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Catalytic DNA circuits are desirable for sensitive bioimaging in living cells; yet, it remains a challenge to monitor these intricate signal communications because of the uncontrolled circuitry leakage and insufficient cell selectivity. Herein, a simple yet powerful DNA-repairing enzyme (APE1) activation strategy is introduced to achieve the site-specific exposure of a catalytic DNA circuit for realizing the selectively amplified imaging of intracellular microRNA and robust evaluation of the APE1-involved drug resistance. Specifically, the circuitry reactants are firmly blocked by the enzyme recognition/cleavage site to prevent undesirable off-site circuitry leakage. The caged DNA circuit has no target-sensing activity until its circuitry components are activated via the enzyme-mediated structural reconstitution and finally transduces the amplified fluorescence signal within the miRNA stimulation. The designed DNA circuit demonstrates an enhanced signal-to-background ratio of miRNA assay as compared with the conventional DNA circuit and enables the cancer-cell-selective imaging of miRNA. In addition, it shows robust sensing performance in visualizing the APE1-mediated chemoresistance in living cells, which is anticipated to achieve in-depth clinical diagnosis and chemotherapy research.
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Técnicas Biossensoriais , DNA Catalítico , MicroRNAs , Neoplasias , Humanos , MicroRNAs/genética , MicroRNAs/química , DNA Catalítico/química , Hibridização de Ácido Nucleico , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , DNA/química , Técnicas Biossensoriais/métodosRESUMO
Epigenetic modification plays an indispensable role in regulating routine molecular signaling pathways, yet it is rarely used to modulate molecular self-assembly networks. Herein, we constructed a bioorthogonal demethylase-stimulated DNA circuitry (DSC) system for high-fidelity imaging of microRNA (miRNA) in live cells and mice by eliminating undesired off-site signal leakage. The simple and robust DSC system is composed of a primary cell-specific circuitry regulation (CR) module and an ultimate signal-transducing amplifier (SA) module. After the modularly designed DSC system was delivered into target live cells, the DNAzyme of the CR module was site-specifically activated by endogenous demethylase to produce fuel strands for the subsequent miRNA-targeting SA module. Through the on-site and multiply guaranteed molecular recognitions, the lucid yet efficient DSC system realized the reliably amplified in vivo miRNA sensing and enabled the in-depth exploration of the demethylase-involved signal pathway with miRNA in live cells. Our bioorthogonally on-site-activated DSC system represents a universal and versatile biomolecular sensing platform via various demethylase regulations and shows more prospects for more different personalized theragnostics.
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DNA Catalítico , MicroRNAs , MicroRNAs/análise , MicroRNAs/metabolismo , DNA Catalítico/metabolismo , DNA Catalítico/química , Animais , Camundongos , Humanos , Metilação de DNA , Imagem ÓpticaRESUMO
It was reported that lowly expressed RING1 indicates poor prognosis in breast cancer (BC) patients, while the mechanism by which RING1 is involved in BC progression is not fully understood. Here, we found that RING1 was lowly expressed in BC tissues and cells than in normal mammary tissues and epithelial cells. Overexpression of RING1 suppressed the cell proliferative and colony formation abilities, and facilitated cell cycle arrest and cell apoptosis in BC cells (T47D and MCF-7 cells). Mechanistically, as an ubiquitin ligase, RING1 bound to HSF1 and induced its proteasome-dependent degradation. HSF1 could bind to the promoter region of MT2A to promote the transcriptional level of MT2A. While RING1 overexpression hindered the transcriptional activation of MT2A induced by HSF1. Moreover, ectopic expression of MT2A reversed the inhibitory effect of RING1 on cell proliferation and clonogenesis, and antagonized the promotion effect of RING1 on cell cycle arrest and apoptosis in BC cells. Additionally, T47D cells infected with or without lentivirus-mediated RING1 overexpression vector (LV-RING1) were injected subcutaneously into the right back of nude mice to evaluate tumorigenicity. And overexpression of RING1 impeded the growth of BC xenografts in mice. In conclusion, RING1 suppressed the transcriptional activation of MT2A induced by HSF1 by facilitating the ubiquitination degradation of HSF1, resulting in cell cycle arrest and apoptosis in BC cells.
