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The aim of this study was to explore the feasibility of a time-resolved reflectance imaging system employing a single photodetector to assess the activity of caries lesions that exploits the differential absorption of water at 1300 and 1950 nm. The time-resolved reflectivity of 10 active and 10 arrested lesions on the proximal surfaces and 5 active and 5 arrested lesions on the occlusal surfaces of extracted teeth were monitored simultaneously at 1300 and 1950 nm during forced air drying for 60 s. The presence of a highly mineralized surface zone measured with microcomputed tomography (microCT) was used to indicate lesion activity. Multiple kinetic parameters were extracted from the acquired short wavelength infrared (SWIR) intensity versus time dehydration curves and used to assess lesion activity. Differences in the reflectivity between curves acquired at 1300 and 1950 nm due to differential absorption of water provided improved discrimination between active and arrested lesions over the use of 1950 nm alone. This study demonstrates that it is feasible to use a device with a single photodetector operating at 1950 nm to collect dehydration curves for the assessment of lesion activity and that a system employing two SWIR wavelengths with differential water absorption can improve the performance of lesion activity assessment.
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Caries Dental , Microtomografía por Rayos X , Humanos , Caries Dental/diagnóstico por imagen , Microtomografía por Rayos X/métodos , Técnicas In Vitro , Estudios de Factibilidad , AguaRESUMEN
BACKGROUND: Enamel is highly transparent at short wavelength infrared imaging (SWIR) wavelengths allowing the detection of dental decay without the need for ionizing radiation. The purpose of this study was to use SWIR imaging methods including cross polarization optical coherence tomography (CP-OCT), occlusal transillumination (SWIR-OT), proximal transillumination (SWIR-PT), and occlusal reflectance (SWIR-R) to image interproximal lesions in vivo and compare the sensitivity with radiography. METHODS: Participants (n = 30) aged 18-80 each with a radiopositive interproximal lesion scheduled for restoration were enrolled in the study. Studies have shown that the opposing proximal surfaces across the contact will likely also have lesions. SWIR images were acquired of the adjoining teeth at each contact with an interproximal lesion scheduled for restoration. Lesion presence and depth were assessed on each side of the contact for radiography and each SWIR imaging method. Lesions on radiographs and in CP-OCT images were identified by a single examiner while lesions in SWIR images were identified by a contrast threshold via semi-automatic image segmentation. RESULTS: All SWIR imaging methods had significantly higher sensitivity (P < 0.05) than radiographs for the detection of interproximal lesions on the teeth opposite those restored. CP-OCT and SWIR-R imaging methods had significantly higher sensitivity than the other methods. SWIR imaging methods showed significantly higher lesion contrast than radiography. CONCLUSIONS: SWIR imaging methods can be used to detect interproximal lesions on posterior teeth with higher diagnostic performance than radiographs. CP-OCT appears well suited as a potential gold standard for the detection of interproximal lesions and assessment of their severity in vivo.
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Caries Dental , Tomografía de Coherencia Óptica , Transiluminación , Humanos , Tomografía de Coherencia Óptica/métodos , Persona de Mediana Edad , Anciano , Adolescente , Anciano de 80 o más Años , Adulto , Caries Dental/diagnóstico por imagen , Caries Dental/patología , Adulto Joven , Transiluminación/métodos , Rayos Infrarrojos , Femenino , Masculino , Esmalte Dental/diagnóstico por imagen , Esmalte Dental/patología , Sensibilidad y Especificidad , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Fatty infiltration denotes the anomalous accrual of adipocytes in non-adipose tissue, thereby generating toxic substances with the capacity to impede the ordinary physiological functions of various organs. With aging, the musculoskeletal system undergoes pronounced degenerative alterations, prompting heightened scrutiny regarding the contributory role of fatty infiltration in its pathophysiology. Several studies have demonstrated that fatty infiltration affects the normal metabolism of the musculoskeletal system, leading to substantial tissue damage. Nevertheless, a definitive and universally accepted generalization concerning the comprehensive effects of fatty infiltration on the musculoskeletal system remains elusive. As a result, this review summarizes the characteristics of different types of adipose tissue, the pathological mechanisms associated with fatty infiltration in bone, muscle, and the entirety of the musculoskeletal system, examines relevant clinical diseases, and explores potential therapeutic modalities. This review is intended to give researchers a better understanding of fatty infiltration and to contribute new ideas to the prevention and treatment of clinical musculoskeletal diseases.
