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To address the extended development cycle, high costs, and maintenance difficulties associated with existing microgravity simulation methods, this study has developed a semi-physical simulation platform for robotic arms tailored to different gravity environments and loading conditions. The platform represents difficult-to-model joints as physical objects, while the easily modeled components are simulated based on principles of similarity. In response to the strong coupling, nonlinearity, and excess force disturbance issues in the electric variable load loading system, a fractional-order linear active disturbance rejection control algorithm was employed. The controller parameters were tuned using an improved particle swarm algorithm with modified weight coefficients, and experimental results demonstrate that a fractional-order linear active disturbance rejection control improves response speed and disturbance rejection performance compared to linear sliding mode control. The study investigated the differences in the drive force of joint motors in space robotic arms under varying gravity environments and loading conditions. Experimental results indicate that load torque is the primary influencing factor on joint motor drive force, while radial force serves as a secondary influencing factor. Additionally, when the axis of the joint motor is perpendicular to the ground, it can, to some extent, simulate microgravity conditions on the ground.
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Goose astrovirus (GoAstV) is an emerging avian pathogen that induces gout in goslings with a mortality of up to 50%. Organ damage caused by GoAstV infection was considered the cause of gout, but it is still unclear whether other factors are involved. Human and murine studies have linked the gut microbiome-derived urate and gout, thus we hypothesized that gut microbiome may also play an important role in gout induced by GoAstV infection. This study tested the pathogenicity of our isolated GoAstV genotype 2 strain on goslings, while the appearance of clinical signs, histopathological changes, viral distribution and the blood level of cytokines were monitored for 18 d postinfection (dpi). The dynamics in the gut microbiome were profiled by 16S sequencing and then correlated with GoAstV infection. Results showed that this study successfully developed an experimental infection model for studying the pathogenicity of the GoAstV infection which induces typical symptoms of gout. GoAstV infection significantly altered the gut microbiome of goslings with the enrichment of potential proinflammatory bacteria and depletion of beneficial bacteria that can produce short-chain fatty acids. More importantly, the microbial pathway involved in urate production was significantly increased in goslings infected with GoAstV, suggesting that gut microbiome-derived urate may also contribute to the gout symptoms. Overall, this study demonstrated the role of gut microbiome in the pathogenesis of GoAstV infection, highlighting the potential of gut microbiome-based therapeutics against gout symptoms.
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Infecções por Astroviridae , Avastrovirus , Microbioma Gastrointestinal , Gansos , Doenças das Aves Domésticas , Animais , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/microbiologia , Avastrovirus/fisiologia , Gota/veterinária , Gota/virologia , Gota/microbiologiaRESUMO
BACKGROUND AND AIMS: Lung adenocarcinoma (LUAD) is the most common and aggressive cancer with a high incidence. N1-specific pseudouridine methyltransferase (EMG1), a highly conserved nucleolus protein, plays an important role in the biological development of ribosomes. However, the role of EMG1 in the progression of LUAD is still unclear. METHODS: The expression of EMG1 in LUAD cells, and LUAD tissues, and adjacent noncancerous tissues was quantified using real-time polymerase chain reaction (PCR) and western blotting. The roles of EMG1 in LUAD cell proliferation, migration, invasion and tumorigenicity were explored in vitro and in vivo. Western blot analysis to underlying molecular mechanism of EMG1 regulating the biological function of LUAD. EMG1 expression and its impact on tumor prognosis were analyzed using a range of databases including GEPIA, UALCAN, cBioPortal, LinkedOmics, and Kaplan-Meier Plotter. RESULTS: EMG1 expression was elevated in LUAD patients compared to normal tissues, and EMG1 expression was strongly correlated with prognosis in LUAD patients. EMG1 expression correlated with age, gender, N stage, T stage, and pathologic stage. EMG1 expression was strongly positively correlated with MRPL51, PHB2, SNRPG, ATP5MD, and TPI1, and strongly negatively correlated with MACF1, DOCK9, RAPGEF2, SYNJ1, and KIDINS220, the major enrichment pathways for EMG1 and related genes include Cell cycle, DNA Replication and Pathways in cancer signaling pathways. EMG1 expression level was significantly increased in LUAD cell lines and tissues. Knockdown of EMG1 could inhibit LUAD cell proliferation, migration, invasion, and tumorigenicity. Besides, EMG1 overexpression could promote LUAD cell proliferation, migration, and invasion. High expression of EMG1 predicts poor prognosis in LUAD patients, and EMG1 may play an oncogenic role in the tumor microenvironment by participating in the infiltration of LUAD immune cells. CONCLUSIONS: EMG1 regulated various functions in LUAD by directly mediating Akt/mTOR/p70s6k signaling pathways activation. The results suggest that EMG1 may be a novel biomarker for assessing prognosis and immune cell infiltration in LUAD.