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BACKGROUND: Breast cancer is a common malignancy, and early detection coupled with standardized treatment is crucial for patient survival and recovery. This study aims to scrutinize the current state of breast cancer diagnosis and treatment in Shaanxi province, providing valuable insights into the local practices and outcomes. METHODS: We selected 25 hospitals that typically represent the current diagnosis and treatment strategy of breast cancer in Shaanxi (a province in northwest China). The questionnaire comprised sections on fundamental information, outpatient consultations, breast-conserving surgery, neoadjuvant and adjuvant therapy, sentinel lymph node biopsy, breast reconstruction surgery. RESULTS: A total of 6665 breast cancer operations were performed in these 25 hospitals in 2021. The overall proportion of breast-conserving surgery (BCS) is 23.6%. There was a statistically significant positive correlation between the annual volume of breast cancer surgery and the implementation rate of BCS (P = 0.004). A total of 2882 cases of neoadjuvant treatment accounted for 43.24% of breast cancer patients treated with surgery in 2017. Hospitals in Xi'an performed more neoadjuvant therapy for patients with breast cancer compared to other districts (P = 0.008). There was a significantly positive correlation between outpatient visits and the implementation rate of sentinel lymph node biopsy (SLNB) (P = 0.005). 14 hospitals in Shaanxi performed reconstructive surgery. CONCLUSIONS: Breast conserving surgery, adjuvant and neoadjuvant therapy and sentinel lymph node biopsy in Shaanxi province have reached the China's average level. Moreover, hospitals in Xi 'an have surpassed this average. However, a disparity is observed in the development of breast reconstruction surgery when compared to top-tier hospitals.
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Neoplasias da Mama , Mamoplastia , Mastectomia Segmentar , Terapia Neoadjuvante , Biópsia de Linfonodo Sentinela , Humanos , Neoplasias da Mama/terapia , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/epidemiologia , Feminino , Estudos Retrospectivos , China/epidemiologia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Terapia Neoadjuvante/estatística & dados numéricos , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Mastectomia Segmentar/estatística & dados numéricos , Mamoplastia/estatística & dados numéricos , Mamoplastia/métodos , Prognóstico , Seguimentos , Adulto , IdosoRESUMO
A bioassay-guided chemical investigation of a bacterium, Streptomyces sp. CMB-MRB032, isolated from sheep feces collected near Bathurst, Victoria, Australia, yielded the known polyketide antimycins A4a (1) and A2a (2) as potent inhibitors of Dirofilaria immitis (heartworm) microfilaria (mf) motility (EC50 0.0013-0.0021 µg/mL), along with the octapeptide surugamide A (3) and the new N-methylated analog surugamide K (4). With biological data suggesting surugamides may also exhibit activity against D. immitis, a GNPS molecular network analysis of a library of microbes sourced from geographically diverse Australian ecosystems identified a further five taxonomically and chemically distinct surugamide producers. Scaled-up cultivation of one such producer, Streptomyces sp. CMB-M0112 isolated from a marine sediment collected at Shorncliff, Qld, Australia, yielded 3 along with the new acyl-surugamides A1-A4 (5-8). Solid-phase peptide synthesis provided additional synthetic analogs, surugamides S1-S3 (9-11), while derivatization of 3 returned the semi-synthetic surugamide S4 (12) and acyl-surugamides AS1-AS3 (13-15). The natural acyl-surugamide A3 (7) and semi-synthetic acyl-surugamide AS3 (15) were shown to selectively inhibit D. immitis mf motility (EC50 3.3-3.4 µg/mL), however, unlike antimycins 1 and 2, were inactive against the gastrointestinal nematode Haemonchus contortus L1-L3 larvae (EC50 > 25 µg/mL) and were not cytotoxic to mammalian cells (human colorectal carcinoma SW620, IC50 > 30 µg/mL). A structure-activity relationship (SAR) study on the surugamides 3-15 revealed that selective acylation of the Lys3-ε-NH2 correlates with anthelmintic activity.
