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Based on a typical ozone ï¼O3ï¼ pollution process in Jinan City from June 16 to 26, 2021, the variation characteristics of O3 and its precursor volatile organic compounds ï¼VOCsï¼ during different pollution periods ï¼clean period ï¼CPï¼, pollution rise period ï¼PRPï¼, heavy pollution period ï¼HPPï¼, and pollution decline period ï¼PDPï¼ï¼ in the urban area were analyzed. Both positive matrix factorization ï¼PMFï¼ and an observation-based model ï¼OBMï¼ were used to identify the main sources of VOCs, O3 production mechanisms, and sensitive species. The results showed that the average value of ρï¼O3-8hï¼ during the HPP period in the urban area was ï¼246.67±11.24ï¼ µg·m-3, and ρï¼O3-1hï¼ had a peak value of 300 µg·m-3. The volume fractions of VOCs and NO2 concentration were affected by the decrease in planetary boundary layer and wind speed, which were 76.99%-145.36% and 127.78%-141.18% higher than those in the other three periods, respectively, and were the main reasons for the aggravation of O3 pollution. Alkanes, oxygenated volatile organic compounds ï¼OVOCsï¼, and halogenated hydrocarbons accounted for 43.81%, 20.98%, and 17.43% of VOCs in urban areas, respectively. All of them showed significant growth during the HPP period, with acetone, propane, and ethane being the top three species by volume in each stage and isopentane showing the highest growth during the HPP period. Alkene, alkanes, and aromatic hydrocarbons accounted for 40.19%, 28.06%, and 21.92% of the ozone generation potential ï¼OFPï¼. 1-butene, toluene, isopentane, and isoprene were the species with higher OFP. Isoprene had the highest OFP during the PRP phase, and 1-butene had the highest OFP during the HPP phase. The volume fraction of isopentane significantly increased OFP. The correlation coefficient between VOCs and CO preliminarily indicated that motor vehicle exhaust and oil and gas volatilization were the main sources of VOCs during the HPP period. Further use of PMF revealed that solvent use sources, combustion sources, motor vehicle exhaust+oil and gas volatilization sources, industrial emission sources, and plant sources were important sources of VOCs in urban areas. The contribution of motor vehicle exhaust+oil and gas volatilization sources in the HPP period to VOCs was 3.09-14.72 times higher than that in other periods. The contribution of solvent use sources to VOCs was approximately 2.50 times higher than that in the CP and PRP periods. The main sources of VOCs volume fraction increase were motor vehicle exhaust, oil and gas volatilization sources, and solvent use sources. Potential sources and concentration weight analysis found that VOCs were also affected by the transmission of VOCs to Binzhou and Dongying in the northeast direction. The OBM results indicated that the main pathway of O3 formation in urban areas was the reaction of peroxide hydroxyl radicals ï¼HO2·ï¼ and methyl peroxide radicals ï¼CH3O2·ï¼ with NO, and the net ozone generation rate during the HPP phase [Pï¼O3ï¼net] was 24×10-9 h-1. Based on the sensitivity experiment results, the alkene components of 1-butene, propylene, cis-2-butene, and ethylene were the dominant species for O3 production.
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Crohn's disease (CD) is an inflammatory bowel disease characterized by transmural inflammation and intestinal fibrosis. Mechanisms of fibrosis in CD are not well understood. Transmural inflammation is associated with inflammatory cell infiltration, stenosis, and distention, which present mechanical stress (MS) to the bowel wall. We hypothesize that MS induces gene expression of profibrotic mediators such as connective tissue growth factor (CTGF), which may contribute to fibrosis in CD. A rodent model of CD was induced by intracolonic instillation of TNBS to the distal colon. TNBS instillation induced a localized transmural inflammation (site I), with a distended colon segment (site P) proximal to site I. We detected significant fibrosis and collagen content not only in site I but also in site P in CD rats by day 7. CTGF expression increased significantly in sites P and I, but not in the segment distal to the inflammation site. Increased CTGF expression was detected mainly in the smooth muscle cells (SMCs). When rats were fed exclusively with clear liquid diet to prevent mechanical distention in colitis, expression of CTGF in sites P and I was blocked. Direct stretch led to robust expression of CTGF in colonic SMC. Treatment of CD rats with anti-CTGF antibody FG-3149 reduced fibrosis and collagen content in both sites P and I and exhibited consistent trends toward normalizing expression of collagen mRNAs. In conclusion, our studies suggest that mechanical stress, by upregulating profibrotic mediators, i.e., CTGF, may play a critical role in fibrosis in CD.NEW & NOTEWORTHY We found that CTGF expression increased significantly not only in the inflammation site but in the distended segment proximal to inflammation in a rodent model of CD-like colitis. Release of mechanical distention prevented CTGF expression in CD rats, whereas direct stretch induced CTGF expression. Treatment with anti-CTGF antibody reduced fibrosis and collagen contents in CD rats. Thus, mechanical stress, via upregulating profibrotic mediators, i.e., CTGF, may play a critical role in fibrosis in CD.
