CARD9S12N facilitates the production of IL-5 by alveolar macrophages for the induction of type 2 immune responses.

The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH1 and TH17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs. Mechanistically, CARD9S12N mediated CLR-induced activation of the non-canonical transcription factor NF-κB subunit RelB, which initiated production of the cytokine IL-5 in alveolar macrophages for the recruitment of eosinophils to drive TH2 cell-mediated allergic responses. We identified the homozygous CARD9 mutation encoding S12N in patients with allergic bronchopulmonary aspergillosis and revealed activation of RelB and production of IL-5 in peripheral blood mononuclear cells from these patients. Our study provides genetic and functional evidence demonstrating that CARD9S12N can turn alveolar macrophages into IL-5-producing cells and facilitates TH2 cell-mediated pathologic responses.

Effects of fermentation on the structures of yellow compounds in citrus pomace.

To enhance the stability and light resistance of the yellow compounds in citrus pomace, our study successfully isolated and purified five compounds using ultrasonic-assisted extraction and column chromatography. The identified compounds include methyl linoleate, (2-ethyl)hexyl phthalate, 1,3-distearoyl-2-oleoylglycerol, 6,6-ditetradecyl-6,7-dihydroxazepin-2(3H)-one, and n-octadeca-17-enoic acid. The monomers extracted from fresh pomace, compounds 1 and 2, exhibit structural similarities to flavonoids and carotenoids. In contrast, the polymers isolated from fermented pomace, compounds 3, 4, and 5, share structural units with the fresh pomace compounds, indicating the transformation to stable polymeric forms. This suggests that the microbial fermentation process not only enhances the value of citrus pomace, but also provides a promising pathway for the synthesis of natural antioxidant yellow pigments with far-reaching theoretical and practical significance.

Association of image-defined risk factors with clinical features, tumor biology, and outcomes in neuroblastoma: a single-center retrospective study.

Image-defined risk factors (IDRF) in neuroblastoma have been developed to predict tumor resectability and surgical complications; however, the potential prognostic value of IDRF in neuroblastoma has been variably reported. Previous studies did not report the IDRF status separately from the International Neuroblastoma Risk Group (INRG) stage. Moreover, the association between IDRF and clinical and pathological factors has not been discussed further. In this retrospective study, we investigated the clinical and biological features of neuroblastoma at different INRG stages based on IDRF. Event-free survival (EFS) and overall survival (OS) related to the INRG stage were analyzed using log-rank tests, and the prognostic value of the IDRF number and type was also evaluated. Among 72 patients, 182 IDRF at diagnosis were found in 79.2%. The distribution of the INRG stages was 10 L1 (13.9.0%), 25 L2 (34.7%), and 37 M/MS (51.4%). Patients with stage M/Ms had a larger tumor volume, a higher percentage of age ≥ 18 months, elevated lactate dehydrogenase (LDH) level, elevated ferritin level, and a higher percentage of COG high-risk compared with stage L1 and L2 patients. EFS and OS were similar for stage L1 and L2 tumors but were significantly poorer for metastatic disease. However, EFS (P = 0.06) and OS (P = 0.07) were similar for IDRF-negative and positive neuroblastomas. Patients with stage M/Ms with IDRF-positive had poorer EFS (P = 0.001) and OS (P < 0.001) compared with patients in stage L2. An IDRF ≥ 4, vascular IDRF, and infiltrative IDRF of the tumor were significant indicators of poor prognosis.   Conclusion: Our study indicates that increasing the INRG stages based on IDRF is associated with various unfavorable clinical features of neuroblastoma. The principal determinant of survival in neuroblastoma is the presence of metastatic disease more than IDRF alone at diagnosis. Both the number and type of IDRF have important clinical significance in the protocol planning of neuroblastoma, rather than just considering the absence or presence of IDRF. What is Known: • The International Neuroblastoma Risk Group Staging System (INRGSS) now employs image-defined risk factors (IDRFs) to stratify and stage disease. • The presence of IDRF at diagnosis are associated with higher rates of operative complications and incomplete surgical resection. What is New: • The principal determinant of survival from neuroblastoma is the presence of metastatic disease at diagnosis, more than IDRF alone. • IDRF number and type should also be considered during the diagnosis and treatment planning of neuroblastoma, rather than just considering the absence or presence of IDRF.

Association between whole blood essential trace elements and cognitive function in older adults.

BACKGROUND: Essential trace elements (ETEs) are essential nutrients for keeping the nervous system functioning. Associations between ETEs and cognitive function are still inconclusive and limited. OBJECTIVES: We aimed to investigate the individual and joint associations between ETEs and cognitive function among older adults. METHODS: A population (N = 2181) at an average age≥ 65 from Yiwu cohort in China was available for this study. Whole blood chromium (Cr), selenium (Se), manganese (Mn), and copper (Cu) concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Cognitive function was assessed using the Mini-Mental State Examination (MMSE), consisting of five specific cognitive domains: orientation, registry, attention and calculation, recall, and language and praxis. Linear regression, restricted cubic spline (RCS) analysis, and Bayesian kernel machine regression (BKMR) were used to analyze the individual and joint associations between ETEs and cognitive function. RESULTS: The association between Cr and MMSE score presented an inverted-U shape (Q3 versus Q1: ß = 0.774, 95 % CI: 0.297, 1.250; Q4 versus Q1: ß = 0.481, 95 % CI: 0.006, 0.956); and Cr was especially associated with the registry, recall, and language and praxis. Per IQR (36.32 µg/L) increase of Se was positively associated with the MMSE score (ß = 0.497, 95 % CI: 0.277, 0.717) and all five cognitive domains. The BKMR showed that the dose-response association between Se and cognitive function increased initially and then decreased with increasing Se concentration when fixed the other ETEs in median. ETEs mixture was positively associated with cognitive function, and Se (posterior inclusion probabilities, PIPs = 0.915) was the most important contributor within the ETEs mixture. CONCLUSIONS: The nonlinear association between Cr and cognitive function suggested further exploration of an appropriate concentration range for ETEs. A positive association between mixed ETEs and cognitive function is a reminder that their joint association should be considered. Further prospective studies or intervention studies are warranted to validate our findings in the future.