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Dirofilaria immitis , Streptomyces , Animais , Streptomyces/química , Dirofilaria immitis/efeitos dos fármacos , Austrália , Ovinos , Fezes/parasitologia , Fezes/microbiologiaRESUMO
Accurate calibration between LiDAR and camera sensors is crucial for autonomous driving systems to perceive and understand the environment effectively. Typically, LiDAR-camera extrinsic calibration requires feature alignment and overlapping fields of view. Aligning features from different modalities can be challenging due to noise influence. Therefore, this paper proposes a targetless extrinsic calibration method for monocular cameras and LiDAR sensors that have a non-overlapping field of view. The proposed solution uses pose transformation to establish data association across different modalities. This conversion turns the calibration problem into an optimization problem within a visual SLAM system without requiring overlapping views. To improve performance, line features serve as constraints in visual SLAM. Accurate positions of line segments are obtained by utilizing an extended photometric error optimization method. Moreover, a strategy is proposed for selecting appropriate calibration methods from among several alternative optimization schemes. This adaptive calibration method selection strategy ensures robust calibration performance in urban autonomous driving scenarios with varying lighting and environmental textures while avoiding failures and excessive bias that may result from relying on a single approach.
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The rapid development of green energy would render a profound impact on the non-ferrous metals markets in China. This paper adopts the quantile vector autoregression (QVAR) to investigate the spillover effects between China's green energy and non-ferrous metals markets as well as their dynamic pattern under normal and extreme conditions. Furthermore, GARCH-MIDAS model and quantile regression method are applied to examine the impact of China's climate policy uncertainty on the spillovers between the two markets. In doing so, we find that green energy markets mainly act as transmitters of return spillover effects to non-ferrous metals markets during normal market times and periods of downturns. However, in upturns, the non-ferrous metals markets would easily transit spillover effects to green energy ones. It is further indicated that China's climate policy uncertainty exacerbates the spillover effect, and the exacerbated effect of high uncertainty on the market relationship when the spillover effect is at high level is the most significant.
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Metais , China , Incerteza , Clima , Mudança Climática , Política AmbientalRESUMO
Isothermal autocatalytic DNA circuits have been proven to be versatile and powerful biocomputing platforms by virtue of their self-sustainable and self-accelerating reaction profiles, yet they are currently constrained by their complicated designs, severe signal leakages, and unclear reaction mechanisms. Herein, we developed a simpler-yet-efficient autocatalytic assembly circuit (AAC) for highly robust bioimaging in live cells and mice. The scalable and sustainable AAC system was composed of a mere catalytic DNA assembly reaction with minimal strand complexity and, upon specific stimulation, could reproduce numerous new triggers to expedite the whole reaction. Through in-depth theoretical simulations and systematic experimental demonstrations, the catalytic efficiency of these reproduced triggers was found to play a vital role in the autocatalytic profile and thus could be facilely improved to achieve more efficient and characteristic autocatalytic signal amplification. Due to its exponentially high signal amplification and minimal reaction components, our self-stacking AAC facilitated the efficient detection of trace biomolecules with low signal leakage, thus providing great clinical diagnosis and therapeutic assessment potential.
