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Sarcomatoid renal cell carcinoma typically signifies an exceptionally poor prognosis, with patients rarely surviving beyond one year. An 83-year-old male presented to our hospital with complaints of headache and left-sided limb weakness. Computed tomography (CT) scans of the head and lungs disclosed a mass within the right temporal lobe, accompanied by peritumoral edema in the right cerebral hemisphere. Brain magnetic resonance imaging (MRI) with contrast enhancement and diffusion-weighted imaging (DWI) delineated a mass in the right temporal lobe, measuring 3 × 3 × 3 cm. He underwent cytoreductive surgery successively in the neurosurgery and urology departments. Despite experiencing postoperative tumour recurrence, the patient has lived close to four years to date. This case report illustrates that cytoreductive surgery combined with systemic pharmacotherapy can still confer significant survival benefits for elderly patients.
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Neoplasias Encefálicas , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Masculino , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/diagnóstico por imagem , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos de Citorredução/métodos , Tomografia Computadorizada por Raios X , Imageamento por Ressonância Magnética , Lobo Temporal/patologia , Lobo Temporal/diagnóstico por imagemRESUMO
The unique properties of metamaterials are determined by the configuration and spatial arrangement of artificially designed unit structures. However, the configuration and mechanical properties of conventional metamaterials are challenging to reverse and adjust. Based on curved beams, two types of novel three-dimensional (3D) multi-stable metamaterials with reconfigurable deformation and tunable mechanical properties are designed and fabricated using a four-dimensional (4D) printing method. The effects of temperature and curved-beam thickness on the force-displacement curves and multi-stable snapping sequence of the 3D multi-stable metamaterials are investigated by finite-element analysis (FEA) and experiments. In addition, based on the designed four-branch multi-stable metamaterials, three- and six-branched multi-stable structures are designed by changing the number of curved-beam branches. It is shown that, owing to shape memory effects, the 3D multi-stable metamaterials can realize mechanical programmability, and the multi-stable deformation sequence can be precisely regulated by varying the temperature and curved-beam thickness. These 4D-printed multi-stable metamaterials provide valuable contributions to the design of programmable multi-stable metamaterials and their applications in soft robots and intelligent structures. This article is part of the theme issue 'Current developments in elastic and acoustic metamaterials science (Part 1)'.
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Camellia seed oil (CO) has high nutritional value and multiple bioactivities. However, the specific anti-fatigue characteristics and the implied mechanism of CO have not yet been fully elucidated. Throughout this investigation, male C57BL/6J mice, aged 8 weeks, underwent exhaustive exercise with or without CO pretreatment (2, 4, and 6 mL/kg BW) for 28 days. CO could extend the rota-rod and running time, reduce blood urea nitrogen levels and serum lactic acid, and increase muscle and hepatic glycogen, adenosine triphosphate, and anti-oxidative indicators. Additionally, CO could upregulate the mRNA and Nrf2 protein expression levels, as well as enhance the levels of its downstream antioxidant enzymes and induce the myofiber-type transformation from fast to slow and attenuate the gut mechanical barrier. Moreover, CO could ameliorate gut dysbiosis by reducing Firmicutes to Bacteroidetes ratio at the phylum level, increasing the percentage of Alistipes, Alloprevotella, Lactobacillus, and Muribaculaceae, and decreasing the proportion of Dubosiella at the genus level. In addition, specific bacterial taxa, which were altered by CO, showed a significant correlation with partial fatigue-related parameters. These findings suggest that CO may alleviate fatigue by regulating antioxidant capacity, muscle fiber transformation, gut mechanical barrier, and gut microbial composition in mice. PRACTICAL APPLICATION: Our study revealed that camellia seed oil (CO) could ameliorate exercise-induced fatigue in mice by modulating antioxidant capacity, muscle fiber, and gut microbial composition in mice. Our results promote the application of CO as an anti-fatigue functional food that targets oxidative stress, myofiber-type transformation, and microbial community.
