Substituent Dependence on Series of Cationic Gyroidal MOFs in utc-c Topology with High CO2 Affinity and Ultrahigh Anionic Dye Adsorption Capacity.

A substituent decorating strategy for modification of the functional cavity is of great importance in the design of metal-organic frameworks (MOFs). Herein, three new isostructural cationic MOFs, [Cu3(Xpip)2]·NO3·nH2O (Xpip stands for X-substituted phenylimidazophenanthroline, where X = adm (SCNU-2), f (SCNU-3), and none for SCNU-4), have been successfully synthesized and shown gyroidal utc-c topology and large pore sizes which can be adjusted by different substituents (-N(CH3)2, -F, and -H). Interestingly, the differences of the substituents (sizes and proton donor/acceptor) show essential effects on the adsorption abilities of carbon dioxide and dyes, where SCNU-4 exhibits the highest CO2 affinity and the biggest adsorption capacity for anionic dyes Fluorescein Sodium, and SCNU-3 adsorbs the largest amount (1503.6 mg/g) of Acid Fuchsin to date for the reported porous materials. The detailed studies in adsorption kinetics, adsorption isotherms, and theoretical calculation of the binding energies between the structures and dye molecules confirm that the electric properties of the frameworks (cationic) and substituents directed to the pore surface are two important factors dramatically affecting the selective dye adsorption.

Redox-Addressable Single-Molecule Junctions Incorporating a Persistent Organic Radical.

Integrating radical (open-shell) species into non-cryogenic nanodevices is key to unlocking the potential of molecular electronics. While many efforts have been devoted to this issue, in the absence of a chemical/electrochemical potential the open-shell character is generally lost in contact with the metallic electrodes. Herein, single-molecule devices incorporating a 6-oxo-verdazyl persistent radical have been fabricated using break-junction techniques. The open-shell character is retained at room temperature, and electrochemical gating permits in situ reduction to a closed-shell anionic state in a single-molecule transistor configuration. Furthermore, electronically driven rectification arises from bias-dependent alignment of the open-shell resonances. The integration of radical character, transistor-like switching, and rectification in a single molecular component paves the way to further studies of the electronic, magnetic, and thermoelectric properties of open-shell species.

[17ß-estradiol inhibits interleukin-1ß-induced rat nucleus pulposus cell apoptosis through the PI3K/Akt/mTOR signal pathway].

The apoptosis of nucleus pulposus cells (NPCs) is the main cellular process of intervertebral disc degeneration (IVDD). Our previous studies showed that 17ß-estradiol (E2) protects rat NPCs from interleukin-1ß (IL-1ß)-induced apoptosis via the PI3K/Akt signaling pathway. This study was aimed to investigate whether downstream proteins of PI3K/Akt pathway were involved in inhibition of E2 on NPCs' apoptosis. Primary culture of rat NPCs was isolated by trypsin digestion. Being pretreated with E2 and different inhibitors of downstream proteins of PI3K/Akt pathway, the NPCs were treated with IL-1ß. Cellular apoptosis was detected by Annexin V/PI staining. Cell viability was detected by CCK-8. Cell adhesion was evaluated by cell-collagen binding assay. Phosphorylation levels of mammalian target of Rapamycin (mTOR), glycogen synthase kinase-3ß (GSK-3ß) and nuclear factor κB (NF-κB) were detected by Western blot. The results showed that E2 significantly inhibited the IL-1ß-induced apoptosis of NPCs, reversed the decrease of cell viability and adhesion induced by IL-1ß, and inhibited the down-regulation of mTOR phosphorylation level induced by IL-1ß. Rapamycin could block these protective effects of E2. These results suggest that E2 may inhibit IL-1ß-induced NPCs' apoptosis through the PI3K/Akt/mTOR signaling pathway.

A Gyroidal MOF with Unprecedented Interpenetrating utc-c Network Exhibiting Exceptional Thermal Stability and Ultrahigh CO2 Affinity.

A zeolite-like gyroidal MOF (denoted as SCNU-1) constructed with Cu ions and 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol has a featured interpenetrating uninodal utc-c network which is for the first time found in the real structure. Moreover, SCNU-1 exhibits high thermal (>773 K), solvent, and acid/base stabilities; the largest CO2 affinity, 90 kJ/mol, among the MOFs functionalized with an aromatic hydroxyl group; and excellent CO2/N2 selectivity.

A novel Met-IR-782 near-infrared probe for fluorescent imaging-guided photothermal therapy in breast cancer.

