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We report a porous three-dimensional anionic tetrazolium based CuI -MOF 1, which is capable of cleaving the N-H bond of ammonia and primary amine, as well as the O-H bond of H2 O along with spontaneous H2 evolution. In the gas-solid phase reaction of 1 with ammonia and water vapor, CuI -MOF 1 was gradually oxidized to NH2 -CuII -MOF and OH-CuII -MOF, through single-crystal-to-single-crystal (SCSC) structural transformations, which was confirmed by XPS, PXRD and X-ray single-crystal diffraction. Density functional theory (DFT) demonstrated that CuI -MOF could lower N-H bond dissociation free energy of ammonia through coordination-induced bond weakening and promote H2 evolution by the reduction potential of 1. To our knowledge, this is the first example of MOFs that activate ammonia and amine in gas-solid manner.
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Herein, a surface site engineering strategy is used to construct a porous Z-scheme heterojunction photocatalyst for photocatalytic hydrogen evolution (PHE) by integration of BiOI in a mesoporous Zr-based metal-organic framework (MOF) NU-1000. Three high-quality and highly dispersed BiOI@NU-1000 heterojunction materials are synthesized, and a set of methods is used to characterize these materials, indicating that the BiOI@NU-1000 heterojunction can retain high porosity and crystallinity of the parent NU-1000. Furthermore, the built-in electric field of the BiOI@NU-1000 composite can effectively tune the band gap, promote the separation of photoinduced charge carriers, improve photocurrent intensity, and reduce photoelectric impedance. Under visible-light irradiation, BiOI@NU-1000-2 showed the best photocatalytic performance in the field of MOF-based photocatalysts for PHE, with a hydrogen production rate of up to 610 µmol h-1 g-1. This study will open up opportunities for the construction of Z-scheme photocatalysts based on the highly porous MOF materials to inspire the development of innovative photocatalysts.
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Metal-organic frameworks (MOFs) have appeared to be promising competitive candidates as crystalline porous materials for proton conduction. Explorations of the method of preparation of proton conductive MOFs and the proton transfer mechanism have enabled them to attract widespread attention, and tremendous efforts have been made to improve the proton conductivity of MOFs. On the basis of our previous work, we explicitly propose that ligand exchange can upgrade the proton conduction performance of MOFs. Using MOF-azo as the precursor, the proton conductivities of exchange products MOF-bpy and MOF-bpe increase by 3.5- and 2.8-fold, respectively. After the MOFs had been doped into the Nafion matrix to prepare composite membranes, the proton conduction performance of composite membranes filled with subproducts (2.6 × 10-2 and 1.95 × 10-2 S cm-1) is significantly better than that of a composite membrane filled with a parent product (1.12 × 10-2 S cm-1) under ambient conditions (without heating or humidifying). The ligand exchange strategy presented herein demonstrates great promise for the development of high-proton conductivity MOFs and MOF composites with expanded future applications.
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Based on entropy characteristics, some complex nonlinear dynamics of the dynamic pressure at the outlet of a centrifugal compressor are analyzed, as the centrifugal compressor operates in a stable and unstable state. First, the 800-kW centrifugal compressor is tested to gather the time sequence of dynamic pressure at the outlet by controlling the opening of the anti-surge valve at the outlet, and both the stable and unstable states are tested. Then, multi-scale fuzzy entropy and an improved method are introduced to analyze the gathered time sequence of dynamic pressure. Furthermore, the decomposed signals of dynamic pressure are obtained using ensemble empirical mode decomposition (EEMD), and are decomposed into six intrinsic mode functions and one residual signal, and the intrinsic mode functions with large correlation coefficients in the frequency domain are used to calculate the improved multi-scale fuzzy entropy (IMFE). Finally, the statistical reliability of the method is studied by modifying the original data. After analysis of the relationships between the dynamic pressure and entropy characteristics, some important intrinsic dynamics are captured. The entropy becomes the largest in the stable state, but decreases rapidly with the deepening of the unstable state, and it becomes the smallest in the surge. Compared with multi-scale fuzzy entropy, the curve of the improved method is smoother and could show the change of entropy exactly under different scale factors. For the decomposed signals, the unstable state is captured clearly for higher order intrinsic mode functions and residual signals, while the unstable state is not apparent for lower order intrinsic mode functions. In conclusion, it can be observed that the proposed method can be used to accurately identify the unstable states of a centrifugal compressor in real-time fault diagnosis.