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Tejido Adiposo , Enfermedades Musculoesqueléticas , Sistema Musculoesquelético , Humanos , Tejido Adiposo/patología , Tejido Adiposo/metabolismo , Enfermedades Musculoesqueléticas/patología , Enfermedades Musculoesqueléticas/metabolismo , Sistema Musculoesquelético/patología , Sistema Musculoesquelético/metabolismo , Sistema Musculoesquelético/fisiopatología , Animales , Músculo Esquelético/patología , Músculo Esquelético/metabolismo , Adipocitos/patología , Adipocitos/metabolismoRESUMEN
Both the catalyst and electrolyte strongly impact the performance of CO2 electrolysis. Despite substantial progress in catalysts, it remains highly challenging to tailor electrolyte compositions and understand their functions at the catalyst interface. Here, we report that the ethylenediaminetetraacetic acid (EDTA) and its analogs, featuring strong Lewis acid-base interaction with metal cations, are selected as electrolyte additives to reshape the catalyst-electrolyte interface for promoting CO2 electrolysis. Mechanistic studies reveal that EDTA molecules are dynamically assembled toward interface regions in response to bias potential due to strong Lewis acid-base interaction of EDTA4--K+. As a result, the original hydrogen-bond network among interfacial H2O is disrupted, and a hydrogen-bond gap layer at the electrified interface is established. The EDTA-reshaped K+ solvation structure promotes the protonation of *CO2 to *COOH and suppressing *H2O dissociation to *H, thereby boosting the co-electrolysis of CO2 and H2O toward carbon-based products. In particular, when 5 mM of EDTA is added into the electrolytes, the Faradaic efficiency of CO on the commercial Ag nanoparticle catalyst is increased from 57.0% to 90.0% at an industry-relevant current density of 500 mA cm-2. More importantly, the Lewis-base ligand-reshaped interface allows a range of catalysts (Ag, Zn, Pd, Bi, Sn, and Cu) to deliver substantially increased selectivity of carbon-based products in both H-type and flow-type electrolysis cells.
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Both the catalyst and electrolyte deeply impact the performance of the carbon dioxide reduction reaction (CO2RR). It remains a challenge to design the electrolyte compositions for promoting the CO2RR. Here, typical anionic surfactants, dodecylphosphonic acid (DDPA) and its analogues, are employed as electrolyte additives to tune the catalysis interface where the CO2RR occurs. Surprisingly, the anionic surfactant-tailored interfacial microenvironment enables a set of typical commercial catalysts for the CO2RR to deliver a significantly enhanced selectivity of carbon products in both neutral and acidic electrolytes. Mechanistic studies disclose that the DDPA addition restructures the interfacial hydrogen-bond environment via increasing the weak H-bonded water, thus promoting the CO2 protonation to CO. Specifically, in an H-type cell, the Faradaic efficiency of CO increases from 70 to 98% at -1.0 V versus the reversible hydrogen electrode. Furthermore, in a flow cell, the DDPA-containing electrolyte maintains over 90% FECO from 50-400 mA cm-2. Additionally, this electrolyte modulation strategy can be extended to acidic CO2RR with a pH of 1.5-3.5.