In this work, a novel photothermal agent based on methionine (Met) was synthesized, which shows strong absorbance in the near infrared ray (NIR) region and is available for NIR imaging and in vivo photothermal therapy in a mouse model. Comparing to free IR-782, the obtained Met modified fluorescent dye (Met-IR-782) exhibited excellent fluorescence stability, preferable photothermal conversion efficiency under 780 nm laser irradiation and specific targeting to MCF7 (human breast adenocarcinoma cell line) cells. The fluorescence imaging ability enabled in situ monitoring of the tumor accumulation of Met-IR-782. The photothermal cytotoxicity assays in vitro and photothermal therapy treatments in vivo indicated that Met-IR-782 could efficiently target and suppress the growth of MCF7 xenograft tumors. Hence, Met-IR-782 is a potential fluorescent agent for NIR imaging-guided cancer photothermal therapy in clinical application. This work highlights the prospect of using light absorbing agents for NIR imaging-guided photothermal therapy.

Unexpected Synthesis of a Bulky Bis-Pocket A3B-Type Meso-Cyano Porphyrin.

A one-pot synthesis of bulky bis-pocket A3B-type meso-cyano porphyrin, 5-cyano-10,15,20-tris(2,4,6-triphenylphenyl)porphyrin, has been accomplished via trifluoroacetic acid (TFA) catalyzed condensation of pyrrole and 2,4,6-triphenylbenzaldehyde in an acceptable yield of about 4%. DDQ served as oxidant and the cyanating agent.

Involvement of microRNAs in HER2 signaling and trastuzumab treatment.

The prognostic value of HER2 has been demonstrated in many human cancer types such us breast cancer, gastric cancer and ovarian cancer. Trastuzumab is the first anti-HER2 monoclonal antibody that has remarkably improved outcomes of patients with HER2-positive breast cancer. For HER2-positive metastatic gastric cancers, the addition of trastuzumab to traditional chemotherapy also significantly prolonged overall survival. However, intrinsic and acquired resistance to trastuzumab is common and results in disease progression. HER2 signaling network and mechanisms underlying the resistance have been broadly investigated in order to develop strategy to overcome the dilemma. Increasing evidence indicates that microRNAs (miRNA), a group of small non-coding RNAs, are involved in HER2 signaling and trastuzumab treatment. This review summarizes all the miRNAs that target HER2 and describes their activity on biological processes. Moreover, miRNAs that regulate trastuzumab resistance and relevant molecular mechanisms are highlighted. MiRNA signatures associated with HER2, miRNAs that mediate trastuzumab activity, and potential miRNA biomarkers of trastuzumab sensitivity are also discussed.

MiR-145, a microRNA targeting ADAM17, inhibits the invasion and migration of nasopharyngeal carcinoma cells.

MiR-145 is downregulated and functions as a tumor suppressor in many malignancies. In this study, the biological function, molecular mechanism, and direct target genes of miR-145 in nasopharyngeal carcinoma (NPC) cells were investigated. Cell survival was detected by cell viability assay, and cell cycle was determined through flow cytometry. Invasion and migration of NPC cells were examined using cell invasion and wound healing assays, respectively. A disintegrin and metalloproteinase 17 (ADAM17) was verified as the target of miR-145 through luciferase reporter assay, qRT-PCR, and Western blot analysis. In NPC cell lines, miR-145 expression was significantly downregulated and ADAM17 protein expression was upregulated. ADAM17 was downregulated at the post-transcriptional level by miR-145 via the binding site of ADAM17-3'UTR. Transfection with miR-145 mimic suppressed cell growth and induced cell cycle arrest in the G0/G1 phase by upregulating key G0/G1 phase regulators, namely, p53 and p21. MiR-145 also inhibited cellular migration and invasion through targeting ADAM17 involving the regulation of EGFR and E-cadherin. Knockdown of ADAM17 elicited similar effects to that of miR-145 on NPC cells. This study reveals that miR-145 suppressed the invasion and migration of NPC cells by targeting ADAM17. Thus, miR-145 could be a therapeutic target for NPC.

Luteolin Inhibits Breast Cancer Development and Progression In Vitro and In Vivo by Suppressing Notch Signaling and Regulating MiRNAs.

