LncRNA OIP5-AS1 Upregulates the Cyclin D2 Levels to Promote Metastasis of Breast Cancer by Targeting miR-150-5p.

OBJECTIVE: Breast cancer (BC) is a cancer that seriously affects women's health. BC cell migration increases the mortality of BC patients. Current studies have shown that long noncoding RNAs (LncRNAs) are related to the metastasis mechanism of BC. This study aimed to explore the function and role of LncRNA OIP5-AS1 in BC. And we analyzed its regulatory mechanism and related modification process. METHODS: Our study analyzed the expression pattern of OIP5-AS1 in BC tissues and cell lines by qRT-PCR. The effects of OIP5-AS1 on the function of BC cells were detected by CCK-8 and transwell experiments. Bioinformatics analysis and double luciferase reporter gene detection were used to confirm the correlation between OIP5-AS1 and miR-150-5p and between miR-150-5p and Cyclin D2 (CCND2). The rescue test analyzed the effect of miR-150-5p regulating OIP5-AS1. In addition, the N6-methyladenosine (m6A) modification process of OIP5-AS1 was analyzed by RNA m6A dot blot, RIP assay, and double luciferase report experiment. RESULTS: OIP5-AS1 was significantly upregulated in BC tissues and cell lines. OIP5-AS1 knockdown inhibited BC cell viability, migration and invasion. OIP5-AS1 upregulated CCND2 by binding with miR-150-5p. This process affected the metastasis of BC. Higher degree of m6A methylation was confirmed in BC cell lines. There were some binding sites between methyltransferase like 3 (METTL3) and OIP5-AS1. Moreover, the silencing of METTL3 inhibited the OIP5-AS1 expression through decreasing the m6A methylation levels. CONCLUSIONS: LncRNA OIP5-AS1 promoted cell viability and metastasis of BC cells by targeting miR-150-5p/CCND2 axis. This process was modified by m6A methylation of METTL3.

Ceriporiopsistianshanensis (Polyporales, Agaricomycetes) and Sideratianshanensis (Hymenochaetales, Agaricomycetes), two new species of wood-inhabiting fungi from Xinjiang, Northwest China.

Wood-inhabiting fungi are abundant in China, but their distribution is uneven, with more fungi in southwest China and fewer fungi in northwest China. During the investigation of wood-inhabiting fungi in Xinjiang, we collected a large number of specimens. Eight specimens growing on Piceaschrenkiana were collected from Tianshan Mountains, and they were described as two new species in Ceriporiopsis and Sidera based on morphological characters and molecular evidence. Ceriporiopsistianshanensis is characterized by a cream to salmon-buff pore surface, larger pores measuring 1-3 per mm, and broadly ellipsoid basidiospores 5-6.5 × 3-4 µm. Sideratianshanensis is characterized by annual to perennial basidiocarps, measuring 15 mm thick, pores 5-7 per mm, cream to rosy buff pore surface, and allantoid basidiospores 3-3.5 × 1-1.4 µm. Detailed illustrations and descriptions of the novel species are provided.

Species diversity, molecular phylogeny and ecological habits of Cyanosporus (Polyporales, Basidiomycota) with an emphasis on Chinese collections.

Cyanosporus is a genus widely distributed in Asia, Europe, North America, South America and Oceania. It grows on different angiosperm and gymnosperm trees and can cause brown rot of wood. Blue-tinted basidiomata of Cyanosporus makes it easy to distinguish from other genera, but the similar morphological characters make it difficult to identify species within the genus. Phylogeny and taxonomy of Cyanosporus were carried out based on worldwide samples with an emphasis on Chinese collections, and the species diversity of the genus is updated. Four new species, C.flavus, C.rigidus, C.subungulatus and C.tenuicontextus, are described based on the evidence of morphological characters, distribution areas, host trees and molecular phylogenetic analyses inferred from the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nSSU), the small subunit of mitochondrial rRNA gene (mtSSU), the largest subunit of RNA polymerase II (RPB1), the second largest subunit of RNA polymerase II (RPB2), and the translation elongation factor 1-α gene (TEF). Our study expanded the number of Cyanosporus species to 35 around the world including 23 species from China. Detailed descriptions of the four new species and the geographical locations of the Cyanosporus species in China are provided.