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Adenocarcinoma de Pulmão , Proliferação de Células , Progressão da Doença , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/metabolismo , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Prognóstico , Masculino , Feminino , Animais , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Movimento Celular , Pessoa de Meia-Idade , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos Nus , Camundongos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Camundongos Endogâmicos BALB CRESUMO
The development of nanomedicines with simplified compositions and synergistic theranostic functionalities remains a great challenge. Herein, we develop a simple method to integrate both atovaquone (ATO, a mitochondrial inhibitor) and cisplatin within tannic acid (TA)-iron (Fe) networks coated with hyaluronic acid (HA) for targeted magnetic resonance (MR) imaging-guided chemo-chemodynamic synergistic therapy. The formed TFP@ATO-HA displayed good colloidal stability with a mean size of 95.5 nm, which could accumulate at tumor sites after circulation and be specifically taken up by metastatic 4T1 cells overexpressing CD44 receptors. In the tumor microenvironment, TFP@ATO-HA could release ATO/cisplatin and Fe3+ in a pH-responsive manner, deplete glutathione, and generate reactive oxygen species with endogenous H2O2 for chemodynamic therapy (CDT). Additionally, ATO could enhance chemotherapeutic efficacy by inhibiting mitochondrial respiration, relieving hypoxia, and amplifying the CDT effect by decreasing intracellular pH and elevating Fenton reaction efficiency. In vivo experiments demonstrated that TFP@ATO-HA could effectively inhibit tumor growth and suppress lung metastases without obvious systemic toxicity. Furthermore, TFP@ATO-HA exhibited a r1 relaxivity of 2.6 mM-1 s-1 and targeted MR imaging of 4T1 tumors. Dual drug-loaded metal-phenolic networks can be easily prepared and act as effective theranostic nanoplatforms for targeted MR imaging and synergistic chemo-chemodynamic therapy.
