Ubiquitin-specific protease 21 promotes tumorigenicity and stemness of colorectal cancer by deubiquitinating and stabilizing ZEB1.

BACKGROUND: Colorectal cancer (CRC) is one very usual tumor together with higher death rate. Ubiquitin-specific protease 21 (USP21) has been confirmed to take part into the regulation of CRC progression through serving as a facilitator. Interestingly, the promotive function of USP21 has also discovered in the progression of CRC. ZEB1 has illustrated to be modulated by USP7, USP22 and USP51 in cancers. However, the regulatory functions of USP21 on ZEB1 in CRC progression need more investigations. AIM: To investigate the relationship between USP21 and ZEB1 in CRC progression. METHODS: The mRNA and protein expressions were assessed through RT-qPCR, western blot and IHC assay. The interaction between USP21 and ZEB1 was evaluated through Co-IP and GST pull down assays. The cell proliferation was detected through colony formation assay. The cell migration and invasion abilities were determined through Transwell assay. The stemness was tested through sphere formation assay. The tumor growth was evaluated through in vivo mice assay. RESULTS: In this work, USP21 and ZEB1 exhibited higher expression in CRC, and resulted into poor prognosis. Moreover, the interaction between USP21 and ZEB1 was further investigated. It was demonstrated that USP21 contributed to the stability of ZEB1 through modulating ubiquitination level. In addition, USP21 strengthened cell proliferation, migration and stemness through regulating ZEB1. At last, through in vivo assays, it was illustrated that USP21/ZEB1 axis aggravated tumor growth. CONCLUSION: For the first time, these above findings manifested that USP21 promoted tumorigenicity and stemness of CRC by deubiquitinating and stabilizing ZEB1. This discovery suggested that USP21/ZEB1 axis may provide novel sights for the treatment of CRC.

K2Cr2O7-induced DNA damage in HT1080 cells: Electrochemical signal response mechanism.

The existing DNA damage detection technology cannot meet the current detection requirements. It is critical to build new methods and discover novel biomarkers. In this study, alkaline comet and 8-OHDG ELISA assays were used to identify DNA damage in HT-1080 cells exposed to K2Cr2O7, and electrochemical behaviors of HT-1080 cells with DNA damage was studied. With an increase in K2Cr2O7 exposure time, two electrochemical signals from HT-1080 cells at 0.69 and 1.01 V steadily grew before decreasing after reaching their highest values. The electrochemical signal's initial response time and peak time decreased as the concentration of K2Cr2O7 increased. The duration of the high dose group was 0.5 and 1 h, while the low dose group was 1.5 and 6 h. Western blotting analysis revealed that DNA damage increased the expression of proteins involved in catabolism and de novo purine synthesis, particularly de novo purine synthesis. Expressions of PRPP amidotransferase, IMPDH, and ADA were all higher than those of ADSS, XOD, and GDA, which resulted in larger concentrations of hypoxanthine, guanine, and xanthine, and in turn improved electrochemical signaling. These findings suggest that intracellular purine identified by linear scan voltammetry is predicted to evolve as a marker of early DNA damage.

Electrochemistry detection of estrogenic effect: Regulation of de novo purine synthesis and catabolism by gibberellin and fulvestrant.

The estrogenic effect of plant growth regulators has been received little attention, which leads to the lack of relevant toxicity data. In this study, the estrogenic effect induced by gibberellin with ERα-dependent manner was found by E-screen and western blot methods, and the electrochemical signals of MCF-7 cells regulated by gibberellin and fulvestrant were investigated. The results showed that the electrochemical signals of MCF-7 cells were increased by gibberellin, while reduced by fulvestrant significantly, and displayed an extremely sensitive response to the effects of estrogenic effect induced by ERα agonist and antagonist. Western blot results showed that the expressions of phosphoribosyl pyrophosphate amidotransferase and hypoxanthine nucleotide dehydrogenase in de novo purine synthesis and adenine deaminase in catabolism were more effective regulated by gibberellin and fulvestrant, resulting in significant changes of the levels of guanine, hypoxanthine and xanthine in cells, and then electrochemical signals. The results provide a theoretical basis for the establishment of new electrochemical detection method of the estrogenic effect of plant regulators.