Prognostic significance of prognostic nutritional index and systemic immune-inflammation index in patients after curative breast cancer resection: a retrospective cohort study.

BACKGROUND: Nutritional status and inflammation are closely associated with poor outcome in malignant tumors. However, the prognostic impact of postoperative in these variables on breast cancer (BC) remains inconclusive. We aimed to determine whether prognostic nutritional index (PNI), systemic immune-inflammation index (SII), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) affect two long-term outcomes among patients after curative resection of BC. METHODS: We retrospectively reviewed 508 patients with BC treated with curative surgery between February 5, 2013 and May 26, 2020. All patients were divided into 3 groups based on tertiles (T1-T3) of PNI, SII, NLR, and PLR. The effects of four indexes on disease-free survival (DFS) and overall survival (OS) have been evaluated using Cox proportional hazards models and Kaplan-Meier method. RESULTS: Compared with PNI-lowest cases, patients with highest PNI showed significantly longer DFS (multivariate adjusted hazard ratio [HR] = 0.37, 95% confident interval [CI] 0.19-0.70, P for trend = 0.002), whereas higher PLR seemed to be marginally associated with poorer DFS (P for trend = 0.086 and 0.074, respectively). Subgroup analyses indicate the potential modification effects of family history of BC and radiotherapy on the prognosis value of PNI to DFS in BC patients (P for interaction = 0.004 and 0.025, respectively). In addition, the levels of three inflammatory indices, namely SII, NLR, and PLR might be positively related with increased age at diagnosis (all P for trend < 0.001). CONCLUSIONS: A high PNI was associated with better DFS, supporting its roles as prognostic parameters for patients with BC. The nutritional status and systemic immune may exert great effects on patient prognosis. Further studies are warrant to explore the prognosis value of PLR.

Morphology and molecular phylogeny reveal five new species of Hydnellum (Bankeraceae, Thelephorales) from China.

The genus Hydnellum is a kind of ectomycorrhizal fungi that can play a role in the material cycle by connecting the plant roots to the soil, and some species of Hydnellum are medicinal fungi with vital research value. The species diversity of Hydnellum is unclear in China. In this study, five new species of Hydnellum are described from China based on morphological characters and phylogenetic analyses inferred from two datasets of ITS + LSU and ITS + LSU + SSU + RPB2 sequences. H. chocolatum is characterized by its chocolate basidiomata with the fibrillose, spongy to tomentose pileal surface, and subglobose to globose basidiospores measuring (4.5-)5-6 × 4-5(-5.8) µm. H. concentricum is characterized by its zonate pileal surface, thin context, short stipe, presence of both simple septa and clamp connections in generative hyphae of spines, and subglobose to ellipsoidal basidiospores measuring (3.5-)4-5(-5.2) × (3.2-)3.5-5 µm. H. crassipileatum is characterized by its thick pileus with the reddish brown to grayish brown pileal surface, and subglobose to ellipsoidal basidiospores measuring 4-6(-6.5) × 4-5.5 µm. H. melanocarpum is characterized by its vinaceous brown to black pileus with spongy pileal surface, presence of both simple septa and clamp connections in generative hyphae of spines, and subglobose basidiospores measuring 4.5-5.5(-6) × (3.5-)3.8-5.1 µm. H. radiatum is characterized by its radially aligned stripes on pileal surface, grayish brown context, short stipe, and subglobose to ellipsoidal basidiospores measuring (3.5-)4-5 × 3-4.5(-5) µm. Full descriptions, illustrations, and phylogenetic trees to show the placement of the new species are provided.

A Phylogenetic and Taxonomic Study on Phellodon (Bankeraceae, Thelephorales) from China.

