Electronic Modulation in Homonuclear Dual-Atomic Catalysts for Enhanced CO2 Electroreduction.

Homonuclear dual-atomic catalysts showcase unique electronic modulation due to their dual metal centres, providing new direction in development of efficient catalysts for CO2 electroreduction. This article highlights a few cutting-edge homonuclear dual-atomic catalysts, focusing on their inherent advantages in efficient and selective CO2 electroreduction, to spotlight the potential application of dual-atomic catalysts in CO2 electroreduction.

Boosting CO2 Photoreduction to Formate or CO with High Selectivity over a Covalent Organic Framework Covalently Anchored on Graphene Oxide.

Covalent organic frameworks (COFs) have been widely studied in photocatalytic CO2 reduction reaction (CO2 RR). However, pristine COFs usually exhibit low catalytic efficiency owing to the fast recombination of photogenerated electrons and holes. In this study, we fabricated a stable COF-based composite (GO-COF-366-Co) by covalently anchoring COF-366-Co on the surface of graphene oxide (GO) for the photocatalytic CO2 reduction. Interestingly, in absolute acetonitrile (CH3 CN), GO-COF-366-Co shows a high selectivity of 94.4 % for the photoreduction of CO2 to formate, with a formate yield of 15.8 mmol/g, which is approximately four times higher than that using the pristine COF-366-Co. By contrast, in CH3 CN/H2 O (v : v=4 : 1), the main product for the photocatalytic CO2 reduction over GO-COF-366-Co is CO (96.1 %), with a CO yield as high as 52.2 mmol/g, which is also approximately four times higher than that using the pristine COF-366-Co. Photoelectrochemical experiments demonstrate the covalent bonding of COF-366-Co and GO to form the GO-COF-366-Co composite facilitates charge separation and transfer significantly, thereby accounting for the enhanced catalytic activity. In addition, theoretical calculations and in situ Fourier transform infrared spectroscopy reveal H2 O can stabilize the *COOH intermediate to further form a *CO intermediate via O-H(aq)⋅⋅⋅O(*COOH) hydrogen bonding, thus explaining the regulated photocatalytic performance.

Combination of an optical waveguide platform and ultra-thin spectrometer that enables increased surface plasmon resonance sensor compactness.

A novel integrated surface plasmon resonance (SPR) sensor that combines an optical waveguide platform and an ultra-thin spectrometer is proposed. The core of the proposed method is a special-shaped optical waveguide structure that employs a wedge-shaped incident surface, which changes the position of the total reflection of the incident light on the sagittal plane without affecting the direction of propagation on the tangential plane. The parameters of the sensing module with the integrated SPR sensor and spectrometer module were designed and optimized to achieve higher performance in a compact optical waveguide platform. An experimental system was built based on the theoretical model, and the spectral sensitivity of the system was analyzed before sample detection, and the results showed that the spectral resolution in the working range could reach 9.9 nm. The refractive index sensitivity of this novel SPR sensor was 3186 nm/RIU with good stability by detecting different concentrations of sodium chloride samples. This new structure does not require an external spectrometer, thereby enabling an increase in the compactness of the SPR sensing system. The proposed method can provide a novel idea for the miniaturization of SPR sensors.

Modulating the Electronic Structures of Dual-Atom Catalysts via Coordination Environment Engineering for Boosting CO2 Electroreduction.

Dual-atom catalysts (DACs) have emerged as efficient electrocatalysts for CO2 reduction owing to the synergistic effect between the binary metal sites. However, rationally modulating the electronic structure of DACs to optimize the catalytic performance remains a great challenge. Herein, we report the electronic structure modulation of three Ni2 DACs (namely, Ni2 -N7 , Ni2 -N5 C2 and Ni2 -N3 C4 ) by the regulation of the coordination environments around the dual-atom Ni2 centres. As a result, Ni2 -N3 C4 exhibits significantly improved electrocatalytic activity for CO2 reduction, not only better than the corresponding single-atom Ni catalyst (Ni-N2 C2 ), but also higher than Ni2 -N7 and Ni2 -N5 C2 DACs. Density functional theory (DFT) calculations revealed that the high electrocatalytic activity of Ni2 -N3 C4 for CO2 reduction could be attributed to the electronic structure modulation to the Ni centre and the resulted proper binding energies to COOH* and CO* intermediates.