Analysis of characteristic features in ultrasound diagnosis of fetal limb body wall complex during 11-13+6 weeks.

BACKGROUND: Limb body wall complex (LBWC) is a fatal malformation characterized by major defects in the fetal abdominal or thoracic wall, visceral herniation, significant scoliosis or spina bifida, limb deformities, craniofacial deformities, and umbilical cord abnormalities (short or absent umbilical cord). Early diagnosis of this condition is of great clinical significance for clinical intervention and pregnancy decision-making. With the rapid development of fetal ultrasound medicine, early pregnancy (11-13+6 wk) standardized prenatal ultrasound examinations have been widely promoted and applied. AIM: To explore the value of prenatal ultrasound in the diagnosis of fetal LBWC syndrome during early pregnancy. METHODS: The ultrasonographic data and follow-up results of 18 cases of fetal LBWC diagnosed by prenatal ultrasound during early pregnancy (11-13+6 wk) were retrospectively analyzed, and their ultrasonographic characteristics were analyzed. RESULTS: Among the 18 fetuses with limb wall abnormalities, there were spinal dysplasia (18/18, 100%), varying degrees of thoracoschisis and gastroschisis (18/18, 100%), limb dysplasia in 6 cases (6/18, 33%), craniocerebral malformations in 4 cases (4/18, 22%), thickening of the transparent layer of the neck in 5 cases (5/18, 28%), and umbilical cord abnormalities in 18 cases (18/18, 100%), single umbilical artery in 5 cases. CONCLUSION: Prenatal ultrasound in early pregnancy can detect LBWC as early as possible, and correct prenatal evaluation provides important guidance value for pregnancy decision-making and early intervention.

Ultrasonic visualization technique for anatomical and functional analyses of the sciatic nerve in rats.

Background and objective: Ultrasound has been widely used in the diagnosis and minimally invasive treatment of peripheral nerve diseases in the clinic, but there is still a lack of feasibility analysis in rodent models of neurological disease. The purpose of this study was to investigate the changes in the cross-sectional area of the sciatic nerve of different genders and body weights and to explore the effectiveness and reliability of an ultrasound-guided block around the sciatic nerve in living rats. Methods: Using ultrasound imaging anatomy of the sciatic nerve of rats, the cross-sectional area of the sciatic nerve in rats of different genders from 6 to 10 weeks old was calculated, and then analyzed its correlation with body weight. Further analyses were conducted through behavioral and cadaveric studies to evaluate the feasibility of ultrasound-guided perineural injection of the sciatic nerve in rats. Results: We first reported that the sciatic nerve cross-sectional area of rats was increased with age (F = 89.169, P < 0.001), males had a higher sciatic nerve cross-sectional area than females (F = 60.770, P < 0.001), and there was a positive correlation with body weight (rMale = 0.8976, P < 0.001; rFemale = 0.7733, P < 0.001). Behavioral observation of rats showed that the lower extremity complete block rate was 80% following the administration of drugs around the sciatic nerve under ultrasound guidance and staining with methylene blue occurred in all sciatic nerves and surrounding muscles and fascia using 20 ultrasound-guided injections. Conclusions: Ultrasound visualization technology can be used as a new auxiliary evaluation and intervention therapy for animal models of peripheral nerve injury, and will provide overwhelming new references for the basic research of neurological diseases.

Correction to: Effective transport network driven by tortuosity gradient enables high-electrochem-active solid-state batteries.

[This corrects the article DOI: 10.1093/nsr/nwac272.].

Soil C, N and P stoichiometry in different forest stand types in the middle and lower reaches of the Beijiang River, China.

