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During coal mining operations, the coal will be deformed and damaged due to multiple mining disturbances (MMD), often resulting in disasters, like rock burst. To understand the evolution rules of coal deformation under MMD and its final fracture characteristics after impact dynamic load loading, reduce the adverse effects of mining disturbances, and improve disaster prevention and control capabilities, quasi-static uniaxial cyclic loading-unloading (L-U) and dynamic axial compression tests were conducted on large-sized coal-like samples. During the tests, three-dimensional (3D) laser scanning and acoustic emission (AE) monitoring technology were utilized to accurately capture the full-field deformation and AE response data, facilitating a systematic analysis of deformation and fracture characteristics. The results show that: (1) Under the cyclic L-U effect induced by MMD, each loading cycle causes compression deformation with partial recovery during unloading, presenting an overall "wavy" variation trend. (2) The maximum load is the most critical factor affecting the damaged coal deformation, with smaller load resulting in less overall sample deformation. (3) After the impact dynamic loading, the damaged samples suffered large-scale impact splitting failure, with the compressive-shear layer failure mainly occurred inside the holes. (4) Lower loading during cyclic L-U process correlate with reduced damage degree, and smaller debris particles with a higher fractal dimension when impact failure occurs, indicating a more severe impact failure. (5) With multiple cycles of L-U, the cracks inside the sample gradually extend and expand from around the hole to the outside. The greater the load and the number of cycles, the more serious the crack damage will be. (6) In the practical mining process, it is crucial to reinforce roadway interiors while minimizing low-loading cyclic disturbances induced by MMD. The study has obtained the deformation evolution rules and failure characteristics of coal under MMD, providing a theoretical basis for the prevention and control of corresponding engineering disasters.
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Recycling waste biomass to pyrolytic carbon has become a development direction of sodium-ion batteries (SIBs) anodes. However, it remains a challenge to precisely control the composition and structure of biomass to modify the properties of derived carbon. Herein, a strategy of hydrolyzing cellulose in phellem with sulfuric acid is proposed, which can promote cellulose fracture, reduce the graphitization and increase the content of closed pores in hard carbon. Accordingly, after the regulation of closed pore structure, the reversible capacity increased from 207 to 330 mAh g-1 at 20 mA g-1, realizing an increase of ≈130 mAh g-1 in the plateau region and the initial Coulombic efficiency (ICE) is enhanced from 78% to 90%. When applied in full cell with O3-Na[Ni1/3Fe1/3Mn1/3]O2, it showed an energy density of 247 Wh kg-1. This strategy has certain universality, and it provides the feasibility to use low-value cellulose-containing biomass to fabricate high-performance hard carbon materials.
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To enhance the impact resistance of hydraulic columns, a theoretical analysis method was employed to develop a dynamic characteristic analysis model for conventional columns under impact loads. This model facilitated the derivation of key parameters such as equivalent stiffness, maximum retraction amount, and impact duration. A fluid-solid coupling model for the conventional column was constructed using finite element and coupled Eulerian-Lagrangian (CEL) methods. Subsequently, numerical simulation results were compared and analyzed against theoretical predictions. Based on this analysis, an energy-absorbing column was designed, and its fluid-solid coupling model was established to investigate its mechanical response under static and dynamic impact loads.The findings indicate that under a static load of 2000 kN, when superimposed with impact loads of 200 kJ, 400 kJ, and 800 kJ respectively, the peak impact forces on energy-absorbing columns are 89.20%, 91.72%, and 98.42% lower than those on normal columns. The yield displacements of energy-absorbing columns increase by 142.26%, 109.15%, and 108.41% compared to normal columns. Energy absorption in energy-absorbing columns is 152.11%, 171.80%, and 145.18% higher than in normal columns. Furthermore, initial velocities of energy-absorbing columns are consistently lower compared to normal columns. After reaching initial velocity, energy-absorbing columns exhibit reduced oscillations due to interactions between the energy absorber, column, and hydraulic fluid system under impact loads. Unlike normal columns, energy-absorbing columns mitigate stress concentration at the column head through interactions between the energy absorber, emulsion, and column. Additionally, the impact resistance time of energy-absorbing columns is 2.19, 1.64, and 1.85 times longer than that of normal columns.Energy-absorbing columns outperform conventional columns across six metrics: peak impact force, column yield displacement, energy absorption, column movement speed, stress distribution, and impact resistance time, demonstrating superior mechanical properties in impact resistance.
