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1.
Mater Horiz ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38973585

ABSTRACT

Two-dimensional magnetic materials are considered as promising candidates for developing next-generation spintronic devices by providing the possibility of scaling down to nanometers. However, a low Curie temperature is a crucial problem for practical applications, being intimately related to weak interlayer exchange coupling. Here, by using density functional theory calculations, we show that interlayer exchange coupling can be enhanced by intercalating 3d transition metals (Sc to Zn) into a bilayer of CrI3 and NiI2. It is found that intercalated Ni and Cr atoms exhibit strong antiferromagnetic coupling with the CrI3 and NiI2 host layers, respectively. This enhances the ferromagnetic interlayer exchange coupling between the host layers by many folds compared to pristine CrI3 and NiI2 bilayers. Moreover, both intercalated compounds show out-of-plane magnetic anisotropy with half metallic nature, which makes them ideal candidates for spintronics applications. Thereby our work provides a rational approach to raise the Curie temperature of non-metallic two-dimensional magnets by intercalation.

2.
Article in English | MEDLINE | ID: mdl-38988090

ABSTRACT

Objectives: This study analyzed the safety of coronavirus disease 2019 (COVID-19) bivalent and monovalent booster vaccines, including the frequency of adverse events (AEs) such as myocarditis and pericarditis, in adolescents aged 12 to 17 years in the Republic of Korea. We aimed to share the safety profile of the COVID-19 bivalent vaccine booster doses. Methods: We analyzed the frequencies of AEs reported to the COVID-19 vaccination management system (CVMS) or self-reported through the text message survey (TMS). Diagnostic eligibility and causality with vaccines were compared using odds ratios (ORs) by vaccine type, and incidence rates per 100,000 person-days were calculated for confirmed cases of myocarditis and pericarditis following monovalent and bivalent booster doses. Results: In the CVMS, the AE reporting rate (per 100,000 doses) was lower after the bivalent booster (66.5) than after the monovalent booster (264.6). Among the AEs reported for both monovalent and bivalent vaccines, 98.2% were non-serious and 1.8% were serious. According to the TMS, both local and systemic AEs were reported less frequently after the bivalent vaccination than after the monovalent vaccination in adolescents aged 12 to 17 years (p<0.001). The incidence rates per 100,000 person-days for confirmed myocarditis/pericarditis following monovalent and bivalent booster doses were 0.03 and 0.05, respectively; this difference was not statistically significant (OR, 1.797; 95% confidence interval, 0.210-15.386). Conclusion: AEs in 12- to 17-year-olds following the bivalent booster were less frequent than those following the monovalent booster in the Republic of Korea, and no major safety issues were identified. However, the reporting rates for AEs were low.

3.
Dig Liver Dis ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39033076

ABSTRACT

BACKGROUND AND AIM: Corticosteroid use is a risk factor for avascular necrosis (AVN) and inflammatory bowel disease (IBD) patients are often exposed to higher corticosteroid usage. We investigated the epidemiology and risk factors of AVN in a nationwide population-based cohort of IBD patients. METHODS: Patients newly diagnosed with IBD were identified, and sex- and age-matched participants from the general population were selected in a 1:3 IBD:non-IBD ratio. We investigated newly diagnosed AVN and assessed the incidence rates and risk of AVN with multivariate Cox regression models. RESULTS: During the median follow-up period of 7.22±3.85 years, 357 (0.62 %) were newly diagnosed with AVN. The risk of AVN was higher in IBD (aHR = 1.42, 95 % CI: 1.25-1.62). Ulcerative colitis (UC) patients showed a particularly elevated risk of developing AVN. IBD patients with higher cumulative corticosteroid intake and exposed to a mean prednisolone-equivalent daily dose>20 mg for >1 month were at higher risk of AVN. In Crohn's disease (CD), longer exposure time to >20 mg prednisolone-equivalent presented a trend in increased risk. CONCLUSION: AVN risk was higher in IBD than in those without, particularly in UC and corticosteroid use in IBD could pose a crucial role. These underscore the importance of considering the AVN etiological factors, particularly corticosteroid use.

