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Li-rich layered oxides are promising candidates for high-capacity Li-ion battery cathode materials. In this study, we employ first-principles calculations to investigate the effect of F doping on Li-rich Li2MnO3 layered cathode materials. Our findings reveal that both Li2MnO3 and Li2MnO2.75F0.25 exhibit significant volume changes (greater than 10%) during deep delithiation, which could hinder the cycling of more Li ions from these two materials. For Li2MnO3, it is observed that oxygen ions lose electrons to compensate for charge during the delithiation process, leading to a relatively high voltage plateau. After F doping, oxidation occurs in both the cationic (Mn) and anionic (O) components, resulting in a lower voltage plateau at the beginning of the charge, which can be attributed to the oxidation of Mn3+ to Mn4+. Additionally, F doping can somewhat suppress the release of oxygen in Li2MnO3, improving the stability of anionic oxidation. However, the increase of the activation barriers for Li diffusion can be observed after F doping, due to stronger electrostatic interactions between F- and Li+, which adversely affects the cycling kinetics of Li2MnO2.75F0.25. This study enhances our understanding of the impact of F doping in Li2MnO3 based on theoretical calculations.
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BACKGROUND: Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM: To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/ß-catenin pathway modulation. METHODS: This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/ß-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION: This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/ß-catenin pathway, contributing to the suppression of liver cancer growth.
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Neoplasias Hepáticas , Camundongos Nus , Simulação de Acoplamento Molecular , Microambiente Tumoral , Macrófagos Associados a Tumor , Via de Sinalização Wnt , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Humanos , Camundongos , Células Hep G2 , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Microambiente Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Masculino , Farmacologia em Rede , beta Catenina/metabolismo , Medicina Tradicional Chinesa/métodosRESUMO
The study of acoustic radiation from spherical sound sources plays a crucial role in understanding the thermoviscous effects in practical acoustic problems. However, finding a general solution of acoustic radiation from spherical sound sources in thermoviscous fluids remains a formidable challenge. To advance this issue, an analytical method is developed in this paper to calculate the acoustic field radiated by spherical sound sources with the isothermal boundary condition and arbitrary velocity boundary condition. The developed method is utilized to present the solutions of the acoustic field generated by an oscillating sphere and a general spherical sound source, and the accuracy and validity of these solutions are verified through analytical and numerical methods.
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The von Hippel-Lindau tumor suppressor protein (VHL), an E3 ubiquitin ligase, functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors. Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway, although the specific molecular mechanisms remain unclear. Herein, the roles of mandarin fish ( Siniperca chuatsi) VHL ( scVHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of scVHL was induced by immune stimulation and MRV infection, indicating a potential role in innate immunity. Dual-luciferase reporter gene assays and reverse transcription quantitative PCR (RT-qPCR) results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα, scIKKß, scIκBα, or scp65. Co-immunoprecipitation (Co-IP) analysis identified scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway. Following MRV infection, NF-κB signaling remained activated, which, in turn, promoted MRV replication. These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.
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Doenças dos Peixes , NF-kappa B , Ranavirus , Transdução de Sinais , Replicação Viral , Animais , NF-kappa B/metabolismo , NF-kappa B/genética , Replicação Viral/fisiologia , Doenças dos Peixes/virologia , Ranavirus/fisiologia , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Infecções por Vírus de DNA/veterinária , Infecções por Vírus de DNA/virologia , Proteínas de Peixes/metabolismo , Proteínas de Peixes/genética , Proteínas I-kappa B/metabolismo , Proteínas I-kappa B/genética , Regulação da Expressão GênicaRESUMO