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Antineoplásicos , Neoplasias da Mama , Imageamento por Ressonância Magnética , Animais , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Taninos/química , Taninos/farmacologia , Camundongos Endogâmicos BALB C , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Cisplatino/farmacologia , Cisplatino/química , Proliferação de Células/efeitos dos fármacos , Ferro/química , Ensaios de Seleção de Medicamentos Antitumorais , Linhagem Celular Tumoral , Tamanho da PartículaRESUMO
The combination of ferroptosis, cuproptosis, and chemodynamic therapy (CDT) would be a potential strategy for tumor diagnosis and enhanced treatment. However, the therapeutic effect was severely limited by the lack of specific delivery of catalytic ions and the low Fenton reaction efficiency in tumor microenvironment (TME) with excess glutathione, limited acidity and insufficient endogenous hydrogen peroxide. In this work, p-carboxybenzenesulfonamide (BS), a carbonic anhydrase IX (CA IX) inhibitor, was modified on the surface of generation-5 poly(amidoamine) dendrimer to load copper peroxide nanoparticles, which were complexed with iron (Fe)-tannic acid (TF) networks for targeted magnetic resonance (MR) imaging and enhanced ferroptosis/cuproptosis/CDT by regulating TME. The formed CuO2@G5-BS/TF nanocomplexes with an average size of 39.4 nm could be specifically accumulated at tumor site and effectively internalized by metastatic 4T1 cells via the specific interaction between BS and CA IX over-expressed on tumor cells. Meanwhile, the inhibition of CA IX activity could not only decrease the intracellular pH to accelerate Fe3+/Cu2+ release, H2O2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity in TME. Moreover, the reduction of Fe3+/Cu2+ by intracellular glutathione (GSH) could further amplify ROS generation and enhance CDT efficacy, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy. In vivo experimental results demonstrated that CuO2@G5-BS/TF could provide better tumor MR imaging, effectively inhibit the growth and metastasis of 4T1 breast tumors, and be metabolized without significant systemic toxicity. Thus, CuO2@G5-BS/TF nanocomplexes provided a new approach for targeted MR imaging and enhanced ferroptosis/cuproptosis/CDT of triple-negative breast cancer. STATEMENT OF SIGNIFICANCE: Taking the advantage of dendrimer and metal-phenolic system, stable CuO2@G5-BS/TF nanocomplexes with an average size of 39.4 nm were synthesized to efficiently load Fe3+ and CuO2 nanoparticles for TNBC treatment and MR imaging. CuO2@G5-BS/TF nanocomplexes could target tumor cells overexpressing CAIX via the specific binding with BS, and the inhibition of CAIX activity could not only decrease the intracellular pH to accelerate Fe3+/Cu2+ release, H2O2 self-supply and Fenton reaction, but also suppress tumor metastasis by alleviating the extracellular acidity. The reduction of Fe3+/Cu2+ by intracellular GSH could further amplify ·OH generation, and the GSH depletion could in turn inhibit GPX-4 mediated antioxidant reaction to induce ferroptosis, resulting in effective therapeutic efficacy by enhanced ferroptosis/cuproptosis/CDT via tumor microenvironment regulation.
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Cobre , Dendrímeros , Ferroptose , Imageamento por Ressonância Magnética , Camundongos Endogâmicos BALB C , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Animais , Dendrímeros/química , Dendrímeros/farmacologia , Cobre/química , Cobre/farmacologia , Camundongos , Linhagem Celular Tumoral , Feminino , Nanopartículas/química , HumanosRESUMO
Background: Gout is the most common inflammatory arthritis in adults. Gout is an arthritic disease caused by the deposition of monosodium urate crystal (MSU) in the joints, which can lead to acute inflammation and damage adjacent tissue. Hyperuricemia is the main risk factor for MSU crystal deposition and gout. With the increasing burden of gout disease, the identification of potential biomarkers and novel targets for diagnosis is urgently needed. Methods: For the analysis of this subject paper, we downloaded the human gout data set GSE160170 and the gout mouse model data set GSE190138 from the GEO database. To obtain the differentially expressed genes (DEGs), we intersected the two data sets. Using the cytohubba algorithm, we identified the key genes and enriched them through GO and KEGG. The gene expression trends of three subgroups (normal control group, intermittent gout group and acute gout attack group) were analyzed by Series Test of Cluster (STC) analysis, and the key genes were screened out, and the diagnostic effect was verified by ROC curve. The expression of key genes in dorsal root nerve and spinal cord of gout mice was analyzed. Finally, the clinical samples of normal control group, hyperuricemia group, intermittent gout group and acute gout attack group were collected, and the expression of key genes at protein level was verified by ELISA. Result: We obtained 59 co-upregulated and 28 co-downregulated genes by comparing the DEGs between gout mouse model data set and human gout data set. 7 hub DEGs(IL1B, IL10, NLRP3, SOCS3, PTGS2) were screened out via Cytohubba algorithm. The results of both GO and KEGG enrichment analyses indicate that 7 hub genes play a significant role in regulating the inflammatory response, cytokine production in immune response, and the TNF signaling pathway. The most representative hub genes SOCS3 and PTGS2 were screened out by Series Test of Cluster, and ROC analysis results showed the AUC values were both up to 1.000. In addition, we found that PTGS2 expression was significantly elevated in the dorsal root ganglia and spinal cord in monosodium urate(MSU)-induced gout mouse model. The ELISA results revealed that the expression of SOCS3 and PTGS2 was notably higher in the acute gout attack and intermittent gout groups compared to the normal control group. This difference was statistically significant, indicating a clear distinction between the groups. Conclusion: Through cross-species comprehensive analysis and experimental verification, SOCS3 and PTGS2 were proved to be new biomarkers for diagnosing gout and predicting disease progression.
