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The ubiquitin-proteasome system (UPS), which involves E3 ligases and deubiquitinases (DUBs), is critical for protein homeostasis. The epigenetic reader ZMYND8 (zinc finger MYND-type containing 8) has emerged as an oncoprotein, and its protein levels are elevated in various types of cancer, including breast cancer. However, the mechanism by which ZMYND8 protein levels are increased in cancer remains elusive. Although ZMYND8 has been reported to be regulated by the E3 ligase FBXW7, it is still unknown whether ZMYND8 could be modulated by DUBs. Here, we identified USP7 (ubiquitin carboxyl-terminal hydrolase 7) as a bona fide DUB for ZMYND8. Mechanically, USP7 directly binds to the PBP (PHD-BRD-PWWP) domain of ZMYND8 via its TRAF (tumor necrosis factor receptor-associated factor) domain and UBL (ubiquitin-like) domain and removes F-box and WD repeat domain containing 7 (FBXW7)-catalyzed poly-ubiquitin chains on lysine residue 1034 (K1034) within ZMYND8, thereby stabilizing ZMYND8 and stimulating the transcription of ZMYND8 target genes ZEB1 (zinc finger E-box binding homeobox 1) and VEGFA (Vascular Endothelial Growth Factor A). Consequently, USP7 enhances the capacity of breast cancer cells for migration and invasion through antagonizing FBXW7-mediated ZMYND8 degradation. Importantly, the protein levels of USP7 positively correlates with those of ZMYND8 in breast cancer tissues. These findings delineate an important layer of migration and invasion regulation by the USP7-ZMYND8 axis in breast cancer cells.
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The performance of Electro-Fenton (EF) cathode materials is primarily assessed by H2O2 yield and Fe3+ reduction efficiency. This study explores the impact of pore structure in chitin-based porous carbon on EF cathode effectiveness. We fabricated mesoporous carbon (CPC-700-2) and microporous carbon (ZPC-700-3) using template and activation methods, retaining nitrogen from the precursors. CPC-700-2, with mesopores (3-5 nm), enhanced O2 diffusion and oxygen reduction, producing up to 778 mg/L of H2O2 in 90 min. ZPC-700-3, with a specific surface area of 1059.83 m2/g, facilitated electron transport and ion diffusion, achieving a Fe2+/Fe3+ conversion rate of 79.9%. EF systems employing CPC-700-2 or ZPC-700-3 as the cathode exhibited superior degradation performance, achieving 99% degradation of Rhodamine B, efficient degradation, and noticeable decolorization. This study provides a reference for the preparation of functionalized carbon cathode materials for efficient H2O2 production and effective Fe3+ reduction in EF systems.
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The concentration of carbon dioxide (CO2) is an important indicator for coal mine safety. Real-time monitoring of CO2 concentration is of great importance for taking actions in advance to avoid the occurrence of potential accidents. To address the issues of poor portability and high cost associated with existing coal mine CO2 detection equipment, this paper develops a miniaturized CO2 detection system based on non-dispersive infrared (NDIR) technology. This sensor integrates an infrared light source and a dual-channel pyroelectric detector into a reflective gas chamber, thereby achieving an extended optical path and higher system sensitivity within limited space. Meanwhile, the noise interference was greatly mitigated by using hardware and software filtering techniques. Based on principle analysis, the Lambert-Beer law was parametrically corrected, and then, a model relationship between the dual-channel voltage ratio and concentration was established. In addition, temperature compensation for zero and span values was introduced to improve the adaptability of the detection results to temperature changes. Testing results indicate that the developed detection system can realize CO2 measurement in the concentration range of 0 to 50 000 ppm within a temperature range of 0-40 °C, with a maximum detection error of less than 0.12% and a repeatability deviation of less than 1.04%. During a stability test for 12 h, the maximum concentration drift is 0.07%, indicating that the developed system meets the requirements for monitoring CO2 safety in coal mines.