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Técnicas Biossensoriais , DNA Catalítico , Animais , Camundongos , Técnicas Biossensoriais/métodos , DNA , CatáliseRESUMO
Excess lead iodide (PbI2 ) aggregation at the charge carrier transport interface leads to energy loss and acts as unstable origins in perovskite solar cells (PSCs). Here, a strategy is reported to modulate the interfacial excess PbI2 by introducing π-conjugated small-molecule semiconductors 4,4'-cyclohexylbis[N,N-bis(4-methylphenyl)aniline] (TAPC) into perovskite films through an antisolvent addition method. The coordination of TAPC to PbI units through the electron-donating triphenylamine groups and π-Pb2+ interactions allows for a compact perovskite film with reduced excess PbI2 aggregates. Besides, preferred energy level alignment is achieved due to the suppressed n-type doping effect at the hole transport layer (HTL) interfaces. As a result, the TAPC-modified PSC based on Cs0.05 (FA0.85 MA0.15 )0.95 Pb(I0.85 Br0.15 )3 triple-cation perovskite achieved an improved PCE from 18.37% to 20.68% and retained ≈90% of the initial efficiency after 30 days of aging under ambient conditions. Moreover, the TAPC-modified device based on FA0.95 MA0.05 PbI2.85 Br0.15 perovskite produced an improved efficiency of 23.15% compared to the control (21.19%). These results provide an effective strategy for improving the performance of PbI2 -rich PSCs.
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The nested Wolter-I type focusing mirror is widely used in the field of X-ray astronomy. The thin-shell mirrors produced by the electroforming replication method will introduce various shape errors during the fabricating and assembling process. This study introduces a non-analytical 3D geometrical ray tracing algorithm capable of predicting optical performance for large mirror deformations. The algorithm's implementation involves error reconstruction, light source and ray simulation, and optical performance calculation. Experimental and simulation validation underscores the algorithm's precision and effectiveness. The results also indicate that edge deformation can seriously affect imaging contrast which is generally considered to be determined only by surface scattering. Applying the 3D ray tracing algorithm, a range of low-frequency fabrication and assembly errors are simulated, such as absolute radius, taper, roundness, edge effects, mirror posture, and hoisting deformation errors, and their effects on imaging quality are analyzed and discussed.
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A detailed understanding the metals binding with algal organic matter (AOM) is essential to gain a deeper insight into the toxicity and migration of metals in algae cell. However, the molecular complexation mechanism of the metals binding with AOM remains unclear. In this study, cadmium ion (Cd2+) binding properties of AOMs from Scenedesmus obliquus, which included extracellular organic matter (EOM) and intracellular organic matter (IOM), were screened. When Cd2+ < 0.5 mg/L, the accumulation of Cd2+ could reach 40%, while Cd2+ > 0.5 mg/L, the accumulation of Cd2+ was only about 10%. EOM decreased gradually (from 8.51 to 3.98 mg/L), while IOM increased gradually (from 9.62 to 21.00 mg/L). The spectral characteristics revealed that IOM was richer in peptides/proteins and had more hydrophilic than EOM. Both EOM and IOM contained three protein-like components (containing tryptophan and tyrosine) and one humic-like component, and their contents in IOM were higher than that in EOM. The tryptophan protein-like substances changed greatly during Cd2+ binding, and that the tryptophan protein-like substances complexed to Cd2+ before tyrosine protein-like substances in IOM was identified. Moreover, the functional groups of N-H, O-H, and CO in AOM played an important role, and the N-H group was priority to interacts with Cd2+ in the complexing process. More functional groups (such as C-O and C-N) were involved in the metals complexing in EOM than in IOM. It could be concluded that Cd2+ stress promoted the secretion of AOM in Scenedesmus obliquus, and proteins in AOM could complex Cd2+ and alleviate its toxicity to algal cell. These findings provided deep insights into the interaction mechanism of AOM with Cd2+ in aquatic environments.