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Rice is a major dietary source of the toxic metal cadmium (Cd). Concentration of Cd in rice grain varies widely at the regional scale, and it is challenging to predict grain Cd concentration using soil properties. The lack of reliable predictive models hampers management of contaminated soils. Here, we conducted a three-year survey of 601 pairs of soil and rice samples at a regional scale. Approximately 78.3% of the soil samples exceeded the soil screening values for Cd in China, and 53.9% of rice grain samples exceeded the Chinese maximum permissible limit for Cd. Predictive models were developed using multiple linear regression and machine learning methods. The correlations between rice grain Cd and soil total Cd concentrations were poor (R 2 < 0.17). Both linear regression and machine learning methods identified four key factors that significantly affect grain Cd concentrations, including Fe-Mn oxide bound Cd, soil pH, field soil moisture content, and the concentration of soil reducible Mn. The machine learning-based support vector machine model showed the best performance (R 2 = 0.87) in predicting grain Cd concentrations at a regional scale, followed by machine learning-based random forest model (R 2 = 0.67), and back propagation neural network model (R 2 = 0.64). Scenario simulations revealed that liming soil to a target pH of 6.5 could be one of the most cost-effective approaches to reduce the exceedance of Cd in rice grain. Taken together, these results show that machine learning methods can be used to predict Cd concentration in rice grain reliably at a regional scale and to support soil management and safe rice production.
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To address the conflict between pressure relief and support effectiveness caused by large-diameter boreholes in roadway surrounding rock, this paper proposes a method involving variable-diameter boreholes for pressure relief and energy dissipation. With a typical rock burst coal mine as the engineering context, the study establishes a mechanical model for variable-diameter boreholes through theoretical analysis to examine the elastic stress distribution around boreholes within the coal body. Physical similarity simulation tests are conducted to investigate the influence of conventional borehole and variable diameter borehole on the transmission pattern of dynamic load stress waves. Furthermore, numerical simulations are employed to explore the effects of reaming diameter, depth, and spacing on pressure relief, energy dissipation, and attenuation of dynamic stress wave transmission in roadway surrounding rock. The results demonstrate that stress within the coal surrounding the variable-diameter borehole correlates with the borehole radius, lateral pressure coefficient, and distance from the point to the borehole center, the extent of the plastic zone is influenced by borehole diameter, spacing, and depth. Increased diameter, reduced spacing, and greater depth of deep reaming holes exacerbate the transfer of stress concentration from the surrounding rock of the roadway to the deeper regions, facilitating the formation of stress double peak areas. Moreover, the variable diameter position should be within the original stress peak position of the surrounding rock in the roadway, with deep reaming passing through the stress concentration area for optimal results. This study offers guidance on the prevention and control technology for rock bursts in deep coal mining operations.