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BACKGROUND: Chronic hepatitis B (CHB) imposes substantial economic and social burdens globally. The management of CHB involves intricate monitoring and adherence challenges, particularly in regions like China, where a high prevalence of CHB intersects with health care resource limitations. This study explores the potential of ChatGPT-3.5, an emerging artificial intelligence (AI) assistant, to address these complexities. With notable capabilities in medical education and practice, ChatGPT-3.5's role is examined in managing CHB, particularly in regions with distinct health care landscapes. OBJECTIVE: This study aimed to uncover insights into ChatGPT-3.5's potential and limitations in delivering personalized medical consultation assistance for CHB patients across diverse linguistic contexts. METHODS: Questions sourced from published guidelines, online CHB communities, and search engines in English and Chinese were refined, translated, and compiled into 96 inquiries. Subsequently, these questions were presented to both ChatGPT-3.5 and ChatGPT-4.0 in independent dialogues. The responses were then evaluated by senior physicians, focusing on informativeness, emotional management, consistency across repeated inquiries, and cautionary statements regarding medical advice. Additionally, a true-or-false questionnaire was employed to further discern the variance in information accuracy for closed questions between ChatGPT-3.5 and ChatGPT-4.0. RESULTS: Over half of the responses (228/370, 61.6%) from ChatGPT-3.5 were considered comprehensive. In contrast, ChatGPT-4.0 exhibited a higher percentage at 74.5% (172/222; P<.001). Notably, superior performance was evident in English, particularly in terms of informativeness and consistency across repeated queries. However, deficiencies were identified in emotional management guidance, with only 3.2% (6/186) in ChatGPT-3.5 and 8.1% (15/154) in ChatGPT-4.0 (P=.04). ChatGPT-3.5 included a disclaimer in 10.8% (24/222) of responses, while ChatGPT-4.0 included a disclaimer in 13.1% (29/222) of responses (P=.46). When responding to true-or-false questions, ChatGPT-4.0 achieved an accuracy rate of 93.3% (168/180), significantly surpassing ChatGPT-3.5's accuracy rate of 65.0% (117/180) (P<.001). CONCLUSIONS: In this study, ChatGPT demonstrated basic capabilities as a medical consultation assistant for CHB management. The choice of working language for ChatGPT-3.5 was considered a potential factor influencing its performance, particularly in the use of terminology and colloquial language, and this potentially affects its applicability within specific target populations. However, as an updated model, ChatGPT-4.0 exhibits improved information processing capabilities, overcoming the language impact on information accuracy. This suggests that the implications of model advancement on applications need to be considered when selecting large language models as medical consultation assistants. Given that both models performed inadequately in emotional guidance management, this study highlights the importance of providing specific language training and emotional management strategies when deploying ChatGPT for medical purposes. Furthermore, the tendency of these models to use disclaimers in conversations should be further investigated to understand the impact on patients' experiences in practical applications.
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As the central hub of the secretory pathway, the Golgi apparatus plays a crucial role in maintaining cellular homeostasis in response to stresses. Recent studies have revealed the involvement of the Golgi tether, GORASP2, in facilitating autophagosome-lysosome fusion by connecting LC3-II and LAMP2 during nutrient starvation. However, the precise mechanism remains elusive. In this study, utilizing super-resolution microscopy, we observed GORASP2 localization on the surface of autophagosomes during glucose starvation. Depletion of GORASP2 hindered phagophore closure by regulating the association between VPS4A and the ESCRT-III component, CHMP2A. Furthermore, we found that GORASP2 controls RAB7A activity by modulating its GEF complex, MON1A-CCZ1, thereby impacting RAB7A's interaction with the HOPS complex. The assembly of both STX17-SNAP29-VAMP8 and YKT6-SNAP29-STX7 SNARE complexes was also attenuated without GORASP2. These findings suggest that GORASP2 helps seal autophagosomes and activate the RAB7A-HOPS-SNAREs membrane fusion machinery for autophagosome maturation, highlighting its membrane tethering function in response to stresses.Abbreviations: BafA1: bafilomycin A1; ESCRT: endosomal sorting complex required for transport; FPP: fluorescence protease protection; GEF: guanine nucleotide exchange factor; GFP: green fluorescent protein; GORASP2: golgi reassembly stacking protein 2; GSB: glucose starvation along with bafilomycin A1; HOPS: homotypic fusion and protein sorting; LAMP2: lysosomal associated membrane protein 2; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; PBS: phosphate-buffered saline; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; PK: proteinase K; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SIM: structured illumination microscopy; UVRAG: UV radiation resistance associated.
