaging , Brain/metabolism , Brain/pathology , Alzheimer Disease/blood , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Thyroxine/blood , Thyrotropin/blood , Cohort StudiesABSTRACT
OBJECTIVE: Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that can develop in patients with connective tissue diseases. Establishing autoimmunity in ILD impacts prognosis and treatment. Patients with ILD are screened for autoimmunity by measuring antinuclear autoantibodies, rheumatoid factors, and other nonspecific tests. However, this approach may miss autoimmunity that manifests as autoantibodies to tissue antigens not previously defined in ILD. METHODS: We use Phage Immunoprecipitation-Sequencing (PhIP-Seq) to conduct an autoantibody discovery screen of patients with ILD and controls. We screened for novel autoantigen candidates using PhIP-Seq. We next developed a radio-labeled binding assay and validated the leading candidate in 398 patients with ILD recruited from two academic medical centers and 138 blood bank individuals that formed our reference cohort. RESULTS: PhIP-Seq identified 17 novel autoreactive targets, and machine learning classifiers derived from these targets discriminated ILD serum from controls. Among the 17 candidates, we validated CDHR5 and found CDHR5 autoantibodies in patients with rheumatologic disorders and importantly, patients not previously diagnosed with autoimmunity. Using survival and transplant free-survival data available from one of the two centers, patients with CDHR5 autoantibodies showed worse survival compared with other patients with connective tissue disease ILD. CONCLUSION: We used PhIP-Seq to define a novel CDHR5 autoantibody in a subset of select patients with ILD. Our data complement a recent study showing polymorphisms in the CDHR5-IRF7 gene locus strongly associated with titer of anticentromere antibodies in systemic sclerosis, creating a growing body of evidence suggesting a link between CDHR5 and autoimmunity.
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[This corrects the article DOI: 10.1155/2017/1763292.].
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The contamination of water sources by pharmaceutical compounds presents global environmental and health risks, necessitating the development of efficient water treatment technologies. In this study, the synthesis, characterization, and evaluation of a novel graphitic carbon nitride-calcined (Fe-Ca) layered double hydroxide (gC3N4-CLDH) composite for electrochemical degradation of sulfamethoxazole (SMX) in water yielded significant outcomes are reported. SEM, XRD, FTIR, and XPS analyses confirmed well-defined composite structures with unique morphology and crystalline properties. Electrochemical degradation experiments demonstrated >98% SMX removal and >75% TOC removal under optimized conditions, highlighting its effectiveness. The composite exhibited excellent mineralization efficiency across various pH levels, with superoxide radicals (O2â-) and hydroxyl radicals (âOH) identified as primary reactive oxygen species. With remarkable regeneration capability for up to 7 cycles, the gC3N4-CLDH composite emerges as a highly promising solution for sustainable water treatment. Humic acid (HA) in water significantly slows SMX degradation, suggests complicating SMX degradation with natural organic matter. Despite this, the gC3N4-CLDH composite effectively degrades SMX in groundwater and industrial wastewater, with slight efficiency reduction in the latter due to higher impurity levels. These findings highlight the complexities of treating pharmaceutical pollutants in various water types. Overall, gC3N4-CLDH's high removal efficiency, broad pH applicability, sustainability, and mechanistic insights provide a solid foundation for future research and real-world environmental applications.
Subject(s)
Graphite , Sulfamethoxazole , Water Pollutants, Chemical , Water Purification , Water Purification/methods , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/analysis , Sulfamethoxazole/chemistry , Graphite/chemistry , Wastewater/chemistry , Hydroxides/chemistry , Groundwater/chemistry , Electrochemical Techniques , Humic Substances/analysis , Nitrogen Compounds/chemistry , Nitrogen Compounds/analysisABSTRACT
Dodecamethylcyclohexasiloxane (D6) is a siloxane substance mainly used in cosmetics and personal care products. While octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) were once commonly used in personal care products, their usage has been restricted due to the classification as persistent, bioaccumulative, and toxic (PBT)/very persistent and very bio-accumulative (vPvB) substances. While D6 has emerged as a substitute for D4 and D5, the risk assessment for D6 remains limited compared to the evaluations for D4 and D5. To address this gap, we conducted a comprehensive risk assessment of D6. In this study, we reviewed the toxicity information on D6 and calculated the exposure level to D6, considering the content of D6 in cosmetic products. No observed adverse effect level (NOAEL) of 1500 mg/kg bw/day was established in a repeated dose toxicity study after oral administration to rats. Negative results were found in tests on the ocular and skin irritation, skin sensitization, and genotoxicity of D6. According to the product content of up to 48% of D6 reported in 2012, the Systemic Exposure Dose (SED) was 5.4E-06 to 7.04 mg/kg bw/day for a 60 kg adult using the exposure factors from Korean cosmetic usage. The Margin of Safety was estimated to be between 35.5 and 4.63E+07, posing a potential health risk of D6 according to the maximum concentration and the product type. Further consideration of the potential of D6 as PBT or vPvB is also required.