Background: Vaccine clinical trials should strive to recruit a racially, socioeconomically, and ethnically diverse range of participants to ensure appropriate representation that matches population characteristics. Yet, full inclusion in research is often limited. Methods: A single-center retrospective study was conducted of adults enrolled at Brigham and Women's Hospital (Boston, MA) between July 2020 and December 2021. Demographic characteristics, including age, race, ethnicity, ZIP code, and sex assigned at birth, were analyzed from both HIV and COVID-19 vaccine trials during the study period, acknowledging the limitations to representation under these parameters. We compared the educational attainment of vaccine trial participants to residents of the Massachusetts metropolitan area, geocoded participants' addresses to their census block group, and linked them to reported median household income levels from publicly available data for 2020. Frequency and quartile analyses were carried out, and spatial analyses were performed using ArcGIS Online web-based mapping software (Esri). Results: A total of 1030 participants from four COVID-19 vaccine trials (n = 916 participants) and six HIV vaccine trials (n = 114 participants) were included in the analysis. The median age was 49 years (IQR 33-63) and 28 years (IQR 24-34) for the COVID-19 and HIV vaccine trials, respectively. Participants identifying as White were the majority group represented for both the COVID-19 (n = 598, 65.3%) and HIV vaccine trials (n = 83, 72.8%). Fewer than 25% of participants identified as Hispanic or Latin. Based on ZIP code of residence, the median household income for COVID-19 vaccine clinical trial participants (n = 846) was 102,088 USD (IQR = 81,442-126,094). For HIV vaccine clinical trial participants (n = 109), the median household income was 101,266 USD (IQR 75,052-108,832). Conclusion: We described the characteristics of participants enrolled for HIV and COVID-19 vaccine trials at a single center and found similitude in geographical distribution, median incomes, and proportion of underrepresented individuals between the two types of vaccine candidate trials. Further outreach efforts are needed to ensure the inclusion of individuals from lower educational and socioeconomic brackets. In addition, continued and sustained efforts are necessary to ensure inclusion of individuals from diverse racial and ethnic backgrounds.
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Vacinas contra a AIDS , Vacinas contra COVID-19 , COVID-19 , Ensaios Clínicos como Assunto , Infecções por HIV , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , Infecções por HIV/prevenção & controle , Seleção de Pacientes , BostonRESUMO
BACKGROUND: This study investigates the potential of novel meniscal parameters as predictive factors for incident radiographic knee osteoarthritis (ROA) over a span of four years, as part of the Osteoarthritis Initiative (OAI) study. OBJECTIVES: Quantitative measurements of meniscal parameters alteration could serve as predictors of OA's occurrence and progression. METHODS AND MATERIALS: A nested matched case-control study design was used to select participants from OAI study. Case knees (n = 178) were defined as those with incident ROA (Kellgren Lawrence Grade (KLG) 0 or 1 at baseline (BL), evolving into KLG 2 or above by year 4). Control knees were matched one-to-one by sex, age and radiographic status with case knees. The mean distance from medial-to-lateral meniscal lesions [Mean(MLD)], mean value of tibial plateau width [Mean(TPW)] and the mean of the relative percentage of the medial-to-lateral meniscal lesions distance [Mean(RMLD)] were evaluated through coronal T2-weighted turbo spin echo (TSE) MRI at P-0 (visit when incident ROA was found on radiograph), P-1(one year prior to P-0) and baseline, respectively. Using the imaging data of one patient, the mechanism was investigated by finite element analysis. RESULTS: Participants were on average 60.22 years old, predominantly female (66.7%) and overweight (mean BMI: 28.15). Mean(MLD) and Mean(RMLD) were significantly greater for incident knees compared to no incident knees at baseline, P-1 and P-0. [Mean(MLD), Mean(RMLD); (42.56-49.73) mean ± (7.70-9.52) mm SD vs. (38.14-40.78) mean ± (5.51-7.05)mm SD; (58.61-68.95) mean ± (8.52-11.40) mm SD vs. (52.52-56.35) mean ± (6.53-7.85)mm SD, respectively]. Baseline Mean(MLD) and Mean(RMLD), [Adjusted OR, 95%CI: 1.11(1.07 to 1.16) and 1.13(1.09 to 1.17), respectively], were associated with incident ROA during 4 years, However, Mean(TPW) [Adjusted OR, 95%CI: 0.98(0.94 to 1.02)] was not associated with incident ROA during 4 years. While Mean(TPW) at P-1 and P-0 was not associated with the risk of incident ROA, Mean(MLD) and Mean(RMLD) at P-1 and P-0 were significantly positively associated with the risk of incident ROA. CONCLUSIONS: The meniscal parameters alteration could be an important imaging biomarker to predict the occurrence of ROA.