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Clorofíceas , Scenedesmus , Cádmio/toxicidade , Triptofano , TirosinaRESUMO
Recently, deep learning models have been widely applied to modulation recognition, and they have become a hot topic due to their excellent end-to-end learning capabilities. However, current methods are mostly based on uni-modal inputs, which suffer from incomplete information and local optimization. To complement the advantages of different modalities, we focus on the multi-modal fusion method. Therefore, we introduce an iterative dual-scale attentional fusion (iDAF) method to integrate multimodal data. Firstly, two feature maps with different receptive field sizes are constructed using local and global embedding layers. Secondly, the feature inputs are iterated into the iterative dual-channel attention module (iDCAM), where the two branches capture the details of high-level features and the global weights of each modal channel, respectively. The iDAF not only extracts the recognition characteristics of each of the specific domains, but also complements the strengths of different modalities to obtain a fruitful view. Our iDAF achieves a recognition accuracy of 93.5% at 10 dB and 0.6232 at full signal-to-noise ratio (SNR). The comparative experiments and ablation studies effectively demonstrate the effectiveness and superiority of the iDAF.
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An imbalance in PI3K/AKT/mTOR pathway signaling in humans often leads to cancer. Therefore, the investigation of anti-cancer medications that inhibit PI3K and mTOR has emerged as a significant area of research. The aim of this study was to explore the effect of XIN-10, a dual PI3K/mTOR inhibitor, on the growth as well as antiproliferation of tumor cells and to investigate the anti-tumor mechanism of XIN-10 by further exploration. We screened three cell lines for more in-depth exploration by MTT experiments. From the AO staining, cell cycle and apoptosis, we found that XIN-10 had a more obvious inhibitory effect on the MCF-7 breast cancer cell line and used this as a selection for more in-depth experiments. A series of in vitro and in vivo experiments showed that XIN-10 has superior antiproliferative activity compared with the positive drug GDC-0941. Meanwhile, through the results of protein blotting and PCR experiments, we concluded that XIN-10 can block the activation of the downstream pathway of mTOR by inhibiting the phosphorylation of AKT(S473) as well as having significant inhibitory effects on the gene exons of PI3K and mTOR. These results indicate that XIN-10 is a highly potent inhibitor with low toxicity and has a strong potential to be developed as a novel PI3Kα/mTOR dual inhibitor candidate for the treatment of positive breast cancer.
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Neoplasias da Mama , Inibidores de MTOR , Fosfatidilinositol 3-Quinases , Inibidores de Fosfoinositídeo-3 Quinase , Feminino , Humanos , Apoptose , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Inibidores de MTOR/farmacologia , Inibidores de MTOR/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer (GC)/gastroesophageal junction cancer (GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy (LTG) for GC/GEJC patients who have received preoperative therapy (PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients. Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405 received LTG (LTG group) and 106 received PT+LTG (PT-LTG group) at Nanfang Hospital between June 2018 and September 2022. The surgical outcomes were compared between the two groups. Results: The surgical duration was significantly longer in the PT-LTG group (P<0.001), while the incidence of intraoperative complications (P=1.000), postoperative complications (LTG group vs. PT-LTG group: 26.2% vs. 23.6%, P=0.587), the classification of complication severity (P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups (LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio (OR)=14.094, 95% confidence interval (95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG (OR=0.945, 95% CI: 0.371-2.408, P=0.905). Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.
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Numerous studies have examined the neural substrates of intertemporal decision-making, but few have systematically investigated separate neural representations of the two attributes of future rewards (i.e., the amount of the reward and the delay time). More importantly, no study has used the novel analytical method of representational connectivity analysis (RCA) to map the two dimensions' functional brain networks at the level of multivariate neural representations. This study independently manipulated the amount and delay time of rewards during an intertemporal decision task. Both univariate and multivariate pattern analyses showed that brain activity in the dorsomedial prefrontal cortex (DMPFC) and lateral frontal pole cortex (LFPC) was modulated by the amount of rewards, whereas brain activity in the DMPFC and dorsolateral prefrontal cortex (DLPFC) was modulated by the length of delay. Moreover, representational similarity analysis (RSA) revealed that even for the regions of the DMPFC that overlapped between the two dimensions, they manifested distinct neural activity patterns. In terms of individual differences, those with large delay discounting rates (k) showed greater DMPFC and LFPC activity as the amount of rewards increased but showed lower DMPFC and DLPFC activity as the delay time increased. Lastly, RCA suggested that the topological metrics (i.e., global and local efficiency) of the functional connectome subserving the delay time dimension inversely predicted individual discounting rate. These findings provide novel insights into neural representations of the two attributes in intertemporal decisions, and offer a new approach to construct task-based functional brain networks whose topological properties are related to impulsivity.
