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BACKGROUND: The quality of life of patients receiving long-term peritoneal dialysis (PD) is significantly impacted by the onset of peritoneal fibrosis (PF), and one of the pathological changes is mesothelial-mesenchymal transition (MMT). In this study, we investigated the potential roles of miR-454-3p and signal transducer and activator of transcription 3 (STAT3) in the progression of peritoneal MMT and the underlying mechanisms. METHODS: Peritoneums were collected to detect morphology via hematoxylin-eosin staining and differentially expressed miRNAs were detected via RT-qPCR. PD effluent-derived cell populations in the peritoneal cavity were isolated from the effluents of 20 PD patients to determine miR-454-3p, STAT3, and MMT markers via Western blotting and RT-qPCR. The relationship between miR-454-3p and STAT3 was examined via a dual-luciferase reporter assay. Western blotting and RT-qPCR were utilized to evaluate the expression of STAT3, MMT markers, and glycolytic enzymes. Immunofluorescence staining revealed the localization and expression of MMT markers and STAT3. RESULTS: MiR-454-3p was downregulated in the peritoneums and PD effluent-derived cell populations of long-term PD patients. High glucose (HG) treatment promoted HMrSV5 cell MMT and glycolysis. MiR-454-3p overexpression alleviated HG-induced MMT and suppressed the expression of STAT3 and glycolytic enzymes. In contrast, the miR-454-3p inhibitor exacerbated HG-induced MMT and promoted the expression of glycolytic enzymes and STAT3. Moreover, STAT3 was the target of miR-454-3p. CONCLUSIONS: This study demonstrated the protective role of miR-454-3p in HG-induced MMT and glycolysis in HMrSv5 cells, suggesting that miR-454-3p may prevent MMT by suppressing glycolytic enzymes via the STAT3/PFKFB3 pathway in the HG environment.
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Transição Epitelial-Mesenquimal , Glucose , Glicólise , MicroRNAs , Diálise Peritoneal , Fibrose Peritoneal , Peritônio , Fator de Transcrição STAT3 , MicroRNAs/metabolismo , MicroRNAs/genética , Fator de Transcrição STAT3/metabolismo , Humanos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/metabolismo , Glucose/farmacologia , Glicólise/efeitos dos fármacos , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/metabolismo , Fibrose Peritoneal/patologia , Fibrose Peritoneal/etiologia , Fibrose Peritoneal/genética , Peritônio/patologia , Peritônio/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Linhagem Celular , Regulação para Baixo , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacosRESUMO
To improve the mess-specific activity of Co supported on zeolite catalysts in Fischer-Tropsch (FT) synthesis, the Co-MCM-22 catalyst was prepared by simply grinding the MCM-22 with nanosized Co3O4 prefabricated by the thermal decomposition of the Co(II)-glycine complex. It is found that this novel strategy is effective for improving the mess-specific activity of Co catalysts in FT synthesis compared to the impregnation method. Moreover, the ion exchange and calcination sequence of MCM-22 has a significant influence on the dispersion, particle size distribution, and reduction degree of Co. The Co-MCM-22 prepared by the physical grinding of prefabricated Co3O4 and H+-type MCM-22 without a further calcination process exhibits a moderate interaction between Co3O4 and MCM-22, which results in the higher reduction degree, higher dispersion, and higher mess-specific activity of Co. Thus, the newly developed method is more controllable and promising for the synthesis of metal-supported catalysts.
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The iconic sabretooth Homotherium is thought to have hunted cooperatively, but the origin of this behaviour and correlated morphological adaptations are largely unexplored. Here we report the most primitive species of Amphimachairodus (Amphimachairodus hezhengensis sp. nov.), a member of Machairodontini basal to Homotherium, from the Linxia Basin, northeastern border of the Tibetan Plateau (9.8-8.7 Ma). The long snout, laterally oriented and posteriorly located orbit of Amphimachairodus suggest a better ability to observe the surrounding environment, rather than targeting single prey, pointing to an adaptation to the open environment or social behaviour. A pathological forepaw of Amphimachairodus provides direct evidence of partner care. Our analyses of trait evolutionary rates support that traits correlated with killing behaviour and open environment adaptation evolved prior to other traits, suggesting that changes in hunting behaviour may be the major evolutionary driver in the early evolution of the lineage. A. hezhengensis represents one of the most important transitions in the evolution of Machairodontini, leading to adaptation in open environments and contributing to their further dispersal and radiation worldwide. This rapid morphological change is likely to be correlated with increasingly arid environments caused by the rise of the Tibetan Plateau, and competition from abundant large carnivores in this area.