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Septins can function as scaffolds for protein recruitment, membrane-bound diffusion barriers, or membrane curvature sensors. Septins are important for cytokinesis, but their exact roles are still obscure. In fission yeast, four septins (Spn1 to Spn4) accumulate at the rim of the division plane as rings. The octameric exocyst complex, which tethers exocytic vesicles to the plasma membrane, exhibits a similar localization and is essential for plasma membrane deposition during cytokinesis. Without septins, the exocyst spreads across the division plane but absent from the rim during septum formation. These results suggest that septins and the exocyst physically interact for proper localization. Indeed, we predicted six pairs of direct interactions between septin and exocyst subunits by AlphaFold2 ColabFold, most of them are confirmed by co-immunoprecipitation and yeast two-hybrid assays. Exocyst mislocalization results in mistargeting of secretory vesicles and their cargos, which leads to cell-separation delay in septin mutants. Our results indicate that septins guide the targeting of exocyst complex on the plasma membrane for vesicle tethering during cytokinesis through direct physical interactions.
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N-methyl-D-aspartate (NMDA)-induced retinal damage has been well studied in rodents, but the detailed mechanisms have not yet been characterized in nonhuman primates. Here, we characterized the retinal degenerative effects of NMDA on rhesus monkeys in vivo. NMDA saline or saline-only control was injected intravitreally to the randomly assigned eyes and contralateral eyes of four rhesus monkeys, respectively. The structural and functional changes of retina were characterized by optical coherence tomography and electroretinography on days 0, 4, 30 and 60 post injection. Both optic discs and macular areas of the NMDA-injected eyes initially presented with a transient retinal thickening, followed by continued retinal thinning. The initial, transient retinal thickening has also been observed in glaucoma patients, but this has not been reported in rodent NMDA models. This initial response was followed by loss of retina ganglion cells (RGCs), which is similar to glaucomatous optic neuropathy and other RGC-related retinal degenerations. The amplitudes of both the photopic negative response and pattern electroretinogram decreased significantly and remained low until the end of the study. Thus, the NMDA monkey model may serve as a more clinically relevant animal model of retinal damage.
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Modelos Animales de Enfermedad , Electrorretinografía , Macaca mulatta , N-Metilaspartato , Retina , Tomografía de Coherencia Óptica , Animales , Retina/patología , Retina/efectos de los fármacos , Células Ganglionares de la Retina/patología , Células Ganglionares de la Retina/efectos de los fármacos , MasculinoRESUMEN
Antimicrobial resistance (AMR) is a growing threat to health globally, with the potential to render numerous medical procedures so dangerous as to be impractical. There is therefore an urgent need for new molecules that function through novel mechanisms of action to combat AMR. The bacterial DNA-repair and SOS-response pathways promote survival of pathogens in infection settings and also activate hypermutation and resistance mechanisms, making these pathways attractive targets for new therapeutics. Small molecules, such as IMP-1700, potentiate DNA damage and inhibit the SOS response in methicillin-resistant S. aureus; however, understanding of the structure-activity relationship (SAR) of this series is lacking. We report here the first comprehensive SAR study of the IMP-1700 scaffold, identifying key pharmacophoric groups and delivering the most potent analogue reported to date, OXF-077. Furthermore, we demonstrate that as a potent inhibitor of the mutagenic SOS response, OXF-077 suppresses the rate of ciprofloxacin resistance emergence in S. aureus. This work supports SOS-response inhibitors as a novel means to combat AMR, and delivers OXF-077 as a tool molecule for future development.