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Pressão , Modelos Teóricos , Minas de Carvão , Estresse Mecânico , Simulação por Computador , Carvão MineralRESUMO
BACKGROUND: Under normal circumstances, high-density lipoprotein (HDL) is considered to have cardiovascular protective effects, but the impact of oxidized HDL (ox-HDL) on vascular endothelial function remains poorly understood. Mitochondrial function is closely related to endothelial function, and hydrogen sulfide (H2S) is a gas with endothelial protective properties. The novel hydrogen sulfide donor AP39 can target mitochondria to release H2S, but the combined effects of ox-HDL and AP39 on vascular endothelium are not well studied. METHODS: We established a cell model of ox-HDL-induced endothelial cell damage and mitochondrial dysfunction using human umbilical vein endothelial cells (HUVECs) and conducted AP39 pretreatment. The experiments confirmed the functional damage and mitochondrial dysfunction in HUVECs caused by ox-HDL. Additionally, to further explore the role of SIRT1 in AS, we analyzed SIRT1 expression in AS carotid artery tissue. This included the analysis of differentially expressed genes from AS-related datasets, presented through volcano plots and heatmaps, with enrichment analysis of downregulated genes in KEGG pathways and GO functions. Furthermore, we evaluated the differences in SIRT1 expression in coronary arteries with varying degrees of stenosis and in early and late-stage AS carotid artery tissues, and analyzed data from SIRT1 knockout mouse models. RESULTS: The experimental results indicate that AP39 effectively alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression. MTT and CCK-8 assays showed that ox-HDL treatment led to decreased cell viability and proliferation in HUVECs, reduced eNOS expression, and significantly increased levels of ICAM-1, IL-6, and TNF-α, along with enhanced monocyte adhesion. These findings reveal the damaging effects of ox-HDL on HUVECs. Transcriptomic data indicated that while SIRT1 expression did not significantly differ in coronary arteries with varying degrees of stenosis, it was notably downregulated in AS carotid artery tissues, especially in late-stage AS tissues. KEGG pathway enrichment analysis revealed that SIRT1 downregulated genes were associated with processes such as vascular smooth muscle contraction, while GO analysis showed that these downregulated genes were involved in muscle system processes and muscle contraction functions, further confirming SIRT1's critical role in AS pathology. In transcriptomic data from the SIRT1 knockout mouse model, elevated levels of inflammation-related proteins IL-6 and TNF-α were observed after SIRT1 knockout, along with decreased expression of the chaperone protein PGC-1α. The expression of mitochondrial-related functional proteins Nrf2 and PGC-1α was positively correlated with SIRT1 expression, while inflammation-related proteins ICAM-1, IL-6, IL-20, and TNF-α were negatively correlated with SIRT1 expression. We further discovered that ox-HDL triggered mitochondrial dysfunction, as evidenced by reduced expression of Mfn2, Nrf2, PGC1-α, UCP-1, and SIRT1, corroborating the results from the previous database analysis. Additionally, mitochondrial dysfunction was characterized by decreased mitochondrial membrane potential (MMP), increased mitochondrial ROS levels, and reduced ATP content, further impacting cellular energy metabolism and respiratory function. Subsequent experimental results showed that the addition of AP39 mitigated these adverse effects, as evidenced by decreased levels of ICAM-1, IL-6, and TNF-α, increased eNOS expression, reduced monocyte adhesion, increased mitochondrial H2S content, and upregulated expression of SIRT1 protein associated with mitochondrial function, reduced ROS levels, and increased ATP content. Furthermore, validation experiments using the SIRT1 inhibitor EX527 confirmed that AP39 alleviated ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1 expression. CONCLUSION: Ox-HDL can induce damage and mitochondrial dysfunction in HUVECs, while AP39 inhibits ox-HDL-induced endothelial cell damage and mitochondrial dysfunction by upregulating SIRT1.