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Factor de Crecimiento del Tejido Conjuntivo , Enfermedad de Crohn , Fibrosis , Ratas Sprague-Dawley , Estrés Mecánico , Animales , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/genética , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Ratas , Masculino , Colitis/metabolismo , Colitis/inducido químicamente , Colitis/patología , Colon/metabolismo , Colon/patología , Modelos Animales de Enfermedad , Ácido Trinitrobencenosulfónico , Colágeno/metabolismoRESUMEN
PURPOSE: Children with comorbidities have a higher risk of severe, coronavirus disease 2019 (COVID-19). This study investigated the clinical features and outcomes of COVID-19 in children and adolescents with diabetes between January and March 2022. METHODS: We retrospectively reviewed the medical records of 123 children and adolescents (73 with type 1 diabetes and 50 with type 2 diabetes, 59 males and 64 females) aged <18 years who had been diagnosed with diabetes. Data were collected from 7 academic medical centers in Daegu, South Korea. RESULTS: Thirty-five children with diabetes were diagnosed with COVID-19 (18 with type 1 and 17 with type 2 diabetes). Eighteen of the 35 children with diabetes and COVID-19 and 50 of the 88 children with diabetes alone received a COVID-19 vaccination. No significant differences were observed between patients with diabetes and COVID-19 and patients with diabetes alone in the type of diabetes diagnosed, sex, age, body mass index, hemoglobin A1c, or vaccination status. All children with diabetes and COVID-19 had mild clinical features and were safely managed in their homes. Fourteen children had a fever of 38â or higher that lasted for more than 2 days, 11 of whom were not vaccinated (p=0.004). None experienced post-COVID-19 conditions. CONCLUSION: All children and adolescents with pre-existing diabetes had mild symptoms of COVID-19 due to low disease severity, high vaccination rates, uninterrupted access to medical care, and continuous glucose monitoring. Unvaccinated children with diabetes who experienced COVID-19 presented with higher and more frequent fevers compared to vaccinated children.
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Zwitterionic hydrogels are electrically neutral materials with both cationic and anionic groups that impart excellent anti-fouling properties and ion channel orientations. However, pure zwitterionic hydrogels generally exhibit low strength and toughness. In this study, it has been discovered that polymerizable zwitterionic monomers in aqueous solution exhibit a unique liquid-liquid phase separation phenomenon at a high monomer concentration of ≥50 wt%, resulting in pure and commercial zwitterionic hydrogels with high compressive strength (6.5 MPa) and high toughness (2.12 kJ m-2). This phase separation and the corresponding aggregations might be caused by strong dipole-dipole interactions among residual zwitterionic monomers under the lack of free-water condition. The synergistic effect of liquid-liquid phase separation and polymer entanglement enhances the mechanical strength, toughness, self-recovery, and anti-freezing properties of pure polyzwitterionic hydrogels. Moreover, the high fracture energy of highly elongated yet tough polyzwitterionic hydrogels facilitates the development of high crack propagation resistance, which supports an expanded role in tissue engineering, soft flexible devices, and electronics applications with improved durability. A wide range of applications for the proposed polyzwitterionic hydrogels is demonstrated by the development and testing of a strain sensor and a triboelectric nanogenerator device. Our findings provide novel insights into the network structure of pure polyzwitterionic hydrogels.