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MAIN CONCLUSION: A comprehensive network of the Arabidopsis transcriptome was analyzed and may serve as a valuable resource for candidate gene function investigations. A web tool to explore module information was also provided. Arabidopsis thaliana is a widely studied model plant whose transcriptome has been substantially profiled in various tissues, development stages and other conditions. These data can be reused for research on gene function through a systematic analysis of gene co-expression relationships. We collected microarray data from National Center for Biotechnology Information Gene Expression Omnibus, identified modules of co-expressed genes and annotated module functions. These modules were associated with experiments/traits, which provided potential signature modules for phenotypes. Novel heat shock proteins were implicated according to guilt by association. A higher-order module networks analysis suggested that the Arabidopsis network can be further organized into 15 meta-modules and that a chloroplast meta-module has a distinct gene expression pattern from the other 14 meta-modules. A comparison with the rice transcriptome revealed preserved modules and KEGG pathways. All the module gene information was available from an online tool at http://bioinformatics.fafu.edu.cn/arabi/ . Our findings provide a new source for future gene discovery in Arabidopsis.
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Arabidopsis/genética , Transcriptoma/genética , Análise por Conglomerados , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/fisiologia , Regiões Promotoras Genéticas/genéticaRESUMO
In this study, some important intrinsic dynamics have been captured after analyzing the relationships between the dynamic pressure at an outlet of centrifugal compressor and fractal characteristics, which is one of powerful descriptions in entropy to measure the disorder or complexity in the nonlinear dynamic system. In particular, the fractal dynamics of dynamic pressure of the flow is studied, as the centrifugal compressor is in surge state, resulting in the dynamic pressure of flow and becoming a serious disorder and complex. First, the dynamic pressure at outlet of a centrifugal compressor with 800 kW is tested and then obtained by controlling the opening of the anti-surge valve at the outlet, and both the stable state and surge are initially tested and analyzed. Subsequently, the fractal dynamics is introduced to study the intrinsic dynamics of dynamic pressure under various working conditions, in order to identify surge, which is one typical flow instability in centrifugal compressor. Following fractal dynamics, the Hurst exponent, autocorrelation functions, and variance in measure theories of entropy are studied to obtain the mono-fractal characteristics of the centrifugal compressor. Further, the multi-fractal spectrums are investigated in some detail, and their physical meanings are consequently explained. At last, the statistical reliability of multi-fractal spectrum by modifying the original data has been studied. The results show that a distinct relationship between the dynamic pressure and fractal characteristics exists, including mono-fractal and multi-fractal, and such fractal dynamics are intrinsic. As the centrifugal compressor is working under normal condition, its autocorrelation function curve demonstrates apparent stochastic characteristics, and its Hurst exponent and variance are lower. However, its autocorrelation function curve demonstrates an apparent heavy tail distribution, and its Hurst exponent and variance are higher, as it is working in an unstable condition, namely, surge. In addition, the results show that the multi-fractal spectrum parameters are closely related to the dynamic pressure. With the state of centrifugal compressor being changed from stable to unstable states, some multi-fractal spectrum parameters Δα, Δf(α), αmax, and f(αmin) become larger, but αmin in the multi-fractal spectrum show the opposite trend, and consistent properties are graphically shown for the randomly shuffled data. As a conclusion, the proposed method, as one measure method for entropy, can be used to feasibly identify the incipient surge of a centrifugal compressor and design its surge controller.