Supramolecular Coordination Cages Based on N-Heterocyclic Carbene-Gold(I) Ligands and Their Precursors: Self-Assembly, Structural Transformation and Guest-Binding Properties.

The incorporation of functional groups into the cavity of discrete supramolecular coordination cages (SCCs) will bring unique functions and applications. Here, three dicarboxylate ligands (H2 L1Cl, H2 L2Cl and H2 L3Cl) containing N-heterocyclic carbene (NHC) precursors as linkers were introduced to construct SCCs by combining with two C3 -symmertic (CpZr)3 (µ3 -O)(µ2 -OH)3 clusters as three-connect vertices, resulted in a series of rugby-like V2 E3 (V=vertex, E=edge) type homoleptic cages (SCC-1, SCC-2 and SCC-3). However, V4 E6 -type tetrahedral cages (SCC-4 and SCC-5), incorporating six Au-NHC moieties, were obtained when the corresponding NHC-gold(I) functionalized ligands (H2 L1Au , H2 L2Au ) were applied. For the first time, we present a trackable CpZr-involved cage to cage conversion to generate a heteroleptic V2 E3 cage (SCC-6) from two homoleptic cages (SCC-2 and SCC-5) with different geometries of V2 E3 and V4 E6 . The heteroleptic assembly SCC-6 can also be formed upon a subcomponent displacement strategy. The structural transformation and reassembly processes were detected and monitored by 1 H NMR spectroscopy and electrospray-ionization mass spectrometry. The formation of heteroleptic assembly was further supported by single crystal X-ray diffraction analysis. Moreover, homoleptic cage SCC-2 possesses a trigonal bipyramidal cationic cavity allowing the encapsulation of a series of sulfonate anionic guests.

Optimizing Chemotherapy of Pancreatic Acinar Cell Carcinoma: Our Experiences and Pooled Analysis of Literature.

Background: Pancreatic acinar cell carcinoma (PACC) is rare, and its appropriate treatment remains unknown. We aim to explore the characteristics and optimal treatment of it. Methods: The data on clinicopathologic characteristics, molecular alteration, treatment, and survival of patients diagnosed with PACC at the Sun Yat-sen University Cancer Center from 2005 to 2020 were collected. The optimal treatment was explored by co-analyzing our results and published literatures. Results: Twenty-two PACC patients were enrolled. Eight of 17 non-metastatic patients received adjuvant chemotherapy. The patients receiving fluoropyrimidine-based regimen (n = 3) had a better median disease-free survival (mDFS) than those with gemcitabine-based regimen (n = 5) (unreached vs 27 months). Eight metastatic patients received first-line chemotherapy. Four patients received second-line chemotherapy. The objective response rate (ORR) of the fluoropyrimidine-based regimen was 85.7% (6/7), much better than that of the gemcitabine-based regimen (0/5). One patient who had responded to the first-line FOLFIRINOX (5-fluorouracil + oxaliplatin + leucovorin + irinotecan) regimen received olaparib as maintenance treatment for 5 months with good tolerance. Thirty-one published literatures, with a total of 86 cases, were included in the co-analysis. The ORR of the first-line fluoropyrimidine-based regimen (n = 47) was higher than that of gemcitabine-based regimen (n = 39) (59.6% vs 15.3%, P < .001). Eight of 11 patients treated with the FOLFIRINOX regimen achieved partial response (PR). Conclusions: For patients with metastasis, a fluorouracil-based regimen such as FOLFIRINOX may be preferred, and maintenance treatment of poly ADP-ribose polymerase (PARP) inhibitors after effective platinum-containing treatment for breast cancer susceptibility gene (BRCA) mutation patients must be assessed.