4.
BMC Pediatr ; 24(1): 467, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033281

ABSTRACT

BACKGROUND: Pulmonary vascular disease (PVD) and pulmonary hypertension (PH) is a significant disorder affecting prognosis of extremely preterm infants. However, there is still a lack of a consensus on the definition and optimal treatments of PH, and there is also a lack of research comparing these conditions with persistent pulmonary hypertension of newborn (PPHN), early PH, and late PH. To investigate PH in extremely preterm infants, this study compared the baseline characteristics, short-term outcomes, and treatment duration, categorized by the timing of requiring PH treatment. METHODS: This study retrospectively analyzed extremely preterm infants admitted to a single tertiary center. Between 2018 and 2022, infants with clinical or echocardiographic diagnosis of PH who required treatment were divided into three groups based on the timing of treatment initiation: initial 3 days (extremely early-period), from day 4 to day 27 (early-period), and after day 28 (late-period). The study compared the outcomes, including mortality rates, bronchopulmonary dysplasia (BPD) severity, PH treatment duration, and oxygen therapy duration, among the three groups. RESULTS: Among the 157 infants, 67 (42.7%) were treated for PH during their stay. Of these, 39 (57.3%) were treatment in extremely early, 21 (31.3%) in early, and seven (11.4%) in late periods. No significant differences were observed in maternal factors, neonatal factors, or morbidity between the three groups. However, infants who received extremely early-period treatment had a higher mortality rate, but shorter duration of noninvasive respiratory support, oxygen therapy, and PH medication use. On the other hand, the late-period treatment group received longer durations of respiratory support and treatment. CONCLUSIONS: This study revealed differences in mortality rates, respiratory outcomes, and treatment duration between the three groups, suggesting varying pathophysiologies over time in extremely preterm infants.


Subject(s)
Bronchopulmonary Dysplasia , Hypertension, Pulmonary , Infant, Extremely Premature , Humans , Infant, Newborn , Retrospective Studies , Female , Male , Hypertension, Pulmonary/therapy , Bronchopulmonary Dysplasia/therapy , Phenotype , Oxygen Inhalation Therapy , Persistent Fetal Circulation Syndrome/therapy , Infant, Premature, Diseases/therapy , Infant, Premature, Diseases/mortality
5.
bioRxiv ; 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-39005348

ABSTRACT

Intra-tumor heterogeneity is an important driver of tumor evolution and therapy response. Advances in precision cancer treatment will require understanding of mutation clonality and subclonal architecture. Currently the slow computational speed of subclonal reconstruction hinders large cohort studies. To overcome this bottleneck, we developed Clonal structure identification through Pairwise Penalization, or CliPP, which clusters subclonal mutations using a regularized likelihood model. CliPP reliably processed whole-genome and whole-exome sequencing data from over 12,000 tumor samples within 24 hours, thus enabling large-scale downstream association analyses between subclonal structures and clinical outcomes. Through a pan-cancer investigation of 7,827 tumors from 32 cancer types, we found that high subclonal mutational load (sML), a measure of latency time in tumor evolution, was significantly associated with better patient outcomes in 16 cancer types with low to moderate tumor mutation burden (TMB). In a cohort of prostate cancer patients participating in an immunotherapy clinical trial, high sML was indicative of favorable response to immune checkpoint blockade. This comprehensive study using CliPP underscores sML as a key feature of cancer. sML may be essential for linking mutation dynamics with immunotherapy response in the large population of non-high TMB cancers.