In this study, phylogenetic analyses of Phellodon from China were carried out based on sequences from the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nSSU), the largest subunit of RNA polymerase II (RPB1), and the second largest subunit of RNA polymerase II (RPB2), combined with morphological characters of the collected specimens in China. The fruiting bodies of the specimens were used to observe their characteristics, and three new species of Phellodon are discovered. Phellodon crassipileatus is characterized by its pale brown to dark brown pileal surface, tomentose pileal margin, white spines, and the presence of clamp connections in generative hyphae of pileal surface, context, and stipe. Phellodon griseofuscus is characterized by its dark brown to black pileal surface, white to pale brown pileal margin, the presence of both simple septa and clamp connections in generative hyphae of spines, and moderately long basidia. Phellodon perchocolatus is characterized by its woody and broad pileus, brown to greyish brown pileal surface when fresh, tomentose pileal margin when young, which becomes glabrous with age, and the presence of both simple septa and clamp connections in the generative hyphae of the spines. This is the first time both single and multi-genes analysis is used in such a phylogenetic and taxonomic study on Phellodon, which can provide the basis for the phylogenetic study of the genus.

Species Diversity, Molecular Phylogeny, and Ecological Habits of Fomitopsis (Polyporales, Basidiomycota).

Fomitopsis is a worldwide brown-rot fungal genus of Polyporales, which grows on different gymnosperm and angiosperm trees and has important ecological functions and economic values. In this study, species diversity, phylogenetic relationships, and ecological habits of Fomitopsis were investigated. A total of 195 specimens from 24 countries representing 29 species of Fomitopsis were studied. Based on the morphological characters and phylogenetic evidence of DNA sequences including the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nSSU), the small subunit of mitochondrial rRNA gene (mtSSU), the translation elongation factor 1-α gene (TEF), and the second subunit of RNA polymerase II (RPB2), 30 species are accepted in Fomitopsis, including four new species: F. resupinata, F. srilankensis, F. submeliae and F. yimengensis. Illustrated descriptions of the novel species and the geographical locations of the Fomitopsis species are provided.

Molecular phylogeny and taxonomy of the remarkable genus Leptoporus (Polyporales, Basidiomycota) with description of a new species from Southwest China.

Leptoporus is a rare and remarkable genus, mainly occurring in coniferous forests in the Northern Hemisphere. Recent phylogenetic studies showed that Leptoporus belongs to Irpicaceae in the phlebioid clade. It is worth noting that most species in the phlebioid clade can cause white-rot decay, except for the Leptoporus species, which can cause a brown-rot decay. In this study, we performed phylogenetic and taxonomic studies of Leptoporus and related genera. Molecular phylogenetic analyses were conducted based on sequences from multiple loci including the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the largest subunit of RNA polymerase II gene (RPB1), the second largest subunit of RNA polymerase II gene (RPB2), and the translation elongation factor 1-α gene (TEF1). Combined with morphological characteristics, a new species, Leptoporus submollis sp. nov., is discovered and illustrated from Southwest China.

Taxonomy and molecular phylogeny of Trametopsis (Polyporales, Basidiomycota) with descriptions of two new species.

Trametopsis is a worldwide genus belonging to Irpicaceae in the phlebioid clade, which can cause a white decay of wood. Previously, only three species were ascribed to the genus. In this study, we performed a morphological and phylogenetic study of Trametopsis. Molecular phylogenetic analyses of multiple loci included the internal transcribed spacer (ITS) regions, the large subunit nuclear ribosomal RNA gene (nLSU), the largest subunit of RNA polymerase II (RPB1), the second largest subunit of RNA polymerase II (RPB2) and the translation elongation factor 1-α gene (TEF1). Phylogenetic trees were inferred from the combined datasets of ITS+nLSU sequences and ITS+nLSU+RPB1+RPB2+TEF1 sequences by using maximum parsimony, maximum likelihood and Bayesian inference analyses. Combined with molecular data, morphological characters and ecological traits, two new species of Trametopsis are discovered. Trametopsisabieticola is characterised by its pileate, solitary or imbricate basidiomata, buff to buff-yellow pileal surface when fresh, becoming pinkish buff to clay-buff when dry, cream to buff pore surface when fresh, becoming pinkish buff to greyish brown upon drying, round to angular and large pores (0.5-1 per mm), cylindrical basidiospores (5.8-7.2 × 1.9-2.6 µm), distributed in the high altitude of mountains and grows on Abies sp. Trametopsistasmanica is characterised by its resupinate basidiomata, cream to pinkish-buff pore surface when fresh, becoming honey-yellow to snuff brown upon drying, cylindrical basidiospores (5.2-6.3 × 1.8-2.2 µm), and by growing on Eucalyptus sp. Detailed descriptions and illustrations of the two novel species are provided.