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Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management.
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Inmunosupresores , Trasplante de Hígado , Tacrolimus , Humanos , Tacrolimus/efectos adversos , Masculino , Trasplante de Hígado/efectos adversos , Anciano , Inmunosupresores/efectos adversos , Enfermedad Veno-Oclusiva HepáticaRESUMEN
BACKGROUND: For enhanced management of anxiety disorders, early screening and accurate diagnostic differentiation are essential. The Screen for Adult Anxiety Related Disorders (SCAARED) has been developed to identify and categorize anxiety disorders, thereby facilitating timely and appropriate interventions. In line with this, we aimed to translate and validate the Korean version of the SCAARED questionnaire for the Korean population. METHODS: The original SCAARED was translated into Korean and administered to community adult population (N = 119) ages 18-45 years old in South Korea. The internal consistency and test-retest reliability of the SCAARED were evaluated. In addition, its factor structure was examined using confirmatory and exploratory factor analysis. Concurrent validity was evaluated by comparing SCAARED with the Depression, Anxiety and Stress Scale-21 (DASS), the Beck's Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI). Test-retest reliability was evaluated one week after the first assessment. RESULTS: The SCAARED showed good internal consistency (Cronbach's α = 0.945) and test-retest reliability (γ = 0.883). The SCAARED had significant correlation with DASS-21 subscales (γ = 0.655-0.701), BAI (γ = 0.788) and STAI subscales (γ = 0.548-0.736), confirming good concurrent validity. The results of the Exploratory Factor Analysis showed four factors comparable to the original SCAARED (Generalized anxiety, Somatic/Panic/Agoraphobia, Social anxiety, and Separation anxiety). The area under the curve of the receiver operating characteristic of total and each of the factor scores ranged from 0.724 to 0.942. CONCLUSIONS: The Korean version of the SCAARED is a reliable and valid instrument to screen for anxiety disorders in the Korean adult populations.
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Trastornos de Ansiedad , Escalas de Valoración Psiquiátrica , Psicometría , Humanos , Adulto , Masculino , Femenino , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/psicología , República de Corea , Reproducibilidad de los Resultados , Persona de Mediana Edad , Encuestas y Cuestionarios/normas , Escalas de Valoración Psiquiátrica/normas , Adolescente , Adulto Joven , Análisis FactorialRESUMEN
CD8+ T cells are crucial for viral elimination and recovery from viral infection. Nonetheless, the current understanding of the T cell response to SARS-CoV-2 at the antigen level remains limited. The Spike protein is an external structural protein that is prone to mutations, threatening the efficacy of current vaccines. Therefore, we have characterised the immune response towards the immunogenic Spike-derived peptide (S976-984, VLNDILSRL), restricted to the HLA-A*02:01 molecule, which is mutated in both Alpha (S982A) and Omicron BA.1 (L981F) variants of concern. We determined that the mutation in the Alpha variant (S982A) impacted both the stability and conformation of the peptide, bound to HLA-A*02:01, in comparison to the original S976-984. We identified a longer and overlapping immunogenic peptide (S975-984, SVLNDILSRL) that could be presented by HLA-A*02:01, HLA-A*11:01 and HLA-B*13:01 allomorphs. We showed that S975-specific CD8+ T cells were weakly cross-reactive to the mutant peptides despite their similar conformations when presented by HLA-A*11:01. Altogether, our results show that the impact of SARS-CoV-2 mutations on peptide presentation is HLA allomorph-specific, and that post vaccination there are T cells able to react and cross-react towards the variant of concern peptides.