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OBJECTIVES: The aim of this analysis was to investigate the worldwide distribution and trends in the burden of female infertility (FI). DESIGN AND SETTING: Analysis of cross-sectional data from 1990 to 2019 from the Global Burden of Disease (GBD) Study 2019. PARTICIPANTS: Adults aged 20-49 years in various geographical regions, Sociodemographic Index (SDI) levels and populations across 204 countries worldwide. OUTCOME MEASURES: Disability-adjusted life years (DALYs), age-standardised DALY rates and estimated annual percentage changes (EAPCs) for FI over the research period. RESULTS: The global burden of FI, as measured by DALYs and age-standardised DALY rates among adults aged 20-49 years, exhibited an upward trend from 1990 to 2019. Regions such as Tropical Latin America (EAPC: 3.76, 95% CI 2.76 to 4.77), South Asia (EAPC: 1.74, 95% CI 1.01 to 2.48) and Andean Latin America (EAPC: 8.54, 95% CI 6.79 to 10.32) had higher DALYs. The age-standardised DALY rates notably increased in low-middle-SDI and low-SDI countries, with EAPCs of 1.42 (95% CI 0.76 to 2.10) and 1.25 (95% CI 0.30 to 2.21), respectively. Despite lower overall DALYs in high-SDI countries, they experienced the highest EAPC in DALYs (1.57, 95% CI 1.30 to 1.83) during the period 1990-2019. China and India consistently had the highest DALYs for FI globally in both 1990 and 2019, while Africa and Latin America bore a significantly greater burden of the disease compared with other regions. CONCLUSION: The GBD Study data on FI among adults aged 20-49 years revealed a rising global trend in FI from 1990 to 2019, with notable variations across different regions.
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Carga Global de Enfermedades , Infertilidad Femenina , Humanos , Femenino , Adulto , Carga Global de Enfermedades/tendencias , Estudios Transversales , Persona de Mediana Edad , Infertilidad Femenina/epidemiología , Adulto Joven , Salud Global , Años de Vida Ajustados por Discapacidad/tendencias , Costo de Enfermedad , Años de Vida Ajustados por Calidad de VidaRESUMEN
Mitochondrial dysfunction is a prominent hallmark of Alzheimer's disease (AD). The transcriptional coactivator PPARγ coactivator 1 (PGC-1a) has been identified as a key regulator of mitochondrial biogenesis and function. However, the precise structure/function relationship between PGC-1a and mitochondrial quality control remains incompletely understood. In this study, we investigated the impact of PGC-1a on AD pathology and its underlying mechanisms with a specific focus on mitochondrial axonal transport. Additionally, we generated two PGC-1α mutants by substituting leucine residues at positions 148 and 149 within the LKKLL motif or at positions 209 and 210 within the LLKYL motif with alanine. Subsequently, we examined the effects of these mutants on mutAPP-induced abnormalities in anterograde and retrograde axonal transport, disrupted mitochondrial distribution, and impaired mitophagy. Mutagenesis studies revealed that the LLKYL motif at amino acid position 209-210 within PGC-1α plays an essential role in its interaction with estrogen-related receptors (ERRα), which is necessary for restoring normal mitochondrial anterograde axonal transport, maintaining proper mitochondrial distribution, and ultimately preventing neuronal apoptosis. Furthermore, it was found that the Leu-rich motif at amino acids 209-210 within PGC-1α is crucial for rescuing mutAPP-induced impairment in mitophagy and loss of membrane potential by restoring normal mitochondrial retrograde axonal transport. Conversely, mutation of residues 148 and 149 in the LKKLL motif does not compromise the effectiveness of PGC-1α. These findings provide valuable insights into the molecular determinants governing specificity of action for PGC-1α involved in regulating mutAPP-induced deficits in mitochondrial axonal trafficking. Moreover, they suggest a potential therapeutic target for addressing Alzheimer's disease.
