How policy promotes the integration of culture and tourism? A fuzzy-set qualitative comparative analysis based on the Policy Instrument Theory.

Crafting pertinent policies to facilitate the high-level integration of culture and tourism has now become a vital agenda within the current discourse in China. However, relatively little is known about the actual implementation of various policies to achieve a high-level integration, especially how combinations of policy instruments are deployed in the process of realization. Based on the Policy Instrument Theory, this study uses fuzzy-set qualitative comparative analysis on a sample of 31 provincial administrative regions in China to investigate the influence of typical policy instruments on the integration level of tourism and culture. The results show that each single policy tool is not necessary for high-level integration of culture and tourism. On the contrary, only through an organic combination of different policy tools can affect the integration level. This study also summarizes five policy instrument configurations, which can be grouped into four driving modes of culture-tourism integration: the environment-driven supply-demand coordination mode, supply-driven demand-environment coordination mode, supply-driven mode, and supply-driven environment coordination mode. This study considerably provides critical theoretical and practical insights into the integration of culture and tourism from the perspective of governmental policies.

High glucose impairs cognitive function through inducing mitochondrial calcium overload in Treg cells.

High glucose has been proved to impair cognitive function in type 2 diabetes, but the underlying mechanisms remain elusive. Here, we found that high glucose increased transcription factors' SP1 O-GlcNAcylation in regulatory T (Treg) cells. Glycosylated SP1 further enhanced HDAC2 recruitment and histone deacetylation on Na+/Ca2+/Li+ exchanger (NCLX) promoter, which downregulated NCLX expression and led to mitochondrial calcium overload and oxidative damage, thereby promoting Treg cell dysfunction, M1 microglia polarization, and diabetes-associated cognitive impairment. Importantly, GLP-1 receptor agonist alleviated these deleterious effects via GLP-1-receptor-mediated upregulation of OGA and inhibition of SP1 O-GlcNAcylation in Treg cells. Our study highlighted a link between high-glucose-mediated SP1 O-GlcNAcylation and HDAC2/NCLX signaling in control of mitochondrial calcium concentrations in Treg cells. It also revealed a mechanism for linking Treg cell dysfunction and cognitive impairment in type 2 diabetes and provides an insight into the mechanism underlying the neuroprotective effects of GLP-1 receptor agonist.

[Distribution, Sources, and Ecological Risk Evaluation of Heavy Metals in Surface Sediments of Taihu Lake].

For the surface sediment samples of Taihu Lake in 2010, the eight physicochemical indices of pH, temperature, Eh, water content, porosity, grain size, total phosphorus, and Loss-on-ignition were measured and analyzed, along with the contents of nine heavy metals:Cu, Zn, Ni, Cr, Pb, Ba, Mn, Co, and V. The order of magnitudes of heavy metal content of surface sediments in Taihu Lake was:Mn>Ba>Zn>Cr>V>Ni>Pb>Cu>Co. This suggested that the contents of the nine heavy metals were beyond the background value, which had a close connection to the geology of the Taihu Lake Basin and were influenced by human activity to varying degrees. The clustering analysis and the spatial distribution of the heavy metals revealed that the concentrations of heavy metals in the North and South Taihu Lake sections decreased from the lake shore to the lake center, the concentrations of heavy metals in the West Taihu Lake section increased from the lake shore to the lake center, and the distribution of heavy metals in the center of the lake remained relatively uniform. According to the correlation study, the metal elements were positively correlated with one another to varying degrees, indicating that they originate from the same source of pollution. According to the PCA and PMF analyses, there were some different sources of heavy metals in Taihu Lake, in which the transportation and industrial complex source were the most important sources, the diagenesis was the second major source, and agriculture was the third major source. Furthermore, the heavy metal pollution was evaluated using the geoaccumulation and the potential ecological risk indices. This offers a solid theoretical backing for the future management of heavy metal pollution in Taihu Lake.