We examined the vertical distribution characteristics of soil organic carbon (C), total nitrogen (N), total phosphorus (P) and their ecological stoichiometric ratios in 0-80 cm soil profile under three forest stand types in the middle and lower reaches of the Beijiang River, including broad-leaved forest, coniferous forest, and mixed coniferous and broad-leaved forest. The results showed that soil C, N and P contents of the three forest stand types were 12.17-14.25, 1.14-1.31, and 0.27-0.30 g·kg-1, respectively. The contents of C and N decreased with the increases of soil depth. The content of C and N in each soil layer showed that coniferous and broad-leaved mixed forest > coniferous forest > broad-leaved forest. There was no significant difference in P content among the three stand types, and there was no obvious variation in the vertical profile. The soil C/N, C/P, and N/P of the three forest types were 11.2-11.3, 49.0-60.3, and 4.5-5.7, respectively. There was no significant difference in soil C/N among the three stand types. The highest soil C/P and N/P were found in the mixed forest. There was no interaction between soil depth and stand type in affecting soil C, N, P contents and their stoichiometric ratios. There was significant positive correlation between C and N, and between N and C/P in each stand type and soil layer. Soil C/P and N/P had stronger ecological indicating effects on stand types. The coniferous and broad-leaved mixed forest was strongly limited by P availability.

Effective transport network driven by tortuosity gradient enables high-electrochem-active solid-state batteries.

Simultaneously achieving high electrochemical activity and high loading for solid-state batteries has been hindered by slow ion transport within solid electrodes, in particular with an increase in electrode thickness. Ion transport governed by 'point-to-point' diffusion inside a solid-state electrode is challenging, but still remains elusive. Herein, synchronized electrochemical analysis using X-ray tomography and ptychography reveals new insights into the nature of slow ion transport in solid-state electrodes. Thickness-dependent delithiation kinetics are spatially probed to identify that low-delithiation kinetics originate from the high tortuous and slow longitudinal transport pathways. By fabricating a tortuosity-gradient electrode to create an effective ion-percolation network, the tortuosity-gradient electrode architecture promotes fast charge transport, migrates the heterogeneous solid-state reaction, enhances electrochemical activity and extends cycle life in thick solid-state electrodes. These findings establish effective transport pathways as key design principles for realizing the promise of solid-state high-loading cathodes.

Effect of poly-γ-glutamic acid on the phytoremediation of ramie (Boehmeria nivea L.) in the Hg-contaminated soil.

Farmlands around the Hg mining areas have suffered from severe Hg contamination issues, triggering a phenomenon of high Hg content in crops, and subsequently threatening human health. In this study, ramie (Boehmeria nivea L.) assisted with poly-γ-glutamic acid (γ-PGA) was employed to remediate the Hg-contaminated soil through incubation experiments. After the soil was amended with γ-PGA, the leaf Hg content increased by 4.4-fold, and the translocation factor value even reached 3.5, indicating that γ-PGA could dramatically enhance the translocation of Hg from root and stem to leaf. γ-PGA could induce the transformation of potentially available Hg to available fractions, resulting in the soil Hg being more bioavailable. Batch trials verified that γ-PGA could mask the adsorption function of Hg ions by soil organic matter, significantly stimulating the desorption of Hg ions from the soil. As a result, the soil Hg would transfer to the aqueous phase and be assimilated by the root of ramie more easily and effectively. The γ-PGA chelated Hg is hydrophilic and has a high affinity with -SH and -S-; thereby, it can easily stride over the Casparian strip, enter the vessel, be translocated upwards, be sequestered in the tissues of leaf, and be incorporated irreversibly. This study can provide a new method for the remediation of Hg-contaminated soil.

Traditional Chinese Medicine Treatment, Gua Sha, can Induce Subtle Molecular Changes in Gene Expression / 生物医学与环境科学（英文）

OBJECTIVE@#Here, we explored molecular changes that could potentially mediate healing effects of Gua Sha - a method employed by the Chinese traditional medicine with proven track records of safe and efficient applications dating back to ancient times as well as support from randomized controlled trials performed by modern medical studies - yet remaining almost entirely unexplored by the modern-day high-throughput methods of the -omics sciences.@*METHODS@#We investigated transcriptome changes occurring shortly after Gua Sha treatment in the whole blood of healthy volunteers using bulk RNA-seq analysis. We applied various analytical tools to identify genes with consistent expression changes in multiple individuals in response to Gua Sha and their networks.@*RESULTS@#We found that while the changes were very subtle and individual-specific, we could identify consistent upregulation of three histone genes. Further analysis of the potential regulatory networks of these histone genes revealed the enrichment of functions involved in the immune response and inflammation.@*CONCLUSION@#The significance of these results in the context of potential effects of Gua Sha and the next steps in exploring the molecular mechanisms of action of this technique are discussed.