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Enfermedad de Alzheimer , Transporte Axonal , Mitocondrias , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Enfermedad de Alzheimer/metabolismo , Mitocondrias/metabolismo , Animales , Humanos , Secuencias de Aminoácidos , Ratones , Mitofagia , Apoptosis , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Mutación , Neuronas/metabolismoRESUMEN
Electrons residing in a flat-band system can play a vital role in triggering spectacular phenomenology due to relatively large interactions and spontaneous breaking of different degeneracies. In this work, we demonstrate chirally twisted triple bilayer graphene, a new moiré structure formed by three pieces of helically stacked Bernal bilayer graphene, as a highly tunable flat-band system. In addition to the correlated insulators showing at integer moiré fillings, commonly attributed to interaction induced symmetry broken isospin flavors in graphene, we observe abundant insulating states at half-integer moiré fillings, suggesting a longer-range interaction and the formation of charge density wave insulators which spontaneously break the moiré translation symmetry. With weak out-of-plane magnetic field applied, as observed half-integer filling states are enhanced and more quarter-integer filling states appear, pointing toward further quadrupling moiré unit cells. The insulating states at fractional fillings combined with Hartree-Fock calculations demonstrate the observation of a new type of correlated charge density wave insulators in graphene and points to a new accessible twist manner engineering correlated moiré electronics.
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OBJECTIVE: Apart from the role of the retinoblastoma gene, the genomic events associated with poor outcomes in patients with ophthalmic tumors are poorly understood. METHODS: We retrospectively analyzed 48 patients with six types of ophthalmic tumors. We searched for high-frequency mutated genes and susceptibility genes in these patients using combined exome and transcriptome analysis. RESULTS: We identified four clearly causative genes (TP53, PTCH1, SMO, BAP1). Susceptibility gene analysis identified hotspot genes, including RUNX1, APC, IDH2, and BRCA2, and high-frequency gene analysis identified several genes, including TP53, TTN, and MUC16. Transcriptome analysis identified 5868 differentially expressed genes, of which TOP2A and ZWINT were upregulated in all samples, while CFD, ELANE, HBA1, and HBB were downregulated. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the phosphoinositide 3-kinase (PI3K)-Akt and Transcriptional misregulation in cancer signaling pathways may be involved in ophthalmic tumorigenesis. CONCLUSIONS: TP53 is clearly involved in ophthalmic tumorigenesis, especially in basal cell carcinoma, and the PI3K-Akt signaling pathway may be an essential pathway involved in ophthalmic tumorigenesis. RUNX1, SMO, TOP2A, and ZWINT are also highly likely to be involved in ophthalmic tumorigenesis, but further functional experiments are needed to verify the mechanisms of these genes in regulating tumorigenesis.
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Neoplasias del Ojo , Genómica , Mutación , Proteína p53 Supresora de Tumor , Humanos , Femenino , Masculino , Proteína p53 Supresora de Tumor/genética , Genómica/métodos , Neoplasias del Ojo/genética , Estudios Retrospectivos , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica , Predisposición Genética a la Enfermedad , Receptor Patched-1/genética , Perfilación de la Expresión Génica , Receptor Smoothened/genética , Receptor Smoothened/metabolismo , Proteínas Supresoras de Tumor/genética , Anciano , Proteínas de Unión a Poli-ADP-Ribosa/genética , Adulto , Transducción de Señal/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Biomarcadores de Tumor/genética , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ADN-Topoisomerasas de Tipo II , Ubiquitina Tiolesterasa , Subunidad alfa 2 del Factor de Unión al Sitio PrincipalRESUMEN
Short-term exposure to air pollution has previously been studied in relation to certain neurological disorders, but there is still a lack of convincing data linking air pollution to epileptic seizures. The study's goal was to investigate how exposure to ambient nitrogen dioxide (NO2) affected the number of patients seeking assistance at the Wuhan Emergency Medical Center due to epileptic seizures. We gathered data on medical emergency calls (MECs), daily ambient air pollution concentrations (SO2, NO2, PM2.5, PM10, CO, and O3), and meteorological variables in Wuhan, China, spanning from January 1, 2017, to November 30, 2019. To investigate the potential influence of ambient nitrogen dioxide on MECs for epileptic seizures, we carried out a time-series investigation using the general additive model (GAM). Additionally, analyses stratified by season, age, and gender were performed. A total of 8989 records of MECs for epileptic seizures were enrolled in our study during the period. Statistical analysis indicates that a rise of 10 µg/m3 in NO2 concentration is linked to a 0.17% increase in daily MECs for epileptic seizures (95% confidence interval [CI]: 0.02%, 0.32%). Furthermore, people aged 14-59 years were more susceptible(2.25%, P < 0.05). The short-term effects of NO2 exposure on daily MECs for epileptic seizures were stronger in warm seasons than in cool seasons (0.55% vs. -0.10%, P < 0.0001). Our findings suggests that short-term exposure to ambient NO2 was positively correlated with daily MECs for epileptic seizures in Wuhan, China. Additionally, we observed that these associations were stronger in patients aged above 14 but under 60 years and the warmer seasons (from April to September).