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Camellia , Microbioma Gastrointestinal , Camundongos , Masculino , Animais , Antioxidantes/farmacologia , Microbioma Gastrointestinal/genética , Camundongos Endogâmicos C57BL , Fadiga/tratamento farmacológico , Fadiga/metabolismo , Óleos de Plantas/farmacologia , Bacteroidetes , Firmicutes , Fibras Musculares EsqueléticasRESUMO
BACKGROUND: Down syndrome (DS), which is characterized by various malfunctions, is the most common chromosomal disorder. As the DS population continues to grow and most of those with DS live beyond puberty, early-onset health problems have become apparent. However, the cellular landscape and molecular alterations have not been thoroughly studied. METHODS: This study utilized single-cell resolution techniques to examine DS in humans and mice, spanning seven distinct organs. A total of 71 934 mouse and 98 207 human cells were analyzed to uncover the molecular alterations occurring in different cell types and organs related to DS, specifically starting from the fetal stage. Additionally, SA-ß-Gal staining, western blot, and histological study were employed to verify the alterations. RESULTS: In this study, we firstly established the transcriptomic profile of the mammalian DS, deciphering the cellular map and molecular mechanism. Our analysis indicated that DS cells across various types and organs experienced senescence stresses from as early as the fetal stage. This was marked by elevated SA-ß-Gal activity, overexpression of cell cycle inhibitors, augmented inflammatory responses, and a loss of cellular identity. Furthermore, we found evidence of mitochondrial disturbance, an increase in ribosomal protein transcription, and heightened apoptosis in fetal DS cells. This investigation also unearthed a regulatory network driven by an HSA21 gene, which leads to genome-wide expression changes. CONCLUSION: The findings from this study offer significant insights into the molecular alterations that occur in DS, shedding light on the pathological processes underlying this disorder. These results can potentially guide future research and treatment development for DS.
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Síndrome de Down , Humanos , Camundongos , Animais , Síndrome de Down/genética , Síndrome de Down/metabolismo , Síndrome de Down/patologia , MamíferosRESUMO
Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.
How many cell types are there in nature? How do they change during the life cycle? These are two fundamental questions that researchers have been trying to understand in the area of biology. In this study, single-cell mRNA sequencing data were used to profile over 2.6 million individual cells from mice, zebrafish and Drosophila at different life stages, 1.3 million of which were newly collected. The comprehensive datasets allow investigators to construct a cross-species cell landscape that helps to reveal the conservation and diversity of cell taxonomies at genetic and regulatory levels. The resources in this study are assembled into a publicly available website at http://bis.zju.edu.cn/cellatlas/.
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Análise de Célula Única , Animais , Camundongos , Análise de Sequência de RNA , Peixe-Zebra/crescimento & desenvolvimento , Drosophila/crescimento & desenvolvimentoRESUMO
Polysaccharides from Enteromorpha prolifera (EP) possess multiple biological activities, while the role of EP in hypercholesterolemia and its relationship with the gut microbiota have not been elucidated. To address this issue, fifty male C57BL/6J mice were randomly subjected to a basal diet and a high-fat and high-cholesterol diet, and 3 treatment groups were fed an HFHC diet supplemented with different dosages of EP (100, 200 and 300 mg kg-1 day-1) for 12 weeks. Here we show that EP intervention lowered serum concentrations of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and inhibited hepatic cholesterol deposition. EP intervention also upregulated the gene expression related to the hepatic cholesterol uptake and bile acid synthetic pathway. Apart from that, EP altered the gut microbiota, pre-dominantly increasing microbes associated with bile acid metabolism, such as norank_f_ Muribaculaceae. Moreover, bile acid profile analysis revealed that EP could alter the fecal bile acid profile and reduce fecal conjugated bile acids. Further correlation analysis indicated the negative correlation of Bacteroides, norank_f_ Muribaculaceae and Ileibacterium abundance with the levels of fecal conjugated bile acids and serum TC and LDL-C, while the abundance of Proteobacteria and Lachnoclosteridium showed a positive association with conjugated bile acids and serum TC. To sum up, the above findings revealed that EP may alleviate hypercholesterolemia and regulate cholesterol metabolism in ways that promote a favorable fecal microbiota composition and modulate bile acid metabolism.