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One-step selective benzene acylation-Nazarov cyclization is an attractive, yet challenging method for the synthesis of the benzocyclopentanone skeleton, which is key intermediate of many natural products. Herein, two metal-cluster-based metal-organic frameworks (MCOFs) {(H3 O)2 [Co4 (pbcd)2 (µ3 -OH)2 ]â CH3 CH2 OHâ 4 H2 O}n (1; pbcd=9,9'-(propan-1,3-diyl)bis(9H-carbazole-3,6-dicarboxylic acid) and {[Co5.25 (mcd)2 (HCO2 )(µ2 -O)0.5 (µ3 -OH)0.5 (H2 O)4 ]â 6 H2 Oâ 5 DMF}n (2; mcd=9,9'-methylenebis(9H-carbazole-3,6-dicarboxylic acid) were developed to catalyze a tandem Nazarov cyclization reaction of 1,3-dimethoxybenzene with α,ß-unsaturated carboxylic acids for the synthesis of cyclopentenone[b]benzenes. MCOFs 1 and 2, which were constructed from tetranuclear CoII cluster [Co4 (µ3 -OH)2 ] and hexanuclear CoII cluster [Co6 (HCO2 )(µ2 -O)(µ3 -OH)], respectively, exhibit high catalytic activity arising not only from their suitable channel size and accessible catalytic sites, but also because of their high density of Lewis acidic sites within the frameworks and the synergic activity among CoII ions. In contrast, {[Co2 (pbcd)(bpe)]â 2 H2 Oâ 2 DMF}n (3; bpe=1,2-bis(pyridin-4-yl)ethane) containing binuclear CoII and having large pore windows is a highly selective catalyst for obtaining exclusively the acylation products. Easy product separation, simple reaction procedures, and catalyst recycling make the catalyst system attractive. This work highlights the synergistic effect among ions of MCOFs in interacting with substrates in a sequential or cooperative manner to achieve tandem catalysis.
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A series of solvent-induced Ag-based coordination polymers (CPs) (1-3), which were synthesized by regulating the size, shape, and polarity of solvent molecules (EtOH, iPrOH, 1,4-dioxane) as structure-directing agents, has been used as heterogeneous catalysts to explore how the metal-metal bonds could serve as cooperative catalysis for tandem acylation-Nazarov cyclization reaction to prepare cyclopentenone[b]pyrroles frameworks. Structural conversions from a three-dimensional (3D) framework of 1 to the structure of 2 with Ag-Ag-Ag bonds and to the two-dimensional (2D) framework of 3 with Ag-Ag bonds, arising from the different sizes, shapes, and polarities of the solvent molecules, were observed. Futhermore, the effective cooperative catalysis for tandem acylation-Nazarov cyclization reaction has been evidenced by the significantly transformed connection modes of Ag-Ag interactions in 1-3. As a result, the unique structural characteristics of 2, especially containing the Ag-Ag-Ag bonds, endow 2 with intact multinuclear reaction pathways and well-defined multinuclear platforms that can execute tandem acylation-Nazarov cyclization reaction through the cooperative effect of Ag-Ag-Ag interactions during the catalytic process.
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Different morphologies and particle sizes of two crystalline zinc-based coordination polymers (CPs), [Zn(pytz)H2 O]n (1; H2 pytz=2,6-bis(tetrazole)pyridine) and [Zn2 (pytz)2 4 H2 O] (2), from the bulk scale to the nanoscale, could be obtained under solvothermal conditions with different surfactants (polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) 2000) as templates. PVP and PEG 2000 could act as capping and structure-directing agents, respectively, to influence the growth of crystalline particles and control their sizes. CP 1 exhibits a two-dimensional framework with window-like units and 2 shows a bimetallic structure. Nanocrystalline 1 and 2 were used as heterogeneous catalysts to study how adjacent catalytic active sites synergistically effected their catalytic reactivities in the direct catalytic conversion of aromatic dinitriles into oxazolines. The results showed that 1 produced bis-oxazolines as the sole products, whereas 2 gave the mono-oxazolines as the major products under the same reaction conditions.