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Mapping cellular activities over large areas is crucial for understanding the collective behaviors of multicellular systems. Biomechanical properties, such as cellular traction force, serve as critical regulators of physiological states and molecular configurations. However, existing technologies for mapping large-area biomechanical dynamics are limited by the small field of view and scanning nature. To address this, we propose a novel platform that utilizes a vast number of optical diffractive elements for mapping large-area biomechanical dynamics. This platform achieves a field-of-view of 10.6 mm X 10.6 mm, a three-orders-of-magnitude improvement over traditional traction force microscopy. Transient mechanical waves generated by monolayer neonatal rat ventricular myocytes were captured with high spatiotemporal resolution (130 fps and 20 µm for temporal and spatial resolution, respectively). Furthermore, its label-free nature allows for long-term observations extended to a week, with minimal disruption of cellular functions. Finally, simultaneous measurements of calcium ions concentrations and biomechanical dynamics are demonstrated.
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Introduction: Dendrolimus punctatus, a major pest endemic to the native Pinus massoniana forests in China, displays major outbreak characteristics and causes severe destructiveness. In the context of global climate change, this study aims to investigate the effects of climatic variations on the distribution of D. punctatus and its host, P. massoniana. Methods: We predict their potential suitable distribution areas in the future, thereby offering a theoretical basis for monitoring and controlling D. punctatus, as well as conserving P. massoniana forest resources. By utilizing existing distribution data on D. punctatus and P. massoniana, coupled with relevant climatic variables, this study employs an optimized maximum entropy (MaxEnt) model for predictions. With feature combinations set as linear and product (LP) and the regularization multiplier at 0.1, the model strikes an optimal balance between complexity and accuracy. Results: The results indicate that the primary climatic factors influencing the distribution of D. punctatus and P. massoniana include the minimum temperature of the coldest month, annual temperature range, and annual precipitation. Under the influence of climate change, the distribution areas of P. massoniana and its pests exhibit a high degree of similarity, primarily concentrated in the region south of the Qinling-Huaihe line in China. In various climate scenarios, the suitable habitat areas for these two species may expand to varying degrees, exhibiting a tendency to shift toward higher latitude regions. Particularly under the high emission scenario (SSP5-8.5), D. punctatus is projected to expand northwards at the fastest rate. Discussion: By 2050, its migration direction is expected to closely align with that of P. massoniana, indicating that the pine forests will continue to be affected by the pest. These findings provide crucial empirical references for region-specific prevention of D. punctatus infestations and for the rational utilization and management of P. massoniana resources.
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This work presents a straightforward method for synthesizing a series of phosphorus-containing polycyclic aromatic hydrocarbons (P-PAHs) featuring an internal ylidic bond. The method involves anion exchange, alkyne annulation, and deprotonation reactions, enabling the efficient production of cyclic phosphonium salts, which serve as pivotal intermediates in the synthesis of P-PAHs. The alkyne annulation reaction exhibits high regioselectivity, ensuring the successful synthesis of λ5-phosphaphenanthrene isomers. Additionally, the incorporation of electron-withdrawing groups effectively stabilizes the internal ylidic bond of P-PAHs.
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Protein homeostasis is predominantly governed through post-translational modification (PTM). UBE3B, identified as an oncoprotein, exhibits elevated protein levels in breast cancer. However, the impact of PTM on UBE3B remains unexplored. In this study, we show that VHL is a bona fide E3 ligase for UBE3B. Mechanistically, VHL directly binds to UBE3B, facilitating its lysine 48 (K48)-linked polyubiquitination at K286 and K427 in a prolyl hydroxylase (PHD)-independent manner. Consequently, this promotes the proteasomal degradation of UBE3B. The K286/427R mutation of UBE3B dramatically abolishes the inhibitory effect of VHL on breast tumor growth and lung metastasis. Additionally, the protein levels of UBE3B and VHL exhibit a negative correlation in breast cancer tissues. These findings delineate an important layer of UBE3B regulation by VHL.