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Carnívoros , Animais , Tibet , Aclimatação , Adaptação Fisiológica , Comportamento SocialRESUMO
AbstractAlthough more frequently discussed recently than previously, the role of ecology in homoploid hybrid and allopolyploid speciation has not been subjected to comparative analysis. We examined abiotic niche divergence of 22 assumed homoploid hybrid species and 60 allopolyploid species from that of their progenitors. Ecological niche modeling was employed in an analysis of each species' fundamental niche, and ordination methods were used in an analysis of realized niches. Both analyses utilized 100,000 georeferenced records. From estimates of niche overlap and niche breadth, we identified for both types of hybrid species four niche divergence patterns: niche novelty, niche contraction, niche intermediacy, and niche expansion. Niche shifts involving niche novelty were common and considered likely to play an important role in the establishment of both types of hybrid species, although more so for homoploid hybrid species than for allopolyploid species. Approximately 70% of homoploid hybrid species versus 37% of allopolyploid species showed shifts in the fundamental niche from their parents, and â¼86% versus â¼52%, respectively, exhibited shifts in the realized niche. Climate was shown to contribute more than soil and landform to niche shifts in both types of hybrid species. Overall, our results highlight the significance of abiotic niche divergence for hybrid speciation, especially without genome duplication.
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Ecologia , Especiação Genética , Ecossistema , Clima , SoloRESUMO
Cell surface thiols can be targeted by thiol-reactive groups of various materials such as peptides, nanoparticles, and polymers. Here, we used the maleimide group, which can rapidly and covalently conjugate with thiol groups, to prepare surface-modified liposomes (M-Lip) that prolong retention of doxorubicin (Dox) at tumor sites, enhancing its efficacy. Surface modification with the maleimide moiety had no effect on the drug loading efficiency or drug release properties. Compared to unmodified Lip/Dox, M-Lip/Dox was retained longer at the tumor site, it was taken up by 4T1 cells to a significantly greater extent, and exhibited stronger inhibitory effect against 4T1 cells. The in vivo imaging results showed that the retention time of M-Lip at the tumor was significantly longer than that of Lip. In addition, M-Lip/Dox also showed significantly higher anticancer efficacy and lower cardiotoxicity than Lip/Dox in mice bearing 4T1 tumor xenografts. Thus, the modification strategy with maleimide may be useful for achieving higher efficient liposome for tumor therapy.
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Neoplasias da Mama , Lipossomos , Animais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/química , Feminino , Humanos , Lipossomos/química , Maleimidas , Camundongos , Camundongos Endogâmicos BALB C , Compostos de SulfidrilaRESUMO
Sex-determining region on the Y chromosome-related high mobility group box 18 (SOX18) has emerged as a key tumor-related protein in a wide range of human tumors. Yet, the involvement of SOX18 in papillary thyroid carcinoma has not been determined. This study aimed to explore the expression and biological function of SOX18 in papillary thyroid carcinoma. There was a significant decrease in SOX18 expression in papillary thyroid carcinoma tissues compared with that in normal tissues. Low expression of SOX18 was also detected in papillary thyroid carcinoma cell lines and upregulation of SOX18 effectively repressed the proliferative, colony-forming and invasive abilities of papillary thyroid carcinoma cells in vitro. In contrast, knockdown of SOX18 in papillary thyroid carcinoma cells was associated with a significant increase in cell proliferation and invasion. Further studies revealed that SOX18 upregulation was associated with the reduced nuclear accumulation of ß-catenin and the downregulation of Wnt/ß-catenin signaling in thyroid carcinoma cells. Moreover, inhibition of Wnt/ß-catenin signaling markedly attenuated SOX18 knockdown-evoked oncogenic effects in papillary thyroid carcinoma cells. In addition, SOX18 overexpression remarkably retarded the tumor growth of papillary thyroid carcinoma cell-derived xenograft tumors in nude mice. Taken together, these results demonstrate that SOX18 suppresses the proliferation and invasion of papillary thyroid carcinoma by inhibiting Wnt/ß-catenin signaling. Our study reveals a tumor-suppressive role of SOX18 in papillary thyroid carcinoma and suggests that SOX18 is an attractive candidate target for treatment of papillary thyroid carcinoma.