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Células Endoteliais da Veia Umbilical Humana , Sulfeto de Hidrogênio , Lipoproteínas HDL , Mitocôndrias , Sirtuína 1 , Regulação para Cima , Animais , Humanos , Camundongos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Lipoproteínas HDL/metabolismo , Camundongos Knockout , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Sirtuína 1/metabolismo , Sirtuína 1/genética , Tionas , Regulação para Cima/efeitos dos fármacosRESUMO
BACKGROUND: According to the theory of traditional Chinese medicine (TCM), the spleen and stomach are the basis of acquired nature and the source of qi and blood biochemistry. After surgery and chemotherapy, patients with colorectal cancer often develop spleen and stomach qi deficiency syndrome, leading to decreased immune function. Buzhong Yiqi decoction, a classic TCM prescription, has the effect of tonifying middle-jiao and invigorating qi, boosting Yang, and suppressing immune-related inflammation. Moreover, it is widely used in the treatment of spleen and stomach qi deficiency syndrome. AIM: To investigate the effect of Buzhong Yiqi decoction on spleen and stomach qi deficiency in patients with colorectal cancer. METHODS: One hundred patients with colorectal cancer who underwent preoperative chemotherapy and laparoscopy at The First TCM Hospital of Changde from January 2022 to October 2023 were retrospectively analyzed. The patients were divided equally into control and observation groups. Both groups underwent conventional rehabilitation surgery, and the observation group was supplemented with Buzhong Yiqi decoction. SPSS 26.0 was used for statistical analyses. The χ 2 test was used for univariate analysis; independent sample t-tests were used in all cases. RESULTS: No significant differences were observed preoperatively in the general characteristics of the two groups. Fourteen days post-surgery, the abdominal distension, emaciation, loose stool, loss of appetite, and vomiting scores were significantly lower in the observation group than in the control group (P < 0.05). Immune function and interleukin (IL)-10 levels in the observation group were significantly higher than those of the control group, whereas IL-6, tumor necrosis factor-α, and C-reactive protein levels, tumor biological indexes, and adverse reactions in the observation group were significantly lower than those of the control group (P < 0.05). One month after surgery, the patients' quality of life in the observation group was significantly higher than that of the patients in the control group (P < 0.05). CONCLUSION: Buzhong Yiqi decoction can regulate inflammatory responses and metabolic processes by enhancing immune function, thereby promoting overall immune nutrition and restoring the body's balance.
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OBJECTIVES: This study investigated the effect of additive manufacturing (AM) methods on the slot height dimensions and accuracy of 3D-printed orthodontic brackets. METHODS: A 3D model of a standard Mclaughlin Bennett Trevisi bracket was used as a reference to print the ceramic bracket in a 90° orientation using two representative AM methods: digital light processing (DLP) and material jetting (MJ). The dimensional accuracy and slot heights were determined using a scanning electron microscope and an optical scanner. Also, all specimens were analysed using the Geomagic Control X 3D inspection software. The root mean square (RMS) values were used for trueness and precision assessment. Statistical analyses were performed using an independent sample t-test. RESULTS: Slot height dimensions, trueness RMS, and precision RMS were statistically affected by different AM methods (p < .01). There was a significant difference between the different printing methods, with DLP meeting the tolerance requirements (mean slot height = 0.557 ± 0.018 mm) and MJ being slightly below them (mean slot height = 0.544 ± 0.021 mm). However, MJ significantly outperformed DLP in terms of accuracy. Among the two printing methods, MJ was associated with higher trueness (RMS = 0.025 ± 0.004 mm) and precision (RMS = 0.038 ± 0.005 mm). CONCLUSIONS: Both tested AM methods yielded clinically acceptable outcomes, with the RMS range set to ±100 µm and the slot height tolerance established at 0.549-0.569 mm. The MJ technology achieved the highest accuracy.
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This paper investigated the effect of total saponins from Rhizoma Panacis Majoris on the proliferation, apoptosis, and autophagy of human cervical carcinoma HeLa cells. The saponin content was detected by ultraviolet-visible spectrophotometry. Cell coun-ting kit-8(CCK-8) assay, 4,6-diamidino-2-phenylindole(DAPI) staining, and flow cytometry were used to detect the effects of total saponins of Panacis Majoris Rhizoma on cell viability, morphology, cell cycle and apoptosis of HeLa cells. Western blot was used to detect the expression of apoptosis-related proteins B cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cleaved caspase-9, and cleaved caspase-3, autophagy-related proteins Beclin-1 and SQSTM1(p62), and the proteins related to the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR) and mitogen-activated protein kinase(MAPK) signaling pathways. It was found that the yield and saponin content of total saponins from Rhizoma Panacis Majoris were 6.3% and 78.3%, respectively. Total saponins from Rhizoma Panacis Majoris could significantly inhibit the proliferation(P<0.001), effect the nuclear morphology, block the G_0/G_1 cycle, and induce cell apoptosis in HeLa cells with a concentration-dependent manner. In addition, total saponins from Rhizoma Panacis Majoris up-regulated the expression of pro-apoptotic proteins Bax, cleaved caspase-9, and cleaved caspase-3, and autophagy-related protein p62(P<0.05), while down-regulated the expression of anti-apoptotic protein Bcl-2 and autophagy-related protein Beclin-1(P<0.01). Total saponins from Rhizoma Panacis Majoris could promote the expression of p-p38/p38, p-Jun N-terminal kinase(JNK)/JNK, p-PI3K/PI3K, p-Akt/Akt, p-mTOR/mTOR proteins in PI3K/Akt/mTOR and MAPK signaling pathways(P<0.05). In contrast, the effect on p-ERK/ERK expression was not obvious. Therefore, total saponins from Rhizoma Panacis Majoris may inhibit autophagy and promote apoptosis of HeLa cells through the activation of the PI3K/Akt/mTOR, c-JNK, and p38 MAPK signaling pathways, which indicates that total saponins from Rhizoma Panacis Majoris may have a potential role in cervical cancer treatment.