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Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.
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Resistencia a Medicamentos Antineoplásicos , Ferroptose , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Simulação de Acoplamento Molecular , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Animais , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , CamundongosRESUMO
INTRODUCTION: Cigarette smoking greatly promotes the progression and poor prognosis of colorectal cancer (CRC) patients, with the molecular mechanism still not fully clear. METHODS: In this study, CRC cells were exposed to tobacco specific nitrosamine 4(methylnitrosamino)1(3pyridyl) 1butanone (NNK), and the differentially expressed smoking-related genes were identified based on both NNK-induced CRC cells and a total of 763 CRC tissues from TCGA cohort. Cox regression analysis, ROC curve and Kaplan-Meier plot were used to establish the risk score model for CRC prognosis. Moreover, qRT-PCR, western blotting, colony formation, migration and invasion assays were performed to verify the core differentially expressed smoking-related gene and its molecular function in NNK-induced CRC progression. RESULTS: Results indicated NNK significantly enhanced CRC cell proliferation, migration and invasion. Moreover, a four-gene signature containing AKR1B10, CALB2, PLAC1, GNA15 was established as CRC prognosis marker. Among these four genes, AKR1B10 was further validated as the core gene, and its expression was significantly inhibited after NNK exposure in CRC cells. Results of gene enrichment analysis and western blotting suggested AKR1B10 might reduce the malignant progression of NNK-induced CRC cells through inhibiting Wnt signaling pathway by promoting E-Cadherin expression and inhibiting the expression of N-Cadherin, ß-Catenin, Vimentin and Snail. CONCLUSION: In conclusion, a new four smoking-related genes can be jointly used as prognostic markers for CRC. AKR1B10 served as a tumor suppressor, can be used as a potential target to inhibit NNK-induced CRC malignant progression through regulating Wnt signaling pathway. IMPLICATIONS: This study demonstrates tobacco-derived NNK dependence would promote the malignant progression of colorectal cancer through regulating the expressions of AKR1B10/Wnt signaling pathway. And a novel four-gene signature is established for the prognosis prediction of smoking CRC patients. These findings have important translational implications given the continued use of tobacco and the difficulty in smoking cessation worldwide, which can be applied to alleviate the adverse effects induced by tobacco dependence on colorectal cancer patients.
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Developing effective nanomedicines to cross the blood-brain barrier (BBB) for efficient glioma theranostics is still considered to be a challenging task. Here, we describe the development of macrophage membrane (MM)-coated nanoclusters (NCs) of ultrasmall iron oxide nanoparticles (USIO NPs) with dual pH- and reactive oxygen species (ROS)-responsivenesses for magnetic resonance (MR) imaging and chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Surface citrate-stabilized USIO NPs were solvothermally synthesized, sequentially modified with ethylenediamine and phenylboronic acid, and cross-linked with gossypol to form gossypol-USIO NCs (G-USIO NCs), which were further coated with MMs. The prepared MM-coated G-USIO NCs (G-USIO@MM NCs) with a mean size of 99.9 nm display tumor microenvironment (TME)-responsive gossypol and Fe release to promote intracellular ROS production and glutathione consumption. With the MM-mediated BBB crossing and glioma targeting, the G-USIO@MM NCs can specifically inhibit orthotopic glioma in vivo through the gossypol-mediated chemotherapy and Fe-mediated CDT. Meanwhile, USIO NPs can be dissociated from the NCs under the TME, thus allowing for effective T1-weighted glioma MR imaging. The developed G-USIO@MM NCs with simple components and drug as a crosslinker are promising for glioma theranostics, and may be extended to tackle other cancer types.