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Imageamento por Ressonância Magnética , Meniscos Tibiais , Osteoartrite do Joelho , Radiografia , Humanos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos de Casos e Controles , Meniscos Tibiais/diagnóstico por imagem , Meniscos Tibiais/patologia , Valor Preditivo dos Testes , Incidência , Progressão da Doença , Lesões do Menisco Tibial/diagnóstico por imagem , Lesões do Menisco Tibial/epidemiologiaRESUMO
Despite the rich blood supply to the scalp, postoperative skin necrosis at the surgical site sometimes occurs, and unresolved defects often present a significant challenge for the surgeon. When planning a free flap for scalp reconstruction, distant anastomoses may be necessary if local recipient vessels are unavailable due to previous surgery. This study presents the authors' treatment strategy, which includes extending the pedicle length with arteriovenous bundle interposition grafts. Two patients who experienced surgical wound necrosis after bypass surgery for moyamoya disease underwent reconstruction for skin and soft tissue coverage. To evaluate the altered anatomical structures after the previous surgery, three-dimensional computed tomography angiography was performed, and preoperative photos were taken to accurately measure the expected defect. The surgical strategy was designed to accommodate their unique conditions, utilizing an arteriovenous interposition graft, which included 2 stages of microvascular anastomoses, for pedicle lengthening. The procedure successfully bridged the gap between distant recipient vessels and the extensive defect, and the wounds healed without major complications such as venous congestion or total flap loss. Both patients were satisfied with the surgical outcomes. Arteriovenous bundle interposition grafts can be a useful option for patients with complex scalp defects who lack local recipient vessels. The use of an anterolateral thigh flap with artery-to-artery anastomosis, utilizing the lateral circumflex femoral artery from the opposite side in this study, offers many advantages compared with traditional pedicle lengthening tools utilizing vein-to-artery anastomosis.
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For an ongoing systematic study of Korean Vespidae, we analyzed the complete mitochondrial genome of a social wasp, Vespula rufa (Linnaeus 1758), from the South Korea. The mitogenome is 17,521 bp in length, comprising 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and two ribosomal RNA (rRNA) genes. The nucleotide composition is 40.5% adenines, 43.0% thymines, 6.0% guanines, and 10.5% cytosines. The GC content is 16.5%. A maximum-likelihood analysis was conducted to understand phylogenetic relationships, based on 13 complete mitogenome sequences of Vespinae species. We recognized that V. rufa is being placed basal within the genus Vespula. The complete mitochondrial genome of V. rufa provides useful genetic information for further studies.
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BACKGROUND: To analyze the risk factors for benign paroxysmal positional vertigo (BPPV) and to construct a predictive nomogram model. METHODS: In this retrospective study, 312 participants were enrolled, including 164 BPPV patients and 148 healthy subjects without BPPV. Risk predictors for BPPV were identified using univariate and multivariate analyses, and a clinical nomogram was constructed. The predictive accuracy was assessed by unadjusted concordance index (C-index) and calibration plot. RESULTS: Univariate and multivariate regression analysis identified stroke (95% CI, 0.575-5.954; P=0.022), hyperlipidemia (95% CI, 0.471-4.647; P=0.003), chronic suppurative otitis media (95% CI, 1.222-45.528; P=0.005), cervical spondylosis (95% CI, 1.232-3.017; P=0.005), and osteoporosis (95% CI, 1.130-3.071; P=0.001) were the independent risk factors for BPPV. These risk factors were used to construct a clinical predictive nomogram. The regression equation was: logit (P) = -6.820 + 0.450 * stroke + hyperlipidemia * 0.312 + chronic suppurative otitis media * 0.499 + cervical spondylosis * 0.916 + osteoporosis * 0.628. The calibration curves demonstrated excellent accuracy of the predictive nomogram. Decision curve analysis showed that the predictive model is clinically applicable when the threshold probability was between 20% and 60%. CONCLUSIONS: Stroke, hyperlipidemia, chronic suppurative otitis media, cervical spondylosis and osteoporosis are independent risk predictors for BPPV. The developed nomogram is useful in predicting the risk of BPPV.