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Apoptose , Autofagia , Proliferação de Células , Rizoma , Saponinas , Neoplasias do Colo do Útero , Humanos , Saponinas/farmacologia , Saponinas/química , Células HeLa , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Rizoma/química , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Sobrevivência Celular/efeitos dos fármacosRESUMO
Microplastics, such as polylactic acid (PLA), are ubiquitous environmental pollutants with unclear implications for health impact. This study aims to elucidate the mechanisms of PLA-induced inflammatory liver injury, focusing on disturbance of bile acid metabolism. The in vitro PLA exposure experiment was conducted using HepG2 cells to assess cell viability, cytokine secretion, and effects on bile acid metabolism. In vivo, male C57BL/6 J mice were exposed to PLA for ten days continuously, liver function and histopathological assessment were evaluated after the mice sacrificed. Molecular analyses including quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting, were applied to evaluate the expression of bile acid metabolizing enzymes and transporters. PLA exposure resulted in decreased cell viability in HepG2 cells, increased inflammation and altered bile acid metabolism. In mice, PLA exposure resulted in decreased body weight and food intake, impaired liver function, increased hepatic inflammation, altered bile acid profiles, and dysregulated expression of bile acid metabolic pathways. PLA exposure disrupts bile acid metabolism through inhibition of the CYP7A1 enzyme and activation of the FGF-JNK/ERK signaling pathway, contributing to liver injury. These findings highlight the potential hepatotoxic effects of environmentally friendly plastics PLA and underscore the need for further research on their biological impact.
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Ácidos e Sais Biliares , Camundongos Endogâmicos C57BL , Poliésteres , Animais , Masculino , Ácidos e Sais Biliares/metabolismo , Humanos , Células Hep G2 , Camundongos , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Microplásticos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Colesterol 7-alfa-Hidroxilase/metabolismo , Colesterol 7-alfa-Hidroxilase/genética , Sobrevivência Celular/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/patologiaRESUMO
Conventionally, the electromechanical system requires the installation of auxiliary displacement sensors and only the amount on the drive part and motion end, which increases volume, cost, and measurement error in the system. This paper presents an integrated measurement method with a sensing head, which takes the equal division characteristics of mechanical structures as part of the sensor, thus, the so-called self-sensing system. Moreover, the displacement is measured by counting the time pulses. The sensing head is integrated with the entire electromechanical system, including the driving, transmitting, and moving parts. Thus, the integration of the sensing part is greatly improved. Taking the rotary table as a special example, and the sensing head embedded into each part of the system, displacement information is obtained by the common processing system and fused by the adaptive weighted average method. The results of the experiment show that the fusion precision of each component is higher than only the motor position information as the feedback. The proposed method is a practical self-sensing technology with significant volume reduction and intelligent control benefits in the industry, especially suitable for extremely small and narrow spaces.