Correction: Pyrrolopyrrole aza-BODIPY near-infrared photosensitizer for dual-mode imaging-guided photothermal cancer therapy.

Correction for 'Pyrrolopyrrole aza-BODIPY near-infrared photosensitizer for dual-mode imaging-guided photothermal cancer therapy' by Chaolong Wu et al., Chem. Commun., 2019, 55, 790-793, https://doi.org/10.1039/C8CC07768A.

Non-canonical function of DPP4 promotes cognitive impairment through ERp29-associated mitochondrial calcium overload in diabetes.

DPP4 has been shown to induce diabetes-associated mitochondrial dysfunction and cognitive impairment through its non-canonical function. Here, we report that enhanced DPP4 expression in diabetes contributes to IP3R2-mediated mitochondria-associated ER membrane (MAM) formation, mitochondria calcium overload, and cognitive impairment, and its knockdown showed opposite effects. Mechanistically, DPP4 binds to PAR2 in hippocampal neurons and activates ERK1/2/CEBPB signaling, which upregulates ERp29 expression and promotes its binding to IP3R2, thereby inhibiting IP3R2 degradation and promoting MAM formation, mitochondria calcium overload, and cognitive impairment. Meanwhile, targeting DPP4-mediated PAR2/ERK1/2/CEBPB/ERp29 signaling achieved satisfactory therapeutic effects on MAM formation, mitochondria calcium overload, and cognitive impairment. Notably, DPP4 activates this pathway in an enzymatic activity-independent manner, suggesting the non-canonical role of DPP4 in the pathogenesis of mitochondria calcium overload and cognitive impairment in diabetes. Together, these results identify DPP4-mediated PAR2/ERK1/2/CEBPB/ERp29 signaling as a promising therapeutic target for the treatment of cognitive impairment in type 2 diabetes.

Nonenzymatic function of DPP4 promotes diabetes-associated cognitive dysfunction through IGF-2R/PKA/SP1/ERp29/IP3R2 pathway-mediated impairment of Treg function and M1 microglia polarization.

BACKGROUND: Impairment of regulatory T (Treg) cells function is implicated in the pathogenesis of immune imbalance-mediated cognitive impairment. A complete understanding of whether and how this imbalance affect cognitive function in type 2 diabetes is lacking, and the driver affecting this imbalance remains unknown. METHODS: We examined the impact of enzymatic and non-enzymatic function of DPP4 on Treg cell impairment, microglia polarization and diabetes-associated cognitive defects and identified its underlying mechanism in type 2 diabetic patients with cognitive impairment and in db/db mice. RESULTS: We report that DPP4 binds to IGF2-R on Treg cell surface and activates PKA/SP1 signaling, which upregulate ERp29 expression and promote its binding to IP3R2, thereby inhibiting IP3R2 degradation and promoting mitochondria-associated ER membrane formation and mitochondria calcium overload in Tregs. This, in turn, impairs Tregs function and polarizes microglia toward a pro-inflammatory phenotype in the hippocampus and finally leads to neuroinflammation and cognitive impairment in type 2 diabetes. Importantly, inhibiting DPP4 enzymatic activity in type 2 diabetic patients or mutating DPP4 enzymatic active site in db/db mice did not reverse these changes. However, IGF-2R knockdown or blockade ameliorated these effects both in vivo and in vitro. CONCLUSION: These findings highlight the nonenzymatic role of DPP4 in impairing Tregs function, which may facilitate the design of novel immunotherapies for diabetes-associated cognitive impairment.

Identification of driver genes based on gene mutational effects and network centrality.