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Mapeamento Encefálico , Desvalorização pelo Atraso/fisiologia , Córtex Pré-Frontal/fisiologia , Desempenho Psicomotor/fisiologia , Recompensa , Adulto , Córtex Pré-Frontal Dorsolateral/diagnóstico por imagem , Córtex Pré-Frontal Dorsolateral/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/diagnóstico por imagem , Fatores de Tempo , Adulto JovemRESUMO
Propolis has a very complex composition, with antibacterial, anti-inflammatory and other properties. To determine the composition of ethanol extracts of Brazilian green propolis (EEP-B) and their protective effect on mouse aortic endothelial cells (MAECs), the chemical composition of EEP-B was analysed by UPLC/Q-TOF-MS/MS, and the protective effect of EEP-B on the proliferation of lipopolysaccharide (LPS)-induced MAECs was determined by Cell Counting Kit-8 (CCK-8) assays. The protein levels of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA), and ICAM-1, VCAM-1 and MCP-1 expressions were analysed by western blotting. The results showed that a total of 24 compounds belonging to cinnamic acids and flavonoids, including 3,5-diisopentenyl-4-hydroxycinnamic acid (artepillin C), kaempferide, 3-isoprenyl p-coumaric acid, pinocembrin and 4'-methoxy pinobanksin, were identified in EEP-B. Among them, a new component, suggested to be 5-isoprenyl caffeic acid p-coumaric acid ester, was reported for the first time. The LPS-induced levels of TNF-α, IL-6, ICAM-1, VCAM-1 and MCP-1 were downregulated in response to 5, 10 and 20 µg/mL EEP-B. This study revealed that EEP-B could reduce LPS-induced inflammatory reactions, improve cell survival, and protect MAECs by regulating ICAM-1, VCAM-1 and MCP-1 expression. These findings could provide a theoretical basis for MAEC treatment using EEP-B.
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Anti-Inflamatórios/química , Células Endoteliais/metabolismo , Própole/química , Animais , Anti-Inflamatórios/farmacologia , Quimiocina CCL2/metabolismo , Células Endoteliais/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
Esophageal squamous cell carcinoma (ESCC) is one of the most serious life-threatening malignancies. Although chemotherapeutic targets and agents for ESCC have made much progress recently, the efficacy is still unsatisfactory. Therefore, there is still an unmet medical need for patients with ESCC. Here, we report the expression status of HDAC1 in human ESCC and matched paracancerous tissues, and the results indicated that HDAC1 was generally upregulated in ESCC specimens. Furthermore, we comprehensively assessed the anti-ESCC activity of a highly active HDAC1 inhibitor quisinostat. Quisinostat could effectively suppress cellular viability and proliferation of ESCC cells, as well as induce cell cycle arrest and apoptosis even at low treatment concentrations. The effectiveness was also observed in KYSE150 xenograft model when quisinostat was administered at tolerated doses (3 mg/kg and 10 mg/kg). Meanwhile, quisinostat also had the ability to suppress the migration and invasion (pivotal steps of tumor metastasis) of ESCC cells. Western blot analysis indicated that quisinostat exerted its anti-ESCC effects mainly through blockade of Akt/mTOR and MAPK/ERK signaling cascades. Overall, HDAC1 may serve as a potential therapeutic target for ESCC, and quisinostat deserves to be further assessed as a promising drug candidate for the treatment of ESCC.