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Microbioma Gastrointestinal , Hipercolesterolemia , Masculino , Camundongos , Animais , Microbioma Gastrointestinal/fisiologia , LDL-Colesterol/metabolismo , Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos , Ácidos e Sais Biliares/metabolismo , Polissacarídeos , Fígado/metabolismoRESUMO
The stable genetic transformation of soybean is time-consuming and inefficient. As a simple and practical alternative method, hairy root transformation mediated by Agrobacterium rhizogenes is widely applied in studying root-specific processes, nodulation, biochemical and molecular functions of genes of interest, gene editing efficiency of CRISPR/Cas9, and biological reactors and producers. Therefore, many laboratories have developed unique protocols to obtain hairy roots in composite plants composed of transgenic roots and wild-type shoots. However, these protocols still suffer from the shortcomings of low efficiency and time, space, and cost consumption. To address this issue, we developed a new protocol efficient regeneration and transformation of hairy roots (eR&T) in soybean, by integrating and optimizing the main current methods to achieve high efficiency in both hairy root regeneration and transformation within a shorter period and using less space. By this eR&T method, we obtained 100% regeneration of hairy roots for all explants, with an average 63.7% of transformation frequency, which promoted the simultaneous and comparative analysis of the function of several genes. The eR&T was experimentally verified Promoter:GUS reporters, protein subcellular localization, and CRISPR/Cas9 gene editing experiments. Employing this approach, we identified several novel potential regulators of nodulation, and nucleoporins of the Nup107-160 sub-complex, which showed development-dependent and tissue-dependent expression patterns, indicating their important roles in nodulation in soybean. Thus, the new eR&T method is an efficient and economical approach for investigating not only root and nodule biology, but also gene function.
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Glycine max , Complexo de Proteínas Formadoras de Poros Nucleares , Glycine max/genética , Transformação Genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Plantas Geneticamente Modificadas/genética , Raízes de Plantas/genética , Agrobacterium/genética , BiologiaRESUMO
The tris(pyridin-4-yl)amine ligand was found to exhibit a radical-actuated coloration phenomenon, and a novel copper-based color-changeable metal-organic framework (MOF) was synthesized via this photoactive ligand. After light irradiation, the photogenerated stable radicals in this framework induced increasing amplitude of magnetization (32%) at room temperature, being the largest enhancement among radical-based photochromic systems.
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The rapid development of high-throughput single-cell RNA sequencing technology offers a good opportunity to dissect cell heterogeneity of animals. A large number of organism-wide single-cell atlases have been constructed for vertebrates such as Homo sapiens, Macaca fascicularis, Mus musculus and Danio rerio. However, an intermediate taxon that links mammals to vertebrates of more ancient origin is still lacking. Here, we construct the first Xenopus cell landscape to date, including larval and adult organs. Common cell lineage-specific transcription factors have been identified in vertebrates, including fish, amphibians and mammals. The comparison of larval and adult erythrocytes identifies stage-specific hemoglobin subtypes, as well as a common type of cluster containing both larval and adult hemoglobin, mainly at NF59. In addition, cell lineages originating from all three layers exhibits both antigen processing and presentation during metamorphosis, indicating a common regulatory mechanism during metamorphosis. Overall, our study provides a large-scale resource for research on Xenopus metamorphosis and adult organs.
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Eritrócitos , Metamorfose Biológica , Animais , Hemoglobinas/metabolismo , Larva/metabolismo , Mamíferos , Camundongos , Xenopus laevis/genética , Peixe-ZebraRESUMO
Waddington's epigenetic landscape is a metaphor frequently used to illustrate cell differentiation. Recent advances in single-cell genomics are altering our understanding of the Waddington landscape, yet the molecular mechanisms of cell-fate decisions remain poorly understood. We constructed a cell landscape of mouse lineage differentiation during development at the single-cell level and described both lineage-common and lineage-specific regulatory programs during cell-type maturation. We also found lineage-common regulatory programs that are broadly active during the development of invertebrates and vertebrates. In particular, we identified Xbp1 as an evolutionarily conserved regulator of cell-fate determinations across different species. We demonstrated that Xbp1 transcriptional regulation is important for the stabilization of the gene-regulatory networks for a wide range of mouse cell types. Our results offer genetic and molecular insights into cellular gene-regulatory programs and will serve as a basis for further advancing the understanding of cell-fate decisions.