BACKGROUND: As one of the deadliest diseases in the world, cancer is driven by a few somatic mutations that disrupt the normal growth of cells, and leads to abnormal proliferation and tumor development. The vast majority of somatic mutations did not affect the occurrence and development of cancer; thus, identifying the mutations responsible for tumor occurrence and development is one of the main targets of current cancer treatments. RESULTS: To effectively identify driver genes, we adopted a semi-local centrality measure and gene mutation effect function to assess the effect of gene mutations on changes in gene expression patterns. Firstly, we calculated the mutation score for each gene. Secondly, we identified differentially expressed genes (DEGs) in the cohort by comparing the expression profiles of tumor samples and normal samples, and then constructed a local network for each mutation gene using DEGs and mutant genes according to the protein-protein interaction network. Finally, we calculated the score of each mutant gene according to the objective function. The top-ranking mutant genes were selected as driver genes. We name the proposed method as mutations effect and network centrality. CONCLUSIONS: Four types of cancer data in The Cancer Genome Atlas were tested. The experimental data proved that our method was superior to the existing network-centric method, as it was able to quickly and easily identify driver genes and rare driver factors.

Photothermal-pH-hypoxia responsive multifunctional nanoplatform for cancer photo-chemo therapy with negligible skin phototoxicity.

Highly specific and effective cancer phototherapy remains as a great challenge. Herein, a smart nanoplatform (TENAB NP) sequentially responsive to light, low pH and hypoxia is demonstrated for multi-mode imaging guided synergistic cancer therapy with negligible skin phototoxicity. Upon 808-nm laser irradiation, TENAB NPs can generate hyperthermia to melt the phase change material (PCM-LASA) coat and thereafter release chemo-drug tirapazamine (TPZ). Meanwhile, under acidic pH, photosensitizer ENAB would turn "off" its charge-transfer state, generating prominent 1O2 for photodynamic therapy (PDT) and heat for photothermal therapy (PTT), respectively. Accompanied with PDT-induced hypoxia, the released TPZ can be activated into its cytotoxic form for tumor cells killing. Notably, owing to phase change material LASA coat and ENAB's pH sensitivity, TENAB NPs show negligible photosensitization to skin and normal tissues. As the multi-stimuli responsive mechanism, TENAB NPs demonstrate a promising future in cancer photo-chemo theranostics with excellent skin protection.

Regorafenib Promotes Antitumor Immunity via Inhibiting PD-L1 and IDO1 Expression in Melanoma.

PURPOSE: Immune checkpoint blockade (ICB) therapy induces durable tumor regressions in a minority of patients with cancer. In this study, we aimed to identify kinase inhibitors that were capable of increasing the antimelanoma immunity. EXPERIMENTAL DESIGN: Flow cytometry-based screening was performed to identify kinase inhibitors that can block the IFNγ-induced PD-L1 expression in melanoma cells. The pharmacologic activities of regorafenib alone or in combination with immunotherapy in vitro and in vivo were determined. The mechanisms of regorafenib were explored and analyzed in melanoma patients treated with or without anti-PD-1 using The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets. RESULTS: Through screening of a kinase inhibitor library, we found approximately 20 agents that caused more than half reduction of cell surface PD-L1 level, and regorafenib was one of the most potent agents. Furthermore, our results showed that regorafenib, in vitro and in vivo, strongly promoted the antitumor efficacy when combined with IFNγ or ICB. By targeting the RET-Src axis, regorafenib potently inhibited JAK1/2-STAT1 and MAPK signaling and subsequently attenuated the IFNγ-induced PD-L1 and IDO1 expression without affecting MHC-I expression much. Moreover, RET and Src co-high expression was an independent unfavorable prognosis factor in melanoma patients with or without ICB through inhibiting the antitumor immune response. CONCLUSIONS: Our data unveiled a new mechanism of alleviating IFNγ-induced PD-L1 and IDO1 expression and provided a rationale to explore a novel combination of ICB with regorafenib clinically, especially in melanoma with RET/Src axis activation.

Smart Aza-BODIPY Photosensitizer for Tumor Microenvironment-Enhanced Cancer Phototherapy.