7.
Curr Issues Mol Biol ; 46(6): 5712-5723, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38921013

ABSTRACT

Aspergillus fumigatus is commonly found in the airway and is associated with airway inflammatory diseases. Zinc oxide (ZO) is known to be an essential microelement that facilitates fungal survival, growth, and proliferation. This study aimed to investigate the impact of ZO on A. fumigatus-induced fungal sinusitis in rabbits. Twenty-eight New Zealand white rabbits were divided into four groups for this study. Group 1 (6 sides) was treated with intramaxillary phosphate buffer saline (PBS) served as the negative control, Group 2 (6 sides) received intramaxillary PBS and ZO, Group 3 (8 sides) was treated with intramaxillary A. fumigatus alone, and Group 4 (8 sides) treated with intramaxillary A. fumigatus with ZO. After 4 and 12 weeks, sinus mucosal cytokine and transcription factor expressions were determined. A histological analysis was performed to determine inflammatory cell infiltration, number of secretory cells, and mucosal thickness. Fungal biofilm formation was determined using confocal laser microscopy. The intramaxillary instillation of A. fumigatus conidia led to an increase in protein and mRNA expression of interleukin (IL)-1ß and IL-8 in the maxillary sinus mucosa. They were associated with mitogen-activated protein kinase and activator protein-1. Furthermore, intramaxillary instillation of fungal conidia resulted in significant enhancement of inflammatory cell infiltration, epithelial thickening, and fungal biofilm formation. However, intramaxillary ZO did not have a significant impact on A. fumigatus-induced cytokine protein and mRNA expression, and inflammatory cell infiltration and epithelial thickness in sinonasal mucosa. While intramaxillary instillation of A. fumigatus increased mucosal inflammation, cytokine production, and biofilm formation, the intramaxillary application of ZO did not have a significant influence on inflammation in the maxillary sinus mucosa.

8.
Sensors (Basel) ; 24(11)2024 May 23.
Article in English | MEDLINE | ID: mdl-38894140

ABSTRACT

Nocturnal enuresis (NE) is involuntary bedwetting during sleep, typically appearing in young children. Despite the potential benefits of the long-term home monitoring of NE patients for research and treatment enhancement, this area remains underexplored. To address this, we propose NEcare, an in-home monitoring system that utilizes wearable devices and machine learning techniques. NEcare collects sensor data from an electrocardiogram, body impedance (BI), a three-axis accelerometer, and a three-axis gyroscope to examine bladder volume (BV), heart rate (HR), and periodic limb movements in sleep (PLMS). Additionally, it analyzes the collected NE patient data and supports NE moment estimation using heuristic rules and deep learning techniques. To demonstrate the feasibility of in-home monitoring for NE patients using our wearable system, we used our datasets from 30 in-hospital patients and 4 in-home patients. The results show that NEcare captures expected trends associated with NE occurrences, including BV increase, HR increase, and PLMS appearance. In addition, we studied the machine learning-based NE moment estimation, which could help relieve the burdens of NE patients and their families. Finally, we address the limitations and outline future research directions for the development of wearable systems for NE patients.


Subject(s)
Nocturnal Enuresis , Wearable Electronic Devices , Humans , Nocturnal Enuresis/physiopathology , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Child , Heart Rate/physiology , Machine Learning , Male , Female , Electrocardiography/methods , Sleep/physiology , Monitoring, Ambulatory/instrumentation , Monitoring, Ambulatory/methods
9.
Medicine (Baltimore) ; 103(24): e38584, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38875378

ABSTRACT

The investigation into individual survival rates within the patient population was typically conducted using the Cox proportional hazards model. This study was aimed to evaluate the performance of machine learning algorithm in predicting survival rates more than 5 years for individual patients with colorectal cancer. A total of 475 patients with colorectal cancer (CRC) and complete data who had underwent surgery for CRC were analyze to measure individual's survival rate more than 5 years using a machine learning based on penalized Cox regression. We conducted thorough calculations to measure the individual's survival rate more than 5 years for performance evaluation. The receiver operating characteristic curves for the LASSO penalized model, the SCAD penalized model, the unpenalized model, and the RSF model were analyzed. The least absolute shrinkage and selection operator penalized model displayed a mean AUC of 0.67 ±â€…0.06, the smoothly clipped absolute deviation penalized model exhibited a mean AUC of 0.65 ±â€…0.07, the unpenalized model showed a mean AUC of 0.64 ±â€…0.09. Notably, the random survival forests model outperformed the others, demonstrating the most favorable performance evaluation with a mean AUC of 0.71 ±â€…0.05. Compared to the conventional unpenalized Cox model, recent machine learning techniques (LASSO, SCAD, RSF) showed advantages for data interpretation.