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Although annexin A1 (ANXA1), a 37 kDa phospholipidbinding antiinflammatory protein expressed in various tissues and cell types, has been investigated extensively for its regulatory role in cancer biology, studies have mainly focused on its intracellular role. However, cancer cells and stromal cells expressing ANXA1 have the ability to transmit signals within the tumor microenvironment (TME) through autocrine, juxtacrine, or paracrine signaling. This bidirectional crosstalk between cancer cells and their environment is also crucial for cancer progression, contributing to uncontrolled tumor proliferation, invasion, metastasis and resistance to therapy. The present review explored the important role of ANXA1 in regulating the cellspecific crosstalk between various compartments of the TME and analyzed the guiding significance of the crosstalk effects in promotion or suppressing cancer progression in the development of cancer treatments. The literature shows that ANXA1 is critical for the regulation of the TME, indicating that ANXA1 signaling between cancer cells and the TME is a potential therapeutic target for the development of novel therapeutic approaches for impeding cancer development.
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Anexina A1 , Microambiente Tumoral , Humanos , Anexina A1/genética , Anexina A1/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Transdução de Sinais , Microambiente Tumoral/genéticaRESUMO
[This corrects the article DOI: 10.3389/fimmu.2022.967040.].
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Introduction: Viral infection is an exogeneous factor for primary Sjogren's syndrome (pSS). This study investigated the association between human papillomavirus (HPV) infections and pSS through a nationwide population based cohort study. Methods: Patients with HPV infections between January, 1999 and December, 2013 were included. The incidence of new-onset pSS in patients with HPV infections and non-HPV controls were derived. The multiple Cox regression model derived the risk of pSS in patients with HPV infections. Subgroup analysis and sensitivity analysis were performed to validate the association. Results: During a follow-up period of 12 years, the adjusted hazard ratio (aHR) of pSS in patients with HPV infections was significantly higher than that in non-HPV controls (aHR=1.64, 95% CI=1.47-1.83, P<0.001). The risk of pSS increased with age and the risk increased by 2.64-fold (95% CI= 2.37-2.93) for those older than 45 years. The significant association between HPV infections and the risk of pSS persisted in the sensitivity analysis restricted in HPV infections that lasted over 12 months (aHR=1.63, 95%CI=1.45-1.83, P<0.0001). Subgroup analyses revealed that both male (aHR=1.83, 95%CI=1.47-2.28, P<0.0001) and female (aHR=1.58, 95%CI=1.40-1.79, P<0.0001) patients with HPV infections and HPV-infected patients aged between 16 and 45 years (aHR=1.60, 95%CI=1.34-1.91, P<0.0001) and over 45 years (aHR=1.67, 95%CI=1.46-1.91, P<0.0001) were associated with a significantly greater risk of pSS. Conclusion: Patients with HPV infections presented with a significantly higher risk of pSS, regardless of age and sex.
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Infecções por Papillomavirus , Síndrome de Sjogren , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Modelos de Riscos Proporcionais , Síndrome de Sjogren/complicações , Síndrome de Sjogren/epidemiologia , Adulto JovemRESUMO
Construction of porous photoactive MOF-based composite systems is regarded as one of the most effective strategies to improve light harvesting, increase the surface area, provide plenty of exposed active sites, and promote the reduction and oxidation abilities of some organic photocatalytic reactions. Herein, we synthesized porous CdS@Zr-MOF photocatalysts based on the representative photocatalyst CdS and crystalline Zr-MOFs, such as MOF-808, NU-1000, and PCN-222, to illustrate their excellent photocatalytic performance for the synthesis of imines in air. The morphology and composition of these photocatalysts were investigated by X-ray powder diffraction (XRD), inductively coupled plasma-atomic emission spectrometry (ICP-AES), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS), indicating their crystallinity, high porosity, and interfacial interaction between constituents. Compared with individual components, these porous CdS@Zr-MOF composites could remarkably promote photocatalytic activity for the oxidative coupling of amines under air and visible-light conditions. The photocatalytic reaction showed broad substrate suitability. More importantly, the conversion yield reached up to 95% for the inactive aliphatic amines, and imines were formed as the single product. The improvement of the photocatalytic performance of CdS@Zr-MOF composites can be mainly ascribed to their high surface areas, more exposed active sites, excellent dispersion of CdS, and special porous photocatalytic systems, which tune the band gap, broaden the light response range, and facilitate the carrier separation.