Photoactivated cancer therapeutic methods emerging in recent decades, such as photothermal therapy (PTT) and photodynamic therapy (PDT), have drawn worldwide research interest. Herein, a smart near-infrared (NIR) photosensitizer 4-(4-(7-(4-Bromophenyl)-1,9-bis(3,4-dimethoxyphenyl)-5,5-difluoro-5H-5l4,6l4-dipyrrolo[1,2-c:2',1'-f][1,3,5,2]triazaborinin-3-yl)phenyl)morpholine (MAB) with morpholine decorating on the aza-BODIPY core is synthesized to achieve dual-modal imaging-guided synergistic PDT/PTT, exhibiting a tumor microenvironment (TME) enhanced cancer theranostic performance. The introduction of electron-donating morpholine offers MAB-enhanced intramolecular charge transfer (ICT) and a pronounced red-shift with maximum absorption peak (λmax) at 730 nm. After encapsulating with amphiphilic polymer DSPE-mPEG2000, as-obtained MAB nanoparticles (NPs) with good biocompatibility can enrich targeting in the lysosomes of tumor cells and afterward be activated under the acidic microenvironment inside the lysosome (pH 5.0) to generate intracellular reactive oxygen species (ROS) for enhanced PDT through interruption of photoinduced electron transfer (PET). Through in vitro cytotoxicity assay studies, the half-maximal inhibitory concentration (IC50) of MAB NPs under irradiation with the 730 nm laser is ∼10 µg/mL, indicating an excellent phototherapy effect. Furthermore, an in vivo study illustrates a prominent PDT/PTT synergistic therapeutic effect, and MAB NPs can be rapidly metabolized.

PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma cell line CNE-2 by inducing endoplasmic reticulum stress, downregulating STAT3 signaling, and modulating the MAPK pathway.

Paris polyphylla var. yunnanensis, named Chong Lou, is considered an antitumor substance. In this study, we investigated the effect of PP-22, a monomer purified from P. polyphylla var. yunnanensis, on the nasopharyngeal carcinoma cell line CNE-2 in vitro. The results showed that PP-22 could inhibit the proliferation of CNE-2 cells via the induction of apoptosis, with evidence of the characteristic morphological changes in the apoptosis in the nucleus and an increase in Annexin V-positive cells. In addition, we found that PP-22 could activate the p38 mitogen-activated protein kinase (MAPK) pathway and that this activation was reversed by SB203580, a specific inhibitor of the p38 MAPK pathway. In contrast, PP-22 promoted apoptosis via an intrinsic pathway, including the endoplasmic reticulum stress pathway, in a caspase-dependent manner. A further study showed that PP-22 also induced apoptosis by downregulating the signal transducers and activators of transcription 3 (STAT3) pathway, and the inhibitory effect was also confirmed by STAT3 small interfering RNA. In addition, PP-22 could promote autophagy by inhibiting the extracellular regulated protein kinases (ERK) pathway. And autophagy plays a protective role against apoptosis. Together, these data show that PP-22 promotes autophagy and apoptosis in the nasopharyngeal carcinoma CNE-2 cell line.

Pyrrolopyrrole aza-BODIPY near-infrared photosensitizer for dual-mode imaging-guided photothermal cancer therapy.

A NIR photosensitizer pyrrolopyrrole aza-BODIPY (PPAB) was synthesized in a straightforward manner. Through the use of PPAB NPs as a photothermal agent, photoacoustic imaging (PAI) and NIR fluorescence imaging (NIR-FI) can be achieved in vivo. In addition, the photothermal ablation of tumor cells can be realized both in vitro and in vivo, even at a low concentration (0.5 mg kg-1).

A light-induced nitric oxide controllable release nano-platform based on diketopyrrolopyrrole derivatives for pH-responsive photodynamic/photothermal synergistic cancer therapy.