Simulation Palynologists for Pollinosis Prevention: A Progressive Learning of Pollen Localization and Classification for Whole Slide Images.

Existing API approaches usually independently leverage detection or classification models to distinguish allergic pollens from Whole Slide Images (WSIs). However, palynologists tend to identify pollen grains in a progressive learning manner instead of the above one-stage straightforward way. They generally focus on two pivotal problems during pollen identification. (1) Localization: where are the pollen grains located? (2) Classification: which categories do these pollen grains belong to? To perfectly mimic the manual observation process of the palynologists, we propose a progressive method integrating pollen localization and classification to achieve allergic pollen identification from WSIs. Specifically, data preprocessing is first used to cut WSIs into specific patches and filter out blank background patches. Subsequently, we present the multi-scale detection model to locate coarse-grained pollen regions (targeting at "pollen localization problem") and the multi-classifiers combination to determine the fine-grained category of allergic pollens (targeting at "pollen classification problem"). Extensive experimental results have demonstrated the feasibility and effectiveness of our proposed method.

The response of electrochemical method to estrogen effect and the tolerance to culture factors: Comparison with MTT and cell counting methods.

Estrogen substances in the environment are increasing dramatically, which interfere with the normal hormone level of human body, lead to the disorder of endocrine system and even cancer. It is difficult to screen a large number of environmental estrogen substances by existing estrogen effect detection methods, and the results are often affected by many factors, thus the development of new method has become an urgent task. Electrochemical method is promising to reflect cell proliferation by tracking intracellular purine bases directly. In this study, the estrogen level in MCF-7 cells on multiwall carbon nanotubes modified glassy carbon electrode (MWCNTs/GCE) could be tracked simply and conveniently, and the estrogen effect of estradiol could be reflected by electrochemistry in time and dose-dependent manners. Electrochemical method displayed the best tolerance to culture factors, such as different cell densities, serum types, culture medium types and serum estrogen-free methods, which responsed to estrogen effect higher than MTT (about 40%) and cell counting methods (about 50%). Further Western blotting analysis showed that the estrogen effect of estradiol promoted purine catabolism and up-regulated guanine deaminase (GDA) and adenine deaminase (ADA) expression, the key enzymes of purine catabolism pathway, in a dose-dependent manner. The up-regulation of GDA and ADA led to the increase of intracellular guanine and xanthine, which enhanced the electrochemical signal derived from guanine and xanthine.

Predictive Value of Preoperative Neutrophil-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma after Transarterial Chemoembolization Combined With Radiofrequency Ablation.

PURPOSE: To determine the predictive value of preoperative inflammatory markers in hepatocellular carcinoma (HCC) prognosis after transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA). MATERIALS AND METHODS: A total of 161 patients with HCC who underwent TACE combined with RFA were enrolled in this retrospective study. Receiver operating characteristic (ROC) curve analysis was used to decide the cutoff value of the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), the platelet-to-lymphocyte ratio (PLR), and the prognostic nutritional index (PNI). The relationship between preoperative NLR, LMR, PLR, PNI, and survival outcomes was analyzed using Kaplan-Meier curves and multivariate Cox regression analyses. RESULTS: The cutoff value of NLR for the best discrimination of HCC prognosis was 2.95. The median recurrence-free survival (RFS) of the low NLR (≤2.95) group was longer than that of the high NLR (>2.95) group (29 months vs. 20 months, p = 0.013). The median overall survival (OS) of the low NLR group was longer than that of the high NLR group (60 months vs. 38 months, p = 0.006). Multivariate analysis showed that the tumor size (≤3 cm vs. >3cm), tumor number (single vs. multiple), and NLR (≤2.95 vs. >2.95) were independent predictors of the PFS and OS. LMR, PLR, and PNI did not have any prognostic significance. CONCLUSION: NLR was confirmed as an independent predictive biomarker for hepatocellular carcinoma prognosis after TACE combined with RFA.

Inhibition of the STAT3 Signaling Pathway Contributes to the Anti-Melanoma Activities of Shikonin.