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Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição SOXF/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , beta Catenina/genética , Animais , Carcinogênese/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Fatores de Transcrição SOXF/antagonistas & inibidores , Fatores de Transcrição SOXF/metabolismo , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Carga Tumoral , Via de Sinalização Wnt , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismoRESUMO
Azo dyes constitute a significant environmental burden due to its toxicity, carcinogenicity, and hard biodegradation. The report here is focused on the decolorization and degradation treatment of azo dye methyl red (MR). Decolorization of MR using Aspergillus versicolor LH1 isolated from activated sludge was investigated. The maximum decolorization rate of 92.3% was obtained under the optimized conditions of sucrose as carbon source, 5d incubation age, pH 6.0, 140 mg/L initial concentration of MR and 2.5 g/L initial concentration of NaNO3. Biodegradation products of MR were investigated using HPLC-MS, FTIR, and GC-MS assays. It was revealed the three bonds of -C-N = in MR aromatic nucleus were disrupted, and benzoic acid was detected. Micronucleus test with Glycine max L. and Vicia faba L. demonstrated that MCN (micronucleus permillage) of MR metabolites was less than MR solution. These findings provided evidence that A. versicolor LH1 is a candidate for MR degradation in industrial wastewater treatment.
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Aspergillus/metabolismo , Compostos Azo/metabolismo , Águas Residuárias/microbiologia , Poluentes Químicos da Água/metabolismo , Purificação da Água , Biodegradação AmbientalRESUMO
In this study, to fabricate diamond concave microlenses in a simple manner, an approach that combines a spin coating process with subsequent dry etching was demonstrated. First, photolithography was used to produce cylindrical holes in the photoresist layer on the diamond surface. Then, another photoresist was spin coated to fill the holes, and the concave structures with meniscus shapes were then obtained because of centrifugal force and interfacial tension. Finally, diamond concave microlenses were formed by transferring photoresist concave structures onto a diamond substrate using a dry etching technique. The fabricated diamond microlens exhibits a low surface roughness with nanometers as well as high-quality imaging and focusing performances, which is expected to have a wider range of potential applications under harsh and special conditions.
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In this study, a biomimetic compound eye (BCE) was realized on diamond by combining thermal reflow with dry etching techniques. Firstly, photoresist pillars were developed on diamond surface by standard photolithography. Then, these pillars were reflowed on a hotplate to form spherical segment patterns. Furthermore, dry etching technique was used to transfer these patterns into diamond surface to form the convex curve surface with diameter of 300 µm, on which, ommatidia with diameter of 18 µm and space of 35 µm were fabricated with the same processes to obtain BCE. Finally, the as-fabricated diamond BCE was characterized, indicating a well-uniformity according to the point spread function and exhibiting clear images of the testing pattern in projection experiment, which is expected to work under harsh conditions such as high intensity irradiation and strong acid.