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Porous two-dimensional metal-organic framework (2D-MOF) nanosheets Zr-BTB-H4TBAPy and PCN-134-2D were synthesized and characterized by X-ray diffraction (XRD), N2 adsorption-desorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and zeta potential and subjected to dye adsorption and separation investigation. These 2D-MOF nanosheets are ultrathin, have large surface area and high water stability and can selectively adsorb cationic dyes, rhodamine B (RhB) and methylene blue (MLB), from aqueous solutions, with removal rates of nearly 100% within 10 min. The adsorption kinetic results showed that Zr-BTB-H4TBAPy and PCN-134-2D could effectively and selectively remove cationic dyes from water, followed a pseudo-second-order kinetic model and fitted well with the Freundlich isotherm. The adsorption mechanism studies further indicated that their excellent adsorption and separation performance could be ascribed to their ultrathin and porous features, plentiful exposed surface-active sites, and favorable electrostatic interactions between the adsorbents and cationic dyes. Moreover, the porous 2D MOF nanosheets displayed excellent recyclability and reusability. These outstanding features make them potentially applicable for rapid and selective cationic dye adsorption and separation.
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Introduction: Ca2+-activated Cl- channel TMEM16A is expressed in endothelial cells, and contributes to many diseases such as hypertension, blood-brain barrier dysfunction, and pulmonary hypertension. It remains unclear whether TMEM16A regulates endothelial angiogenesis, which participates in many physiological and pathological processes. Cholesterol regulates many ion channels including TMEM16A, and high cholesterol levels contribute to endothelial dysfunction. It remains to be determined whether cholesterol regulates TMEM16A expression and function in endothelial cells. Objective: This study aimed to investigate whether cholesterol regulated TMEM16A expression and function in endothelial angiogenesis. Methods: Whole-cell patch clamp techniques were used to record Ca2+-activated Cl- currents in human aortic endothelial cells (HAECs) and HEK293 cells transfected with TMEM16A-overexpressing plasmids. Western blot was used to examine the expression of TMEM16A and DNA methyltransferase 1 (DNMT1) in HAECs. CCK-8 assay, would healing assay, and tube formation assay were used to test endothelial cell proliferation, migration and angiogenesis, respectively. Results: TMEM16A mediates the Ca2+-activated Cl- channel in HAECs. Cholesterol treatment inhibited TMEM16A expression via upregulation of DNMT1 in HAECs, and the inhibitory effect of cholesterol on TMEM16A expression was blocked by 5-aza, the DNMT1 inhibitor. In addition, direct application of cholesterol inhibited TMEM16A currents in heterologous HEK293 cells with an IC50 of 0.1209 µM. Similarly, cholesterol directly inhibited TMEM16A currents in HAECs. Furthermore, TMEM16A knockdown increased in vitro tube formation, cell migration and proliferation of HAECs, and TMEM16A overexpression produced the opposite effect. Conclusion: This study reveals a novel mechanism of cholesterol-mediated TMEM16A inhibition, by which cholesterol reduces TMEM16A expression via DNMT1-mediated methylation and directly inhibits channel activities. TMEM16A channel inhibition promotes endothelial cell angiogenesis.