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The relative severity between chromium (Cr)-mediated ecotoxicity and its bioaccumulation has rarely been compared and evaluated. This study employed pot incubation experiments to simulate the soil environment with increased Cr pollution and study their effects on the growth of crops, including pepper, lettuce, wheat, and rice. Results showed that increasing total Cr presented ascendant ecotoxicity in upland soils when pH > 7.5, and significantly reduced the yield of pepper, lettuce and wheat grain by 0.3-100 %, whereas, this effect was weakened even reversed as the pH decreased. Surprisingly, a series of soils with Cr concentration of 22.7-623.5 mg kg-1 did not cause Cr accumulation in four crops over the Chinese permissible limit. The toxicity of Cr was highly associated with extractable Cr, where Cr (VI) made the greater contributions than Cr (III). Conclusively, the ecotoxicity of Cr poses a greater environmental issue as compared to the bioaccumulation of Cr in crops in upland soils, while extractable Cr (VI) makes the predominant contributions to the ecotoxicity of Cr as the total Cr increased. Our study proposes a synchronous consideration involving total Cr and Cr (VI) as the theoretical basis to establish a more reliable soil quality standard for safe production in China.
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Cromo , Produtos Agrícolas , Poluentes do Solo , Cromo/toxicidade , Poluentes do Solo/toxicidade , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/efeitos dos fármacos , Produtos Agrícolas/metabolismo , Agricultura , Solo/química , ChinaRESUMO
OBJECTIVES: Parents of children diagnosed with severe-to-profound sensorineural hearing loss may experience a range of emotions owing to a lack of knowledge and experience in dealing with such children. However, most audiology clinics only attend to children with deaf and hard of hearing (DHH) and not their parents. Thus, parents' emotional and support needs are frequently excluded from the intervention sessions, making their own needs invisible. This study aimed to identify academic and clinical instruments used for assessing parental emotional status (PES) and ecological support systems (ESS) in early intervention and determine the factors affecting PES and ESS among parents of DHH children undergoing cochlear implantation. MATERIALS AND METHODS: This scoping review followed the rigorous methodological framework; searched Medline (via OVID and EMBSCO), Scopus, and Web of Science; and selected studies relevant to validated instruments used to evaluate the PES and ESS among parents of DHH children below 6 years old. Before selecting and reviewing relevant articles, two reviewers independently assessed article titles and abstracts from the data sources. Two reviewers verified half of the first reviewer's extracted data. RESULTS: Overall, 3060 articles were retrieved from the database search, and 139 were selected for full-text review following title and abstract reviews. Ultimately, this study included 22 articles. Among them, 23 and 12 validated instruments, most of which are generic measures, were used for assessing PES and ESS, respectively. Three condition-specific instruments were identified and designed to be administered following cochlear implantation surgery. CONCLUSIONS: This study revealed that healthcare professionals who interact with parents of DHH children lack the necessary instruments, particularly for parents of children undergoing cochlear implantation surgery. Therefore, it is necessary to develop condition-specific instruments for parents who consider cochlear implantation for their children.
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Implante Coclear , Emoções , Perda Auditiva , Pais , Humanos , Pais/psicologia , Perda Auditiva/cirurgia , Perda Auditiva/psicologia , Criança , Pré-EscolarRESUMO
Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1-4) and 12 known lignans (5-16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1-16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1-16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2, 6-8 and 13-16 demonstrate better COX-2 inhibitory effects with IC50 values from 0.75 to 8.17 µΜ. These findings provide useful information for the search for natural selective COX-2 inhibitors.
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Inibidores de Ciclo-Oxigenase 2 , Eleutherococcus , Lignanas , Lignanas/farmacologia , Lignanas/química , Lignanas/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Eleutherococcus/química , Estrutura Molecular , Ciclo-Oxigenase 2/metabolismo , Relação Estrutura-Atividade , Ciclo-Oxigenase 1/metabolismo , Elastase de Leucócito/antagonistas & inibidores , Elastase de Leucócito/metabolismo , Relação Dose-Resposta a Droga , Casca de Planta/química , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/químicaRESUMO
Pancreatic cancer (PC) responds weakly to conventional immunotherapy. RNA N6-methyladenosine (m6A) modification has an essential role in the immune response, while its potential role in PC tumor microenvironment (TME) immune cell infiltration remains unknown. In this study, we thoroughly assessed the m6A modification patterns of 472 PC samples using 19 m6A regulators, and we systematically correlated these modification patterns with TME immune cell infiltration characteristics. We also created the m6Ascore and evaluated the m6A modification patterns of individual tumors, identified three different m6A modification patterns, and explored the role of the important m6A "writer" RBM15 in the regulation of macrophage function in PC. Two independent PC cohorts confirmed that patients with higher m6Ascore showed significant survival benefit. We verified that knockdown of RBM15 has the ability to inhibit PC growth and to promote macrophage infiltration and enhance phagocytosis of PC cells by macrophages. In conclusion, m6A modifications play a non-negligible role in the formation of TME diversity and complexity in PC. We reveal that inhibition of RBM15 suppresses PC development and modulates macrophage phagocytosis, and provide a more effective immunotherapeutic strategy for PC.
