RESUMO
Rapid urbanization has highlighted ecological problems in the metropolitan area, with increasing landscape fragmentation and severe threats to ecosystem health (EH). Studying the spatio-temporal coupled relationship between landscape pattern and EH and its response to urbanization in the Fuzhou metropolitan area (FMA) can provide scientific reference for its long-term development planning. We examined the coupled relationship between landscape pattern and EH and its driving mechanism in the FMA at grid and township scales to address the gap. The results show that landscape heterogeneity, diversity, and dispersion are gradually increasing, and EH is rising progressively in the FMA from 2000 to 2020. The spatial distribution of landscape pattern indices and EH indicators showed a "high in the south and low in the north" trend. During the study period, the coupled relationship between landscape patterns and EH was increasingly powerful but with remarkable spatial heterogeneity. The study also found an inverted U-shaped relationship between urbanization and coupled relationships. Ecological landscapes' heterogeneity, diversity, and connectivity in low-urbanization areas are conducive to EH. The opposite is true for high-urbanization areas. This study provides a valuable reference for optimizing landscape planning and ecological management in metropolitan areas.
Assuntos
Ecossistema , Urbanização , Conservação dos Recursos NaturaisRESUMO
Since the emergence of the term "materia medica", scholars have proposed different opinions on its concept. This term has been used to refer to traditional Chinese medicines, or medical books, or traditional pharmacology. Due to the differences in the concept of materia medica, scholars also have controversies about the concept of herbalism. Herbalism is usually understood as traditional Chinese pharmacology. After years of evolution, the term "herbalism" has now possessed the characteristics of an independent discipline, which can be defined as an applied basic discipline that comprehensively utilizes traditional and modern technological methods to study the formation, development, and changes of traditional pharmacology and reveal the basic theories and application laws of traditional medicine. At present, the research content of herbalism mainly includes three aspects: materia medica history, materia medica literature, and traditional pharmacology. This study explores the disciplinary concepts and main research content of herbalism based on a systematic review of the literature about the concepts of materia medica and herbalism, with the aim of attracting more attention to promote the establishment and development of the discipline of herbalism.
Assuntos
Medicamentos de Ervas Chinesas , Materia Medica , China , Medicina Herbária , Medicina Tradicional Chinesa , TecnologiaRESUMO
Live cell dissection of microRNA activities is crucial for basic and translational medicine, but current hybridization-based strategies may fail to dissect surrounding-dependent activities. Here, we develop a genetically encoded miRNA-induced light-up RNA amplifier (iLAMP) that enables fast-activated, signal-amplified, fluorogenic imaging of miRNA activities in live cells. iLAMP responds to miRNA targets in the mode of "activation upon cleavage", in which the light-up RNA aptamer restores its fluorescence rapidly upon cleavage by the RNA-induced silencing complex. We demonstrate that iLAMP affords substantial signal amplification of â¼100-fold and high specificity in single nucleotide discrimination because of the miRNA-mediated cyclic cleavage. Combined with a Mango RNA aptamer reference module and a pseudoknot terminal stabilizer, iLAMP is shown for quantitative ratiometric imaging and dynamic monitoring of miRNA activities under exogenous stimulations. iLAMP is featured by a modular "plug and play" design and can be readily adapted to the detection of other miRNAs, highlighting its potential in tracking cell differentiation and screening miRNA therapeutics.
Assuntos
Aptâmeros de Nucleotídeos , MicroRNAs , MicroRNAs/genética , Aptâmeros de Nucleotídeos/genética , Hibridização de Ácido NucleicoRESUMO
MicroRNAs (miRNAs) play essential roles in regulating gene expression and cell fate. However, it remains a great challenge to image miRNAs with high accuracy in living cells. Here, we report a novel genetically encoded dual-color light-up RNA sensor for ratiometric imaging of miRNAs using Mango as an internal reference and SRB2 as the sensor module. This genetically encoded sensor is designed by expressing a splittable fusion of the internal reference and sensor module under a single promoter. This design strategy allows synchronous expression of the two modules with negligible interference. Live cell imaging studies reveal that the genetically encoded ratiometric RNA sensor responds specifically to mir-224. Moreover, the sensor-to-Mango fluorescence ratios are linearly correlated with the concentrations of mir-224, confirming their capability of determining mir-224 concentrations in living cells. Our genetically encoded light-up RNA sensor also enables ratiometric imaging of mir-224 in different cell lines. This strategy could provide a versatile approach for ratiometric imaging of intracellular RNAs, affording powerful tools for interrogating RNA functions and abundance in living cells.