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Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Histona Desacetilase 1/antagonistas & inibidores , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Camundongos SCID , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Carga TumoralRESUMO
Governments are increasingly emphasizing emergency management in response to public emergencies that cause extensive consequences and involve multiple government agencies. One of the influential measures adopted by governments is the establishment of cross-agency networks. Scholars have validated the importance of cross-agency collaboration and networks, but only a few studies have examined cross-agency information sharing and utilization mechanism of joint emergency actions. Inspired by the theory of network embeddedness, we study the joint effects of informational and task attributes of embeddedness and absorptive capacity of the leading agency on collaborative emergency capacity. Our data consist of 110 local government contingency plans collected from F District in Shanghai, China. We found that a well-structured cross-agency network and a leading department with great information accessibility will significantly affect the efficiency of emergency collaborations. The capacity to absorb information significantly enhances the improvement of emergency collaboration.
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Effects of three different nutrient loadings (low nutrient loading, medium nutrient loading and high nutrient loading, denoted as LNS, MNS and HNS, respectively) on the structure and functions of algal biofilm using Anabaena flos-aquae were investigated using synthetic wastewater. Nutrients removal efficiencies, biofilm thickness, microalgae dehydrogenase activity (DHA) and exopolysaccharide (EPS) productions were examined. Results showed that the changes of nutrient concentration were insignificant after 4 days of experiment for the case of HNS condition; 9 days for the case of MNS condition, and 6 days for the case of LNS condition, respectively. The biofilm thickness, nutrient removal efficiencies, algae DHA and EPS productions increased with the increase of nutrient loadings in synthetic wastewater. For the case of HNS condition, the microalgal biofilm exhibited the best performance in terms of C, N and P removal efficiencies, reaching the removal rates of 68.45, 3.56 and 1.61 mg·L(-1)·d(-1) for C, N, P, respectively. This was likely because, fact with the high nutrient loading, the high biological activity could be achieved, thus resulting in high nutrient removals. The thickness of the biofilm in HNS condition was 75 µm, which was closely related to EPS production. DHA and EPS concentrations were 7.24 and 1.8 × 10(-2) mg·mm(-2), respectively. It was also shown that apart from the nutrient loading, the structure and functions of microalgal biofilm were also influenced by other factors, such as illumination and temperature.
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Biofilmes/crescimento & desenvolvimento , Dolichospermum flosaquae/fisiologia , Microalgas/fisiologia , Águas Residuárias/análise , Poluentes Químicos da Água/metabolismo , Proteínas de Algas/metabolismo , Dolichospermum flosaquae/enzimologia , Dolichospermum flosaquae/crescimento & desenvolvimento , Eutrofização , Microalgas/enzimologia , Microalgas/crescimento & desenvolvimento , Oxirredutases/metabolismo , Polissacarídeos Bacterianos/metabolismoRESUMO
Abnormal extracellular deposition of ß-amyloid (Aß) is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Preventing Aß-induced neurotoxicity has become a potential therapeutic approach to improve the onset and progression of AD. Here we report the synthesis of 1,1'-(biphenyl-4,4'-diyl)-bis(3-(dimethylamino)-propan-1-one) (BDBDP) and evaluate whether it protects PC12 cells from Aß1-42-induced cytotoxicity in PC12 cells. Treating cells with Aß1-42 significantly reduced cell viability and mitochondrial membrane potential while also significantly increasing apoptosis and production of reactive oxygen species (ROS). Pretreating the cells with BDBDP significantly ameloriated these Aß1-42-induced effects. Futhermore, BDBDP strongly reduced pro-apoptotic signaling in response to ROS by reducing levels of activated caspase-3 and increasing the ratio of Bcl-2 to Bax. These findings provide evidence that BDBDP protects against Aß1-42-induced neurotoxicity in PC12 cells by inhibiting oxidative stress and cell apoptosis.