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Compared to filiform needle therapy, fire-needle therapy has both the stimulation of needles and the warming effect of heat, making it have unexpected effects on some chronic diseases and incurable diseases. Osteoporosis (OP) has a high incidence in postmenopausal women and middle-aged and elderly men, and the treatment cycle is long. According to Traditional Chinese Medicine (TCM), Lingnan fire-needle therapy has shown potential in treating osteoporosis. However, there is still a long way to go before it can be widely used. This article focuses on the application of Lingnan fire-needle therapy in the intervention of OP in rats. It covers the selection of needle tools, acupuncture point selection, positioning of rats' bodies, and fixation methods. We also outline the steps and precautions to be taken during and after needling with fire needles. The experiment was done with three groups: a normal group, a model group, and a fire-needle group, each containing 10 rats. The rats in the fire-needle group were treated with fire-needle intervention for six sessions. After the intervention period, we collected femoral specimens and performed micro-CT scans. The results suggest that fire needling can enhance bone morphology and mineral density in OP rats. This information can serve as a methodological basis for conducting basic research on fire-needle therapy.
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Terapia por Acupuntura , Modelos Animales de Enfermedad , Osteoporosis , Animales , Ratas , Osteoporosis/terapia , Femenino , Terapia por Acupuntura/métodos , Terapia por Acupuntura/instrumentación , Ratas Sprague-Dawley , Agujas , Medicina Tradicional China/métodos , MasculinoRESUMEN
Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, the existing literature on the role of adipocytes in the tumor microenvironment (TME) to elucidate the correlation between obesity and cancer remains insufficient. Here, we aim to investigate the formation of cancer-associated adipocytes (CAAs) and their contribution to tumor growth using mouse models harboring dysfunctional adipocytes. Specifically, we employ adipocyte-specific BECN1 KO (BaKO) mice, which exhibit lipodystrophy due to dysfunctional adipocytes. Our results reveal the activation of YAP/TAZ signaling in both CAAs and BECN1-deficient adipocytes, inducing adipocyte dedifferentiation and formation of a malignant TME. The additional deletion of YAP/TAZ from BaKO mice significantly restores the lipodystrophy and inflammatory phenotypes, leading to tumor regression. Furthermore, mice fed a high-fat diet (HFD) exhibit decreased BECN1 and increased YAP/TAZ expression in their adipose tissues. Treatment with the YAP/TAZ inhibitor, verteporfin, suppresses tumor progression in BaKO and HFD-fed mice, highlighting its efficacy against mice with metabolic dysregulation. Overall, our findings provide insights into the key mediators of CAA and their significance in developing a TME, thereby suggesting a viable approach targeting adipocyte homeostasis to suppress cancer growth.
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Proteínas Adaptadoras Transductoras de Señales , Adipocitos , Dieta Alta en Grasa , Ratones Noqueados , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Microambiente Tumoral , Proteínas Señalizadoras YAP , Animales , Ratones , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Adipocitos/metabolismo , Adipocitos/patología , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Dieta Alta en Grasa/efectos adversos , Progresión de la Enfermedad , Lipodistrofia/metabolismo , Lipodistrofia/patología , Lipodistrofia/genética , Ratones Endogámicos C57BL , Neoplasias/metabolismo , Neoplasias/patología , Neoplasias/genética , Obesidad/metabolismo , Obesidad/patología , Transducción de Señal , Transactivadores/metabolismo , Transactivadores/genética , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Verteporfina/farmacología , Proteínas Señalizadoras YAP/metabolismoRESUMEN
Thread-embedding therapy (TEAT) is a treatment that prevents and manages diseases by inserting a biodegradable suture into an acupoint, providing long-lasting stimulation. TEAT is a simple approach that avoids the discomfort of regular acupuncture and provides sustained therapeutic effects. This article discusses the potential impact of TEAT on the learning and memory abilities of rats with Alzheimer's disease-like symptoms. Since chemically induced neuronal degeneration and cognitive impairments in rats does not entirely reflect the true pathological changes observed in Alzheimer's disease. Consequently, our research group has designated these manifestations as Alzheimer's disease-like symptoms. A protocol has been established to outline the selection of acupoints, the operation process, and necessary precautions for the head and lower back. The experiment was conducted on three groups: a control group, a model group, and a TEAT group, each containing 6 rats. To induce Alzheimer's disease-like symptoms, rats were intraperitoneally injected with D-galactose for 7 weeks (49 days). The rats in the TEAT group received acupoint catgut embedding treatment. Following the intervention period, a Morris Water Maze (MWM) was conducted to evaluate the rats' learning and memory. Subsequently, the rats were sacrificed, and their brain tissue was examined. A histological examination was performed to understand the effects of TEAT on the pathology of rats exhibiting symptoms of Alzheimer's disease. This study suggests that TEAT may improve learning and memory in rats with Alzheimer's disease-like symptoms, indicating a potentially promising new treatment approach for this neurodegenerative condition.