Taxonomy and Phylogeny of the Fomitopsis pinicola Complex With Descriptions of Six New Species From East Asia.

Fomitopsis pinicola is a common brown-rot fungal species found in northern hemisphere. It grows on many different gymnosperm and angiosperm trees. Recent studies show that it is a species complex; three species from North America and one species from Europe have been recognized in this complex. In the current study, six new species in the Fomitopsis pinicola complex were discovered from East Asia, based on morphological characters and phylogenetic analyses inferred from the sequence data of the internal transcribed spacer (ITS) regions, the second subunit of RNA polymerase II (RPB2), and the translation elongation factor 1-α gene (TEF). Detailed descriptions of the six new species are provided. Our results also indicates that species of the F. pinicola complex from East Asia usually have limited distribution areas and host specialization.

Species Diversity and Molecular Phylogeny of Cyanosporus (Polyporales, Basidiomycota).

Cyanosporus is a cosmopolitan brown-rot fungal genus, recognizable by blue-tinted basidiocarps. Species in this genus were usually treated as belonging to the Postia caesia complex, however, recent phylogenetic analyses showed that this complex represents an independent genus. During further studies on Cyanosporus, five new species were discovered based on morphological features and molecular data. Phylogenetic analyses of Cyanosporus were conducted using the internal transcribed spacer (ITS) regions, the large subunit of nuclear ribosomal RNA gene (nLSU), the small subunit of nuclear ribosomal RNA gene (nSSU), the small subunit of mitochondrial rRNA gene (mtSSU), the largest subunit of RNA polymerase II (RPB1), the second largest subunit of RNA polymerase II (RPB2), and the translation elongation factor 1-α gene (TEF); illustrated descriptions of the new species are provided. In addition, fifteen species previously belonging to the Postia caesia complex are transferred to Cyanosporus and proposed as new combinations.

Association between matrix metalloproteinase 9 polymorphisms and breast cancer risk: An updated meta-analysis and trial sequential analysis.

BACKGROUND: Numerous studies have sought associations between matrix metalloproteinase 9 (MMP-9) polymorphisms and breast cancer risk. However, these studies have yielded conflicting results. Hence, we performed an updated meta-analysis to clarify the effects of four MMP-9 gene polymorphisms (rs3918242, rs2250889, rs3787268, and rs17576) on breast cancer risk. METHODS: A comprehensive literature search for eligible studies was conducted in five electronic databases, including PubMed, Embase and Web of Science, up to March 1, 2020. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations in random-effects models. For the reduction of type I errors, a trial sequential analysis (TSA) was performed. RESULTS: Twenty-one studies (8813 breast cancer cases and 9323 controls) were included in the quantitative analysis. For rs3918242, the overall ORs were significant under allelic comparison (OR A vs. G = 1.34; 95% CI 1.03, 1.74, P = 0.028) and the recessive genetic model (OR AA vs. GG+GA = 1.40; 95% CI 1.06, 1.84, P = 0.016). For rs2250889, the ORs were significant under homozygote comparison (OR GG vs. CC = 2.57; 95% CI 1.22, 5.42, P = 0.013), heterozygote comparison (OR GC vs. CC = 2.48; 95% CI 1.17, 5.23, P = 0.018), and the dominant genetic model (OR GG+GC vs. CC = 2.53; 95% CI 1.23, 5.20, P = 0.012). No associations were observed for rs3787268 or rs17576. The subgroup analyses indicated that the risk effect of the rs3918242 A allele was observed only among Asians. TSA showed that the findings for rs3918242, rs3787268, and rs17576 were robust, but many more patients are needed before definitive conclusions can be made for rs2250889. CONCLUSION: Our meta-analysis suggests that MMP-9 rs3918242, but not rs3787268 and rs17576 polymorphisms, may be risk factors for breast cancer. The effect of rs2250889 needs further confirmation with a larger sample size.

Elaphroporia ailaoshanensis gen. et sp. nov. in Polyporales (Basidiomycota).