Diagnostic value of four serum exosome microRNAs panel for the detection of colorectal cancer.

BACKGROUND: Early detection, early diagnosis, and early treatment are currently accepted methods that can effectively improve the efficacy of colorectal cancer (CRC) treatment. Exosomes were demonstrated to be potential tumor molecular markers. AIM: To evaluate the diagnostic value of CRC by detecting four exosomal microRNAs (miRNAs) (miR-15b, miR-16, miR-21, and miR-31) that were demonstrated to have potential diagnostic value in serum. METHODS: Relative expression levels of miR-15b, miR-16, miR-21, and miR-31 in 123 CRC, 117 colorectal adenoma, and 150 healthy controls were detected, and single and panel models were evaluated. The 2-ΔΔCt method was used to calculate the relative expression of miRNA compared to the internal control (U6). Eighty-one CRC patients, 67 colorectal adenoma patients, and 90 healthy controls were used for validation. RESULTS: Compared to the healthy control group, the best indicator of the four miRNAs was miR-15b, and the sensitivity and specificity were 81.33% and 91.80%, respectively. For miR-15b, miR-21, and miR-31 individually, the sensitivity and specificity were 91.95% and 97.62%, 95.06% and 94.44%, respectively. Compared to the colorectal adenoma group, miR-15b, miR-16, and miR-21 in the CRC group showed significant differences (P < 0.05). The best single indicator was miR-16, with a sensitivity and specificity of 79.05% and 71.55%. The sensitivity and specificity of a panel that included miR-15b, miR-16, and miR-21 were 81.21% and 81.03%, and 85.19% and 82.09%, respectively, in the validation. CONCLUSION: We built and validated a diagnostic model containing miR-15b, miR-21, and miR-31 expression levels to discriminate the healthy control group and CRC group, and its sensitivity and specificity were 95.06% and 94.44%, respectively. The miR-15b, miR-16, and miR-21 panel was used to discriminate the colorectal adenoma group and CRC group with a sensitivity and specificity of 85.19% and 82.09%, respectively.

Association of adenylate cyclase-2 gene polymorphism with bipolar disorder.

The pathogenesis of the Bipolar Disorder(BPD) is still unclear. Some studies suggest that abnormal signal transduction in specific pathways may play an important role in the pathogenesis of BPD (Sui et al., 2015). Adenylate cyclase (ADCY) is an essential component of the adenylate signaling pathway. Previous studies have shown that some SNPs within the adenylate cyclase gene could affect the therapeutic response to mood stabilizers and antidepressants. Moreover, in 2014, one whole-genome study suggested that the ADCY-2 gene may be associated with BPD (Mühleisen et al., 2014). This study aims to investigate the association between ADCY-2 gene polymorphism and BPD in Chinese Han population.

High WDR34 mRNA expression as a potential prognostic biomarker in patients with breast cancer as determined by integrated bioinformatics analysis.