Assuntos
Proteínas Luminescentes/genética , MicroRNAs/química , Imagem Óptica/métodos , RNA/química , Técnicas Biossensoriais , Linhagem Celular , Engenharia Genética/métodos , Humanos , Imagem Molecular/métodosRESUMO
Investigating the multimolecule patterns in living cells is of vital importance for clinical and biomedical studies. Herein, we reported for the first time the engineering of gold nanoflares as smart automata to implement computing-based diagnosis in living mammalian cells. Defining the logic combinations of miR122 and miR21 as the detection patterns, the corresponding OR and AND diagnostic automata were designed. The results showed that they could recognize the correct patterns rapidly and sensitively. The automata could enter cells via self-delivery and have good biocompatibility. They enabled accurate diagnosis on miRNA signatures in different cell lines and differentiation of fluctuations in the same cell line at single cell resolution. Moreover, the automata afforded an innovative diagnostic mode. It simplified the complicated process of detecting, data-collecting, computing, and evaluating. The direct diagnosing result ("1" or "0") was exported according to the embedded computation code. It highlighted the new possibility of using smart automata for intelligent diagnostics and cancer therapy at single cell resolution.
Assuntos
Computadores Moleculares , Nanopartículas Metálicas/química , MicroRNAs/análise , Neoplasias/diagnóstico , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Ouro/química , Células HEK293 , Humanos , Lógica , MicroRNAs/genética , Microscopia Confocal , Microscopia de Fluorescência , Hibridização de Ácido Nucleico , Oligonucleotídeos/química , Oligonucleotídeos/genética , Rodaminas/químicaRESUMO
DNA molecular probes have emerged as a powerful tool for RNA imaging. Hurdles in cell-specific delivery and other issues such as insufficient stability, limited sensitivity, or slow reaction kinetics, however, hinder the further application of DNA molecular probes in vivo. Herein, we report an aptamer-tethered DNA polymer for cell-specific transportation and amplified imaging of RNA in vivo via a DNA cascade reaction. DNA polymers are constructed through an initiator-triggered hybridization chain reaction using two functional DNA monomers. The prepared DNA polymers show low cytotoxicity and good stability against nuclease degradation and enable cell-specific transportation of DNA circuits via aptamer-receptor binding. Moreover, assembling the reactants of hairpins C1 and C2 on the DNA polymers accelerates the response kinetics and improves the sensitivity of the cascade reaction. We also show that the DNA polymers enable efficient imaging of microRNA-21 in live cells and in vivo via intravenous injection. The DNA polymers provide a valuable platform for targeted and amplified RNA imaging in vivo, which holds great implications for early clinical diagnosis and therapy.
Assuntos
Sondas de DNA/metabolismo , MicroRNAs/metabolismo , Imagem Molecular/métodos , Aptâmeros de Nucleotídeos/metabolismo , Linhagem Celular , Sobrevivência Celular , Sondas de DNA/química , HumanosRESUMO
CRISPR-dCas9 systems that are precisely activated by cell-specific information facilitate the development of smart sensors or therapeutic strategies. We report the development of an activatable dCas9 transcriptional circuit that enables sensing and silencing of mRNA in living cells using hybridization-mediated structure switching for gRNA activation. The gRNA is designed with the spacer sequence blocked by a hairpin structure, and mRNA hybridization induces gRNA structure switching and activates the transcription of reporter RNA. An mRNA sensor developed using a light-up RNA reporter shows high sensitivity and fast-response imaging of survivin mRNA in cells under drug treatments and different cell lines. Furthermore, a feedback circuit is engineered by incorporating a small hairpin RNA in the reporter RNA, demonstrating a smart strategy for dynamic sensing and silencing of survivin with induced tumor cell apoptosis. This circuit illustrates a broadly applicable platform for the development of cell-specific sensing and therapeutic strategies.