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Depression is highly prevalent among patients with chronic obstructive pulmonary disease (COPD). However, depression with COPD comorbidity is often underdiagnosed and undertreated, and pathogenic research is also insufficient. In the present study, we characterised pulmonary and hippocampal dysfunction by researching the interaction between inflammasome-regulated cytokines and glucocorticoid receptor (GR) signalling by investigating the role of fluoxetine (FLU), one of the most widely used antidepressants in clinical practice. Mice were exposed to cigarette smoke (CS) to induce the model of COPD with comorbid depression, and pathological alterations in serum, hippocampus, lung, and bronchoalveolar lavage fluid were determined. Our results showed that the CS procedure induced the accumulation of inflammatory cells (macrophages, neutrophils, and lymphocytes), the production of cytokines, the activation of inflammasome components (NLRP3, ASC, caspase-1), depression-related behaviours, and the stimulation of GR signalling. Intriguingly, glucocorticoid resistance occurred in CS-exposed mice, with elevated serum corticosterone and suppressed hippocampal GR levels, which suggested a novel potential regulatory mechanism underlying COPD-induced depression comorbidity. Furthermore, chronic CS exposure decreased the pGR-S211/pGR-S226 ratio, increased the active nuclear GR, and impaired cytosolic GR binding capacity and GR transcriptional activity, which might be responsible for the activation of the inflammasome-induced inflammatory cascade. These alterations were reversed by chronic FLU treatment, indicating that FLU-mediated GR signalling was involved in the COPD induced inflammasome activation. Our research explored the underlying molecular mechanism of comorbid COPD/depression and provided in vivo evidence that glucocorticoid resistance occurred during CS-induced central nervous system inflammation, a potential mechanism underlying the cross talk between the lung and brain.
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Inflamassomos/metabolismo , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Receptores de Glucocorticoides/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Líquido da Lavagem Broncoalveolar/química , Caspase 1/metabolismo , Fumar Cigarros/efeitos adversos , Citocinas/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Transtorno Depressivo/metabolismo , Modelos Animais de Doenças , Fluoxetina/farmacologia , Inflamassomos/imunologia , Inflamação/metabolismo , Pulmão/patologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/complicações , Receptores de Glucocorticoides/imunologia , Transdução de Sinais , FumarRESUMO
In this study, a Ti-diamond-Ti structured ultraviolet photodetector was fabricated on a homoepitaxial diamond layer with an oxygen-terminated surface. The properties of the Ti/diamond schottky contact were measured using X-ray photoelectron spectroscopy, and the barrier height was found to be 1.15 eV. At a bias of 3 V, the responsivity at 210 nm was only 4.29 mA/W, while at 12 V, the responsivity increased rapidly to 51 mA/W. The increase can be ascribed to the photocurrent gain. With the further increase in voltage, an avalanche effect was produced, and the responsivity could reach 1.18 A/W at 50 V. Moreover, the transient response behavior of the photodetector exhibited a good repeatability and response speed.
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We introduce a chemical reflow method to fabricate diamond microlenses. First, photoresist pillars developed by photolithography are reflowed in organic solvent vapor atmosphere at 20 °C to form spherical segment patterns on diamond substrate. The effects of chemical solvent type and reflow time on photoresist pattern profiles are investigated. Second, via dry etching, diamond microlenses are fabricated by transferring the spherical segment pattern into substrate. Furthermore, these diamond microlenses demonstrate low numerical aperture, well-controllable curvature, and good imaging performance with projecting experiment.
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BACKGROUND: Cervical cancer is the second most common cancer among women worldwide. The potential of microRNAs as novel biomarkers in cervical cancer is growing. OBJECTIVES: In this study, we investigated the functions and targets of miR-466 in cervical cancer tissues. METHODS: Fresh cervical tissues were obtained from 157 patients with cervical cancer, cervical intraepithelial neoplasia (CIN), and healthy controls, and the tissues were immediately frozen in liquid nitrogen until use. The RNA was extracted and quantitative real-time polymerase chain reaction (PCR) was performed. RESULTS: A total of 157 participants were summarized, including 56 patients with cervical cancer, 60 patients with CIN, and 49 healthy controls. The expression levels of miR-466 in cervical cancers (0.68) were higher than that in healthy controls (0.082) (P < 0.01). The average fold changes of miR-466 in the patients with CIN group and people group were 0.28 and 0.082, respectively (P < 0.01). It was a statistically significant difference in patients with lymph node involvement (P = 0.022). However, the expression of miR-466 was not correlated with International Federation of Gynecology and Obstetrics stages, tumor size, or vascular invasion (P = 0.506, P = 0.667, and P = 0.108, respectively). CONCLUSIONS: Our results indicate that the aberrant expression of miR-466 is closely associated with the occurrence and development of cervical cancer.