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OBJECTIVES: To investigate the role of the Wuwei Zishen formula (WWZSF) in treating and preventing perimenopausal syndrome (PMS) and to understand its mechanism. METHODS: Network pharmacology and molecular docking was used to predict active compounds, potential targets, and pathways for PMS treatment using WWZSF. Female Sprague-Dawley (SD) rats were induced with D-galactose (D-gal) to establish a PMS model and treated with Kunbao pill (KBP) and WWZSF. Estrus cycles were observed using vaginal smears. Serum sex hormones were measured using the enzyme-linked immunosorbent assay (ELISA). Histological changes in the uterus and ovaries were evaluated using hematoxylin-eosin staining (HE). Western blot was used to assess the protein expression levels of Cleaved Caspase-3, p62, BAX/Bcl-2, p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR in the uterus and ovaries. RESULTS: A total of 70 active compounds and 440 potential targets were screened out. Important targets and pathways, including AKT1, Bcl-2, Caspase-3, mTOR, and the PI3K/AKT/mTOR pathways, and molecular docking verified their high affinities to key WWZSF components. In vivo experiments showed that WWZSF can ameliorate the morphological abnormalities of the uterus and ovaries, increase sex hormone levels and organ index, and restore the estrus cycles in PMS rats. Moreover, the western blot results showed decreased Cleaved Caspase-3 and BAX/Bcl-2 protein levels in the ovarian and uterine tissues after WWZSF therapy. Concurrently, there was an increase in the expression of p62 and the ratios of p-AKT/AKT, p-mTOR/mTOR, and p-PI3K/PI3K. CONCLUSION: The PI3K/AKT/mTOR signaling pathway-mediated apoptosis and autophagy pathways may be how WWZSF efficiently reduces PMS.
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The aggressive nature of lung cancer is frequently accompanied by a high incidence of bone metastasis; however, proximal femoral metastasis from lung cancer is comparatively uncommon when compared to other malignancies. In this report, we present the case of a 53-year-old Asian male who presented with pain in the left thigh and back. Magnetic resonance imaging revealed severe bone destruction with involvement of adjacent soft tissue mass at the left thigh, exhibiting imaging findings that mimic osteosarcoma. Subsequent bone biopsy confirmed the diagnosis of epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma with bone metastasis. The patient achieved survival following administration of osimertinib and underwent surgery for femoral metastases without palliative surgery for lung cancer. Therefore, proximal femoral metastasis from EGFR-mutated lung adenocarcinoma should be considered as a differential diagnosis in patients suspected to have osteosarcoma. The imaging findings of proximal femoral metastasis from EGFR-mutated lung adenocarcinoma were presented, and their therapeutic management was discussed.
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Obesity-induced chronic inflammation exacerbates multiple types of tissue/organ deterioration and stem cell dysfunction; however, the effects on skeletal tissue and the underlying mechanisms are still unclear. Here, we show that obesity triggers changes in the microRNA profile of macrophage-secreted extracellular vesicles, leading to a switch in skeletal stem/progenitor cell (SSPC) differentiation between osteoblasts and adipocytes and bone deterioration. Bone marrow macrophage (BMM)-secreted extracellular vesicles (BMM-EVs) from obese mice induced bone deterioration (decreased bone volume, bone microstructural deterioration, and increased adipocyte numbers) when administered to lean mice. Conversely, BMM-EVs from lean mice rejuvenated bone deterioration in obese recipients. We further screened the differentially expressed microRNAs in obese BMM-EVs and found that among the candidates, miR-140 (with the function of promoting adipogenesis) and miR-378a (with the function of enhancing osteogenesis) coordinately determine SSPC fate of osteogenic and adipogenic differentiation by targeting the Pparα-Abca1 axis. BMM miR-140 conditional knockout mice showed resistance to obesity-induced bone deterioration, while miR-140 overexpression in SSPCs led to low bone mass and marrow adiposity in lean mice. BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration. More importantly, we used an SSPC-specific targeting aptamer to precisely deliver miR-378a-3p-overloaded BMM-EVs to SSPCs via an aptamer-engineered extracellular vesicle delivery system, and this approach rescued bone deterioration in obese mice. Thus, our study reveals the critical role of BMMs in mediating obesity-induced bone deterioration by transporting selective extracellular-vesicle microRNAs into SSPCs and controlling SSPC fate.