Subject(s)
Colorectal Neoplasms , Machine Learning , Proportional Hazards Models , Humans , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Male , Female , Middle Aged , Aged , Survival Rate , ROC Curve , Precision Medicine/methods , Algorithms
10.
Front Cardiovasc Med ; 11: 1367623, 2024.
Article in English | MEDLINE | ID: mdl-38915744

ABSTRACT

Background: Data on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce. Objectives: We prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion. Methods: The multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose. Results: Of 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the "marginal zone," defined as age 75-80 years, weight 60-65 kg, and creatinine levels 1.2-1.5 mg/dL. Conclusions: In real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

11.
Ecotoxicol Environ Saf ; 280: 116544, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38838463

ABSTRACT

Benzyl butyl phthalate (BBP) is a widely used plasticizer that poses various potential health hazards. Although BBP has been extensively studied, the direct mechanism underlying its toxicity in male germ cells remains unclear. Therefore, we investigated BBP-mediated male germ cell toxicity in GC-1 spermatogonia (spg), a differentiated mouse male germ cell line. This study investigated the impact of BBP on reactive oxygen species (ROS) generation, apoptosis, and autophagy regulation, as well as potential protective measures against BBP-induced toxicity. A marked dose-dependent decrease in GC-1 spg cell proliferation was observed following treatment with BBP at 12.5 µM. Exposure to 50 µM BBP, approximating the IC50 of 53.9 µM, markedly increased cellular ROS generation and instigated apoptosis, as evidenced by augmented protein levels of both intrinsic and extrinsic apoptosis-related markers. An amount of 50 µM BBP induced marked upregulation of autophagy regulator proteins, p38 MAPK, and extracellular signal-regulated kinase and substantially downregulated the phosphorylation of key kinases involved in regulating cell proliferation, including phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin (mTOR), c-Jun N-terminal kinase. The triple combination of N-acetylcysteine, parthenolide, and 3-methyladenine markedly restored cell proliferation, decreased BBP-induced apoptosis and autophagy, and restored mTOR phosphorylation. This study provides new insights into BBP-induced male germ cell toxicity and highlights the therapeutic potential of the triple inhibitors in mitigating BBP toxicity.


Subject(s)
Acetylcysteine , Adenine , Apoptosis , Autophagy , Cell Proliferation , Phthalic Acids , Reactive Oxygen Species , Sesquiterpenes , Male , Animals , Mice , Phthalic Acids/toxicity , Autophagy/drug effects , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Sesquiterpenes/pharmacology , Acetylcysteine/pharmacology , Adenine/analogs & derivatives , Adenine/pharmacology , Adenine/toxicity , Cell Proliferation/drug effects , Cell Line , Plasticizers/toxicity , Spermatogonia/drug effects
13.
Mol Genet Genomic Med ; 12(6): e2466, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38860480

ABSTRACT

BACKGROUND: Spinocerebellar ataxia 29 (SCA29) is a rare genetic disorder characterized by early-onset ataxia, gross motor delay, and infantile hypotonia, and is primarily associated with variants in the ITPR1 gene. Cases of SCA29 in Asia are rarely reported, limiting our understanding of this disease. METHODS: A female Korean infant, demonstrating clinical features of SCA29, underwent evaluation and rehabilitation at our outpatient clinic from the age of 3 months to the current age of 4 years. Trio-based genome sequencing tests were performed on the patient and her biological parents. RESULTS: The infant initially presented with macrocephaly, hypotonia, and nystagmus, with nonspecific findings on initial neuroimaging. Subsequent follow-up revealed gross motor delay, early onset ataxia, strabismus, and cognitive impairment. Further neuroimaging revealed atrophy of the cerebellum and vermis, and genetic analysis revealed a de novo pathogenic heterozygous c.800C>T, p.Thr267Met missense mutation in the ITPR1 gene (NM_001378452.1). CONCLUSION: This is the first reported case of SCA29 in a Korean patient, expanding the genetic and phenotypic spectrum of ITPR1-related ataxias. Our case highlights the importance of recognizing early-onset ataxic symptoms, central hypotonia, and gross motor delays with poor ocular fixation, cognitive deficits, and isolated cerebellar atrophy as crucial clinical indicators of SCA29.