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Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , MicroRNAs/biossíntese , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , RNA Neoplásico/genética , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Displasia do Colo do Útero/metabolismo , Displasia do Colo do Útero/patologiaRESUMO
This study aims to investigate the differential expression of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) in the peritoneal dialysate among patients with different durations of peritoneal dialysis and its association with the angiogenic marker vascular* endothelial growth factor (VEGF), the fibronectin (FN), and various clinical indicators. A cohort of 122 peritoneal dialysis patients was categorized into short-term (≤1 year, n = 33), mid-term (>1 and ≤5 years, n = 55), and long-term (>5 years, n = 34) groups based on dialysis duration. We utilized enzyme-linked immunosorbent assay (ELISA) and western blot assays to quantify the levels of IGF2BP3, VEGF, and FN in the dialysate. Our findings showed a progressive increase in IGF2BP3 levels with the duration of PD, with the long-term group exhibiting significantly higher levels than both the short-term and mid-term groups (p < 0.001). A positive correlation between IGF2BP3 and VEGF (r = 0.386, p = 0.013), as well as between IGF2BP3 and FN (r = 0.340, p = 0.030), was observed. IGF2BP3 levels also correlated positively with serum creatinine, calcium, and phosphorus levels. In vitro analysis further confirmed that IGF2BP3 expression is enhanced in human peritoneal mesothelial cells under high-glucose conditions (p < 0.05). The study highlights the potential of IGF2BP3 in PD effluent as a biomarker for monitoring PF progression, with its expression significantly correlated with the duration of PD (Pearson r = 0.897, p < 0.001). In conclusion, our results underscore a correlation between elevated IGF2BP3 levels and PD duration, suggesting the clinical significance of IGF2BP3 as a biomarker for PF progression.
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Diálise Peritoneal , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/análise , Fator A de Crescimento do Endotélio Vascular/metabolismo , Peritônio/química , Peritônio/metabolismo , Relevância Clínica , Soluções para Diálise/metabolismo , Biomarcadores/metabolismoRESUMO
Due to high proliferative capacity, multipotent differentiation, immunomodulatory abilities, and lack of ethical concerns, dental pulp stem cells (DPSCs) are promising candidates for clinical application. Currently, clinical research on DPSCs is in its early stages. The reason for the failure to obtain clinically effective results may be problems with the production process of DPSCs. Due to the different preparation methods and reagent formulations of DPSCs, cell characteristics may be affected and lead to inconsistent experimental results. Preparation of clinical-grade DPSCs is far from ready. To achieve clinical application, it is essential to transit the manufacturing of stem cells from laboratory grade to clinical grade. This review compares and analyzes experimental data on optimizing the preparation methods of DPSCs from extraction to resuscitation, including research articles, invention patents and clinical trials. The advantages and disadvantages of various methods and potential clinical applications are discussed, and factors that could improve the quality of DPSCs for clinical application are proposed. The aim is to summarize the current manufacture of DPSCs in the establishment of a standardized, reliable, safe, and economic method for future preparation of clinical-grade cell products.
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The long-trunked elephantids underwent a significant evolutionary stage characterized by an exceptionally elongated mandible. The initial elongation and subsequent regression of the long mandible, along with its co-evolution with the trunk, present an intriguing issue that remains incompletely understood. Through comparative functional and eco-morphological investigations, as well as feeding preference analysis, we reconstructed the feeding behavior of major groups of longirostrine elephantiforms. In the Platybelodon clade, the rapid evolutionary changes observed in the narial region, strongly correlated with mandible and tusk characteristics, suggest a crucial evolutionary transition where feeding function shifted from the mandible to the trunk, allowing proboscideans to expand their niches to more open regions. This functional shift further resulted in elephantids relying solely on their trunks for feeding. Our research provides insights into how unique environmental pressures shape the extreme evolution of organs, particularly in large mammals that developed various peculiar adaptations during the late Cenozoic global cooling trends.