BACKGROUND/AIMS: This study aims to investigate the effect of Luteolin on breast cancer in vitro and in vivo and the interaction between miRNAs and Notch signaling after Luteolin intervention, and illustrates the possible underlying mechanism and regulation loop. METHODS: Cell growth/survival assays and cell cycle analyses were performed to evaluate cell survival in vitro. Scratch tests, cell invasion assays and tube formation assays were carried out to analyze cell viability and identify the impact of Luteolin on angiogenesis. Critical components in the Notch pathway including proteins and mRNAs were detected by Western blotting analyses, ELISA assays and real-time reverse transcription-polymerase chain reaction. Matrix metalloproteinases activity was evaluated by gelatin zymography analyses. MiRNAs were analyzed by miRNA expression assays. After MDA-MB-231 cells were separately transfected with Notch-1 siRNA/cDNA and miRNA mimics, the above assays were also carried out to examine potential tumor cell changes. Xenograft models were applied to evaluate the treatment potency of Luteolin in breast cancer. RESULTS: Luteolin significantly inhibited breast cancer cell survival, cell cycle, tube formation and the expression of Notch signaling-related proteins and mRNAs, and regulated miRNAs. After introducing Notch-1 siRNA and miRNA mimics, MDA-MB-231 cells presented with changes in miRNA levels, reduced Notch signaling-related proteins, and decreased tumor survival, invasion and angiogenesis. CONCLUSION: Luteolin inhibits Notch signaling by regulating miRNAs. However, the effect of miRNAs on the Notch pathway could be either Luteolin-dependent or Luteolin-independent. Furthermore, Notch-1 alteration may inversely change miRNAs levels. Our data demonstrates that Luteolin, miRNAs and the Notch pathway are critical in breast cancer development and prognosis.

Downregulating HMGA2 attenuates epithelial-mesenchymal transition-induced invasion and migration in nasopharyngeal cancer cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is associated with invasion and metastasis of cancer cells. High-mobility group AT-hook 2 (HMGA2) has been found to play a critical role in EMT in a number of malignant tumors. However, whether HMGA2 regulates the EMT in human nasopharyngeal carcinoma (NPC) is unclear. OBJECTIVE: The aim of this study was to investigate the effect and mechanism of HMGA2 in inducing invasion and migration in NPC. METHODS: In NPC tissues samples, the association of HMGA2 mRNA expression with clinicopathological characteristics were estimated by real-time quantitative RT-PCR(qRT-PCR). In vitro, following the silencing of HMGA2 in CNE-1 and CNE-2 cell lines, the viability and metastatic ability were analyzed using Cell Counting Kit-8 (CCK8), colony formation assay, and transwell assay. EMT and transforming growth factor-beta (TGFß)/Smad3 signaling pathway-related protein expression changes were evaluated using western blot. RESULTS: HMGA2 was upregulated in NPC cell lines and clinical specimens (P < 0.01), and HMGA2 expression correlated significantly with metastasis (P = 0.02) and disease-free survival of NPC (hazard ratio: 3.52; 95% confidence interval: 1.34-7.79; P = 0.01). In addition, following in vitro knockdown of HMGA2, the aggressiveness of cells was markedly inhibited, Vimentin and Snail level was downregulated and E-cadherin expression was upregulated. Moreover, the expression of key proteins TGFßRII and p-Smad3 of the TGFß/Smad3 signaling pathway was inhibited by the downregulation of HMGA2. CONCLUSION: HMGA2 might maintain EMT-induced invasion and migration through the TGFß/Smad3 signaling pathway in NPC cell lines.

MiR-139-5p inhibits the biological function of breast cancer cells by targeting Notch1 and mediates chemosensitivity to docetaxel.

OBJECTIVES: MiRNA-139 is located at 11q13.4 and it has anti-oncogenic and antimetastatic activity in humans. However, its role in controlling apoptosis, invasion and metastasis and the development of chemosensitivity to docetaxel in breast cancer cells are not fully understood. The aim of this study was to research the biological function of miR-139-5p and the efficacy of chemosensitivity to docetaxel. METHODS: MiR-139-5p expression in MCF-7, MCF-7/Doc cells and in selected breast cancer tissue samples was confirmed by real-time PCR; cell viability was analyzed by Cell Counting Kit-8 assay; apoptosis and cell cycle were analyzed by flow cytometry; control of metastasis and invasion of breast cancer cells was measured by transwell assay; expression of Notch1 was measured by western blot; a luciferase reporter vector was constructed to identify the miR-139-5p target gene. RESULTS: MiR-139-5p was significantly down-regulated in breast cancer cells. MiR-139-5p inhibits the viability of breast cancer cells. MiR-139-5p induces apoptosis, causes cell cycle arrest in S phase, inhibits migration and invasion in breast cancer cells, however, MiR-139-5p play the opposite role in docetaxel-induced breast cancer cells. CONCLUSIONS: MiR-139-5p not only attenuated the development of breast cancer cells but also mediated drug-resistance by regulating the expression of the downstream target gene Notch1.

HAP1 gene expression is associated with radiosensitivity in breast cancer cells.