A new poroid wood-inhabiting fungal genus, Elaphroporia, typified by E. ailaoshanensissp. nov., is proposed based on a combination of morphological features and molecular evidence. The genus is characterised by an annual growth habit, resupinate basidiocarps, becoming rigid and light-weight up on drying, a monomitic hyphal system with thick-walled generative hyphae bearing both clamp connections and simple septa, slightly amyloid, CB+ and ellipsoid, hyaline, thin-walled, smooth and IKI-, CB- basidiospores. Sequences of ITS and LSU nrRNA gene regions of the studied samples were generated, and phylogenetic analyses were performed with maximum likelihood, maximum parsimony and bayesian inference methods. The phylogenetic analysis based on molecular data of ITS+nLSU sequences showed that Elaphroporia belonged to the residual polyporoid clade and was closely related to Junghuhnia crustacea. Further investigation was obtained for more representative taxa in the Meruliaceae based on ITS+nLSU sequences, in which the result demonstrated that the genus Elaphroporia formed a monophyletic lineage with a strong support (100 % BS, 100 % BP, 1.00 BPP) and then grouped with Flaviporus and Steccherinum.

Retrospective analysis of the utility of multiparametric MRI for differentiating between benign and malignant breast lesions in women in China.

We explored the utility of time-resolved angiography with interleaved stochastic trajectories dynamic contrast-enhanced magnetic resonance imaging (TWIST DCE-MRI), readout segmentation of long variable echo-trains diffusion-weighted magnetic resonance imaging- diffusion-weighted magnetic resonance imaging (RESOLVE-DWI), and echo-planar imaging- diffusion-weighted magnetic resonance imaging (EPI-DWI) for distinguishing between malignant and benign breast lesions.This retrospective analysis included female patients with breast lesions seen at a single center in China between January 2016 and April 2016. Patients were allocated to a benign or malignant group based on pathologic diagnosis. All patients received routine MRI, RESOLVE-DWI, EPI-DWI, and TWIST DCE-T1WI. Variables measured included quantitative parameters (K, Kep, and Ve), semiquantitative parameters (rate of contrast enhancement for contrast agent inflow [W-in], rate of contrast decay for contrast agent outflow [W-out], and time-to-peak enhancement after contrast agent injection [TTP]) and apparent diffusion coefficient (ADC) values for RESOLVE-DWI (ADCr) and EPI-DWI (ADCe). Receiver-operating characteristic (ROC) curve analysis was used to evaluate the diagnostic utility of each parameter for differentiating malignant from benign breast lesions.A total of 87 patients were included (benign, n = 20; malignant, n = 67). Compared with the benign group, the malignant group had significantly higher K, Kep and W-in and significantly lower W-out, TTP, ADCe, and ADCr (all P < .05); Ve was not significantly different between groups. RESOLVE-DWI was superior to conventional EPI-DWI at illustrating lesion boundary and morphology, while ADCr was significantly lower than ADCe in all patients. Kep, W-out, ADCr, and ADCe showed the highest diagnostic efficiency (based on AUC value) for differentiating between benign and malignant lesions. Combining 3 parameters (Kep, W-out, and ADCr) had a higher diagnostic efficiency (AUC, 0.965) than any individual parameter and distinguished between benign and malignant lesions with high sensitivity (91.0%), specificity (95.0%), and accuracy (91.9%).An index combining Kep, W-out, and ADCr could potentially be used for the differential diagnosis of breast lesions.

Clinical Effects of CpG-Based Treatment on the Efficacy of Hepatocellular Carcinoma by Skewing Polarization Toward M1 Macrophage from M2.

OBJECTIVE: This study aims to explore the clinical efficacy of CpG-based therapy for treating hepatocellular carcinoma (HCC) by skewing polarization toward M1 macrophage from M2. METHODS: Pulmonary metastasis rate, overall survival time, and remission rate of 10 patients with HCC treated with transcatheter arterial chemoembolization (TACE) combined with CpG therapy and 10 age-, gender-, and TNM0-matched patients treated with TACE (control group) were compared. RESULTS: No pulmonary metastasis rate was 70% in the combined treatment group and 40% in the control group, respectively; and the differences between the two groups were statistically significant (p < 0.05). Median overall survival time was 22 months in the combined treatment group, compared with 6.65 months in the control group (p < 0.05). Remission rate in the combined treatment group (70%) was higher than in the control group (30%), but the differences between these two groups were not statistically significant (p > 0.05). CONCLUSION: Compared with TACE, CpG combined with TACE can decrease the pulmonary metastasis rate. This combined therapy can also improve the overall survival time of patients.