The WD-repeat domain (WDR) family is distributed in the majority of eukaryotes and has several unique biological functions. It serves important roles in signal transduction, cytoskeleton assembly, protein transport, RNA processing, chromatin modification and transcription mechanisms. WD repeat domain 34 (WDR34) has been recently identified as a member of the WDR family. Overexpression of WDR34 was accompanied by the presence of multiple centrioles in the cell, suggesting that it was associated with tumor occurrence. However, its association with breast cancer was unclear. To the best of our knowledge, it has not yet been confirmed whether WDR34 gene expression is associated with breast cancer. Therefore, the current study attempted to clarify this by performing a comprehensive study using multiple datasets in the Oncomine, Breast Cancer Gene-Expression Miner and Kaplan-Meier Plotter databases. The analysis indicated that the mRNA expression levels of WDR34 were increased in breast cancer tissues compared with normal tissues. Consistent with this result, the Broad-Novartis Cancer Cell Line Encyclopedia revealed that WDR34 mRNA expression levels were upregulated in breast cancer cell lines compared with other cancer cells. It was noted that high WDR34 mRNA expression was associated with forkhead box M1 and PTTG1 regulator of sister chromatid separation, securing in co-expression analysis. Expression profile characteristics of WDR34 mRNA were identified in different molecular subtypes of breast cancer. Furthermore, survival analysis revealed that increased expression levels of WDR34 mRNA were associated with poor overall survival in patients with breast cancer, particularly in luminal B, lymph node status-positive and estrogen receptor (ER)-negative subgroups. Additionally, Kaplan-Meier curves revealed that high WDR34 mRNA expression was associated with shorter relapse-free survival in patients with breast cancer, particularly in ER-positive, human epidermal growth factor receptor 2-negative and progesterone receptor-positive subgroups. These results suggested that WDR34 may be used as a prognosis predictor in breast cancer and may provide a novel target for the diagnosis and treatment of breast cancer.

Radiofrequency Thermocoagulation Through Foramen Rotundum Versus Foramen Ovale for the Treatment of V2 Trigeminal Neuralgia.

BACKGROUND: Percutaneous radiofrequency thermocoagulation through the foramen rotundum (FR) is a new approach for the treatment of V2 trigeminal neuralgia (TN). OBJECTIVES: This study aimed to compare the efficacy and safety of the FR approach with that of the foramen ovale (FO) approach. STUDY DESIGN: Nonrandomized controlled clinical trial. SETTING: The study was conducted at Huaian Hospital of Huaian City, Huaian, China. METHODS: From July 2014 to December 2016, 80 consecutive patients with V2 TN were prospectively assigned into the FO group (n = 40) or the FR group (n = 40). All radiofrequency thermocoagulation procedures were performed under the guidance of digital subtraction angiography (DSA). Patients in the FO group were treated with Gasserian ganglion ablation through the Hartel approach. Patients in the FR group received ablation of the maxillary nerve at the internal opening of the FR. Facial pain was evaluated using the Visual Analog Scale preoperatively and postoperatively at 1 week, 6 months, and 1 year. RESULTS: All surgical procedures were successfully completed using DSA guidance. The FR group had no facial pain at postoperative 1 week, 6 months, and 1 year. The facial fain was not relieved in 4 patients of the FO group. They were treated with radiofrequency thermocoagulation of the maxillary nerve through the FR and maintained painless at postoperative 1 week, 6 months, and 1 year. At postoperative 1 year, another 3 patients relapsed in the FO group. The incidences of facial numbness and swelling did not differ significantly between the 2 groups (all P > 0.05). There was no postoperative corneal involvement or masticatory weakness in the FR group. However, corneal involvement and masticatory weakness occurred postoperatively in 22 (55%) patients and 31 (77.5%) patients in the FO group. The FR group had significantly shorter operation time than the FO group (19.3 ± 5.9 vs. 32.7 ± 8.7 minutes; P < 0.05). LIMITATIONS: We were unable to avoid the V1 and V3 branches, despite multiple adjustments of the needed position in 35 of the 40 patients in this group. CONCLUSIONS: For the treatment of V2 TN, thermocoagulation of the maxillary nerve through the FR had better efficacy and fewer complications in comparison with the Gasserian ganglion ablation through the FO. KEY WORDS: Neuralgia, pain, radiology, facial pain.

PLC-dependent intracellular Ca2+ release was associated with C6-ceramide-induced inhibition of Na+ current in rat granule cells.