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AIM: To identify genetic defects in a Chinese family with congenital posterior polar cataracts and assess the pathogenicity. METHODS: A four-generation Chinese family affected with autosomal dominant congenital cataract was recruited. Nineteen individuals took part in this study including 5 affected and 14 unaffected individuals. Sanger sequencing targeted hot-spot regions of 27 congenital cataract-causing genes for variant discovery. The pathogenicity of the variant was evaluated by the guidelines of American College of Medical Genetics and InterVar software. Confocal microscopy was applied to detect the subcellular localization of fluorescence-labeled ephrin type-A receptor 2 (EPHA2). Co-immunoprecipitation assay was implemented to estimate the interaction between EphA2 and other lens membrane proteins. The mRNA and protein expression were analyzed by reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assay, respectively. The cell migration was analyzed by wound healing assay. Zebrafish model was generated by ectopic expression of human EPHA2/p.R957P mutant to demonstrate whether the mutant could cause lens opacity in vivo. RESULTS: A novel missense and pathogenic variant c.2870G>C was identified in the sterile alpha motif (SAM) domain of EPHA2. Functional studies demonstrated the variant's impact: reduced EPHA2 protein expression, altered subcellular localization, and disrupted interactions with other lens membrane proteins. This mutant notably enhanced human lens epithelial cell migration, and induced a central cloudy region and roughness in zebrafish lenses with ectopic expression of human EPHA2/p.R957P mutant under differential interference contrast (DIC) optics. CONCLUSION: Novel pathogenic c.2870G>C variant of EPHA2 in a Chinese congenital cataract family contributes to disease pathogenesis.
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Conjunctival fibrosis is a common postoperative complication of glaucoma filtration surgery, resulting in uncontrolled intraocular pressure and surgery failure. Therefore, there is an urgent need to understand the molecular mechanisms underlying conjunctival fibrosis and to explore novel pharmacologic anti-fibrosis therapies for glaucoma filtration surgery. Herein, the 4-dimensional data-independent acquisition (4D-DIA) quantitative proteomic results, coupled with experimental data, revealed the activation of the Wnt/ß-catenin pathway in transforming growth factor (TGF)-ß1-induced human conjunctival fibroblasts (HConFs). Treatment with ICG-001, a Wnt/ß-catenin inhibitor, effectively inhibited cell proliferation and migration in TGFß1-treated HConFs. ICG-001 treatment alleviated the increased generation of extracellular matrix proteins induced by TGFß1. In addition, ICG-001 reduced the expression level of α smooth muscle actin (α-SMA) and inhibited cell contractility in TGFß1-treated HConFs. Proteomics data further suggested that αB-crystallin (CRYAB) was a downstream target of Wnt/ß-catenin, which was up-regulated by TGFß1 and down-regulated by ICG-001. Immunoblotting assay also indicated that ICG-001 reduced the expressions of ubiquitin and ß-catenin in TGFß1-treated HConFs, implying that CRYAB stabilized ß-catenin by inhibiting its ubiquitination degradation. Exogenous CRYAB promoted cell viability, increased extracellular matrix protein levels, and up-regulated α-SMA expression of HConFs under TGFß1 stimulation. CRYAB rescued TGFß1-induced fibrotic responses that were suppressed by ICG-001. In conclusion, this study elucidates the regulatory mechanism of the Wnt/ß-catenin/CRYAB pathway in conjunctival fibrosis, offering promising therapeutic targets for mitigating bleb scarring after glaucoma filtration surgery.