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Terapia por Acupuntura , Enfermedad de Alzheimer , Animales , Enfermedad de Alzheimer/terapia , Terapia por Acupuntura/métodos , Ratas , Modelos Animales de Enfermedad , Puntos de Acupuntura , Suturas , Masculino , Ratas Sprague-Dawley , Aprendizaje por Laberinto/fisiologíaRESUMEN
It remains a big challenge to fabricate low / medium internal phase gel emulsion for the safe wound dressing with low stimulation to the skin. Herein, utilizing the self-assembly and gelation of amphiphilic herbal small molecule-glycyrrhizic acid (GA) derived from traditional Chinese medicine, a new type of supramolecular gel emulsion (SGE) with antibacterial activity and low / medium internal phase was proposed. In the SGE, the oil droplets were stabilized by the nanofibers self-assembled from GA, and the SGE was formed by the supramolecular assembly of GA nanofibers in the presence of Pickering emulsions. As a result, under low / medium internal phase (φ = 30-50 %), SGEs could be readily prepared. Antibacterial tests demonstrated that the growth of gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli) could be effectively inhibited by the SGE. Additionally, compared to high internal phase SGE, SGE with φ = 50 % displayed lower cytotoxicity and a positive impact on the healing process of infectious diabetic wounds. This work provided a novel approach for constructing low / medium internal phase gel emulsion via herbal small molecule-based supramolecular assembly.
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Antibacterianos , Emulsiones , Escherichia coli , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Emulsiones/química , Animales , Geles/química , Ratones , Tamaño de la Partícula , Humanos , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacosRESUMEN
The purpose of this study was to investigate the volatile flavor changes in silver carp mince (SCM) gel glycated with different reducing sugars (glucose, L-arabinose, and xylose) based on E-nose, GC-IMS, and sensory evaluation. These results showed that glycation reduced the fishy smell of SCM gel and increased the meaty, toasty, and burnt smell. A total of 10 volatile compounds were considered as characteristic flavor compounds and potential markers. Among them, the main contributors of fishy included hexanal, heptanal, n-nonanal, octanal, etc. Toasty and burnt were mainly related to the production of 3-methylbutanal and furfurol. These results heralded that glycation could be used to improve the volatile flavor of SCM. This research provided a theoretical basis and technical support for glycation in aquatic food flavor quality control, aquatic pre-made food development, and aquatic leisure food processing.
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Although previous studies have examined the signaling pathway involved in melanogenesis through which ultraviolet (UV) or α-melanocyte-stimulating hormones (α-MSH) stimuli act as key inducers to produce melanin at the stratum basal layer of the epidermis, the signaling pathway regulating melanogenesis is still controversial. This study reports that α-MSH, not UVA and UVB, acted as a major stimulus of melanogenesis in B16F10 melanoma cells. Signaling pathway analysis using gene knockdown technology and chemical inhibitors, the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/p90 ribosomal S6 kinase 2 (RSK2) played an important role in melanogenesis. Unexpectedly, LY294002, a PI3K inhibitor, increased melanogenesis without UV or α-MSH stimulation, suggesting that the PI3K/AKT signaling pathway may not be a major signaling pathway for melanogenesis. Chemical inhibition of the MEKs/ERKs/RSK2 signaling pathway using U0126 or BI-D1870 suppressed melanogenesis by stimulation of UVA or α-MSH stimulation, or both. In particular, the genetic depletion of RSK2 or constitutive active (CA)-RSK2 overexpression showed that RSK2 plays a key role in melanogenesis. Interestingly, forkhead box protein O4 (FOXO4) was phosphorylated by RSK2, resulting in the increase of FOXO4's transactivation activity. Notably, the FOXO4 mutant harboring serine-to-alanine replacement at the phosphorylation sites totally abrogated the transactivation activity and reduced melanin production, indicating that RSK2-mediated FOXO4 activity plays a key role in melanogenesis. Furthermore, kaempferol, a flavonoid inhibiting the RSK2 activity, suppressed melanogenesis. In addition, FOXO4-wt overexpression showed that FOXO4 enhance melanin synthesis. Overall, the RSK2-FOXO4 signaling pathway plays a key role in modulating melanogenesis.