Assuntos
Sistemas CRISPR-Cas/genética , RNA Guia de Cinetoplastídeos/metabolismo , RNA Mensageiro/metabolismo , Apoptose , Técnicas Biossensoriais , Inativação Gênica , Células HeLa , Humanos , Microscopia Confocal , Hibridização de Ácido Nucleico , Plasmídeos/genética , Plasmídeos/metabolismo , RNA Mensageiro/análise , RNA Interferente Pequeno/metabolismo , Survivina/genética , Ativação TranscricionalRESUMO
One of the most common protein tyrosine phosphatase-2 (SHP2) mutations in Noonan syndrome is the N308D mutation, and it increases the activity of the protein. However, the molecular basis of the activation of N308D mutation on SHP2 conformations is poorly understood. Here, molecular dynamic simulations were performed on SHP2 and SHP2-N308D to explore the effect of N308D mutation on SHP2 cause gain of function activity, respectively. The principal component analysis, dynamic cross-correlation map, secondary structure analysis, residue interaction networks, and solvent accessible surface area analysis suggested that the N308D mutation distorted the residues interactions network between the allosteric site (residue Gly244-Gly246) and C-SH2 domain, including the hydrogen bond formation and the binding energy. Meanwhile, the activity of catalytic site (residue Gly503-Val505) located in the Q-loop in mutant increased due to this region's high fluctuations. Therefore, the substrate had more chances to access to the catalytic activity site of the precision time protocol domain of SHP2-N308D, which was easy to be exposed. In addition, we had speculated that the Lys244 located in the allosteric site was the key residue which lead to the protein conformation changes. Consequently, overall calculations presented in this study ultimately provide a useful understanding of the increased activity of SHP2 caused by the N308D mutation.
Assuntos
Simulação de Dinâmica Molecular , Proteína Fosfatase 2/química , Proteína Fosfatase 2/metabolismo , Domínio Catalítico/genética , Mutação com Ganho de Função/genética , Mutação/genética , Conformação Proteica , Proteína Fosfatase 2/genética , Estabilidade Proteica , Estrutura Secundária de ProteínaRESUMO
Diabetic macular edema, also known as diabetic eye disease, is mainly caused by the overexpression of vascular endothelial protein tyrosine phosphatase (VE-PTP) at hypoxia/ischemic. AKB-9778 is a known VE-PTP inhibitor that can effectively interact with the active site of VE-PTP to inhibit the activity of VE-PTP. However, the binding pattern of VE-PTP with AKB-9778 and the dynamic implications of AKB-9778 on VE-PTP system at the molecular level are poorly understood. Through molecular docking, it was found that the AKB-9778 was docked well in the binding pocket of VE-PTP by the interactions of hydrogen bond and Van der Waals. Furthermore, after molecular dynamic simulations on VE-PTP system and VE-PTP AKB-9778 system, a series of postdynamic analyses found that the flexibility and conformation of the active site undergone an obvious transition after VE-PTP binding with AKB-9778. Moreover, by constructing the RIN, it was found that the different interactions in the active site were the detailed reasons for the conformational differences between these two systems. Thus, the finding here might provide a deeper understanding of AKB-9778 as VE-PTP Inhibitor.
Assuntos
Compostos de Anilina/química , Inibidores Enzimáticos/química , Hipoglicemiantes/química , Simulação de Acoplamento Molecular , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/química , Ácidos Sulfônicos/química , Motivos de Aminoácidos , Compostos de Anilina/metabolismo , Domínio Catalítico , Inibidores Enzimáticos/metabolismo , Humanos , Ligação de Hidrogênio , Hipoglicemiantes/metabolismo , Cinética , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/antagonistas & inibidores , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/metabolismo , Ácidos Sulfônicos/metabolismo , TermodinâmicaRESUMO
Juvenile myelomonocytic leukemia (JMML), an invasive myeloproliferative neoplasm, is a childhood disease with very high clinical lethality. Somatic mutation E76K in SHP2 is the most commonly identified mutation found in up to 35% of patients with JMML. To investigate the effect of gain-of-function mutation-E76K on SHP2 activity, molecular dynamic simulations on the wild-type SHP2 (SHP2-WT) system and the mutated E76K (SHP2-E76K) system were performed. The evaluation of stability of these two systems indicated that the simulated trajectories were stable after simulation for 3 nanoseconds. The root mean square fluctuation and the per-residue root mean square deviation illustrated that there were two regions (residues Tyr 81-Glu 83 and Glu 258-Leu 261) in the wild-type system and the mutated system, which had large differences. The principal component analysis, dynamic cross correlation maps analysis, as well as secondary structure analysis suggested that the mutated E76K impacted the movement of these two regions in SHP2 protein. Furthermore, residue interaction network analysis, hydrogen bond occupancy, and binding free energies analysis were used to explain how the two regions were specifically affected by the mutant. The results indicated that the primary variances between SHP2-WT and SHP2-E76K were the different interactions between Glu/Lys 76 and Arg 265, Tyr 80 and Leu 77, Leu 77 and Tyr 81, Thr 73 and Glu 258, Ala 75 and Cys 259, Phe 71 and Tyr 81, Ala 75 and Glu 258, and Tyr 73 and Glu/Lys 76. Consequently, these findings here might provide insights into the increased activity in SHP2-E76K.