Tumor necrosis factor alpha-238G/A polymorphism and risk of breast cancer: An update by meta-analysis.

BACKGROUND: The association between the tumor necrosis factor-alpha gene (TNF-a) -238G/A polymorphism and the breast cancer has been analyzed in several studies, but the results have been inconclusive. We then performed a meta-analysis to get a precise estimation of the association. METHODS: Eight case-control studies with a total of 37,257 cases and 39,564 controls were identified by searching the ISI Web of Knowledge database and the PubMed database up to August 2014. RESULTS: Overall, no association was found between TNF-alpha-238G/A polymorphism and breast cancer in any of genetic model (additive model OR = 1.06, 95%CI: 0.94-1.21, Pheterogeneity = .02; homozygous model OR = 1.04, 95%CI: 0.83-1.30, Pheterogeneity = .98; dominant model OR = 1.06, 95%CI: 0.92-1.21, Pheterogeneity = .01; recessive model OR = 1.04, 95%CI: 0.83-1.30, Pheterogeneity = .98). Furthermore, no significant association was identified when stratified by ethnicity (Caucasian, Asian). CONCLUSION: This meta-analysis indicated that the TNF-alpha-238G/A polymorphism is not associated with breast cancer risk in the overall population.

Hairpin DNA as a biobarcode modified on gold nanoparticles for electrochemical DNA detection.

Hairpin DNA (hpDNA) as a novel biobarcode was conjugated with gold nanoparticles (AuNPs) and a reporter DNA (rpDNA) to form hpDNA/AuNP/rpDNA nanoparticles for the detection of an oligonucleotide sequence associated with Helicobacter pylori as a model target. The rpDNA is complementary to about a half-portion of the target DNA sequence (tDNA). A capture DNA probe (cpDNA), complementary to the other half of the tDNA, was immobilized on the surface of a gold electrode. In the presence of tDNA, a sandwich structure of (hpDNA/AuNP/rpDNA)/tDNA/cpDNA was formed on the electrode surface. The differential pulse voltammetry (DPV) detection was based on [Ru(NH3)5(3-(2-phenanthren-9-yl-vinyl)-pyridine)](2+), an electroactive complex that binds to the sandwich structure by its intercalation with the hpDNA and the double-stranded DNA (dsDNA) of the sandwich structure. The several factors--high density of biobarcode hpDNA on the surface of AuNPs, multiple electroactive complex molecules intercalated with each hpDNA and dsDNA molecule, and the intercalation binding mode of the electroactive complex with the DNA sandwich structure--contribute to the DNA sensor with highly selective and sensitive sensing properties. The DNA sensor exhibited a detection limit of 1 × 10(-15) M (i.e., 1 fM), the DNA levels in physiological samples, with linearity down to 2 × 10(-15) M. It can differentiate even one single mismatched DNA from the complementary tDNA. This novel biobarcode-based DNA sensing approach should provide a general platform for development of direct, simple, repetitive, sensitive, and selective DNA sensors for various important applications in analytical, environmental, and clinical chemistry.

Direct electron transfer of glucose oxidase-boron doped diamond interface: a new solution for a classical problem.