In this report, the effects of C(6)-ceramide on the voltage-gated inward Na(+) currents (I(Na)), two types of main K(+) current [outward rectifier delayed K(+) current (I(K)) and outward transient K(+) current (I(A))], and cell death in cultured rat cerebellar granule cells were investigated. At concentrations of 0.01-100 microM, ceramide produced a dose-dependent and reversible inhibition of I(Na) without alteration of the steady-state activation and inactivation properties. Treatment with C(2)-ceramide caused a similar inhibitory effect on I(Na). However, dihydro-C(6)-ceramide failed to modulate I(Na). The effect of C(6)-ceramide on I(Na) was abolished by intracellular infusion of the Ca(2+)-chelating agent, 1,2-bis (2-aminophenoxy) ethane-N, N, N9, N9-tetraacetic acid, but was mimicked by application of caffeine. Blocking the release of Ca(2+) from the sarcoplasmic reticulum with ryanodine receptor blocker induced a gradual increase in I(Na) amplitude and eliminated the effect of ceramide on I(Na). In contrast, the blocker of the inositol 1,4,5-trisphosphate-sensitive Ca(2+) receptor did not affect the action of C(6)-ceramide. Intracellular application of GTPgammaS also induced a gradual decrease in I(Na) amplitude, while GDPbetaS eliminated the effect of C(6)-ceramide on I(Na). Furthermore, the C(6)-ceramide effect on I(Na) was abolished after application of the phospholipase C (PLC) blockers and was greatly reduced by the calmodulin inhibitors. Fluorescence staining showed that C(6)-ceramide decreased cell viability and blocking I(Na) by tetrodotoxin did not mimic the effect of C(6)-ceramide, and inhibiting intracellular Ca(2+) release by dantrolene could not decrease the C(6)-ceramide-induced cell death. We therefore suggest that increased PLC-dependent Ca(2+) release through the ryanodine-sensitive Ca(2+) receptor may be responsible for the C(6)-ceramide-induced inhibition of I(Na), which does not seem to be associated with C(6)-ceramide-induced granule neuron death.

The Expression of MicroRNA-155 in Plasma and Tissue Is Matched in Human Laryngeal Squamous Cell Carcinoma.

PURPOSE: Tumor-associated microRNAs have been detected in cancer, though whether plasma microRNA-155 (miR-155) could be a potential biomarker for laryngeal squamous cell carcinoma (LSCC) prognosis is unclear. We aimed to determine how miR-155 can be used to predict the clinical characteristics of patients with LSCC and correctly diagnose them. MATERIALS AND METHODS: We collected tissue samples and peripheral blood samples before and after treatment from 280 LSCC cases and 560 controls. Real-time quantitative reverse transcription PCR was employed in this study to compare the relative expression of miR-155. RESULTS: A total of 280 LSCC patients and 560 age- and sex-matched controls were included in the study. The miR-155 level was more up-regulated in LSCC tissue than in the non-tumor tissues (13.6 ± 2.4 vs. 3.1 ± 0.80, p<0.001). Additionally, a significantly higher miR-155 level in plasma samples from LSCC patients than in those of the controls (8.9 ± 1.25 vs. 1.8 ± 0.8, p<0.001) was reported. Tissue miR-155 showed an area under the curve (AUC) of 0.933, with a sensitivity of 82.6% and a specificity of 89.2%. The AUC for plasma miR-155 was 0.757, with a sensitivity of 58.4% and a specificity of 69.5%. When early LSCC in TNM I stage was considered, tissue miR-155 showed an area under the curve of 0.804, with a sensitivity of 85.2% and a specificity of 87.3%. CONCLUSION: The expression of tissue and plasma miR-155 were significantly up-regulated in patients with LSCC. Our work will serve as a basis for further investigation, preferably large-scale validation in clinical trials.

Association between 8473T>C polymorphism in the cyclooxygenase-2 gene and the risk of nasopharyngeal carcinoma.