Subject(s)
Inositol 1,4,5-Trisphosphate Receptors , Mutation, Missense , Spinocerebellar Degenerations , Humans , Female , Inositol 1,4,5-Trisphosphate Receptors/genetics , Spinocerebellar Degenerations/genetics , Spinocerebellar Degenerations/pathology , Child, Preschool , Cerebellar Ataxia/genetics , Cerebellar Ataxia/pathology , Spinocerebellar Ataxias/genetics , Spinocerebellar Ataxias/pathology , Infant
14.
Cancer Discov ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38885349

ABSTRACT

Over-consumption of iron-rich red meat and hereditary or genetic iron overload are associated with increased risk of colorectal carcinogenesis, yet the mechanistic basis of how metal-mediated signaling leads to oncogenesis remains enigmatic. Using fresh colorectal cancer (CRC) samples we identify Pirin, an iron sensor, that overcomes a rate-limiting step in oncogenesis, by re-activating the dormant human-reverse-transcriptase (hTERT) subunit of telomerase holoenzyme in an iron-(Fe3+)-dependent-manner and thereby drives CRCs. Chemical genetic screens combined with isothermal-dose response fingerprinting and mass-spectrometry identified a small molecule SP2509, that specifically inhibits Pirin-mediated hTERT reactivation in CRCs by competing with iron-(Fe3+) binding. Our findings, first to document how metal ions reactivate telomerase, provide a molecular mechanism for the well-known association between red meat, and increased incidence of CRCs. Small molecules like SP2509 represent a novel modality to target telomerase that acts as driver of 90% human cancers and is yet to be targeted in clinic.

15.
Environ Res ; 255: 119132, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38735380

ABSTRACT

The anaerobic digestion (AD) process has become significant for its capability to convert organic wastewater into biogas, a valuable energy source. Excessive acetic acid accumulation in the anaerobic digester can inhibit methanogens, ultimately leading to the deterioration of process performance. Herein, the effect of magnetite particles (MP) as an enhancer on the methanogenic degradation of highly-concentrated acetate (6 g COD/L) was examined through long-term sequential AD batch tests. Bioreactors with (AM) and without (AO) MP were compared. AO experienced inhibition and its methane production rate (qm) converged to 0.45 L CH4/g VSS/d after 10 sequential batches (AO10, the 10th batch in a series of the sequential batch tests conducted using bioreactors without MP addition). In contrast, AM achieved 3-425% higher qm through the sequential batches, indicating that MP could counteract the inhibition caused by the highly-concentrated acetate. MP addition to inhibited bioreactors (AO10) successfully restored them, achieving qm of 1.53 L CH4/g VSS/d, 3.4 times increase from AO10 after 8 days lag time, validating its potential as a recovery strategy for inhibited digesters with acetate accumulation. AM exhibited higher microbial populations (1.8-3.8 times) and intracellular activity (9.3 times) compared to AO. MP enriched Methanosaeta, Peptoclostridium, Paraclostridium, OPB41, and genes related to direct interspecies electron transfer and acetate oxidation, potentially driving the improvement of qm through MP-mediated methanogenesis. These findings demonstrated the potential of MP supplementation as an effective strategy to accelerate acetate-utilizing methanogenesis and restore an inhibited anaerobic digester with high acetate accumulation.


Subject(s)
Acetic Acid , Bioreactors , Methane , Anaerobiosis , Methane/metabolism , Bioreactors/microbiology , Acetic Acid/metabolism , Ferrosoferric Oxide/metabolism , Waste Disposal, Fluid/methods
16.
J Clin Invest ; 134(13)2024 May 09.
Article in English | MEDLINE | ID: mdl-38722683