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Neoplasias de la Mama , Ubiquitina-Proteína Ligasas , Ubiquitinación , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau , Animales , Femenino , Humanos , Ratones , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular , Células HEK293 , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Ratones Desnudos , Metástasis de la Neoplasia , Unión Proteica , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genéticaRESUMEN
PURPOSE: Dentin hypersensitivity (DH) is a prevalent condition, but long-term effective treatments are scarce. Differentiation of odontoblast-like cells is promising for inducing tertiary dentinogenesis and ensuring sustained therapeutic efficacy against DH. This study examined the effects and mechanism of action of mild heat stress (MHS) on the differentiation of odontoblast-like MDPC-23 cells. METHODS: We used a heating device to accurately control the temperature and duration, mimicking the thermal microenvironment of odontoblast-like cells. Using this device, the effects of MHS on cell viability and differentiation were examined. Cell viability was assessed using the MTT assay. The expression and nucleoplasmic ratio of the yes-associated protein (YAP) were examined by western blotting and immunofluorescence. The gene expression levels of heat shock proteins (HSPs) and dentin matrix protein-1 (DMP1) were measured using qPCR. Dentin sialophosphoprotein (DSPP) expression was evaluated using immunofluorescence and immunoblotting. Verteporfin was used to inhibit YAP activity. RESULTS: Mild heat stress (MHS) enhanced the odontoblast differentiation of MDPC-23 cells while maintaining cell viability. MHS also increased YAP activity, as well as the levels of HSP25 mRNA, HSP70 mRNA, HSP90α mRNA, DMP1 mRNA, and DSPP protein. However, after YAP inhibition, both cell viability and the levels of HSP90α mRNA, DMP1 mRNA, and DSPP protein were reduced. CONCLUSION: YAP plays a crucial role in maintaining cell viability and promoting odontoblast differentiation of MDPC-23 cells under MHS. Consequently, MHS is a potential therapeutic strategy for DH, and boosting YAP activity could be beneficial for maintaining cell viability and promoting odontoblast differentiation.
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Diferenciación Celular , Respuesta al Choque Térmico , Odontoblastos , Proteínas Señalizadoras YAP , Odontoblastos/metabolismo , Animales , Proteínas Señalizadoras YAP/metabolismo , Ratones , Línea Celular , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Supervivencia CelularRESUMEN
In this study, the process conditions, physicochemical properties, structural composition and activity of polysaccharides isolated from leechee peel (LPP) by ultrasound-assisted extraction (UAE) with enzyme and alkali solution extraction (ASE) were compared. The results showed that the total sugar content of LPP extracted by UAE accounted for 75.65 %, which was significantly higher than that extracted by alkali solution. The optimum conditions were as follows: extraction temperature of 68.78 â, ultrasonic enzymolysis time of 39.68 min, pectinase dosage of 4.03 %, solid-liquid ratio of 1:30 g/mL, and ultrasonic power of 360 W. The antioxidant activities and structure of leechee peel polysaccharide (LPP) prepared under different conditions were compared. It was found that UAE-LPP was an α-type polysaccharide containing 15.83 % uronic acid. Moreover, LPP extracted by UAE showed strong activity in anti-lipid peroxidation and reducing ability. Ultrasound-assisted enzymatic method is an effective means to improve the content and activity of natural plant polysaccharides, and this method has the advantages of short time-consuming, simple process and easy operation, which can greatly improve the utilization rate of polysaccharides and lay a theoretical and scientific basis for the development and utilization of LPP.
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Antioxidantes , Fraccionamiento Químico , Polisacáridos , Ondas Ultrasónicas , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Fraccionamiento Químico/métodos , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Poligalacturonasa , Temperatura , Peroxidación de Lípido/efectos de los fármacosRESUMEN
Antimicrobial peptides (AMPs) are becoming next-generation alternative antibacterial agents because of the rapid increase in resistance in bacteria against existing antibiotics, which can also be attributed to the formation of resilient biofilms. However, their widespread use is limited because of their poor absorption, higher dosage requirements, and delayed onset of the bioactivity to elicit a desired response. Here we developed a short AMP that specifically targeted Fusobacterium nucleatum. We conjugated 23R to a statherin-derived peptide (SDP) through rational design; this conjugate binds to FomA, a major porin protein of F. nucleatum. The SDP-tagged 23R exhibited rapid and highly specific bactericidal efficacy against F. nucleatum. Further, IC50 values were in the nanomolar range, and they were 100-fold lower than those obtained with unconjugated 23R. In a human gut microbiota model, 0.1 nM SDP-23R achieved 99% clearance of F. nucleatum ATCC 25586 without markedly altering resident microbiota. Here we demonstrated that binding-peptide-coupled AMPs show increased killing efficacy and specificity for the target pathogen without affecting the resident microbiota.