BACKGROUND: No studies have examined the relationship between COX-2 8473T>C polymorphism and the risk of nasopharyngeal carcinoma in Chinese population. MATERIAL AND METHODS: 296 patients with nasopharyngeal carcinoma and 300 age and gender-matched healthy controls recruited were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Cancer risk associated with the genotypes was estimated as odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditioned logistic regression. RESULTS: There was significant difference in the distribution of COX-2 8473T>C polymorphism genotype between nasopharyngeal carcinoma patients and healthy controls (P=0.027). When the TT genotype was used as the reference group, the CC genotype was associated with significantly decreased risk for nasopharyngeal carcinoma (adjusted OR=0.67, 95% CI=0.33-0.83; P=0.01). Under the recessive model of inheritance, the CC genotype was associated with significantly decreased risk for nasopharyngeal carcinoma (adjusted OR=0.43, 95% CI=0.37-0.81; P=0.007). Furthermore, the C allele was associated with significantly decreased risk for nasopharyngeal carcinoma (adjusted OR=0.48, 95% CI=0.39-0.85; P=0.009). CONCLUSION: These data suggested that COX-2 8473T>C polymorphism was associated with reduced risk of nasopharyngeal carcinoma.

Immobilization of FLAG-Tagged Recombinant Adeno-Associated Virus 2 onto Tissue Engineering Scaffolds for the Improvement of Transgene Delivery in Cell Transplants.

The technology of virus-based genetic modification in tissue engineering has provided the opportunity to produce more flexible and versatile biomaterials for transplantation. Localizing the transgene expression with increased efficiency is critical for tissue engineering as well as a challenge for virus-based gene delivery. In this study, we tagged the VP2 protein of type 2 adeno-associated virus (AAV) with a 3×FLAG plasmid at the N-terminus and packaged a FLAG-tagged recombinant AAV2 chimeric mutant. The mutant AAVs were immobilized onto the tissue engineering scaffolds with crosslinked anti-FLAG antibodies by N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP). Cultured cells were seeded to scaffolds to form 3D transplants, and then tested for viral transduction both in vitro and in vivo. The results showed that our FLAG-tagged AAV2 exerted similar transduction efficiency compared with the wild type AAV2 when infected cultured cells. Following immobilization onto the scaffolds of PLGA or gelatin sponge with anti-FLAG antibodies, the viral mediated transgene expression was significantly improved and more localized. Our data demonstrated that the mutation of AAV capsid targeted for antibody-based immobilization could be a practical approach for more efficient and precise transgene delivery. It was also suggested that the immobilization of AAV might have attractive potentials in applications of tissue engineering involving the targeted gene manipulation in 3D tissue cultures.

Histological study of experimental reconstructive materials for repair of lateral skull base and dura mater defects in dogs.

OBJECTIVE: In order to assess the reconstructive properties of fascia lata, superficial fascia lata and bone morphogenetic protein (BMP) in skull base surgery, lateral skull base bone and dura mater defect models were established in dogs MATERIAL AND METHODS: As a repair material we selected fascia lata, either alone or in combination with BMP, for reconstructing large cranial defects in dogs. Twenty dogs undergoing a 3.0 x 4.0 cm2 full-thickness excision of the parietal bone were divided into four equal groups as follows: fascia lata reconstruction; fascia lata reconstruction plus BMP; controls; and fascia lata reconstruction plus BMP with direct exposure of fascia lata. The implants were harvested at 2-15 weeks and examined histologically. Results-Treated and untreated implants were quite different: formation of new bone occurred in the dogs treated with BMP whereas the unreconstructed controls demonstrated only a bridge of fibrovascular connective tissue. CONCLUSION: The results of this study suggest that it is better to combine BMP and reconstructive material for the treatment of bone defects.

[Analysis of allergen variation for 3292 patients with allergic rhinitis].