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Adenosina , Macrófagos , Neoplasias Pancreáticas , Fagocitose , Proteínas de Ligação a RNA , Microambiente Tumoral , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Humanos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Adenosina/análogos & derivados , Adenosina/metabolismo , Microambiente Tumoral/imunologia , Linhagem Celular Tumoral , AnimaisRESUMO
OBJECTIVES: This study was designed to explore and validate the value of different machine learning models based on ultrasound image-omics features in the preoperative diagnosis of lymph node metastasis in pancreatic cancer (PC). METHODS: This research involved 189 individuals diagnosed with PC confirmed by surgical pathology (training cohort: n = 151; test cohort: n = 38), including 50 cases of lymph node metastasis. Image-omics features were extracted from ultrasound images. After dimensionality reduction and screening, eight machine learning algorithms, including logistic regression (LR), support vector machine (SVM), K-nearest neighbors (KNN), random forest (RF), extra trees (ET), extreme gradient boosting (XGBoost), light gradient boosting machine (LightGBM), and multilayer perceptron (MLP), were used to establish image-omics models to predict lymph node metastasis in PC. The best omics prediction model was selected through ROC curve analysis. Machine learning models were used to analyze clinical features and determine variables to establish a clinical model. A combined model was constructed by combining ultrasound image-omics and clinical features. Decision curve analysis (DCA) and a nomogram were used to evaluate the clinical application value of the model. RESULTS: A total of 1561 image-omics features were extracted from ultrasound images. 15 valuable image-omics features were determined by regularization, dimension reduction, and algorithm selection. In the image-omics model, the LR model showed higher prediction efficiency and robustness, with an area under the ROC curve (AUC) of 0.773 in the training set and an AUC of 0.850 in the test set. The clinical model constructed by the boundary of lesions in ultrasound images and the clinical feature CA199 (AUC = 0.875). The combined model had the best prediction performance, with an AUC of 0.872 in the training set and 0.918 in the test set. The combined model showed better clinical benefit according to DCA, and the nomogram score provided clinical prediction solutions. CONCLUSION: The combined model established with clinical features has good diagnostic ability and can be used to predict lymph node metastasis in patients with PC. It is expected to provide an effective noninvasive method for clinical decision-making, thereby improving the diagnosis and treatment of PC.