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Anoctamina-1/antagonistas & inibidores , Canais de Cloreto/metabolismo , Colesterol/farmacologia , Células Endoteliais/efeitos dos fármacos , Neovascularização Patológica/metabolismo , Anoctamina-1/metabolismo , Aorta/metabolismo , Barreira Hematoencefálica/metabolismo , Cálcio/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Células Endoteliais/metabolismo , Células HEK293 , Humanos , Hipertensão/metabolismo , Técnicas de Patch-ClampRESUMO
PURPOSE: Ca2+-activated chloride channel TMEM16A has been found to be overexpressed in many cancers including head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of TMEM16A in oral squamous cell carcinoma (OSCC) remains unclear. Although simvastatin is known to produce anti-tumor effect, the mechanisms by which simvastatin inhibits cancer remain unclear. METHODS: In this study, we explored the role of TMEM16A expression in human OSCC tissues using both TCGA dataset and immunohistochemistry. CCK-8 assay was applied to evaluate cell proliferation. Patch clamp technique was applied to record TMEM16A Cl- currents. RESULTS: We found that high TMEM16A expression is related with large tumor size, lymph node metastasis, and poor clinical outcome in patients with OSCC. In addition, TMEM16A overexpression could promote cell proliferation, and inhibition of TMEM16A channel activities could suppress cell proliferation in OSCC cells. Furthermore, simvastatin could suppress TMEM16A channel activities, and inhibited cell proliferation in OSCC cells via TMEM16A. CONCLUSION: Our findings identify a novel anti-tumor mechanism of simvastatin by targeting TMEM16A. Simvastatin may represent an innovative strategy for treating OSCC with high TMEM16A expression.
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Anoctamina-1/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Neoplasias Bucais/patologia , Proteínas de Neoplasias/genética , Sinvastatina/farmacologia , Anoctamina-1/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Proliferação de Células/genética , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HaCaT , Humanos , Ativação do Canal Iônico/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/mortalidade , Proteínas de Neoplasias/metabolismo , Estadiamento de NeoplasiasRESUMO
Introduction: Transmembrane protein 16A (TMEM16A) is a Ca2+-activated chloride channel that plays a role in cancer cell proliferation, migration, invasion, and metastasis. However, whether TMEM16A contributes to breast cancer metastasis remains unknown. Objective: In this study, we investigated whether TMEM16A channel activation by ROCK1/moesin promotes breast cancer metastasis. Methods: Wound healing assays and transwell migration and invasion assays were performed to study the migration and invasion of MCF-7 and T47D breast cancer cells. Western blotting was performed to evaluate the protein expression, and whole-cell patch clamp recordings were used to record TMEM16A Cl- currents. A mouse model of breast cancer lung metastasis was generated by injecting MCF-7 cells via the tail vein. Metastatic nodules in the lung were assessed by hematoxylin and eosin staining. Lymph node metastasis, overall survival, and metastasis-free survival of breast cancer patients were assessed using immunohistochemistry and The Cancer Genome Atlas dataset. Results: TMEM16A activation promoted breast cancer cell migration and invasion in vitro as well as breast cancer metastasis in mice. Patients with breast cancer who had higher TMEM16A levels showed greater lymph node metastasis and shorter survival. Mechanistically, TMEM16A promoted migration and invasion by activating EGFR/STAT3/ROCK1 signaling, and the role of the TMEM16A channel activity was important in this respect. ROCK1 activation by RhoA enhanced the TMEM16A channel activity via the phosphorylation of moesin at T558. The cooperative action of TMEM16A and ROCK1 was supported through clinical findings indicating that breast cancer patients with high levels of TMEM16A/ROCK1 expression showed greater lymph node metastasis and poor survival. Conclusion: Our findings revealed a novel mechanism underlying TMEM16A-mediated breast cancer metastasis, in which ROCK1 increased TMEM16A channel activity via moesin phosphorylation and the increase in TMEM16A channel activities promoted cell migration and invasion. TMEM16A inhibition may be a novel strategy for treating breast cancer metastasis.