Assuntos
Mutação com Ganho de Função , Leucemia Mielomonocítica Juvenil/genética , Simulação de Dinâmica Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Humanos , Ligação de Hidrogênio , Mutação de Sentido Incorreto , Conformação Proteica , Proteína Tirosina Fosfatase não Receptora Tipo 11/química , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismoRESUMO
DNA nanodevices that mimic natural biomolecular machines changing configurations in response to external inputs have enabled smart sensors to live cell imaging. We report for the first time the development of a dynamic DNA nanomachine that is anchored on a cell's surface and undergoes pH-responsive triplex-duplex conformation switching, allowing tunable sensing and imaging of extracellular pH. Results reveal that the DNA nanomachine can be stably anchored on the cell surface via multiple anchors, and the adjustment of C+G-C content in the switch element confers tunability of pH response windows. The anchored DNA nanomachine also demonstrates desirable sensitivity, excellent reversibility, and quantitative ability for extracellular pH detection and imaging. This cell surface-anchored pH-responsive DNA nanomachine can provide a useful platform for pH sensing in extracellular microenvironments and diagnostics of different pH-related diseases.
Assuntos
Técnicas Biossensoriais/métodos , DNA/química , Espaço Extracelular/química , Imagem Molecular/métodos , Nanotecnologia/métodos , Linhagem Celular , Concentração de Íons de Hidrogênio , Conformação de Ácido Nucleico , Propriedades de SuperfícieRESUMO
Light-up RNA aptamers are valuable tools for fluorescence imaging of RNA in living cells and thus for elucidating RNA functions and dynamics. However, no light-up RNA sensor has been reported for imaging of microRNAs (miRs) in mammalian cells. We report a novel genetically encoded RNA sensor for fluorescent imaging of miRs in living tumor cells using a light-up RNA aptamer that binds to sulforhodamine and separates it from a conjugated contact quencher. On the basis of the structural switching mechanism for molecular beacon, we show that the RNA sensor activates high-contrast fluorescence from the sulforhodamine-quencher conjugate when its stem-loop responsive motif hybridizes with target miR. The RNA sensor can be stably expressed within a designed tRNA scaffold in tumor cells and deliver light-up response to miR target. We also realize the RNA sensor for dual-emission, ratiometric imaging by coexpression of RNA sensor with GFP, enabling quantitative studies of target miR in living cells. Our design may provide a new paradigm for developing robust, sensitive light-up RNA sensors for RNA imaging applications.
Assuntos
Aptâmeros de Nucleotídeos/genética , Fluorescência , Código Genético/genética , MicroRNAs/análise , MicroRNAs/genética , Imagem Óptica/métodos , Sobrevivência Celular , Células HeLa , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria de FluorescênciaRESUMO
Our objective was to determine whether continuous transcranial Doppler (TCD) monitoring could safely enhance the efficacy of batroxobin, a thrombin-like enzyme extracted from Bothrops atrox moojeni venom, in the treatment for acute cerebral stroke beyond the thrombolytic time window. Ninety patients suffering an acute cerebral stroke were recruited into the study within 12 hours after the onset of symptoms. Patients were randomized to receive batroxobin with (target group) or without 1 hour of continuous TCD monitoring (control group). Clinical evaluation of stroke was based on the National Institutes of Health Stroke Scale (NIHSS) score, Barthel index (BI), Thrombolysis in Brain Ischemia score (TIBI), the incidence of advancing stroke, and the recurrence of cerebral infarction. The patients receiving continuous TCD monitoring showed significant improvement in NIHSS score at 57 days post treatment compared with the control. Similarly, patients receiving continuous TCD monitoring also showed significant improvement in BI at 3 months compared with the controls. Consistently, both the incidence of advancing stroke after 1 week and the incidence of stroke recurrence after 3 months were significantly lower in TCD monitored group than control group. Moreover, the safety of the employment of TCD monitoring in the treatment of these patients was confirmed as there was no significant difference of the incidence of intracranial hemorrhage at 1 week after the treatment between the target and control groups. Taken together, our study showed that batroxobin, in combination with continuous TCD monitoring at the middle cerebral artery, reduced the incidence of advancing stroke and stroke recurrence after treatment without adverse effects in terms of poststroke intracranial hemorrhage.