Emerging treatment approaches, such as gas therapy (GT), photodynamic therapy (PDT) and photothermal therapy (PTT), have received widespread attention. The development of an intelligent multifunctional nano-platform responding to tumor microenvironments for multimodal therapy is highly desirable. Herein, a near-infrared (NIR) light-responsive nitric oxide (NO) photodonor (4-nitro-3-trifluoromethylaniline, NF) and a pH-sensitive group (dimethylaminophenyl) have been introduced into a diketopyrrolopyrrole core (denoted as DPP-NF). The DPP-NF nanoparticles (NPs) can be activated under weakly acidic conditions of lysosomes (pH 4.5-5.0) to generate reactive oxygen species (ROS) and enhance photothermal efficiency. The fluorescence detection demonstrated that NO controllable release can be realized by "on-off" switching of the NF unit under NIR light irradiation or dark conditions. The controllable NO release of DPP-NF NPs can not only trigger tumor cell death by DNA damage, but also overcome PDT inefficiencies caused by hypoxia in tumors. Additionally, DPP-NF NPs displayed 45.6% photothermal conversion efficiency, making them superior to other reported DPP derivatives. In vitro studies showed that DPP-NF NPs possessed low dark toxicity and high phototoxicity with a half-maximal inhibitory concentration of about 38 µg mL-1. In vivo phototherapy indicated that DPP-NF NPs exhibited excellent tumor phototherapeutic efficacy with passive targeting of the tumor site via the enhanced permeability and retention (EPR) effect. These results highlight that the nano-platform has promising potential for NO-mediated multimodal synergistic phototherapy in clinical settings.

2-Pyridone-functionalized Aza-BODIPY photosensitizer for imaging-guided sustainable phototherapy.

To overcome irradiation-dependence of cancer phototherapy, a near infrared aza-BODIPY-based photothermogenic photosensitizer BDY with 2-Pyridone group has been synthesized for imaging-guided photothermal synergistic sustainable photodynamic therapy. Multifunctional water-soluble BDY nanoparticles (NPs), with high photothermal conversion efficiency of 35.7% and excellent singlet oxygen (1O2) generation ability, are prepared by self-assembling. The reversible transformation between 2-pyridone moiety and its endoperoxide form endows BDY with continuous 1O2 generation ability under illumination and non-illumination conditions. Simultaneously, BDY NPs exhibit excellent tumor targeting properties by enhanced permeability and retention (EPR) effect and photoacoustic imaging (PAI) ability. Furthermore, the photothermal assisted sustainable photodynamic therapy can significantly inhibit tumor growth (93.4% inhibition) with almost no side effects by intermittent laser illumination. The finding highlights that this photothermal synergistic sustainable phototherapy presents great potential for clinical applications.

RNA-Seq identification of candidate defense genes targeted by endophytic Bacillus cereus-mediated induced systemic resistance against Meloidogyne incognita in tomato.

BACKGROUND: The endophytic bacteria Bacillus cereus BCM2 has shown great potential as a defense against the parasitic nematode Meloidogyne incognita. Here, we studied endophytic bacteria-mediated plant defense against M. incognita and searched for defense-related candidate genes using RNA-Seq. RESULTS: The induced systemic resistance of BCM2 against M. incognita was tested using the split-root method. Pre-inoculated BCM2 on the inducer side was associated with a dramatic reduction in galls and egg masses on the responder side, but inoculated BCM2 alone did not produce the same effect. In order to investigate which plant defense-related genes are specifically activated by BCM2, four RNA samples from tomato roots were sequenced, and four high-quality total clean bases were obtained, ranging from 6.64 to 6.75 Gb, with an average of 21 558 total genes. The 34 candidate defense-related genes were identified by pair-wise comparison among libraries, representing the targets for BCM2 priming resistance against M. incognita. Functional characterization revealed that the plant-pathogen interaction pathway (ID: ko04626) was significantly enriched for BCM2-mediated M. incognita resistance. CONCLUSION: This study demonstrates that B. cereus BCM2 maintains a harmonious host-microbe relationship with tomato, but appeared to prime the plant, resulting in more vigorous defense response toward the infection nematode. © 2018 Society of Chemical Industry.