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Background: OA (osteoarthritis) is a common joint disease characterized by damage to the articular cartilage and affects the entire joint tissue, with its main manifestations being joint pain, stiffness, and limited movement.Currently,we know that OA is a complex process composed of inflammatory and metabolic factors.It is reported that the occurrence and development of OA is related to the change of tryptophan metabolism.Therefore, the study of tryptophan metabolism and OA related genes is hopeful to find a new therapeutic target for OA. Methods: Differentially expressed genes (DEGs) in GSE55235 were gained via differential expression analysis (OA samples vs normal samples). The tryptophan metabolic related DEGs (TMR-DEGs) were obtained by overlapping tryptophan metabolism related genes (TMRGs) and DEGs. Further, biomarkers were screening via Least absolute shrinkage and selection operator (LASSO), naive bayes (NB) and supportvector machine-recursive feature elimination (SVM-RFE) algorithm to establish a diagnostic model. Afterward, Gene Set Enrichment Analysis (GSEA) and drug prediction were performed based on diagnostic biomarkers by multiple software and databases. Eventually, expression level of biomarker public databases was verified using real-time quantitative polymerase chain reaction (RT-qPCR). Results: Three tryptophan metabolism related biomarkers (TDO2, AOX1 and SLC3A2) were identified in OA. GSEA analysis demonstrated that biomarkers were associated with the function of 'FoxO signaling pathway', 'spliceosome' and 'ribosome'. There were seven drugs with therapeutic potential on TDO2 and AOX1. Ultimately, compared with normal group, expression of AOX1 and SLC3A2 in OA group remarkable lower. Conclusion: Overall, three tryptophan metabolic related diagnostic biomarkers that associated with OA were obtained, which provided a original direction for the diagnosis and treatment of OA.
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PURPOSE: To compare the efficacy of a 0.15% HA with that of 0.1% HA eye drops for DES after cataract surgery. METHODS: This study was double blinded, randomized and prospective study, and conducted in 69 participants (70 eyes) from Pusan National University Yangsan Hospital and executed from February 1, 2022 to November 30, 2022. Participants were adult cataract patients with normal lid position, not suffering from any other ocular disease and not meet the exclusion cirteria of clinical trial. Participants were randomly divided into two groups: 35 participants (17 males and 18 females) in the 0.1% HA group and 34 participants (19 males and 15 females) in the 0.15% HA group, receiving treatment six times daily for 6 weeks following cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits, including ocular surface disease index score, tear break up time, corneal staining score, Schirmer's I test score, lipid layer thickness), meiboscore, and biochemical analysis of the eye drops. RESULTS: Throughout the study, the postoperative ocular surface disease index score was significantly lower in the group receiving 0.15% hyaluronic acid than in the group receiving 0.1% hyaluronic acid. Additionally, the postoperative ocular surface disease index score showed a significant positive correlation with the postoperative use of 0.15% hyaluronic acid and the preoperative Schirmer's I test score. In multivariate analysis, treatment with 0.15% hyaluronic acid and the preoperative ocular surface disease index score were significant independent parameters affecting the postoperative ocular surface disease index score. CONCLUSION: The use of 0.15% hyaluronic acid is recommended for its potential advantages in alleviating symptoms following cataract surgery, making it a viable alternative to traditional 0.1% hyaluronic acid treatment. TRIAL REGISTRATION: ISRCTN95830348.
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Extração de Catarata , Ácido Hialurônico , Glândulas Tarsais , Soluções Oftálmicas , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/uso terapêutico , Masculino , Feminino , Idoso , Extração de Catarata/efeitos adversos , Estudos Prospectivos , Pessoa de Meia-Idade , Glândulas Tarsais/efeitos dos fármacos , Glândulas Tarsais/metabolismo , Soluções Oftálmicas/administração & dosagem , Método Duplo-Cego , Lipídeos , Resultado do TratamentoRESUMO
A series of chromone-deferiprone hybrids were designed, synthesized, and evaluated as inhibitors of human monoamine oxidase B (hMAO-B) with iron-chelating activity for the treatment of Alzheimer's disease (AD). The majority exhibited moderate inhibitory activity towards hMAO-B and potent iron-chelating properties. Particularly, compound 25c demonstrated remarkable selectivity against hMAO-B with an IC50 value of 1.58 µM and potent iron-chelating ability (pFe3+ = 18.79) comparable to that of deferiprone (pFe3+ = 17.90). Molecular modeling and kinetic studies showed that 25c functions as a non-competitive hMAO-B inhibitor. According to the predicted results, compound 25c can penetrate the blood-brain barrier (BBB). Additionally, it has been proved to display significant antioxidant activity and the ability to inhibit neuronal ferroptosis. More importantly, compound 25c reduced the cognitive impairment induced by scopolamine and showed significant non-toxicity in short-term toxicity assays. In summary, compound 25c was identified as a potential anti-AD agent with hMAO-B inhibitory, iron-chelating and anti-ferroptosis activities.