Assuntos
Batroxobina/administração & dosagem , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Ultrassonografia Doppler Transcraniana/métodos , Adulto , Idoso , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Prognóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Acidente Vascular Cerebral/mortalidade , Taxa de Sobrevida , Resultado do TratamentoRESUMO
The outbreak of SARS-CoV-2 poses a serious threat to human life and health. A rapid nucleic acid tests can effectively curb the spread of the disease. With the advantages of fluorescent RNA aptamers, low background and high sensitivity. A variety of fluorescent RNA aptamer sensors have been developed for the detection of nucleic acid. Here, we report a hypersensitive detection platform in which SARS-CoV-2 initiates RTF-EXPAR to amplify trigger fragments. This activation leads to the reassembled of the SRB2 fluorescent RNA aptamer, restoring its secondary structure for SR-DN binding and turn-on fluorescence. The platform completes the assay in 30 min and all reactions occur in one tube. The detection limit is as low as 116 aM. Significantly, the platform's quantitative analyses were almost identical to qPCR results in simulated tests of positive samples. In conclusion, the platform is sensitive, accurate and provides a new protocol for point-of-care testing of viruses.
Assuntos
Aptâmeros de Nucleotídeos , COVID-19 , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico , RNA Viral , SARS-CoV-2 , Aptâmeros de Nucleotídeos/química , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Humanos , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/análise , COVID-19/diagnóstico , COVID-19/virologia , Corantes Fluorescentes/química , Teste de Ácido Nucleico para COVID-19/métodosRESUMO
Inducible CRISPR-dCas9 transcription system has become a powerful tool for transcription regulation and sensing. Here, we develop a new concept of small-molecule-mediated split-aptamer assembly for inducible CRISPR-dCas9 transcription activation, allowing quantitative detection and imaging of S-adenosyl methionine (SAM) in live cells. This inducible transcription system is designed by integrating one fragment of a split SAM aptamer to guide RNA (gRNA) and the other to MS2 arrays. SAM-mediated reassembly of the split fragments recruits an MCP-fused transcription activator to the gRNA-dCas9 complex, activating the expression of a near-infrared fluorescent protein for imaging. We demonstrate that this inducible transcription system achieves quantitative detection of SAM with high sensitivity in live cells. Our system shows that methionine adenosyltransferase 1A (MAT1A) and MAT2A can both catalyze SAM production in live cells and the SAM levels in cancer cells can be increased via upregulation of MAT1A mRNA by epigenetic inhibitors. This split-aptamer assembly strategy could afford a new approach for controlling the CRISPR-dCas9 system, enabling conditional transcription regulation in response to endogenous metabolites in live cells.
Assuntos
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , RNA Guia de Cinetoplastídeos , Sistemas CRISPR-Cas , Regulação da Expressão Gênica , RNA Guia de Cinetoplastídeos/genética , S-Adenosilmetionina , Ativação TranscricionalRESUMO
We propose and realize a novel packaged microsphere-taper coupling structure (PMTCS) with a high quality factor (Q) up to 5×10(6) by using the low refractive index (RI) ultraviolet (UV) glue as the coating material. The optical loss of the PMTCS is analyzed experimentally and theoretically, which indicate that the Q is limited by the glue absorption and the radiation loss. Moreover, to verify the practicability of the PMTCS, thermal sensing experiments are carried out, showing the excellent convenience and anti-jamming ability of the PMTCS with a high temperature resolution of 1.1×10(-3) â¦C. The experiments also demonstrate that the PMTCS holds predominant advantages, such as the robustness, mobility, isolation, and the PMTCS can maintain the high Q for a long time. The above advantages make the PMTCS strikingly attractive and potential in the fiber-integrated sensors and laser.