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Antibacterianos , Péptidos Antimicrobianos , Fusobacterium nucleatum , Fusobacterium nucleatum/efectos de los fármacos , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Pruebas de Sensibilidad Microbiana , Microbioma Gastrointestinal/efectos de los fármacos , Biopelículas/efectos de los fármacos , Porinas/metabolismo , Porinas/genética , Porinas/química , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas de la Membrana Bacteriana Externa/genéticaRESUMEN
Graphene films grown by the chemical vapor deposition (CVD) method suffer from contamination and damage during transfer. Herein, an innovative ice-enabled transfer method under an applied electric field and in the presence of Cu2O (or Cu2O-Electric-field Ice Transfer, abbreviated as CEIT) is developed. Ice serves as a pollution-free transfer medium while water molecules under the electric field fully wet the graphene surface for a bolstered adhesion force between the ice and graphene. Cu2O is used to reduce the adhesion force between graphene and copper. The combined methodology in CEIT ensures complete separation and clean transfer of graphene, resulting in successfully transferred graphene to various substrates, including polydimethylsiloxane (PDMS), Teflon, and C4F8 without pollution. The graphene obtained via CEIT is utilized to fabricate field-effect transistors with electrical performances comparable to that of intrinsic graphene characterized by small Dirac points and high carrier mobility. The carrier mobility of the transferred graphene reaches 9090 cm2 V-1 s-1, demonstrating a superior carrier mobility over that from other dry transfer methods. In a nutshell, the proposed clean and efficient transfer method holds great potential for future applications of graphene.
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OBJECTIVE: The purpose of the study was to investigate the association between discrimination by multiple sources (ie, teachers, students, and other adults) and early adolescents' behavioral problems (ie, internalizing, externalizing, and attention problems), also considering the protective role of parental warmth in the association. METHOD: Cross-sectional analyses were conducted with 3,245 early adolescents of color obtained from the Adolescent Brain Cognitive Development Study (ABCD Study) at year 1 follow-up (Y1), a large and diverse sample of children (mean age = 9.48 years) in the United States. Racially-ethnically minoritized adolescents reported sources of discrimination, parental warmth, and symptoms of psychopathology. Regression with interaction terms was conducted to investigate the associations among sources of discrimination, parental warmth, and behavioral problems among racially-ethnically minority adolescents. Sensitivity analyses were conducted to examine (1) race/ethnicity and sex/gender variations; (2) whether the associations between different sources of discrimination and behavioral problems were reliably different; and (3) effects of discrimination, parental warmth, and their interplay at Y1 in predicting adolescents' behavioral problems at year 2 follow-up. RESULTS: Early adolescents experiencing interpersonal racial-ethnic discrimination by multiple sources, including teachers, students, and other adults, reported higher levels of attention, internalizing, and externalizing problems. Parental warmth was protective for the association between interpersonal racial-ethnic discrimination and early adolescents' behavioral problems. CONCLUSION: Experiencing interpersonal racial-ethnic discrimination from teachers, peers, and other adults is related to heightened attention, internalizing, and externalizing problems among racially-ethnically minoritized early adolescents. Parental warmth may reduce the risk of developing behavioral problems among early adolescents who experience interpersonal racial-ethnic discrimination from students, teachers, and other adults outside of school. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. We actively worked to promote sex and gender balance in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.
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We report a massive field-of-view and high-speed videography platform for measuring the sub-cellular traction forces of more than 10,000 biological cells over 13 mm2 at 83 frames per second. Our Single-Pixel Optical Tracers (SPOT) tool uses 2-dimensional diffraction gratings embedded into a soft substrate to convert cells' mechanical traction force into optical colors detectable by a video camera. The platform measures the sub-cellular traction forces of diverse cell types, including tightly connected tissue sheets and near isolated cells. We used this platform to explore the mechanical wave propagation in a tightly connected sheet of Neonatal Rat Ventricular Myocytes (NRVMs) and discovered that the activation time of some tissue regions are heterogeneous from the overall spiral wave behavior of the cardiac wave.