The elephant's trunk is one of the most efficient food-gathering organs in the animal kingdom. From large branches to thin blades of grass, it can coil around and bring many types of vegetation to the animals' strong, short mandibles. This versatility allows elephants to thrive in a range of environments, including grasslands. Trunks are not the only spectacular feature to emerge in Proboscideans, the family of which elephants are the only surviving group. During the early and middle Miocene (between 23 to 11.6 million years ago), many of these species had dramatically elongated lower jaws; how and why this trait emerged then disappeared is poorly understood. The role that lengthened mandibles and trunks played during feeding also remains unclear. To address these questions, Li et al. focused on Platybelodon, Choerolophodon and Gomphotherium, which belong to three Proboscidean families that roamed Northern China between 17 and 15 million years ago. Each had elongated lower jaws, but with strikingly distinct lengths and morphologies. Chemical analyses on enamel samples helped determine which habitat the families occupied, while mathematical modelling revealed how their mandibles tackled different types of plants. Trunk shape was assessed via analyses of the nasal region. The results suggest that Choerolophodon had mandibles better suited for processing branches and a short, 'primitive' trunk. Gomphotherium sported a versatile jaw that could handle both grass and trees, as well as a rather 'elephant-like' trunk. The jaw of Platybelodon seemed well-adapted to cut grass, and remarkable bone structures point towards a long, strong and flexible trunk. While modern elephants fully depend on their trunks to eat, morphological constraints suggest that, in these species, the appendage only served to assist feeding (e.g., by pressing down on branches). All families shared an environment that included grasslands and forests, but analyses suggest that, for a period, Choerolophodon favored relatively closed habitats while Platybelodon spread into grasslands and Gomphotherium navigated both landscapes. This suggests that the evolution of long, strong and flexible trunks is tightly associated with grazing. About 14 million years ago, a global cooling event led to grasslands expanding worldwide. The fossil record shows the mandibles of Proboscideans starting to shorten after this period, including in the descendants of Gomphotherium that would give rise to modern elephants. The work by Li et al. sheds light onto these evolutionary processes, and the environmental pressures which helped shape the trunk.
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Evolução Biológica , Elefantes , Comportamento Alimentar , Mandíbula , Animais , Mandíbula/anatomia & histologia , Mandíbula/fisiologia , Comportamento Alimentar/fisiologia , Elefantes/fisiologia , Elefantes/anatomia & histologia , Fósseis , FilogeniaRESUMO
OBJECTIVES: The effects of wild Cordyceps proteins (WCPs) on the gut microbiota and the immune system of MRL/lpr mice were studied. METHODS: The effects of WCP on serum metabolic indexes (total triglyceride, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) content was measured by a biochemical analyzer. CD4+, CD8+ cells, intestinal inflammation, and intestinal barrier function in MRL/lpr mice were measured by flow cytometry, 16S ribosomal RNA, western blot, and quantitative real-time polymerase chain reaction RT-PCR. KEY FINDINGS: The results showed that after the intervention of WCP, the content of CD4+ cells in lupus mice increased, and the levels of proinflammatory cytokines were down-regulated, such as tumor necrosis factor-α and interleukin-6. Secondly, WCP up-regulated the proteins and mRNA levels of ZO-1, Claudin-1, and Occludin. Thirdly, it also increased the Firmicutes/Bacteroidetes ratio and the abundance of Oscillospirales, Lachnospirales, Lachnospiraceae, and Clostridia, as well as negatively regulated the MAPK/NF-кB signaling pathway in lupus nephritis (LN) mice. CONCLUSIONS: These findings suggested that WCP may improve the symptoms of LN by altering immune factors and the intestinal barrier.