ABSTRACT

This study reports that targeting intrinsically disordered regions of the voltage-gated sodium channel 1.7 (NaV1.7) protein facilitates discovery of sodium channel inhibitory peptide aptamers (NaViPA) for adeno-associated virus-mediated (AAV-mediated), sensory neuron-specific analgesia. A multipronged inhibition of INa1.7, INa1.6, INa1.3, and INa1.1 - but not INa1.5 and INa1.8 - was found for a prototype and named NaViPA1, which was derived from the NaV1.7 intracellular loop 1, and is conserved among the TTXs NaV subtypes. NaViPA1 expression in primary sensory neurons (PSNs) of dorsal root ganglia (DRG) produced significant inhibition of TTXs INa but not TTXr INa. DRG injection of AAV6-encoded NaViPA1 significantly attenuated evoked and spontaneous pain behaviors in both male and female rats with neuropathic pain induced by tibial nerve injury (TNI). Whole-cell current clamp of the PSNs showed that NaViPA1 expression normalized PSN excitability in TNI rats, suggesting that NaViPA1 attenuated pain by reversal of injury-induced neuronal hypersensitivity. IHC revealed efficient NaViPA1 expression restricted in PSNs and their central and peripheral terminals, indicating PSN-restricted AAV biodistribution. Inhibition of sodium channels by NaViPA1 was replicated in the human iPSC-derived sensory neurons. These results summate that NaViPA1 is a promising analgesic lead that, combined with AAV-mediated PSN-specific block of multiple TTXs NaVs, has potential as a peripheral nerve-restricted analgesic therapeutic.


Subject(s)
Dependovirus , NAV1.7 Voltage-Gated Sodium Channel , Sensory Receptor Cells , Animals , Rats , Dependovirus/genetics , Sensory Receptor Cells/metabolism , Male , Humans , Female , NAV1.7 Voltage-Gated Sodium Channel/metabolism , NAV1.7 Voltage-Gated Sodium Channel/genetics , Ganglia, Spinal/metabolism , Rats, Sprague-Dawley , Neuralgia/metabolism , Neuralgia/genetics , Neuralgia/drug therapy , Analgesia
17.
Environ Toxicol Pharmacol ; 108: 104466, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38759847

ABSTRACT

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in consumer products, raising concerns about their impact on human health. This study investigates the effects of TiO2 NPs on male germ cells while focusing on cell proliferation inhibition and underlying mechanisms. This was done by utilizing mouse GC-1 spermatogonia cells, an immortalized spermatogonia cell line. TiO2 NPs induced a concentration-dependent proliferation inhibition with increased reactive oxygen species (ROS) generation. Notably, TiO2 NPs induced autophagy and decreased ERK phosphorylation. Treatment with the ROS inhibitor N-Acetyl-l-cysteine (NAC) alleviated TiO2 NPs-induced autophagy, restored ERK phosphorylation, and promoted cell proliferation. These findings call attention to the reproductive risks posed by TiO2 NPs while also highlighting NAC as a possible protective agent against reproductive toxins.


Subject(s)
Acetylcysteine , Autophagy , Cell Proliferation , Metal Nanoparticles , Reactive Oxygen Species , Titanium , Titanium/toxicity , Male , Autophagy/drug effects , Animals , Acetylcysteine/pharmacology , Mice , Reactive Oxygen Species/metabolism , Cell Line , Cell Proliferation/drug effects , Metal Nanoparticles/toxicity , Spermatogonia/drug effects , Nanoparticles/toxicity
18.
Environ Res ; 252(Pt 3): 119034, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38701888