A tumor-mitochondria dual targeted aza-BODIPY-based nanotheranostic agent for multimodal imaging-guided phototherapy.

Mitochondria targeted phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has excelled as an effective approach among other non-specific techniques for its high selectivity, non-invasiveness and low systemic toxicity. Derivatives of porphyrins, indocyanine dyes and rhodamine are widely utilized for cancer PDT or PTT. However, limitations, such as hypoxia and heat resistance of PDT and PTT, have restricted their efficacy in tumor treatment, making it urgent to develop highly efficient theranostic agents with synergistic effects. Aza-boron-dipyrromethene (aza-BODIPY) has shown promising prospects for synergistic phototherapy due to its outstanding reactive oxygen species (ROS) generation and photothermal effect. Herein, we designed and synthesized a near-infrared (NIR) aza-BODIPY derivative MeOABBr (ΦΔ = 84%). By encapsulating it with polyethylene glycol-folic acid (PEG-FA) and polyethylene glycol-triphenylphosphonium (PEG-TPP), tumor and mitochondria dual targeting nanoparticles (FMAB NPs) have been obtained. Triggered by NIR irradiation, FMAB NPs could generate ROS and hyperthermia (η = 40%) to cause mitochondrial dysfunction, resulting in cell apoptosis. Simultaneously, FMAB NPs, with unique optical properties, can be monitored precisely by photoacoustic, fluorescence and photothermal imaging in vivo. In particular, as proved by both in vitro and in vivo experiments, tumor-mitochondria dual targeted FMAB NPs exhibit high phototherapeutic efficacy without toxicity to normal tissues.

NIR-Absorbing water-soluble conjugated polymer dots for photoacoustic imaging-guided photothermal/photodynamic synergetic cancer therapy.

"Theranostics" become increasingly significant in current personalized precision medicine. Herein, we developed a new NIR-absorbing photo-theranostic agent based on water-soluble diketopyrrolopyrrole (DPP) conjugated polymer (WSCP) dots. The WSCPs can be easily self-assembled into WSCP dots under ultrasonication only, instead of any other nano-technology. Compared to the monomers of WSCPs, WSCP dots have no fluorescence emission but produce photoacoustic (PA) signal detected upon laser irradiation due to the reduced energy loss from excited state. PA imaging in vivo indicated that WSCP dots can accumulate at tumor site within 4 h post-injection. More importantly, WSCP dots not only generate heat with a photothermal conversion efficiency of ∼54%, but also produce reactive oxygen species (ROS, QY ∼13%). Furthermore, in vitro and in vivo experiments confirmed effective inhibition of tumor growth by WSCP dots via synergetic photothermal/photodynamic therapy. All results indicate a great potential of WSCP dots as highly efficient theranostic agents in PA imaging-guided synergetic cancer treatment.

Endophytic Bacillus cereus Effectively Controls Meloidogyne incognita on Tomato Plants Through Rapid Rhizosphere Occupation and Repellent Action.

Root-knot nematodes (Meloidogyne spp.), which cause severe global agricultural losses, can establish a special niche in the root vascular cylinder of crops, making them difficult to control. Endophytic bacteria have great potential as biocontrol organisms against Meloidogyne incognita. Three endophytic bacteria were isolated from plant tissues and showed high nematicidal activity against M. incognita second-stage juveniles (J2) in vitro. The gyrB gene sequence amplification results indicated that the three isolates were Bacillus cereus BCM2, B. cereus SZ5, and B. altitudinis CCM7. The isolates colonized tomato roots rapidly and stably during the colonization dynamic experiment. Three pot experiments were designed to determine the potential of three endophytic bacterial isolates on control of root-knot nematodes. The results showed that the preinoculated B. cereus BCM2 experiment significantly reduced gall and egg mass indexes. The inhibition ratio of gall and egg mass was up to 81.2 and 75.6% on tomato roots and significantly enhanced shoot length and fresh weight. The other two experiments with inoculated endophytic bacteria and M. incognita at the same time or after morbidity had lower inhibition ratios compared with the preinoculated endophytic bacteria experiment. The confocal laser-scanning microscopy method was used to further study the possible mechanism of endophytic bacteria in the biocontrol process. The results showed the localization pattern of the endophytic bacteria B. cereus BCM2-(str')-pBCgfp-1 in tomato root tissues. Root tissue colonized by endophytic bacteria repelled M. incognita J2 infection compared with the untreated control in a repellence experiment. We isolated an endophytic B. cereus strain that stably colonized tomato and controlled M. incognita effectively. This strain has potential for plant growth promotion, successful ecological niche occupation, and M. incognita J2 repellent action induction. It plays an important role in endophytic bacteria against root-knot nematodes.