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Neoplasias da Mama , Animais , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Proteínas dos Microfilamentos , Quinases Associadas a rho/genéticaRESUMO
BACKGROUND AND PURPOSE: Ca2+ -activated Cl- channels (Ano1 channels) contribute to the pathogenesis of colorectal cancer. Honokiol is known to inhibit cell proliferation and tumour growth in colorectal cancer. However, the molecular target of honokiol remains unclear. This study aimed to investigate whether honokiol inhibited cell proliferation of colorectal cancer by targeting Ano1 channels. EXPERIMENTAL APPROACH: Patch-clamp techniques were performed to study the effect of honokiol on Ca2+ -activated Cl- currents in HEK293 cells overexpressing Ano1- or Ano2-containing plasmids or in human colorectal carcinoma SW620 cells. Site-directed mutagenesis was used to identify the critical residues for honokiol-induced Ano1 inhibition. Proliferation of SW620 cells or human intestinal epithelial NCM460 cells by CCK-8 assays. KEY RESULTS: Honokiol blocked Ano1 currents in Ano1-overexpressing HEK293 cells and SW620 cells. Honokiol more potently inhibited Ano1 currents than Ano2 currents. Three amino acids (R429, K430 and N435) were critical for honokiol-induced Ano1 inhibition. The R429A/K430L/N435G mutation reduced the sensitivity of Ano1 to honokiol. Honokiol inhibited SW620 cell proliferation, and this effect was reduced by Ano1-shRNAs. Furthermore, Ano1 overexpression promoted proliferation in NCM460 cells with low Ano1 endogenous expression and resulted in an increased sensitivity to honokiol. Overexpression of the R429A/K430L/N435G mutation reduced WT Ano1-induced increase in the sensitivity of NCM460 cells to honokiol. CONCLUSION AND IMPLICATIONS: We identified a new anticancer mechanism of honokiol, through the inhibition of cell proliferation, by targeting Ano1 Ca2+ -activated Cl- channels.
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Canais de Cloreto , Neoplasias Colorretais , Anoctamina-1 , Compostos de Bifenilo , Cálcio/metabolismo , Proliferação de Células , Canais de Cloreto/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Células HEK293 , Humanos , LignanasRESUMO
In this paper, two energy-transfer photochromic metal-organic frameworks (MOFs) {[Zn(L)0.5(bpy)]·H2O·DMF}n (1) and {[Zn(L)0.5(bpe)]·2H2O·DMF}n (2) (H4L = 9,9'-(1,4-phenylenebis(methylene))bis(9H-carbazole-3,6-dicarboxylic acid), bpy = 4,4'-bipyridine, bpe = 4,4'-vinylenedipyridine) were designed and synthesized. Both 1 and 2 showed similar pillared-paddle wheel type frameworks with bpy and bpe as the chromophore, respectively, and L4- as the antenna-type light harvester, yielding strut-to-strut energy transfer (antenna behavior) within the well-ordered structures. Among them, 1 displayed excellent energy-transfer photochromic behavior under UV light accompanied by color transformation from colorless to purple. In addition, the photochromic behavior of 1 has obvious, fast, controllable and reversible characteristics. On the other hand, 2 showed a different energy-transfer photochromic behavior in the aspects of color changing, gamut, and sensitivity. The variation has been ascribed to the substitution of chromophore bpy in 1 with bpe in 2, which influences the efficiency of energy transfer within the MOFs. Therefore, with the structural diversity and tunability of MOFs, the sensitivity, color, and gamut of energy-transfer of the photochromic MOFs can be tuned by the appropriate choice of the constitutions of MOFs. This work will provide useful guidance for developing novel energy-transfer photochromic MOF materials.
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Two new three-dimensional (3D) LnIII metal-organic frameworks (MOFs) were designed and successfully obtained via a solvothermal reaction between lanthanide(III) nitrates and a semi-flexible carbazole tetracarboxylate acid linker as a high-performance chromophore. 1 and 2 possess porous 3D networks with channels along the a axis, and more importantly, they show a highly sensitive and selective fluorescence quenching response to Fe3+ and CrVI anions. The sensing mechanism investigation revealed that the weak interactions of Fe3+ with nitrogen atoms of carbazole and deprotonated carboxylic acids protruding into the pores of MOFs quenched the luminescence of 1 and 2 effectively. In addition, the competition absorption also played an important role in the luminescence quenching detection of Fe3+ based on 1, and CrVI anions based on 1 and 2. Therefore, 1 and 2 represent an alternative example of regenerable luminescence based sensors for the quantitative detection of Fe3+ and CrVI anions.