OBJECTIVES: The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells. METHODS: HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo. RESULTS: Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1+RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb+RT group. CONCLUSION: The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity.

MicroRNA-224: as a potential target for miR-based therapy of cancer.

MicroRNAs (miRNAs) are small noncoding RNA molecules which regulate the target gene expression posttranscriptionally. Increasing studies have shown that microRNAs play important roles in multiple biological pathways. For instance, aberrant expression of microRNA-224 (miR-224) plays a vital role in tumor biology in various types of human cancer. Here, we aim to summarize the molecular mechanisms that lead to the overexpression of miR-224 in cancers, analyze the effect of miR-224 on tumor biology, and reveal the clinical significance of miR-224. MiR-224 regulates its targets by modulating messenger RNA (mRNA) stability and/or protein translation, and it would provide new insight into molecular targeting cancer treatment.

In situ detection of salicylic acid binding sites in plant tissues.

The determination of hormone-binding sites in plants is essential in understanding the mechanisms behind hormone function. Salicylic acid (SA) is an important plant hormone that regulates responses to biotic and abiotic stresses. In order to label SA-binding sites in plant tissues, a quantum dots (QDs) probe functionalized with a SA moiety was successfully synthesized by coupling CdSe QDs capped with 3-mercaptopropionic acid (MPA) to 4-amino-2-hydroxybenzoic acid (PAS), using 1-ethyl-3-(3-dimethyllaminopropyl) carbodiimide (EDC) as the coupling agent. The probe was then characterized by dynamic light scattering and transmission electron microscopy, as well as UV/vis and fluorescence spectrophotometry. The results confirmed the successful conjugation of PAS to CdSe QDs and revealed that the conjugates maintained the properties of the original QDs, with small core diameters and adequate dispersal in solution. The PAS-CdSe QDs were used to detect SA-binding sites in mung bean and Arabidopsis thaliana seedlings in vitro and in vivo. The PAS-CdSe QDs were effectively transported into plant tissues and specifically bound to SA receptors in vivo. In addition, the effects of the PAS-CdSe QDs on cytosolic Ca(2+) levels in the tips of A. thaliana seedlings were investigated. Both SA and PAS-CdSe QDs had similar effects on the trend in cytosolic-free Ca(2+) concentrations, suggesting that the PAS-CdSe QDs maintained the bioactivity of SA. To summarize, PAS-CdSe QDs have high potential as a fluorescent probe for the in vitro/in vivo labeling and imaging of SA receptors in plants.

ß-elemene reverses chemoresistance of breast cancer via regulating MDR-related microRNA expression.

BACKGROUND: Multidrug resistance (MDR) directly contributes to the clinical failure of chemotherapy in breast cancer (BCA). ß-elemene is a natural antitumor drug from plants. We previously confirmed that MDR could be reversed by ß-elemene. In this study, we intended to investigate the reversal effect of ß-elemene on MDR in human BCA adriacin (Adr) -resistant MCF-7 cells (MCF-7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) through the gene regulatory network. METHODS: MTT-cytotoxic, miRNA microarray, Real-time quantitative PCR, Dual Luciferase Activity Assay, Western blot analysis were performed to investigate the impact of ß-elemene on chemo-resistant BCA cell suvival, and its impact on the expression of chemo-resistance specific miRNA and the downstream target genes PTEN and Pgp. RESULTS: Compared with the miRNAs expression profiles of MCF-7/Adr and MCF-7/Doc cell lines from our previous studies, there were 322 differentially expressed miRNAs in MCF-7/Adr and MCF-7/Doc breast cancer cells with ß-elemene intervention (50µM/L) for 30h, and 6 miRNAs were significantly up-regulated and 12 miRNAs were significantly down-regulated in both MCF-7/Adr and MCF-7/Doc. We have testified that 5 miRNA is related to MDR before, in this study, the expression of miR-34a, miR-222, miR-452 and miR-29a can lead to changes of the characteristics of chemo-resistant MCF-7/Adr and MCF-7/Doc. The PTEN expression under intervention of ß-elemene was significantly increased and Pgp expression under ß-elemene intervention was significantly decreased in both cell lines. CONCLUSIONS: ß-elemene could influence MDR related miRNA expression and subsequently regulate the expression of the target genes PTEN and Pgp, which may lead to reduction of the viability of the chemo-resistant breast cancer cells.

2-[2,6-Bis(pyrazin-2-yl)pyridin-4-yl]benzoic acid.