BACKGROUND: Malignant melanoma is an extremely aggressive and metastatic cancer, and highly resistant to conventional therapies. Signal transducer and activator of transcription 3 (STAT3) signaling promotes melanoma development and progression, which has been validated as an effective target in melanoma treatment. Natural naphthoquinone shikonin is reported to exert anti-melanoma effects. However, the underlying mechanisms have not been fully elucidated. PURPOSE: This study aims to evaluate the anti-melanoma activities of shikonin and explore the involvement of STAT3 signaling in these effects. METHODS: Zebrafish tumor model was established to evaluate the anti-human melanoma effects of shikonin in vivo. MTT assay and colony formation assay were employed to investigate the anti-proliferative effects of shikonin on human melanoma A375 and A2058 cells. Flow cytometry was used to analyze cell cycle distribution and apoptosis induction. Wound healing assay and Transwell chamber assay were conducted to examine the cell migratory and invasive abilities. Immunofluorescence assay was used to observe F-actin, Tubulin, and STAT3 localization. Western blotting was used to determine the expression levels of proteins associated with apoptosis and key proteins in the STAT3 signaling pathway. Immunoblotting was performed in DSS cross-linked cells to determine the homo-dimerization of STAT3. Gelatin zymography was employed to evaluate the enzymatic activity of MMP-2 and MMP-9. Transient transfection was used to overexpress STAT3 in cell models. RESULTS: Shikonin suppressed melanoma growth in cultured cells and in zebrafish xenograft models. Shikonin induced melanoma cells apoptosis, inhibited cell migration and invasion. Mechanistic study indicated that shikonin inhibited the phosphorylation and homo-dimerization of STAT3, thus reduced its nuclear localization. Further study showed that shikonin decreased the levels of STAT3-targeted genes Mcl-1, Bcl-2, MMP-2, vimentin, and Twist, which are involved in melanoma survival, migration, and invasion. More importantly, overexpression of constitutively active STAT3 partially abolished the anti-proliferative, anti-migratory, and anti-invasive effects of shikonin. CONCLUSION: The anti-melanoma activity of shikonin is at least partially attributed to the inhibition on STAT3 signaling. These findings provide new insights into the anti-melanoma molecular mechanisms of shikonin, suggesting its potential in melanoma treatment.

Crystal Morphology Prediction and Anisotropic Evolution of 1,1-Diamino-2,2-dinitroethylene (FOX-7) by Temperature Tuning.

Temperature-induced morphological changes are one of the strategies for designing crystal shapes, but the role of temperature in enhancing or inhibiting crystal growth is not well understood yet. To meet the requirements of high density and low sensitivity, we need to control the crystal morphology of the energetic materials. We studied the crystal morphology of 1,1-diamino-2,2-dinitroethylene (FOX-7) in dimethyl sulfoxide/water mixed solvent by using the modified Hartman-Perdok theorem. Molecular dynamics simulations were used to determine the interaction of FOX-7 and solvents. The results showed that the crystal shape of FOX-7 is hexagonal, the (101) face is the largest exposed face and is adjacent to six crystal faces at 354 K. As the temperature goes down, the area of the (001) face is significantly reduced. The crystal morphology of FOX-7 at 324 K has a smaller aspect ratio of 4.72, and this temperature is suitable for tuning the morphology from slender hexagon into diamond. The prediction results are in remarkable agreement with the experiments. Moreover, we predicted the evolution path of FOX-7 morphology by Gibbs-Curie-Wulff theorem and explained the variation of crystal shape caused by different external conditions in the actual crystallization process.

[Clinical Value of Peripheral Blood Circulating Tumor Cells Detection in Early Cervical Infiltrating Carcinoma Screening].