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Glioma , Macrófagos , Nanomedicina Teranóstica , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Animais , Camundongos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Nanopartículas Magnéticas de Óxido de Ferro/química , Imageamento por Ressonância Magnética , Humanos , Linhagem Celular Tumoral , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Espécies Reativas de Oxigênio/metabolismo , Membrana Celular/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacosRESUMO
Colorectal cancer (CRC) is a typical cancer that accounts for 10% of all new cancer cases annually and nearly 10% of all cancer deaths. Despite significant progress in current classical interventions for CRC, these traditional strategies could be invasive and with numerous adverse effects. The poor prognosis of CRC patients highlights the evident and pressing need for more efficient and targeted treatment. Novel strategies regarding mRNA vaccines for anti-tumor therapy have also been well-developed since the successful application for the prevention of COVID-19. mRNA vaccine technology won the 2023 Nobel Prize in Physiology or Medicine, signaling a new direction in human anti-cancer treatment: mRNA medicine. As a promising new immunotherapy in CRC and other multiple cancer treatments, the mRNA vaccine has higher specificity, better efficacy, and fewer side effects than traditional strategies. The present review outlines the basics of mRNA vaccines and their advantages over other vaccines and informs an available strategy for developing efficient mRNA vaccines for CRC precise treatment. In the future, more exploration of mRNA vaccines for CRC shall be attached, fostering innovation to address existing limitations.
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Vacinas Anticâncer , Neoplasias Colorretais , Imunoterapia , Vacinas de mRNA , Animais , Humanos , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Imunoterapia/métodos , Vacinas de mRNA/imunologia , Vacinas de mRNA/uso terapêuticoRESUMO
Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease treatment. This article provides an overview of the innovative and feasible application of neutrophils as drug carriers. It explores the mechanisms underlying neutrophil function, elucidates the mechanism of drug delivery mediated by neutrophil-hitchhiking, and discusses the potential applications of this strategy in the treatment of cancer, immune diseases, inflammatory diseases, and other medical conditions.
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Nanopartículas , Neoplasias , Humanos , Neutrófilos , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Nanopartículas/uso terapêuticoAssuntos
Artrite Reumatoide , Linfadenite Histiocítica Necrosante , Humanos , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Diagnóstico Diferencial , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/complicações , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Resultado do TratamentoRESUMO
Due to its stability and low cost, the tunnel-style sodium-manganese oxide (Na0.44MnO2) material is deemed a popular cathode choice for sodium-ion rechargeable batteries. However, the Jahn-Teller effect caused by Mn3+ in the material results in poor capacity and cycling stability. The purpose of this experimental study is to partially replace Mn3+ with Fe3+, in order to reduce the Jahn-Teller effect of the material during charging and discharging process. The results of Raman spectroscopy and X-ray photoelectron spectroscopy confirmed that the content of Mn3+ decreased after Fe3+ doping. Electrochemical studies show that the Na0.44Mn0.994Fe0.006O2 cathode has better rate performance (exhibits a reversible capacity of 87.9 mAh/g at 2 C) and cycle stability in sodium-ion batteries. The diffusion coefficient of sodium ions increases by Fe3+ doping. The excellent rate performance and capacity improvement are verified by density functional theory (DFT) calculation. After doping, the band gap decreases significantly, and the results show that the state density of O 2p increases near the Fermi level, which promotes the oxidation-reduction of oxygen. This work provides a straightforward approach to enhance the performance of Na0.44MnO2 nanorods, and this performance improvement has guiding significance for the design of other materials in the energy storage domain.