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Epigênese Genética , Modelos Genéticos , Animais , Diferenciação Celular/genética , Linhagem da Célula/genética , Epigenômica , Redes Reguladoras de Genes/genética , CamundongosRESUMO
Cell types are the basic building units of multicellular life, with extensive diversities. The evolution of cell types is a crucial layer of comparative cell biology but is thus far not comprehensively studied. We define a compendium of cell atlases using single-cell RNA-seq (scRNA-seq) data from seven animal species and construct a cross-species cell-type evolutionary hierarchy. We present a roadmap for the origin and diversity of major cell categories and find that muscle and neuron cells are conserved cell types. Furthermore, we identify a cross-species transcription factor (TF) repertoire that specifies major cell categories. Overall, our study reveals conservation and divergence of cell types during animal evolution, which will further expand the landscape of comparative genomics.
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Linhagem da Célula , Evolução Molecular , Perfilação da Expressão Gênica , Células Musculares/metabolismo , Neurônios/metabolismo , Análise de Célula Única , Fatores de Transcrição/genética , Transcriptoma , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Ciona intestinalis/genética , Ciona intestinalis/metabolismo , Bases de Dados Genéticas , Regulação da Expressão Gênica no Desenvolvimento , Genômica , Humanos , Camundongos , Células Musculares/classificação , Neurônios/classificação , Especificidade da Espécie , Fatores de Transcrição/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
BACKGROUND: Acute myeloid leukemia (AML) is a fatal hematopoietic malignancy and has a prognosis that varies with its genetic complexity. However, there has been no appropriate integrative analysis on the hierarchy of different AML subtypes. METHODS: Using Microwell-seq, a high-throughput single-cell mRNA sequencing platform, we analyzed the cellular hierarchy of bone marrow samples from 40 patients and 3 healthy donors. We also used single-cell single-molecule real-time (SMRT) sequencing to investigate the clonal heterogeneity of AML cells. RESULTS: From the integrative analysis of 191727 AML cells, we established a single-cell AML landscape and identified an AML progenitor cell cluster with novel AML markers. Patients with ribosomal protein high progenitor cells had a low remission rate. We deduced two types of AML with diverse clinical outcomes. We traced mitochondrial mutations in the AML landscape by combining Microwell-seq with SMRT sequencing. We propose the existence of a phenotypic "cancer attractor" that might help to define a common phenotype for AML progenitor cells. Finally, we explored the potential drug targets by making comparisons between the AML landscape and the Human Cell Landscape. CONCLUSIONS: We identified a key AML progenitor cell cluster. A high ribosomal protein gene level indicates the poor prognosis. We deduced two types of AML and explored the potential drug targets. Our results suggest the existence of a cancer attractor.
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Exame de Medula Óssea/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia Mieloide Aguda/patologia , Análise de Célula Única/métodos , Linhagem da Célula , Células Clonais , Sistemas Computacionais , DNA Mitocondrial/genética , DNA de Neoplasias/genética , Regulação Leucêmica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Leucemia Monocítica Aguda/genética , Leucemia Monocítica Aguda/patologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/química , Células-Tronco Neoplásicas/patologia , Fenótipo , Prognóstico , RNA Mensageiro/análise , RNA Neoplásico/análise , Recidiva , Proteínas Ribossômicas/genética , Fatores de Transcrição/fisiologiaRESUMO
A three-branch viscoelastic model based on fractional derivatives is proposed for the viscoelastic behaviours of solid propellants. The simulation results show a satisfactory agreement with the stress relaxation modulus and complex modulus of solid propellants. As a comparison, the static modulus is also characterized by traditional viscoelastic model with integer-order derivatives. Results show that the application of the fractional derivatives to the viscoelastic constitutive model can effectively reduce the number of the required parameters while giving an accurate prediction of viscoelastic behaviours of solid propellants. Moreover, a simple and effective direct search method based on simulated annealing and Powell's mothed is proposed for the data fitting. This article is part of the theme issue 'Advanced materials modelling via fractional calculus: challenges and perspectives'.