A planar boron-doped diamond (BDD) electrode was treated with KOH and functionalized with 3-aminopropyltriethoxysilane (APTES) to serve as a biosensing platform for biomolecule immobilization with glucose oxidase (GOx) as a test model. The free amino groups of GOx and APTES were cross-linked by glutaraldehyde (X), a bifunctional chemical to form a stable enzyme layer (GOx-X-APTES) on BDD. Micrographs obtained by scanning electron microscopy revealed that a mesoporous structure uniformly covered the BDD surface. Cyclic voltammetry of GOx immobilized showed a pair of well-defined redox peaks in neutral phosphate buffer solution, corresponding to the direct electron transfer of GOx. The apparent heterogeneous electron transfer rate constant of the immobilized GOx was estimated to be 8.85 ± 0.47 s(-1), considerably higher than the literature reported values. The determination of glucose was carried out by amperometry at -0.40 V, and the developed biosensor showed good reproducibility and stability with a detection limit of 20 µM. Both ascorbic and uric acids at normal physiological conditions did not provoke any signals. The dynamic range of glucose detection was further extended by covering the enzyme electrode with a thin Nafion layer. The Nafion/GOx-X-APTES/BDD biosensor showed excellent stability, a detection limit of 30 µM, a linear range between 35 µM and 8 mM, and a dynamic range up to 14 mM. Such analytical performances were compared favorably with other complicated sensing schemes using nanomaterials, redox polymers, and nanowires. The APTES-functionalized BDD could be easily extended to immobilize other redox enzymes or proteins of interests.

Amphetamine modulation of long-term potentiation in the prefrontal cortex: dose dependency, monoaminergic contributions, and paradoxical rescue in hyperdopaminergic mutant.

Amphetamine can improve cognition in healthy subjects and patients with schizophrenia, attention-deficit hyperactivity disorder, and other neuropsychiatric diseases; higher doses, however, can impair cognitive function, especially those mediated by the prefrontal cortex. We investigated how amphetamine affects prefrontal cortex long-term potentiation (LTP), a cellular correlate of learning and memory, in normal and hyperdopaminergic mice lacking the dopamine transporter. Acute amphetamine treatment in wild-type mice produced a biphasic dose-response modulation of LTP, with a low dose enhancing LTP and a high dose impairing it. Amphetamine-induced LTP enhancement was prevented by pharmacological blockade of D(1) - (but not D(2)-) class dopamine receptors, by blockade of ß-adrenergic receptors, or by inhibition of cAMP-PKA signaling. In contrast, amphetamine-induced LTP impairment was prevented by inhibition of post-synaptic protein phosphatase-1, a downstream target of PKA signaling, or by blockade of either D(1) - or D(2)-class dopamine, but not noradrenergic, receptors. Thus, amphetamine biphasically modulates LTP via cAMP-PKA signaling orchestrated mainly through dopamine receptors. Unexpectedly, amphetamine restored the loss of LTP in dopamine transporter-knockout mice primarily by activation of the noradrenergic system. Our results mirror the biphasic effectiveness of amphetamine in humans and provide new mechanistic insights into its effects on cognition under normal and hyperdopaminergic conditions.

D1 and D2 dopamine receptors in separate circuits cooperate to drive associative long-term potentiation in the prefrontal cortex.

Dopamine release associated with motivational arousal is thought to drive goal-directed learning and consolidation of acquired memories. This dopamine hypothesis of learning and motivation directly suggests that dopamine is necessary for modifications of excitatory synapses in dopamine terminal fields, including the prefrontal cortex (PFC), to "stamp in" posttrial memory traces. It is unknown how such enabling occurs in native circuits tightly controlled by GABAergic inhibitory tone. Here we report that dopamine, via both D1-class receptors (D1Rs) and D2-class receptors (D2Rs), enables the induction of spike timing-dependent long-term potentiation (t-LTP) in layer V PFC pyramidal neurons over a "window" of more than 30 ms that is otherwise closed under intact inhibitory constraint. Dopamine acts at D2Rs in local GABAergic interneurons to suppress inhibitory transmission, gating the induction of t-LTP. Moreover, dopamine activates postsynaptic D1Rs in excitatory synapses to allow t-LTP induction at a substantially extended, normally ineffective, timing interval (+30 ms), thus increasing the associability of prepost coincident stimuli. Although the D2R-mediated disinhibition alone is sufficient to gate t-LTP at a normal timing (+10 ms), t-LTP at +30 ms requires concurrent activation of both D1Rs and D2Rs. Our results illustrate a previously unrecognized circuit-level mechanism by which dopamine receptors in separate microcircuits cooperate to drive Hebbian synaptic plasticity across a significant temporal window under intact inhibition. This mechanism should be important in functioning of interconnected PFC microcircuits, in which D1Rs and D2Rs are not colocalized but their coactivation is necessary.