ABSTRACT

Cumulative human exposure to the environmental toxin, bisphenol A (BPA), has raised important health concerns in recent decades. However, the direct genomic regulation of BPA in skeletal muscles and its clinical significance are poorly understood. Therefore, we conducted a genome-wide transcriptome analysis after daily oral administration of BPA at the lowest observed adverse-effect level (LOAEL, 50 mg/kg) in male mice for six weeks to explore the gene-expression regulations in skeletal muscle induced by BPA. The primary Gene Ontology terms linked to BPA-dependent, differentially expressed genes at LOAEL comprised adaptive-immune response, positive regulation of T cell activation, and immune system process. The gene-set enrichment analysis disclosed increased complement-associated genes [complement components 3 (C3) and 4B, complement factor D, complement receptor 2, and immunoglobulin lambda constant 2] in the group administered with BPA, with a false-discovery rate of <0.05. Subsequent validation analysis conducted in BPA-fed animal skeletal muscle tissue and in vitro experiments confirmed that BPA induced immune activation, as evidenced by increased levels of C3 and C4α proteins in mice, C2C12 myoblasts, and mouse skeletal muscle cells. In addition, BPA markedly upregulated the transcription of tumor necrosis factor-α (Tnfα) in C2C12 myoblasts and mouse skeletal muscle cells, which was substantially inhibited by 5z-7-oxozeanol and parthenolide, providing further evidence of BPA-induced inflammation in muscle cells. Our bioinformatics and subsequent animal and in vitro validations demonstrate that BPA can activate inflammation in skeletal muscle, which could be a risk factor underlying chronic muscle weakness and wastage.


Subject(s)
Benzhydryl Compounds , Gene Expression Profiling , Muscle, Skeletal , Phenols , Benzhydryl Compounds/toxicity , Animals , Phenols/toxicity , Male , Mice , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Transcriptome/drug effects , Mice, Inbred C57BL
19.
Article in English | MEDLINE | ID: mdl-38725426

ABSTRACT

PURPOSE: The aims of this study were 1) to investigate the effects of a subepithelial connective tissue graft (SCTG) and a volume-stable collagen matrix (VCMX) on soft-tissue volume gain in the immediate implant placement protocol, and 2) to determine whether polydeoxyribonucleotide (PDRN) can enhance the effects of a VCMX. METHODS: Dental implants were placed in 4 mongrel dogs immediately after extracting the distal roots of their third and fourth mandibular premolars. The gap between the implant and the buccal bone plate was filled with synthetic bone substitute particles. The following soft-tissue augmentation modalities were applied buccally: 1) control (no augmentation), 2) SCTG, 3) VCMX, and 4) VCMX/PDRN. After 4 months, histomorphometric analysis was performed. Tissue changes were evaluated using superimposed standard tessellation language (STL) files. RESULTS: Wound dehiscence was found in more than half of the test groups, but secondary wound healing was successfully achieved in all groups. Histomorphometrically, tissue thickness was favored in group SCTG at or above the implant platform level (IP), and group SCTG and the groups with VCMX presented similar tissue thickness below the IP. However, the differences in such thickness among the groups were minor. The keratinized tissue height was greater in group VCMX/PDRN than in groups SCTG and VCMX. Superimposing the STL files revealed a decrease in soft-tissue volume in all groups. CONCLUSIONS: Wound dehiscence after soft-tissue volume augmentation might be detrimental to obtaining the expected outcomes. PDRN appears not to have a positive effect on the soft-tissue volume gain.

20.
Nat Commun ; 15(1): 3889, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719796

ABSTRACT

There is a growing demand for adsorption technologies for recovering and recycling precious metals (PMs) in various industries. Unfortunately, amine-functionalized polymers widely used as metal adsorbents are ineffective at recovering PMs owing to their unsatisfactory PM adsorption performance. Herein, a star-shaped, hydrazide-functionalized polymer (S-PAcH) is proposed as a readily recoverable standalone adsorbent with high PM adsorption performance. The compact chain structure of S-PAcH containing numerous hydrazide groups with strong reducibility promotes PM adsorption by enhancing PM reduction while forming large, collectable precipitates. Compared with previously reported PM adsorbents, commercial amine polymers, and reducing agents, S-PAcH exhibited significantly higher adsorption capacity, selectivity, and kinetics toward three PMs (gold, palladium, and platinum) with model, simulated, and real-world feed solutions. The superior PM recovery performance of S-PAcH was attributed to its strong reduction capability combined with its chemisorption mechanism. Moreover, PM-adsorbed S-PAcH could be refined into high-purity PMs via calcination, directly utilized (upcycled) as catalysts for dye reduction, or regenerated for reuse, demonstrating its high practical feasibility. Our proposed PM adsorbents would have a tremendous impact on various industrial sectors from the perspectives of environmental protection and sustainable development.

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