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Background: Mild cognitive impairment (MCI), an intermediate stage between normal aging and dementia, has emerged as a prominent research area in geriatric care due to its heightened propensity for progressing toward dementia. Sleep plays a pivotal role in cognitive function, with dyssomnias not only exacerbating cognitive and affective symptoms associated with neurodegenerative diseases but also contributing to disease progression. Aim: This bibliometric analysis investigates the global research on MCI with dyssomnias over the past two decades, aiming to discern key findings, research domains, and emerging trends in this field. Methods: In this study, a bibliometric analysis was conducted using the search terms "MCI" and "sleep". Data were extracted from the Web of Science Core Collection database, and visualization and collaborative analysis were performed using CiteSpace and VOSviewer. Results: This study encompassed 546 publications from 2003 to 2023. The publication volume and citation rate consistently increased over time. Neurosciences, Clinical Neurology, and Geriatrics Gerontology emerged as the top three research fields. The Journal of Alzheimer's Disease had the highest publication count, while Sleep Medicine received the most citations. USA, China, and Italy led in publication output. Collaborative clusters among authors and institutions were identified, but cooperation between clusters was limited. Active cocited reference clusters included "obstructive sleep apnea", "possible mediating pathways", and "isolated rapid eye movement sleep behaviour disorder". The top frequently mentioned keywords, besides "MCI", were "Alzheimer's disease", "dementia", "risk factor", and "Parkinson's Disease". Notable keyword clusters spanned circadian rhythm, Parkinson's disease, MCI, dementia with Lewy body, subjective cognitive impairment, Lewy body disease, Alzheimer's disease, and dietary patterns. Conclusion: The field of MCI with dyssomnias is rapidly expanding, encompassing a wide range of neurodegenerative disorders and sleep disturbances. Current research endeavors are primarily focused on elucidating the underlying pathogenesis, predicting disease progression, and developing innovative treatment strategies for individuals affected by MCI with dyssomnias.
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Doença de Alzheimer , Disfunção Cognitiva , Dissonias , Humanos , Idoso , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/complicações , Progressão da Doença , Bibliometria , Dissonias/complicaçõesRESUMO
Transmembrane protein 64 (TMEM64), a member of the family of transmembrane protein, is an α-helical membrane protein. Its precise role in various types of tumors, including glioma, is unclear. This study used immunohistochemical (IHC) staining, western blotting, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) techniques to show that TMEM64 expression was significantly higher in glioma cells and tissues compared to normal cells and tissues, respectively. Additionally, a correlation between high TMEM64 expression and higher grade as well as a worse prognosis was found. TMEM64 enhanced cell proliferation and tumorigenicity while inhibiting glioma cell apoptosis in vitro and in vivo, according to loss- and gain-of-function studies. Mechanistically, it was discovered that TMEM64 increased the malignant phenotype of gliomas by accelerating the translocation of ß-catenin from the cytoplasm to the nucleus, thereby activating the Wnt/ß-catenin signaling pathway. Stimulation with the Wnt/ß-catenin signaling pathway activator CHIR-99021 successfully reversed the malignant phenotype of glioma; however, these effects were inhibited upon TMEM64 silencing. Stimulation with the Wnt/ß-catenin signaling pathway inhibitor XAV-939 successfully rescued the malignant phenotype of glioma, which was promoted upon TMEM64 overexpression. Our results provide that TMEM64 as a novel prognostic biomarker and a potential treatment target for glioma.