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Single-cell analysis is a valuable tool for dissecting cellular heterogeneity in complex systems1. However, a comprehensive single-cell atlas has not been achieved for humans. Here we use single-cell mRNA sequencing to determine the cell-type composition of all major human organs and construct a scheme for the human cell landscape (HCL). We have uncovered a single-cell hierarchy for many tissues that have not been well characterized. We established a 'single-cell HCL analysis' pipeline that helps to define human cell identity. Finally, we performed a single-cell comparative analysis of landscapes from human and mouse to identify conserved genetic networks. We found that stem and progenitor cells exhibit strong transcriptomic stochasticity, whereas differentiated cells are more distinct. Our results provide a useful resource for the study of human biology.
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Células/citologia , Células/metabolismo , Análise de Célula Única/métodos , Adulto , Animais , Povo Asiático , Diferenciação Celular , Linhagem Celular , Separação Celular , China , Bases de Dados Factuais , Corpos Embrioides/citologia , Corpos Embrioides/metabolismo , Etnicidade , Feto/citologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunidade , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Camundongos , Especificidade de Órgãos , RNA Mensageiro/análise , RNA Mensageiro/genética , Análise de Sequência de RNA , Análise de Célula Única/instrumentação , Processos EstocásticosRESUMO
PURPOSE: To determine the value of the polymerase chain reaction analysis of aqueous humor specimens as a tool to diagnose cytomegalovirus retinitis in AIDS patients. METHODS: In all, 63 AIDS patients were evaluated in this study. They were sorted into two diagnostic categories: eyes with active cytomegalovirus retinitis and eyes without active cytomegalovirus retinitis. The aqueous humor and blood samples were collected and analyzed by polymerase chain reaction. RESULTS: A total of 49 patients had active cytomegalovirus retinitis (77.8%) and 14 patients had inactive cytomegalovirus retinitis or normal fundus (22.2%). The mean average of patients was 39 years (range: 22-59). The majority of patients were male (90.5%). Cytomegalovirus DNA was detected in 46 and 7 of 49 aqueous and blood samples, respectively, from AIDS patients with active cytomegalovirus retinitis. We did not detect cytomegalovirus DNA in any of the eyes without active cytomegalovirus retinitis. The sensitivity of polymerase chain reaction in the detection of cytomegalovirus in aqueous humor and blood samples was 93.5% and 14.3%, respectively. CONCLUSIONS: The polymerase chain reaction analysis is a safe, highly specific, and sensitive method to diagnose cytomegalovirus retinitis.
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Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Humor Aquoso/virologia , Retinite por Citomegalovirus/diagnóstico , Citomegalovirus/genética , DNA Viral/genética , Reação em Cadeia da Polimerase , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Sangue/virologia , Contagem de Linfócito CD4 , Retinite por Citomegalovirus/sangue , Retinite por Citomegalovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto JovemRESUMO
For decades, people have been trying to define cell type with the combination of expressed genes. The choice of the limited number of genes for the classification limits the precision of this system. Here, we build a "single-cell Mouse Cell Atlas (scMCA) analysis" pipeline based on scRNA-seq datasets covering all mouse cell types. We build the scMCA reference and then use the tool "scMCA" to match single-cell digital expression to its closest cell type.
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Expressão Gênica/genética , Animais , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Camundongos , RNA/genética , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos , SoftwareRESUMO
Identification of effective culture conditions to maintain and possibly expand human HSPCs in vitro is an important goal. Recent advances highlight the efficacy of chemicals in maintaining and converting cell fates. We screened 186 chemicals and found that a combination of CHIR-99021, Forskolin and OAC1 (CFO) maintained human CD34-positive cells in vitro. Efficiency of the culture system was characterized using flow cytometry for CD34-positive cells, a colony-forming assay and xeno-transplants. We found that human CD34-positive cells treated with this combination had enhanced expression of human HSPC markers and increased haematopoietic re-populating ability in immune-deficient mice. Single-cell RNA-seq analyses showed that the in vitro cultured human CD34-positive cells were heterogeneous. We found that CFO supports maintenance of human CD34-positive cells by activating HOXA9, GATA2 and AKT-cAMP signaling pathway. These data have implications in therapies requiring maintenance and/or expansion of human HSPCs.