Microwave-Assisted Synthesis of Arene Ru(II) Complexes Induce Tumor Cell Apoptosis Through Selectively Binding and Stabilizing bcl-2 G-Quadruplex DNA.

A series of arene Ru(II) complexes coordinated with phenanthroimidazole derivatives, [(η6-C6H6)Ru(l)Cl]Cl(1b L = p-ClPIP = 2-(4-Chlorophenyl)imidazole[4,5f] 1,10-phenanthroline; 2b L = m-ClPIP = 2-(3-Chlorophenyl)imidazole[4,5f] 1,10-phenanthroline; 3b L = p-NPIP = 2-(4-Nitrophenyl)imidazole[4,5f] 1,10-phenanthroline; 4b L = m-NPIP = 2-(3-Nitrophenyl) imidazole [4,5f] 1,10-phenanthroline) were synthesized in yields of 89.9%-92.7% under conditions of microwave irradiation heating for 30 min to liberate four arene Ru(II) complexes (1b, 2b, 3b, 4b). The anti-tumor activity of 1b against various tumor cells was evaluated by MTT assay. The results indicated that this complex blocked the growth of human lung adenocarcinoma A549 cells with an IC50 of 16.59 µM. Flow cytometric analysis showed that apoptosis of A549 cells was observed following treatment with 1b. Furthermore, the in vitro DNA-binding behaviors that were confirmed by spectroscopy indicated that 1b could selectively bind and stabilize bcl-2 G-quadruplex DNA to induce apoptosis of A549 cells. Therefore, the synthesized 1b has impressive bcl-2 G-quadruplex DNA-binding and stabilizing activities with potential applications in cancer chemotherapy.

microRNA-22 acts as a metastasis suppressor by targeting metadherin in gastric cancer.

microRNA (miR)-22 has been reported to be downregulated in hepatocellular, lung, colorectal, ovarian and breast cancer, acting as a tumor suppressor. The present study investigated the potential effects of miR-22 on gastric cancer invasion and metastasis and the molecular mechanism. miR-22 expression was examined in tumor tissues of in 89 gastric cancer patients by in situ hybridization (ISH) analysis. Additionally, the association between miR-22 levels and clinicopathological parameters was analyzed. A luciferase assay was conducted for target identification. The ability of invasion and metastasis of gastric cancer cells in vitro and in vivo was evaluated by cell migration and invasion assays and in a xenograft model. The results showed that miR-22 was downregulated in the gastric cancer specimens and significantly correlated with the advanced clinical stage and lymph node metastasis. In addition, metadherin (MTDH) was shown to be a direct target of miR-22 and the expression of MTDH was inversely correlated with miR-22 expression in gastric cancer. Ectopic expression of miR-22 suppressed cell invasion and metastasis in vitro and in vivo. The present study suggested that miR-22 may be a valuable prognostic factor in gastric cancer. miR-22 inhibited gastric cancer cell invasion and metastasis by directly targeting MTDH. The novel miR-22/MTDH link confirmed in the present study provided a novel, potential therapeutic target for the treatment of gastric cancer.