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Glioma , Via de Sinalização Wnt , Humanos , Via de Sinalização Wnt/genética , Glioma/patologia , beta Catenina/genética , beta Catenina/metabolismo , Proliferação de Células , Fenótipo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
Long noncoding RNAs (lncRNAs) play crucial roles in tumor progression and are dysregulated in glioma. However, the functional roles of lncRNAs in glioma remain largely unknown. In this study, we utilized the TCGA (the Cancer Genome Atlas database) and GEPIA2 (Gene Expression Profiling Interactive Analysis 2) databases and observed the overexpression of lncRNA CHASERR in glioma tissues. We subsequently investigated this phenomenon in glioma cell lines. The effects of lncRNA CHASERR on glioma proliferation, migration, and invasion were analyzed using in vitro and in vivo experiments. Additionally, the regulatory mechanisms among PTEN/p-Akt/mTOR and Wnt/ß-catenin, lncRNA CHASERR, Micro-RNA-6893-3p(miR-6893-3p), and tripartite motif containing14 (TRIM14) were investigated via bioinformatics analyses, quantitative real-time PCR (qRT-PCR), western blot (WB), RNA immunoprecipitation (RIP), dual luciferase reporter assay, fluorescence in situ hybridization (FISH), and RNA sequencing assays. RIP and RT-qRCR were used to analyze the regulatory effect of N6-methyladenosine(m6A) on the aberrantly expressed lncRNA CHASERR. High lncRNA CHASERR expression was observed in glioma tissues and was associated with unfavorable prognosis in glioma patients. Further functional assays showed that lncRNA CHASERR regulates glioma growth and metastasis in vitro and in vivo. Mechanistically, lncRNA CHASERR sponged miR-6893-3p to upregulate TRIM14 expression, thereby facilitating glioma progression. Additionally, the activation of PTEN/p-Akt/mTOR and Wnt/ß-catenin pathways by lncRNA CHASERR, miR-6893-3p, and TRIM14 was found to regulate glioma progression. Moreover, the upregulation of lncRNA CHASERR was observed in response to N6-methyladenosine modification, which was facilitated by METTL3/YTHDF1-mediated RNA transcripts. This study elucidates the m6A/lncRNACHASERR/miR-6893-3p/TRIM14 pathway that contributes to glioma progression and underscores the potential of lncRNA CHASERR as a novel prognostic indicator and therapeutic target for glioma.
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Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Glioma , MicroRNAs , RNA Longo não Codificante , Proteínas com Motivo Tripartido , Regulação para Cima , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Glioma/genética , Glioma/patologia , Glioma/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação para Cima/genética , Linhagem Celular Tumoral , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Animais , Camundongos Nus , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Proliferação de Células/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Movimento Celular/genética , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Spinal cord injury (SCI) can lead to severe motor, sensory and autonomic nervous dysfunction, cause serious psychosomatic injury to patients. There is no effective treatment for SCI at present. In recent years, exciting evidence has been obtained in the application of cell-based therapy in basic research. These studies have revealed the fact that cells transplanted into the host can exert the pharmacological properties of treating and repairing SCI. Olfactory ensheathing cells (OECs) are a kind of special glial cells. The application value of OECs in the study of SCI lies in their unique biological characteristics, that is, they can survive and renew for life, give full play to neuroprotection, immune regulation, promoting axonal regeneration and myelination formation. The function of producing secretory group and improving microenvironment. This provides an irreplaceable treatment strategy for the repair of SCI. At present, some researchers have explored the possibility of treatment of OECs in clinical trials of SCI. Although OECs transplantation shows excellent safety and effectiveness in animal models, there is still lack of sufficient evidence to prove the effectiveness of their clinical application in clinical trials. There has been an obvious stagnation in the transformation of OECs transplantation into routine clinical practice, and clinical trials of cell therapy in this field are still facing major challenges and many problems that need to be solved. Therefore, this paper summarized and analyzed the clinical trials of OECs transplantation in the treatment of SCI, and discussed the problems and challenges of OECs transplantation in clinical trials.