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Doença de Alzheimer , Cromonas , Deferiprona , Quelantes de Ferro , Inibidores da Monoaminoxidase , Monoaminoxidase , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/síntese química , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Quelantes de Ferro/farmacologia , Quelantes de Ferro/química , Quelantes de Ferro/síntese química , Deferiprona/farmacologia , Deferiprona/química , Monoaminoxidase/metabolismo , Humanos , Cromonas/química , Cromonas/farmacologia , Cromonas/síntese química , Relação Estrutura-Atividade , Animais , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/síntese química , Ferroptose/efeitos dos fármacos , Estrutura Molecular , Simulação de Acoplamento Molecular , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Relação Dose-Resposta a DrogaRESUMO
Visible light serves as a crucial medium for vision formation.;however, prolonged or excessive exposure to light is recognized as a significant etiological factor contributing to retinal degenerative diseases. The retina, with its unique structure and adaptability, relies on the homeostasis of cellular functions to maintain visual health. Under normal conditions, the retina can mount adaptive responses to various insults, including light-induced damage. Unfortunately, exposure to intense and excessive light triggers a cascade of pathological alterations in retinal photoreceptor cells, pigment epithelial cells, ganglion cells, and glial cells. These alterations encompass disruption of intracellular REDOX and Ca²âº homeostasis, pyroptosis, endoplasmic reticulum stress, autophagy, and the release of inflammatory cytokines, culminating in irreversible retinal damage. We first delineate the mechanisms of retinal light damage through 4 main avenues: mitochondria function, endoplasmic reticulum stress, cell autophagy, and inflammation. Subsequently, we discuss protective strategies against retinal light damage, aiming to guide research toward the prevention and treatment of light-induced retinal conditions.
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PURPOSE: This is an extremely rare case of complicated fetal esophageal atresia (EA) with tracheoesophageal fistula (TEF) and interrupted inferior vena cava (IVC) diagnosed by prenatal ultrsonography and successfully treated with surgical repair. METHODS: A 35-year-old pregnant woman was referred to our center for prenatal ultrasound, and the fetus was found to have a series of abnormalities, such as an interrupted IVC associated with a dilated azygos vein, an upper neck pouch sign of the thorax, and polyhydramnios. With suspicion of EA with TEF and interrupted IVC, the infant was born at 39 weeks of gestation, and successfully underwent the surgical operation. RESULTS: The baby was doing well after 21 months of follow-up. CONCLUSION: It is beneficial for the prenatal ultrasonic diagnosis of EA with TEF in optimizing labor care, postpartum treatment, and prompting neonatal management.
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The conventional direct absorption spectroscopy (DAS) technique has been plagued by the difficulty of obtaining accurate baseline, which is caused by photoelectric drift and the absence of non-absorbing regions in the transmitted light intensity signal. An inverse fitting direct absorption spectroscopy (IF-DAS) technique has been proposed to address this difficulty. The technique leverages the intrinsic nonlinear intensity response of tunable lasers to achieve baseline-free concentration measurements. It offers the advantages of being straightforward to implement, baseline-free, calibration-free, and resistant to photoelectric signal drift. Its efficacy was validated using an example under ambient temperature and atmospheric pressure conditions. The performance of the IF-DAS technique was compared with that of the conventional DAS technique through standard experimental tests. The results demonstrate that the IF-DAS technique is less susceptible to fluctuations in light intensity, exhibits superior linearity and accuracy, with an R2 value of 0.99986 and an overall error of less than 2%. This technique shows potential for application in harsh scenarios such as reactive flow fields and long-term engineering applications.
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We design and construct a broadband integrated multi-channel imaging spectrometer (MCIS) from visible light to near-infrared. This system can directly obtain spectral images that conform to the consistent visual habits of the human eyes through a single exposure of the detector. The genetic algorithm is used to calculate system parameters to minimize pixel waste between spectral channels, achieving nearly 100% utilization of detector pixels. The field stop suppresses stray light in the system. This device is used for imaging an optical-resolution target, an object, and a furnace to verify the basic principles of the system. The results indicate that the system can effectively utilize detectors to monitor high-temperature objects in the visible to near-infrared wavelength range.