In the title compound, C20H13N5O2, the two pyrazine rings are nearly coplanar with the central pyridine ring, forming dihedral angles of 2.21 (9) and 4.57 (9)°. In contrast, the strong steric hindrance caused by the ortho-carboxyl group on the phenyl ring makes this ring rotate out of the attached pyridine ring plane by 52.60 (9)°. The carboxyl group is twisted from the phenyl ring by 22.6 (1)°. In the crystal, aromatic π-π stacking inter-actions [centroid-centroid distances = 3.9186 (4) and 3.9794 (5) Å] occur between the anti-parallel mol-ecules, generating infinite chains along [100]. O-H⋯O hydrogen bonds connect the chains, leading to the formation of a two-dimensional supra-molecular network parallel to (010). Inter-molecular C-H⋯N hydrogen bonds are also observed.

[Influence of parameters of ZnS film on the organic/inorganic composite luminescence devices].

In the present paper, to fabricate electroluminescent devices CdSe QDs were used as active materials, TPD (N,N'-biphenyl-N,N'-bis-(3-methylphenyl)-1,1'-biphenyl-4,4'-diamine) was used as a hole transport layer, and ZnS was used as an electron transport layer. The electroluminescent properties of the organic/inorganic composite ITO/TPD/CdSe QDs/ZnS/Ag light emitting devices were studied. Both TPD and CdSe QDs thin films were spin-coated and ZnS thin films were deposited by magnetron sputtering. The surfaces of the devices are smooth. The luminescence (EL) peak of the CdSe QDs is at 580 nm which is assigned to the band-edge exciton emission. Compared to the previous EL device of ITO/ZnS/CdSe QDs/ZnS/Ag, it is seen that the new devices do not display surface state related emission peaks and EL intensity is about 10 folds that of the previous device. The enhancement of luminescence efficiency is attributed to both of the excitation of CdSe QDs by accelerated electron collision and carriers injection into QDs: (1) electrons are accelerated by the ZnS layer and collide with CdSe QDs, which excites electrons in QDs to excited states and allows them to emit photons; (2) the holes injected into QDs recombine with some of electrons excited in the QDs. The authors further studied the influence of thickness variation of ZnS on the luminescent properties. ZnS thin films are of 80, 120, and 160 nm thickness, respectively. It was found that as the thickness of ZnS increases the threshold voltage rises and EL intensity increases, but breakdown voltage decreases. The EL peak position blue shifts when the thickness of ZnS decreases. The explanation of underlying mechanism is given.

Imaging of jasmonic acid binding sites in tissue.

Hormones regulate the mechanism of plant growth and development, senescence, and plants' adaptation to the environment; studies of the molecular mechanisms of plant hormone action are necessary for the understanding of these complex phenomena. However, there is no measurable signal for the hormone signal transduction process. We synthesized and applied a quantum dot-based fluorescent probe for the labeling of jasmonic acid (JA) binding sites in plants. This labeling probe was obtained by coupling mercaptoethylamine-modified CdTe quantum dots with JA using N-hydroxysuccinimide (NHS) as a coupling agent. The probe, CdTe-JA, was characterized by transmission electron microscopy, dynamic light scattering, and fluorescent spectrum and applied in labeling JA binding sites in tissue sections of mung bean seedlings and Arabidopsis thaliana root tips. Laser scanning confocal microscopy (LSCM) revealed that the probe selectively labeled JA receptor. The competition assays demonstrated that the CdTe-JA probe retained the original bioactivity of JA. An LSCM three-dimensional reconstruction experiment demonstrated excellent photostability of the probe.

Supramolecular networks of 10-(2-hydroxyethyl)acridin-9(10H)-one and 10-(2-chloroethyl)acridin-9(10H)-one.

Both 10-(2-hydroxyethyl)acridin-9(10H)-one, C15H13NO2, and 10-(2-chloroethyl)acridin-9(10H)-one, C15H12ClNO, have monoclinic (P21/c) symmetry and supramolecular three-dimensional networks. But the differences in the intermolecular interactions displayed by the hydroxy group and the chlorine substituent lead to stronger intermolecular π-stacking interactions and hydrogen bonding, and hence a significantly higher melting point for the former.

Hydrogen-bonding network of N,N'-bis[2-(tert-butyldimethylsiloxy)ethyl]ethylenediammonium dichloride.

The title salt, C18H46N2O2Si2(2+)·2Cl(-), has been synthesized by reaction of N,N'-bis(2-hydroxyethyl)ethylenediamine with tert-butyldimethylsilyl chloride. The zigzag backbone dication is located across an inversion centre and the two chloride anions are related by inversion symmetry. The ionic components form a supramolecular two-dimensional network via N-H···Cl hydrogen bonding, which is responsible for the high melting point compared with the oily compound N,N'-bis[2-(tert-butyldimethylsiloxy)ethyl]ethylenediamine.