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Melaninas , Pteridinas , Proteínas Quinasas S6 Ribosómicas 90-kDa , Transducción de Señal , alfa-MSH , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Melaninas/biosíntesis , Melaninas/metabolismo , Animales , alfa-MSH/metabolismo , alfa-MSH/farmacología , Ratones , Línea Celular Tumoral , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Rayos Ultravioleta , Morfolinas/farmacología , Cromonas/farmacología , Nitrilos/farmacología , Butadienos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Melanoma Experimental/metabolismo , MelanogénesisRESUMEN
In the field of bone tissue engineering, which is being developed for the ideal restoration of bone defects, researchers are exploring the improvement of the bone regeneration efficacy of scaffolds through various approaches involving osteoconductive, osteoinductive, and angiogenic factors. In the current trend of research, there is also a suggestion that the topological factors of recent scaffolds may influence the attachment, migration, proliferation, and differentiation of bone cells. Building upon experimental confirmation of the effect of scaffold conformity with the defect site on enhanced bone regeneration in previous studies, we conducted this research to experimentally investigate the relationship between contact area with the defect site and bone regeneration efficacy. The results demonstrated that as the contact area of the scaffold increased, not only did the resistance to bone tissue growth increase, more significant bone regeneration also occurred, as evidenced through histological analysis and micro-CT analysis. This research confirms that the contact area between the scaffold and the defect site is a critical variable affecting bone regeneration efficacy, emphasizing its importance when designing customized scaffolds. This finding holds promising implications for future studies and applications in the field.
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Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease), but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood. Cellular senescence is considered to contribute to cellular dysfunction and inflammaging. According to the threshold theory of senescent cell accumulation, the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain. Given the role of microglia in eliminating senescent cells, the accumulation of senescent microglia may lead to the acceleration of brain aging, contributing to inflammaging and increased vulnerability to neurodegenerative diseases. In this review, we propose the idea that the senescence of microglia, which is notably vulnerable to aging, could potentially serve as a central catalyst in the progression of neurodegenerative diseases. The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.
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Esclerosis Amiotrófica Lateral , Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/patología , Microglía/patología , Encéfalo/patología , Senescencia Celular , Esclerosis Amiotrófica Lateral/patologíaRESUMEN
Hemerocallis citrina Borani is a commonly consumed food in Asia and possesses many biologically active ingredients. In this study, a protein named Hemerocallis citrina Borani protein (HcBP) was purified using ammonium sulfate fractionation and anion exchange chromatography. Protease assays revealed that HcBP has peroxidase activity. Meanwhile, the UV absorption spectrum showed that HcBP contains heme. Notably, HcBP showed significant inhibitory effects on human hepatoma cancer cell proliferation. Mechanism investigations indicated that HcBP treatment resulted in overproduction of reactive oxygen species (ROS) and induced mitochondria-dependent apoptosis in human hepatoma cancer cells. Furthermore, we found HcBP not only downregulated pyruvate kinase M2 (PKM2) activity but also decreased the expression and nuclear levels of PKM2. The inhibition of PKM2 led to the downregulation of GLUT1, LDHA and PDK, and thus caused the suppression of glycolysis. In summary, our results suggested that HcBP has potential anti-hepatocellular carcinoma activity.