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Conjuntiva , Fibroblastos , Fibrosis , Factor de Crecimiento Transformador beta1 , Vía de Señalización Wnt , Humanos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroblastos/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Vía de Señalización Wnt/efectos de los fármacos , Conjuntiva/patología , Conjuntiva/metabolismo , Conjuntiva/efectos de los fármacos , beta Catenina/metabolismo , Proliferación Celular/efectos de los fármacos , Proteómica/métodos , Pirimidinonas/farmacología , Compuestos Bicíclicos Heterocíclicos con PuentesRESUMEN
Electro-Fenton is an effective process for degrading hard-to-degrade organic pollutants, such as tetracycline (TC). However, the degradation efficiency of this process is limited by the activity and stability of the cathode catalyst. Herein, a temperature gradient pyrolysis strategy and oxidation treatment is proposed to modulate the coordination environment to prepare oxygen-doped cobalt monoatomic electrocatalysts (CoNOC). The CoNOC catalysts can achieve the selectivity of 93 % for H2O2 with an electron transfer number close to 2. In the H-cell, the prepared electrocatalysts can achieve more than 100 h of H2O2 production with good stability and the yield of 1.41 mol gcatalyst-1 h-1 with an average Faraday efficiency (FE) of more than 88 %. The calculations indicate that the epoxy groups play a crucial role in modulating the oxygen reduction pathway. The O doping and unique N coordination of Co single-atom active sites (CoN(Pd)3N(Po)1O1) can effectively weaken the O2/OOH* interaction, thereby promoting the production of H2O2. Finally, the electro-Fenton system could achieve a TC degradation rate of 94.9 % for 120 min with a mineralization efficiency of 87.8 % for 180 min, which provides a reliable option for antibiotic treatment. The significant involvement of OH in the electro-Fenton process was confirmed, and the plausible mineralization pathway for TC was proposed.
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BACKGROUND: Promoting the balance between bone formation and bone resorption is the main therapeutic goal for postmenopausal osteoporosis (PMOP), and bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation plays an important regulatory role in this process. Recently, several long non-coding RNAs (lncRNAs) have been reported to play an important regulatory role in the occurrence and development of OP and participates in a variety of physiological and pathological processes. However, the role of lncRNA tissue inhibitor of metalloproteinases 3 (lncTIMP3) remains to be investigated. METHODS: The characteristics of BMSCs isolated from the PMOP rat model were verified by flow cytometry assay, alkaline phosphatase (ALP), alizarin red and Oil Red O staining assays. Micro-CT and HE staining assays were performed to examine histological changes of the vertebral trabeculae of the rats. RT-qPCR and western blotting assays were carried out to measure the RNA and protein expression levels. The subcellular location of lncTIMP3 was analyzed by FISH assay. The targeting relationships were verified by luciferase reporter assay and RNA pull-down assay. RESULTS: The trabecular spacing was increased in the PMOP rats, while ALP activity and the expression levels of Runx2, Col1a1 and Ocn were all markedly decreased. Among the RNA sequencing results of the clinical samples, lncTIMP3 was the most downregulated differentially expressed lncRNA, also its level was significantly reduced in the OVX rats. Knockdown of lncTIMP3 inhibited osteogenesis of BMSCs, whereas overexpression of lncTIMP3 exhibited the reverse results. Subsequently, lncTIMP3 was confirmed to be located in the cytoplasm of BMSCs, implying its potential as a competing endogenous RNA for miRNAs. Finally, the negative targeting correlations of miR-214 between lncTIMP3 and Smad4 were elucidated in vitro. CONCLUSION: lncTIMP3 may delay the progress of PMOP by promoting the activity of BMSC, the level of osteogenic differentiation marker gene and the formation of calcium nodules by acting on the miR-214/Smad4 axis. This finding may offer valuable insights into the possible management of PMOP.