OBJECTIVE: To investigate the variation of common allergens in patients with allergic rhinitis in recent 4 years in Tianjin First Center Hospital. METHODS: The medical records of skin prick test on 3292 patients with allergic rhinitis between 2009 and 2012 were restrospectively analyzed. The changing trend of various allergens in 4 years and distribution differences were compared. The differences of the top 5 allergens in under age group, adult group and different gender group were further analyzed by SPSS 19.0 software. RESULTS: The positive rate of dermatophagoides farinae was increasing year by year, from 45.1% in 2009 to 66.3% in 2012, and the positive rate of dermatophagoides pteronyssinus increased from 42.0% in 2009 to 58.6% in 2012, the difference was statistically significant (χ(2) value was 68.70, 41.55, all P < 0.01). The positive rate of dermatophagoides farinae and dermatophagoides pteronyssinus in adult group and male group showed significant upward trend year by year (χ(2) value was 75.85, 69.93, 274.25, 42.62, all P < 0.01), but not in adult group and female group. The positive rate of quinoa, mugwort and humulus scandens decreased year by year between 2009 and 2011(χ(2) value was 22.08, 11.64, 203.19, all P < 0.01), but increased again in 2012(χ(2) value was 21.55, 29.38, 12.40, all P < 0.01). CONCLUSIONS: There is a tendency of change of allergens in patients with AR. This phenominon may be helpful for doctors to choose the type of skin prick liquid.

Mefenamic acid bi-directionally modulates the transient outward K+ current in rat cerebellar granule cells.

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on ion channels has been widely studied in several cell models, but less is known about their modulatory mechanisms. In this report, the effect of mefenamic acid on voltage-activated transient outward K(+) current (I(A)) in cultured rat cerebellar granule cells was investigated. At a concentration of 5 microM to 100 microM, mefenamic acid reversibly inhibited I(A) in a dose-dependent manner. However, mefenamic acid at a concentration of 1 microM significantly increased the amplitude of I(A) to 113+/-1.5% of the control. At more than 10 microM, mefenamic acid inhibited the amplitude of I(A) without any effect on activation or inactivation. In addition, a higher concentration of mefenamic acid induced a significant acceleration of recovery from inactivation with an increase of the peak amplitude elicited by the second test pulse. Intracellular application of mefenamic acid could significantly increase the amplitude of I(A), but had no effect on the inhibition induced by extracellular mefenamic acid, implying that mefenamic acid may exert its effect from both inside and outside the ion channel. Furthermore, the activation of current induced by intracellular application of mefenamic acid was mimicked by other cyclooxygenase inhibitors and arachidonic acid. Our data demonstrate that mefenamic acid is able to bi-directionally modulate I(A) channels in neurons at different concentrations and by different methods of application, and two different mechanisms may be involved.

[Construction of bicistronic eukaryotic vector containing basic fibroblast growth factor and study of their functions in gene therapy for hearing impairment].

OBJECTIVE: To construct basic fibroblast growth factor(bFGR) and enhance green fluorescence protein(EGFP) fusion gene eukaryotic expression vector internal ribosome entry site (pIRES)-bFGF-GFP and to evaluate the effect of transduction bFGF gene on noise induced hearing-loss in inner ear hair cells of guinea pigs. METHODS: Human bFGF cDNA was inserted into mammalian expressed plasmid pIRES-EGFP. The recombinant expression plasmid pIRES-bFGF-EGFP was transfected into inner ear of guinea pigs, using lipofectin method. The transduced bFGF gene was mediated by SA lipidsome. IRES- bFGF-GFP was administered into the round window as rescue agent at the same time of noise exposure or as a protective agent 7 days before. RESULTS: SA liposome-mediated bFGF expressed at a high level in the cochlea of guinea pigs, and in the rescue group, a significant lower hearing thresholds was displayed. pIRES- bFGF-EGFP could protect hair cells. It demonstrated that pIRES- bFGF-GFP could protect the inner ear both structurally and functionally. bFGF/EGFP gene could be transcripted and translated into inner ear hair cells of guinea pig. bFGF/EGFP gene could express a specific protein. The recombinant bFGF/EGFP had significant protective effect as well as manifestation of autonomous fluorescence. CONCLUSION: bFGF/EGFP fusion protein not only expressed in hair cells of guinea pig but also showed significant bFGF activity and autonomous fluorescence. IRES induced exogenous gene could enter the hair cells.