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Metástase Linfática , Aprendizado de Máquina , Neoplasias Pancreáticas , Ultrassonografia , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Metástase Linfática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Processamento de Imagem Assistida por Computador/métodos , AdultoRESUMO
BACKGROUND: Alzheimer's disease is characterized by abnormal ß-amyloid (Aß) plaque accumulation, tau hyperphosphorylation, reactive oxidative stress, mitochondrial dysfunction and synaptic loss. Myricetin, a dietary flavonoid, has been shown to exert neuroprotective effects in vitro and in vivo. Here, we aimed to elucidate the mechanism and pathways involved in the protective effect of myricetin. METHODS: The effect of myricetin was assessed on Aß42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. Behavioral tests were performed to assess the cognitive effects of myricetin (14 days, ip) in 3×Tg mice. The levels of beta-amyloid precursor protein (APP), synaptic and mitochondrial proteins, glycogen synthase kinase3ß (GSK3ß) and extracellular regulated kinase (ERK) 2 were assessed via Western blotting. Flow cytometry assays, immunofluorescence staining, and transmission electron microscopy were used to assess mitochondrial dysfunction and reactive oxidative stress. RESULTS: We found that, compared with control treatment, myricetin treatment improved spatial cognition and learning and memory in 3×Tg mice. Myricetin ameliorated tau phosphorylation and the reduction in pre- and postsynaptic proteins in Aß42 oligomer-treated neuronal SH-SY5Y cells and in 3×Tg mice. In addition, myricetin reduced reactive oxygen species generation, lipid peroxidation, and DNA oxidation, and rescued mitochondrial dysfunction via the associated GSK3ß and ERK 2 signalling pathways. CONCLUSIONS: This study provides new insight into the neuroprotective mechanism of myricetin in vitro in cell culture and in vivo in a mouse model of Alzheimer's disease.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Disfunção Cognitiva , Flavonoides , Camundongos Transgênicos , Estresse Oxidativo , Proteínas tau , Animais , Estresse Oxidativo/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Proteínas tau/metabolismo , Flavonoides/farmacologia , Fosforilação/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Humanos , Peptídeos beta-Amiloides/metabolismo , Camundongos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Masculino , Fármacos Neuroprotetores/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Hard carbon anode demonstrates exceptional potential in sodium-ion batteries due to their cost-effectivenss and superior plateau capacity. However, the proximity of the plateau capacity to the cut-off voltage of battery operation and the premature cut-off voltage response caused by polarization at high rates greatly limit the exploitation of plateau capacities, raising big concerns about inferior rate performance of high-plateau-capacity hard carbon. In this work, a facile pre-oxidation strategy is proposed for fabricating lignin-derived hard carbon. Both high-plateau capacity and sodiation kinetics are significantly enhanced due to the introduction of expanded pseudo-graphitic domains and high-speed closed pores. Impressively, the optimized hard carbon exhibits an increased reversible capacity from 252.1 to 302.0 mAh g-1, alongside superior rate performance (174.7 mAh g-1 at 5 C) and stable cyclability over 500 cycles. This study paves a low-cost and effective pathway to modulate the microstructure of biomass-derived hard carbon materials for facilitating plateau sodium storage kinetics.
RESUMO
BACKGROUND: Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. METHODS: A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. RESULTS: The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. CONCLUSION: The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.
Assuntos
Úlceras Orais , Humanos , Masculino , Feminino , Estudos Retrospectivos , Adulto , Fatores Sexuais , Pessoa de Meia-Idade , Fatores Etários , Úlceras Orais/etiologia , Adolescente , Adulto Jovem , Idoso , Criança , Pré-Escolar , Fatores de Risco , Idoso de 80 Anos ou maisRESUMO
Dimethylsulfoniopropionate (DMSP) is one of the most abundant sulfur-containing organic compounds on the earth, which is an important carbon and sulfur source and plays an important role in the global sulfur cycle. Marine microorganisms are an important group involved in DMSP metabolism. The strain Cobetia sp. D5 was isolated from seawater samples in the Yellow Sea area of Qingdao during an algal bloom. There is still limited knowledge on the capacity of DMSP utilization of Cobetia bacteria. The study reports the whole genome sequence of Cobetia sp. D5 to understand its DMSP metabolism pathway. The genome of Cobetia sp. D5 consists of a circular chromosome with a length of 4,233,985 bp and the GC content is 62.56%. Genomic analysis showed that Cobetia sp. D5 contains a set of genes to transport and metabolize DMSP, which can cleave DMSP to produce dimethyl sulphide (DMS) and 3-Hydroxypropionyl-Coenzyme A (3-HP-CoA). DMS diffuses into the environment to enter the global sulfur cycle, whereas 3-HP-CoA is catabolized to acetyl CoA to enter central carbon metabolism. Thus, this study provides genetic insights into the DMSP metabolic processes of Cobetia sp. D5 during a marine algal bloom, and contributes to the understanding of the important role played by marine bacteria in the global sulfur cycle.