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Diferenciación Celular , Células Madre Mesenquimatosas , MicroARNs , Osteogénesis , Osteoporosis Posmenopáusica , ARN Largo no Codificante , Proteína Smad4 , Animales , Femenino , Humanos , Ratas , Células de la Médula Ósea/metabolismo , Diferenciación Celular/genética , Modelos Animales de Enfermedad , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Osteogénesis/genética , Osteoporosis Posmenopáusica/genética , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/patología , Ratas Sprague-Dawley , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteína Smad4/metabolismo , Proteína Smad4/genética , Inhibidor Tisular de Metaloproteinasa-3/genéticaRESUMEN
Retinal neurodegenerative diseases are a category of refractory blinding eye conditions closely associated with oxidative stress induced by mitochondrial dysfunction in retinal cells. SARM1, a core driver molecule leading to axonal degeneration, possesses NAD+ enzyme (NADase) activity. However, the role of the SARM1-NAD+ axis in oxidative stress-induced retinal cell death remains unclear. Here, we employed the SARM1 NADase inhibitor DSRM-3716 and established a glucose oxidase (GOx)-induced oxidative stress cell model. We found that compared to the GOx group, the DSRM-3716 pre-treated group reduced the hydrolysis of NAD+, inhibited the elevation of oxidative stress markers induced by GOx, decreased mitochondrial dysfunction, lowered the phosphorylation level of JNK, and attenuated the occurrence of pyroptosis in retinal and nerve cells, thereby providing protection for neurite growth. Further utilization of the JNK activator Anisomycin activated JNK, revealed that the JNK/c-Jun pathway down-regulated NMNAT2 expression. Consequently, it reduced cellular NAD+ synthesis, exacerbated mitochondrial dysfunction and cell pyroptosis, and reversed the protective effect of DSRM-3716 on cells. In summary, the inhibition of SARM1 NADase activity substantially mitigates oxidative damage to retinal cells and mitochondrial damage. Additionally, JNK simultaneously serves as both an upstream and downstream regulator in the SARM1-NAD+ axis, regulating retinal cell pyroptosis and neurite injury. Thus, this study provides new insights into the pathological processes of retinal cell oxidative stress and identifies potential therapeutic targets for retinal neurodegenerative diseases.
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Proteínas del Dominio Armadillo , Proteínas del Citoesqueleto , NAD , Estrés Oxidativo , Proteínas del Dominio Armadillo/metabolismo , Proteínas del Dominio Armadillo/genética , Estrés Oxidativo/efectos de los fármacos , Animales , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/genética , NAD/metabolismo , Retina/patología , Retina/metabolismo , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ratones , Nicotinamida-Nucleótido Adenililtransferasa/metabolismo , Nicotinamida-Nucleótido Adenililtransferasa/genética , Línea Celular , Piroptosis/efectos de los fármacos , Humanos , NAD+ Nucleosidasa/metabolismoRESUMEN
Katsuwonus pelamis is a tuna species mostly sold for canned fillets, its livers were lack of utilization. This study thus investigated an oil production method combining microwave (MW) pretreatment and subcritical dimethyl ether (SDME) in aim to reach improved efficiency and oil quality. The heating characteristics from different MW powers (400, 600, and 800 W) were evaluated, and SEM showed MW having hydrolysis effect on matrix lipoprotein, the fortified recovery rate was also found. Under the MW-SDME condition with 600 W power, 1:5 solid-to-liquid ratio, and 100 min, the recovery reached 93.21% in maximal (SDME â¼50%). To further improve quality, MW powers was noticed affecting lipid types, fatty acid composition, and oxidative stability of produced oils. 1286 lipid types (mostly glyceride and phospholipid-type) were identified, while higher MW lowered the emulsifying phospholipids prompting phase separation. Several oxidation indexes consistently increased with the rising MW power, GC-MS suggested 400 W for higher DHA.
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Stains produced by bacteria or those found in blood and food byproducts accumulate in highly porous caries lesions. They can interfere with accurate diagnosis and the selective removal of carious tissue during cavity preparations. Short-wavelength infrared (SWIR) imaging studies have shown that stain molecules do not absorb light beyond 1200 nm. The objective of this study was to image affected and infected dentin atSWIR wavelengths. Sections of 3 mm thickness were cut from the extracted teeth with deep dentinal lesions. The sound (normal), affected (stained), and infected (demineralized) dentin on each section were examined with reflected light at wavelengths from 400 to 1700 nm, red and green fluorescence, and with optical coherence tomography (OCT). Microcomputed tomography (microCT) was used to measure the mineral density at each location investigated. Significant (p < 0.05) differences were observed in the reflected light intensity at 400-850 nm and for fluorescence between the sound, affected, and infected dentin. SWIR imaging did not show significant reductions in reflectivity for the affected and infected dentin. SWIR images may be valuable for monitoring the lateral spread of dentinal lesions on the occlusal surfaces of teeth.