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BACKGROUND: MT1G inactivation mediated by promoter methylation has been reported in thyroid cancer. However, the role of MT1G in thyroid carcinogenesis remains unclear. The aim of this study is to examine the biological functions and related molecular mechanisms of MT1G in thyroid cancer. METHODS: Methylation-specific PCR (MSP) was performed to analyze promoter methylation of MT1G and its relationship with clinicopathological characteristics of papillary thyroid cancer (PTC) patients. Conventional and real-time quantitative RT-PCR assays were used to evaluate mRNA expression. The functions of ectopic MT1G expression were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays. RESULTS: MT1G expression was frequently silenced or down-regulated in thyroid cancer cell lines, and was also significantly decreased in primary thyroid cancer tissues compared with non-malignant thyroid tissues. Promoter methylation, along with histone modification, contributes to MT1G inactivation in thyroid tumorigenesis. Moreover, our data showed that MT1G hypermethylation was significantly positively associated with lymph node metastasis in PTC patients. Importantly, restoring MT1G expression in thyroid cancer cells dramatically suppressed cell growth and invasiveness, and induced cell cycle arrest and apoptosis through inhibiting phosphorylation of Akt and Rb. CONCLUSIONS: We have for the first time revealed that MT1G appears to be functional tumor suppressor involved in thyroid carcinogenesis mainly through modulating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway and partially through regulating the activity of Rb/E2F pathway in this study.
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Metalotioneína/genética , Metalotioneína/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Metilação de DNA , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Estadiamento de Neoplasias , Regiões Promotoras Genéticas , Neoplasias da Glândula Tireoide/patologia , Carga Tumoral , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Adulto JovemRESUMO
Nanocarriers entering the body are usually coated by plasma protein, leading to a protein "corona" easily recognized by tissues and cells. Adjusting the composition of protein coronas may be an efficient way to change the properties and behavior of nanoparticles in vivo. In this study, we modified doxorubicin-loaded liposomes (Lip/DOX) with an albumin-binding domain (ABD) to prepare nanoparticles (ABD-Lip/DOX) that can specifically bind to albumin and form albumin-based protein coronas in vivo for targeted tumor therapy. The prepared liposomes were spherical with a particle size of about 100 nm. After incubating the liposomes with rat serum, the albumin content was eight times higher on ABD-Lip than on control liposomes. ABD-Lip significantly inhibited adsorption of IgG and complement activation in rat serum in vitro, while corona-coated ABD-Lip was internalized to a significantly greater extent than corona-coated control liposomes. In addition, ABD-Lip showed longer blood circulation time, higher tumor accumulation and greater antitumor efficacy than control liposomes in mice bearing 4 T1 tumors, while both liposome formulations showed similar biocompatibility. These results confirm that adjusting the component of protein coronas around nanoparticles can improve their therapeutic efficacy.
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Lipossomos , Coroa de Proteína , Ratos , Camundongos , Animais , Lipossomos/química , Linhagem Celular Tumoral , Peptídeos/química , Doxorrubicina/química , AlbuminasRESUMO
In this work, a numerical method is proposed to predict the electrokinetic phenomena and combined with an experimental study of the surface charge density (ρs) and zeta potential (ζ) behavior is investigated for borosilicate immersed in KCl and NaCl electrolytes, and for imogolite immersed in KCl, CaCl2, and MgCl2 electrolytes. Simulations and experiments of the electrokinetic flows with electrolyte solutions were performed to accurately determine the electric double layer (EDL), ζ, and ρs at various electrolyte concentrations and pH. The zeta potential was experimentally determined and numerically predicted by solving the coupled governing equations of mass, species, momentum, and electrical field iteratively. Our numerical prediction shows that ζ for borosilicate develops strong nonlinear behavior with the ion concentration following a power-law. Likewise, the ρs obeys a nonlinear behavior, decreasing as the concentration increases. Moreover, for imogolite, both ζ and the ρs behave nonlinearly with the pH. The EDL for borosilicate and imogolite becomes thinner as the electrolyte concentration and pH increase; this behavior is caused by increased ρs, resulting in the higher attraction of the free charges. The reported nonlinear behavior describes more accurately the interaction of the nanoparticle surface charge with the electrolytes and its effect on the electrolyte transport properties.