OBJECTIVE: To observe the difference of circulating tumor cells (CTC) in peripheral blood of patients with different degrees of cervical lesions, and to evaluate the effectiveness of CTC detection in screening early invasive cervical cancer. METHODS: From December 2015 to October 2017, 63 cases of cervicitis, low-grade and high-grade intraepithelial lesions (LSIL, HSIL) and early invasive cervical cancer were confirmed by histopathological and clinical stages in Zhongshan Boai Hospital and Zhongshan Hospital Affiliated to Zhongshan University. The immunomagnetic bead negative enrichment technique combined with immunofluorescence was used. In situ hybridization (imFISH) was used to detect CTC in peripheral blood of patients. The positive rate and quantity of CTC in four groups were analyzed. The diagnostic efficacy of CTC in early invasive cervical cancer was evaluated based on the results of histopathological diagnosis and clinical staging. RESULTS: ①The positive rates of CTC in cervicitis group, LSIL group, HSIL group and early invasive cervical cancer group were 0, 0, 19.05% and 84.13% respectively. The overall difference was statistically significant ( χ 2=504.00， P<0.05). The positive rate of CTC in early invasive cervical cancer group was higher than that in other groups ( P<0.008 3). The positive rates of CTC in HSIL group were significantly different from those in LSIL group and cervicitis group ( P<0.008 3). ②The average number (median) of CTC positive in cervicitis group, LSIL group, HSIL group and early invasive cervical cancer group was 0, 0, 1/4 mL, 3/4 mL, respectively. The average number of positive CTC in early invasive cervical cancer group was higher than that in other groups, and the difference was significant compared with other groups ( P<0.008 3). The average number of CTC positive in HSIL group was significantly different from that in LSIL and cervicitis group ( P<0.008 3). ③The sensitivity, specificity, coincidence rate, positive predictive value and negative predictive value of CTC positive results in the diagnosis of early invasive cervical cancer were 84.13%, 93.65%, 91.27%, 81.54% and 94.65%, respectively. CONCLUSION: CTC exists in patients with HSIL and early invasive cervical cancer. With the aggravation of cervical lesions, the positive rate and number of CTC test results increase. CTC detection in early invasive cervical cancer screening has a certain practical value in clinic.

A label-free approach to detect cell viability/cytotoxicity based on intracellular xanthine/guanine by electrochemical method.

INTRODUCTION: Cell viability and cytotoxicity is one of the most important toxicology indicators. In this study, an electrochemical method for detecting cell viability and cytotoxicity was discussed with the intracellular small molecule metabolite purines as indexes. METHODS: The electrochemical behaviors of Balb/c 3T3, CHO, PC-12 and V79 cell suspensions were studies by cyclic voltammetry, and cell viability and cytotoxicity of four cell lines were compared by electrochemical, cell counting, 3-(4,5-dimethyl-2-Thiazyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) and trypan blue exclusion methods. RESULTS: Four cell lines all showed an oxidation peak derived from mixture of xanthine and guanine at about 0.7 V. Using intracellular xanthine and guanine as index, the electrochemical method could not only describe the cell growth curves of four cell lines, but also reflect the changes of cell viability at various phases of the cell growth prior to the counting method. Compared with MTT, cell counting and trypan blue staining methods, the electrochemical method could detect the cytotoxicity of carcinogen earlier and more sensitively. DISCUSSION: The electrochemical method could track the change of intracellular xanthine and guanine contents, and used it as index to detect cell viability and cytotoxicity at the molecular level without markers, showing greater advantages over the method with apparent cell proliferation as the endpoint.

Ammoxetine attenuates diabetic neuropathic pain through inhibiting microglial activation and neuroinflammation in the spinal cord.

BACKGROUND: Diabetic neuropathic pain (DNP) is a common and distressing complication in patients with diabetes, and the underlying mechanism remains unclear. Tricyclic antidepressants (TCAs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first-line drugs for DNP. Ammoxetine is a novel and potent SNRI that exhibited a strong analgesic effect on models of neuropathic pain, fibromyalgia-related pain, and inflammatory pain in our primary study. The present study was undertaken to investigate the chronic treatment properties of ammoxetine on DNP and the underlying mechanisms for its effects. METHODS: The rat model of DNP was established by a single streptozocin (STZ) injection (60 mg/kg). Two weeks after STZ injection, the DNP rats were treated with ammoxetine (2.5, 5, and 10 mg/kg/day) for 4 weeks. The mechanical allodynia and locomotor activity were assayed to evaluate the therapeutic effect of ammoxetine. In mechanism study, the activation of microglia, astrocytes, the protein levels of pro-inflammatory cytokines, the mitogen-activated protein kinases (MAPK), and NF-κB were evaluated. Also, microglia culture was used to assess the direct effects of ammoxetine on microglial activation and the signal transduction mechanism. RESULTS: Treatment with ammoxetine for 4 weeks significantly relieved the mechanical allodynia and ameliorated depressive-like behavior in DNP rats. In addition, DNP rats displayed increased activation of microglia in the spinal cord, but not astrocytes. Ammoxetine reduced the microglial activation, accumulation of pro-inflammatory cytokines, and activation of p38 and c-Jun N-terminal kinase (JNK) in the spinal cord of DNP rats. Furthermore, ammoxetine displayed anti-inflammatory effects upon challenge with LPS in BV-2 microglia cells. CONCLUSION: Our results suggest that ammoxetine may be an effective treatment for relieving DNP symptoms. Moreover, a reduction in microglial activation and pro-inflammatory release by inhibiting the p-p38 and p-JNK pathways is involved in the mechanism.