Assuntos
Refratometria/instrumentação , Dióxido de Silício/efeitos da radiação , Termografia/instrumentação , Transdutores , Desenho Assistido por Computador , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Microesferas , Espalhamento de RadiaçãoRESUMO
In this study, firstly, the pharmacophore model was established based on LAR inhibitors. ZINC database and drug-like database were screened by Hypo-1-LAR model, and the embryonic compound ZINC71414996 was obtained. Based on this compound, we designed 9 compounds. Secondly, the synthetic route of the compound was determined by consulting Reaxys and Scifinder databases, and 9 compounds (1a-1i) were synthesized by nucleophilic substitution, Suzuki reaction and so on. Meanwhile, their structures were confirmed by 1H NMR and 13C NMR. Thirdly, the Enzymatic assays was carried out, the biological evaluation of compounds 1a-1i led to the identification of a novel PTP-LAR inhibitor 1c, which displayed an IC50 value of 4.8 µM. At last, molecular dynamics simulation showed that compounds could interact strongly with the key amino acids LYS1350, LYS1352, ARG1354, TYR1355, LYS1433, ASP1435, TRP1488, ASP1490, VAL1493, SER1523, ARG1528, ARG1561, GLN1570, LYS1681, thereby inhibiting the protein activity. This study constructed the pharmacophore model of LAR protein, designed small-molecule inhibitors, conducted compound synthesis and enzyme activity screening, so as to provide a basis for searching for drug-capable lead compounds.
Assuntos
Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/farmacologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Modelos Moleculares , Estrutura Molecular , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/químicaRESUMO
PURPOSE: To investigate the potential safety and efficacy of drug-eluting bead-transcatheter arterial chemoembolization (DEB-TACE) in treating TACE-refractory hepatocellular carcinoma (HCC). METHODS: We retrospectively evaluated the treatment outcomes of DEB-TACE for 41 HCC nodules in 30 patients who were refractory to conventional TACE (c-TACE) according to tumor response. The antitumor response was evaluated according to mRECIST criteria, and changes in alpha-fetoprotein (AFP), albumin-bilirubin score, the incidence of adverse events, and the time to disease progression were observed. RESULTS: The objective response rate and disease control rates were 60.98% and 95.12% at 4 weeks after DEB-TACE, 63.41% and 92.68% at 8 weeks, respectively. The median time of disease progression was 4.60 ± 0.23 months. The AFP of patients decreased continuously at 2-6 weeks after operation, and the AFP at 4 weeks was significantly lower than that at 2 weeks (P = 0.038). Adverse reactions were well tolerated, and no grade 4 adverse reactions were reported. The albumin-bilirubin score did not deteriorate within 6 weeks. CONCLUSION: DEB-TACE has potential efficacy and safety after failure of c-TACE in patients with advanced liver cancer. Further studies are needed to confirm the efficacy of DEB-TACE treatment after failure of c-TACE.
RESUMO
Genetically encoded light-up RNA aptamers afford a valuable platform for developing RNA sensors toward live cell imaging. However, quantitative imaging of intracellular RNAs remains a grand challenge. Here we reported a novel genetically encoded RNA sensor strategy using a plasmid that expresses a splittable fusion of the RNA sensor and the GFP mRNA in an individual transcript using a single promoter system. This splittable fusion design enables synchronous co-expression of the RNA sensor with GFP mRNA while alleviates the interference with correct folding of RNA aptamers due to intramolecular hybridization. This single-promoter system is applied to ratiometric imaging of survivin mRNA in tumor cells. The results reveal that the ratiometric images dynamically correlated with survivin mRNA concentrations and allow quantitative imaging of survivin mRNA in different tumor cells. The RNA sensor strategy may provide a new paradigm for developing a robust imaging platform for quantitative mRNA studies in living cells.
RESUMO
The low molecular weight protein tyrosine phosphatase (LMW-PTP) could regulate many signaling pathways, and it had drawn attention as a potential target for cancer. As previous report has indicated that the aplidin could inhibit the LMW-PTP, and thus, the relevant cancer caused by the abnormal regulation of the LMW-PTP could be remission. However, the molecular mechanism of inhibition of the LMW-PTP by the aplidin had not been fully understood. In this study, various computational approaches, namely molecular docking, MDs and post-dynamic analyses were utilized to explore the effect of the aplidin on the LMW-PTP. The results suggested that the intramolecular interactions of the residues in the two sides of the active site (Ser43-Ala55 and Pro121-Asn134) and the P-loop region (Leu13-Ser19) in the LMW-PTP was disturbed owing to the aplidin, meanwhile, the π-π interaction between Tyr131 and Tyr132 might be broken. The Asn15 might be the key residue to break the residues interactions. In a word, this study may provide more information for understanding the effect of inhibition of the aplidin on the LMW-PTP.