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BACKGROUND: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. METHODS: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. RESULTS: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy. CONCLUSIONS: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. TRIAL REGISTRATION: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).
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Dislipidemias , Polimorfismo Genético , Adulto , Humanos , Atorvastatina/uso terapéutico , Regiones no Traducidas 3'/genética , LDL-Colesterol , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , ChinaRESUMEN
Purpose: To investigate the potential effects and mechanism of nicotinamide riboside (NR) on the oxidative stress and fibrosis model of human trabecular meshwork (HTM) cell line cells. Methods: HTM cells were pretreated with NR, followed by the induction of oxidative injury and fibrosis by hydrogen peroxide (H2O2) and TGF-ß2, respectively. Cell viability was tested using Hoechst staining and MTT assays, cell proliferation was assessed by EdU assay, and cell apoptosis was detected by flow cytometry and western blotting. DCFH-DA and DHE probes were used to measure the level of reactive oxygen species (ROS), and MitoTracker staining was used to measure the mitochondrial membrane potential (MMP). Fibrotic responses, including cell migration and deposition of extracellular matrix (ECM) proteins, were detected via Transwell assays, qRT-PCR, and immunoblotting. Results: NR pretreatment improved the viability, proliferation, and MMP of H2O2-treated HTM cells. Compared to cells treated solely with H2O2, HTM cells treated with both NR and H2O2, exhibited a reduced rate of apoptosis and generation of ROS. Compared with H2O2 pretreatment, NR pretreatment upregulated expression of the JAK2/Stat3 pathway but inhibited mitogen-activated protein kinase (MAPK) pathway expression. Moreover, 10-ng/mL TGF-ß2 promoted cell proliferation and migration, which were inhibited by NR pretreatment. Both qRT-PCR and immunoblotting showed that NR inhibited the expression of fibronectin in a TGF-ß2-induced fibrosis model. Conclusions: NR has a protective effect on oxidative stress and fibrosis in HTM cells, which may be related to the JAK2/Stat3 pathway and MAPK pathway. Translational Relevance: Our research provides the ongoing data for potential therapy of NAD+ precursors in glaucoma.
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Niacinamida/análogos & derivados , Compuestos de Piridinio , Malla Trabecular , Factor de Crecimiento Transformador beta2 , Humanos , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/farmacología , Factor de Crecimiento Transformador beta2/metabolismo , Factor de Crecimiento Transformador beta2/farmacología , Malla Trabecular/metabolismo , Malla Trabecular/patología , Peróxido de Hidrógeno/farmacología , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo/fisiología , FibrosisRESUMEN
BACKGROUND/AIM: To investigate the independent relationships of visual impairment (VI) and Subjective cognitive complaints (SCC) with physical function impairment (PFI) and the interaction effect between VI and SCC on PFI in American older adults. METHODS: The data of this cross-sectional study was obtained from the 2005-2008 National Health and Examination Survey (NHANES) conducted in the United States. The VI criterion included both subjective self-reported eyesight conditions and objective visual acuity test results. The self-reported questionnaires were utilized to determine PFI and SCC. According to the survey design of NHANS, original data were weighted to produce nationally representative estimates. Both the unweighted original data and weighted estimates underwent analysis. Crude and adjusted logistic models were employed to assess the pairwise associations among VI, SCC, and PFI. To assess the interactive effect, measures such as the relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were calculated. RESULTS: A total of 2,710 subjects (weighted n = 38,966,687) aged 60 years or older were included. Compared with subjects without subjective visual impairment (SVI), those with SVI had a significant positive association with PFI [weighted OR (95%CI): 3.11 (2.25, 4.31)]. After multi-variable adjusting, the relationship remained significant [weighted OR (95%CI): 1.90 (1.32, 2.72)]. Similarly, those with objective visual impairment (OVI) were positively associated with the risk of PFI in the crude model [weighted OR (95%CI): 2.35 (1.53, 3.61)] and adjusted model [weighted OR (95%CI): 1.84 (1.07, 3.17)]. Moreover, we found the association of SCC with an increased risk of FPI [crude weighted OR (95%CI): 5.02 (3.40, 7.40); adjusted weighted OR (95%CI): 3.29 (2.01, 5.38)]. Ultimately, the additive interaction showed there was a significant positive interaction term between SVI and SCC on PFI, while OVI and SCC did not. CONCLUSION: Both VI and SCC were significantly associated with PFI in elder adults. Besides, there was a significant synergistic interaction between SVI and SCC on PFI, which indicated the improvement of SVI and SCC may be beneficial for the prevention of PFI. For the elderly, especially those with multiple disabilities, comprehensive and targeted approaches are imperative to foster their overall well-being and health.