Design and synthesis of functionalized coordination polymers as recyclable heterogeneous photocatalysts.

The functionalized ligand 9,10-anthraquinone-1,4-dicarboxylate acid (H2AQDC) was designed and synthesized in order to develop metal-organic coordination polymers as heterogeneous catalysts with a photosensitizing feature. Two major considerations of the ligand design are anthraquinone moieties for photosensitizing to harvest light and carboxylate groups for polymeric coordination toward less solubility. A series of transition metal complexes based on this ligand were synthesized subsequently, namely {Co(AQDC)(H2O)3·2H2O}n (Co-AQDC), {Ni(AQDC)(H2O)3·2H2O}n (Ni-AQDC), {[Cu(AQDC)(H2O)3][Cu(AQDC)(H2O)2(DMF)]·(H2O)4}n (Cu-AQDC), {Zn1.5(AQDC)(OH)(H2O)2·H2O}n (Zn-AQDC), {Ag2(AQDC)(CH3OH)}n (Ag-AQDC). Both the ligand and its transition metal complexes are able to catalyze the visible-light driven oxidation reactions of alkynes into 1,2-diketones in air under mild conditions, in which compound Ni-AQDC demonstrates the best activity. This catalyst can be easily isolated from the reaction mixture by filtration with a trace amount of loss in solution and is ready for recycled use after simple washing and drying without any need for regeneration. Remarkably, the catalyst shows no loss of activity after five catalytic cycles and X-ray powder diffraction proves no change in the structure after five runs. This designed metal-organic coordination polymer represents an environmentally friendly, economical and recyclable photocatalyst, constituting a good candidate for photocatalytic organic syntheses in terms of green chemistry.

ZBP-89 and Sp1 contribute to Bak expression in hepatocellular carcinoma cells.

BACKGROUND: Kruppel family member zinc binding protein 89 (ZBP-89), also known as ZNF148, regulates Bak expression via binding to GC-rich promoter domain. It is not clear if other GC-rich binding factors, such as Sp family members, can interact with ZBPp-89 on Bak expression. This study aims to elucidate the mechanism of Bak expression regulation by ZBP-89 and Sp proteins, based on in vitro experiment and The Cancer Genome Atlas (TCGA) hepatocellular carcinoma (HCC) data cohort. METHODS: We downloaded TCGA hepatocellular carcinoma (HCC) cohort data to analysis the association of Bak transcription level with ZBP-89 and Sp proteins transcription level. HCC cell lines and liver immortal non-tumour cell lines were used for mechanism study, including western blotting analysis, expression vector mediated gene expression and siRNA interference. RESULTS: Results showed that cancer tissues have higher Bak transcription level compared with adjacent non-cancer tissues. Bak transcription level was correlated with Sp1 and Sp3 expression level, while no correlation was found in ZBP-89 and Bak, neither Sp2 nor Sp4. Mithramycin A (MMA) induced Bak expression in a dose-dependent manner. Western blotting results showed Sp1 overexpression increased Bak expression both in liver immortal non-tumour cells and HCC cells. Interference Sp1 expression could inhibit Bak expression alone. ZBP-89 siRNA suppressed Bak expression even in the presence of MMA treatment and S1 overexpression. Additionally, Bak and Sp1 level were associated with HCC patient survival. CONCLUSIONS: Bak expression required ZBP-89 and Sp1 cooperative regulation simultaneously.