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BACKGROUND AND AIMS: Exclusive enteral nutrition (EEN) with a liquid diet is the only established dietary treatment for Crohn's' disease (CD). However, the mechanism of action of EEN in CD is unclear. T helper 17 (Th17) immune response plays a critical role in CD. We hypothesized that EEN alleviates Th17 response by eliminating mechanical stress-induced expression of Th17-polarizing cytokines. METHODS: A rat model of Crohn's-like colitis was established by intracolonic instillation of TNBS (65 mg/kg in 250 µL of 40% ethanol). Control rats were treated with saline. We characterized immunophenotypes and molecular changes of the colon in control and colitis rats with and without EEN treatment. Th17 differentiation was determined using coculture assays. RESULTS: TNBS instillation induced transmural inflammation with stenosis in the inflammation site and a marked increase of Th17-polarizing cytokines interleukin (IL)-6 and osteopontin and the Th17 cell population in the mechanically distended preinflammation site (P-site). EEN treatment eliminated mechanical distention and the increase of IL-6, osteopontin, and Th17 response in the P-site. IL-6 and osteopontin expression was found mainly in the muscularis externa. Mechanical stretch of colonic smooth muscle cells in vitro induced a robust increase of IL-6 and osteopontin. When naïve T cells were cultured with conditioned media from the P-site tissue or stretched cells, Th17 differentiation was significantly increased. Inhibition of IL-6, but not deletion of osteopontin, blocked the increase of Th17 differentiation. CONCLUSIONS: Mechanical stress induces Th17-polarizing cytokines in the colon. EEN attenuates Th17 immune response by eliminating mechanical stress-induced IL-6 in Crohn's-like colitis.
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Colitis , Enfermedad de Crohn , Animales , Ratas , Citocinas , Osteopontina , Interleucina-6 , Nutrición Enteral , Estrés Mecánico , Colitis/inducido químicamente , Inflamación/etiología , Inflamación/prevención & control , Enfermedad de Crohn/terapiaRESUMEN
Breathing techniques, particularly slow-paced breathing (SPB), have gained popularity among athletes due to their potential to enhance performance by increasing cardiac vagal activity (CVA), which in turn can help manage stress and regulate emotions. However, it is still unclear whether the frequency of SPB affects its effectiveness in increasing CVA. Therefore, this study aimed to investigate the effects of a brief SPB intervention (i.e., 5 min) on CVA using heart rate variability (HRV) measurement as an index. A total of 75 athletes (22 female; Mage = 22.32; age range = 19-31) participated in the study, attending one lab session where they performed six breathing exercises, including SPB at different frequencies (5 cycles per minute (cpm), 5.5 cpm, 6 cpm, 6.5 cpm, 7 cpm), and a control condition of spontaneous breathing. The study found that CVA was significantly higher in all SPB conditions compared to the control condition, as indexed by both root mean square of the successive differences (RMSSD) and low-frequency HRV (LF-HRVms2). Interestingly, LF-HRVms2 was more sensitive in differentiating the respiratory frequencies than RMSSD. These results suggest that SPB at a range of 5 cpm to 7 cpm can be an effective method to increase CVA and potentially improve stress management and emotion regulation in athletes. This short SPB exercise can be a simple yet useful tool for athletes to use during competitive scenarios and short breaks in competitions. Overall, these findings highlight the potential benefits of incorporating SPB into athletes' training and competition routines.
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Frecuencia Respiratoria , Nervio Vago , Humanos , Femenino , Adulto Joven , Adulto , Frecuencia Cardíaca/fisiología , Frecuencia Respiratoria/fisiología , Nervio Vago/fisiología , Ejercicios Respiratorios , Corazón , RespiraciónRESUMEN
This study investigates the crystal structure, epitaxial relation, and magnetic properties in CoFe thin films deposited on a flexible mica substrate. The epitaxial growth of CoFe thin films was successfully achieved by DC magnetron sputtering, forming three CoFe(002) domains exhibiting four-fold symmetry on the mica substrate. A notable achievement of this work was the attainment of the highest anisotropic magnetoresistance (AMR) value reported to date on a flexible substrate. Additionally, it was observed that the magnetic characteristics of the CoFe films on the flexible mica substrate display reversibility upon strain release. More importantly, the AMR effect of epitaxial CoFe films on flexible mica shows lesser dependence on the crystalline orientation and remains the same under different bending states. These findings demonstrate the potential of utilizing CoFe films on flexible substrates to develop wearable magnetoresistance sensors with diverse applications.