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Baja Visión , Anciano , Humanos , Estados Unidos/epidemiología , Encuestas Nutricionales , Estudios Transversales , Ejercicio Físico , CogniciónRESUMEN
PURPOSE: To identify RHO mutations in patients with non-syndromic retinitis pigmentosa (NS-RP). METHODS: A total of 143 probands (46 family history and 97 sporadic cases) with NS-RP were recruited from Southeast China. The coding exons and adjacent intronic regions of RHO were PCR-amplified and sequenced by Sanger sequencing. The candidate variant was evaluated by the guidelines of American College of Medical Genetics and further validated through co-segregation analysis within the family. RESULTS: Five heterozygous mutations in RHO were detected in 5 out of 143 probands, where the frequency of RHO mutations in our cohort was approximately 3.5% (5/143) and 10.8% (5/46) for probands and families with NS-RP, respectively. Three known disease-causing mutations including c.C1030T (p.Q344X), c.C173G (p.T58R), and c.G266A (p.G89D) were identified in three unrelated families. The other two previously unreported mutations c.557C>A (p.S186X) and c.944delA (p.N315TfsX43) were confirmed in Family RP-087 and Family RP-139, respectively. These mutations co-segregated with available affected individuals in each family were not observed in the unaffected family members or in the 112 unrelated controls. CONCLUSIONS: This report expands the mutational spectrum of RHO gene associated with NS-RP and demonstrates the frequency of RP RHO mutations in Southeast Chinese populations.
Asunto(s)
Retinitis Pigmentosa , Rodopsina , Humanos , Rodopsina/genética , Linaje , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/genética , Mutación , Secuencia de Bases , Análisis Mutacional de ADNRESUMEN
The unique properties of high entropy alloy (HEA) catalysts, particularly their severe lattice distortion and the synergistic effect of multiple components, endow them with exceptional multifunctional catalytic performance. Herein, it is revealed for the first time, that the ultrasmall PtRhNiFeCu HEA nanoparticles catalyst shows outstanding catalytic activity for both hydrogen evolution reaction (HER) and oxygen reduction reaction (ORR). The catalyst exhibits an impressively low overpotential of 13 mV at 10 mA cm-2, a Tafel slope of 29.6 mV dec-1, and high mass activity of 7.6 A mgPt -1 at -50 mV in alkaline media, and long-term stability of at least 20 h. Moreover, the catalyst also demonstrates effective catalytic activity for acidic ORR with a commendable performance of 1.23 A mgPt -1, much exceeding the commercial Pt/C catalyst. Density functional theory (DFT) calculations unveil that the efficient electrocatalytic performance for HER and ORR can be primarily attributed to the synergistic effect between components tailors and optimizes the electronic structure of PtRhNiFeCu/C HEA, which not only enhances the HER activity through increasing water capture capability, decreasing energetic barrier for water dissociation, and optimizing hydrogen absorption but also initiates non-platinum active sites with high ORR activity, achieving the improved ORR performance.