Assuntos
Traumatismos da Medula Espinal , Animais , Humanos , Traumatismos da Medula Espinal/terapia , Transplante de Células , Neuroglia , Bulbo Olfatório , Regeneração Nervosa , Medula EspinalRESUMO
Based on the online monitoring data of volatile organic compounds(VOCs) and ozone(O3) in Liaocheng in June 2021, the concentration levels, compositional characteristics, daily variation characteristics, and ozone formation potential(OFP) of VOCs on polluted days and clean days were systematically analyzed. Potential source areas of VOCs were identified by the potential source contribution function(PSCF) and concentration-weighted trajectory(CWT). The sources of VOCs in Liaocheng were analyzed using the characteristic species ratio and positive matrix factorization(PMF). The results showed that the hourly mean values of VOCs concentrations on polluted days and clean days in Liaocheng in June 2021 were(115.38±59.12) µg·m-3 and(88.10±33.04) µg·m-3, respectively, and the concentration levels of VOCs in each category showed that oxygenated volatile organic compounds(OVOCs)>alkanes>halogenated hydrocarbons>aromatic hydrocarbons>alkenes>alkynes>organosulfur. VOCs species with large differences in concentrations between polluted and clean days were among the top ten species of the hourly mean VOCs concentrations. The daily trends of concentrations of total VOCs, alkanes, alkynes, aromatic hydrocarbons, halogenated hydrocarbons, and organosulfur showed that the daytime concentrations were lower than the nighttime concentrations, and the daily changes in OVOCs concentrations showed the characteristics of high in the daytime and low at nighttime. The OFP was 285.29 µg·m-3 on polluted days and 212.00 µg·m-3 on clean days, and OVOCs, alkenes, and aromatic hydrocarbons contributed significantly to ozone formation. The PSCF and CWT results found that the potential source areas of VOCs in Liaocheng were concentrated in the northern and northeastern part of Dongchangfu District and the central and southwestern part of Chiping District. The results of the characteristic species ratio indicated that the VOCs in Liaocheng might have been more from coal combustion, gasoline volatilization, and motor vehicle exhaust. The results of PMF showed that industrial emission sources(30.57%), motor vehicle exhaust and oil and gas volatilization sources(19.44%), combustion sources(17.23%), air aging and secondary generation sources(13.69%), solvent usage sources(12.75%), and natural sources(6.32%) were the main sources of VOCs in Liaocheng.
RESUMO
This study examined the associations of long-term exposure to ambient fine particulate matter (PM2.5) compositions/ozone with methylation of peripheral brain-derived neurotrophic factor (BDNF) promoters. A total of 101 participants were recruited from a cohort in Shijiazhuang, Hebei province, China. They underwent baseline and follow-up surveys in 2011 and 2015. DNA methylation levels were detected by bisulfite-PCR amplification and pyrosequencing. Participants' three-year average levels of PM2.5 compositions and ozone were estimated. Bayesian kernel machine regression (BKMR) models were used to examine the joint effects of pollutants on methylation levels. Exposure to PM2.5 compositions and ozone mixtures at the 75th percentile was associated with increased methylation levels at CpG2 of BDNF promoter (203%, 95% CI: 89, 316) than the lowest level of exposure, and sulfate dominated the effect in the BKMR models.Our findings provide clues to the epigenetic mechanisms for the associations of PM2.5 compositions and ozone with BDNF.
RESUMO
The eukaryotic genome is organized to enable the precise regulation of gene expression. This organization is established as the embryo transitions from a fertilized gamete to a totipotent zygote. To understand the factors and processes that drive genomic organization, we focused on the pioneer factor GAGA factor (GAF) that is required for early development in Drosophila. GAF transcriptionally activates the zygotic genome and is localized to subnuclear foci. This non-uniform distribution is driven by binding to highly abundant GA repeats. At GA repeats, GAF is necessary to form heterochromatin and silence transcription. Thus, GAF is required to establish both active and silent regions. We propose that foci formation enables GAF to have opposing transcriptional roles within a single nucleus. Our data support a model in which the subnuclear concentration of transcription factors acts to organize the nucleus into functionally distinct domains essential for the robust regulation of gene expression.