Clonidine ameliorates cerebral ischemia-reperfusion injury by up-regulating the GluN3 subunits of NMDA receptor.

This study aimed to investigate the protective effects of the alpha-2 adrenergic receptor (α2-AR) agonist, clonidine, on the cerebral ischemia-reperfusion (I/R) injury and elaborate the underlying mechanisms. Cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 4 h in adult male SD rats. Saline, clonidine and yohimbine (an α2-AR antagonist) were intraperitoneally administered each day for one week before surgery. Neurological deficit was evaluated just before decapitation. TTC staining was applied for correlation of cerebral infarction volume. HE staining was performed to observe the neuron morphology. Immunohistochemical staining was performed to detect the localization and expression of GluN3 proteins. Western blot analysis also was used to detect the expression levels of GluN3 proteins. Our data showed that clonidine ameliorated neurological deficit and reduced the cerebral infarction volume of the rats with cerebral I/R. It is worth noting that treatment with clonidine up-regulated the protein expression of GluN3 in the rats with the cerebral I/R, especially in the cell membrane. Moreover, clonidine also up-regulated the transposition from cytoplasm to cell membrane of GluN3 after cerebral I/R. In addition, yohimbine abolished the neuroprotective effects of clonidine. The results indicated that clonidine played a protective role in cerebral I/R injury through regulation of the protein expression of GluN3 subunits of N-methyl-D-aspartate (NMDA) receptor.

Radiomics model of contrast-enhanced MRI for early prediction of acute pancreatitis severity.

BACKGROUND: Computed tomography (CT) or MR images may cause the severity of early acute pancreatitis (AP) to be underestimated. As an innovative image analysis method, radiomics may have potential clinical value in early prediction of AP severity. PURPOSE: To develop a contrast-enhanced (CE) MRI-based radiomics model for the early prediction of AP severity. STUDY TYPE: Retrospective. SUBJECTS: A total of 259 early AP patients were divided into two cohorts, a training cohort (99 nonsevere, 81 severe), and a validation cohort (43 nonsevere, 36 severe). FIELD STRENGTH/SEQUENCE: 3.0T, T1 -weighted CE-MRI. ASSESSMENT: Radiomics features were extracted from the portal venous-phase images. The "Boruta" algorithm was used for feature selection and a support vector machine model was established with optimal features. The MR severity index (MRSI), the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the bedside index for severity in acute pancreatitis (BISAP) were calculated to predict the severity of AP. STATISTICAL TESTS: Independent t-test, Mann-Whitney U-test, chi-square test, Fisher's exact tests, Boruta algorithm, receiver operating characteristic analysis, DeLong test. RESULTS: Eleven potential features were chosen to develop the radiomics model. In the training cohort, the area under the curve (AUC) of the radiomics model, APACHE II, BISAP, and MRSI were 0.917, 0.750, 0.744, and 0.749, and the P value of AUC comparisons between the radiomics model and scoring systems were all less than 0.001. In the validation cohort, the AUC of the radiomics model, APACHE II, BISAP, and MRSI were 0.848, 0.725, 0.708, and 0.719, respectively, and the P value of AUC comparisons were 0.96 (radiomics vs. APACHE II), 0.40 (radiomics vs. BISAP), and 0.46 (radiomics vs. MRSI). DATA CONCLUSION: The radiomics model had good performance in the early prediction of AP severity. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:397-406.

Synthesizing Crystalline Chalcogenidoarsenates in Thiol-Amine Solvent Mixtures.

Thiol-amine solvent mixtures have been widely applied in the solution processing of binary chalcogenide thin films due to their excellent ability to dissolve various bulk binary chalcogenides. However, application of this solvent system in preparing new crystalline chalcogenidometalates has not been explored. In this work, by using a thiol-amine solvent mixture of n-butylamine (BA) and 1,2-ethanedithiol (EDT) as the reaction medium and protonated piperazine (pip) cation as the template, we synthesized a series of new chalcogenidoarsenates with structures ranging from discrete clusters to two-dimensional layers, namely, [pipH2][pipH][AsS4] (1), [pipH2][pipH][As(Se0.4S0.6)4] (2), [pipH2]2[pipH]2[In2AsIII2AsV2S13.3(S2)0.7] (3), [pipH2]2[pipH]2[In2AsIII2AsV2S10.2Se3.1(Se2)0.7] (4), [pipH2]0.5[AsS(S2)] (5), [pipH2]0.5[AsS2] (6), [pipH]2[AgAsS4] (7), [pipH2]1.5[GaAsIIIAsVS7] (8), and Cs2[pipH]2[InAs6S12]Cl (9). Particularly, compounds 3, 4, and 8 contain mixed-valent AsIII and AsV ions in their discrete clusters and one-dimensional chain. In addition, compound 5 could thermodynamically transform to compound 6 with increasing reaction temperature, which may be attributed to the thermodynamically unstable S-S species in the chains of 5. The BA-EDT solvent mixture was crucial to the synthesis of these compounds, since no title crystals can be prepared by replacing the BA-EDT solvent mixture with other conventional solvents or removing one component of the BA-EDT solvent mixture from the reaction system. Our research demonstrates that thiol-amine solvent systems could be promising reaction media for growing novel crystalline chalcogenidometalates.

Expression of lipid metabolism genes provides new insights into intramuscular fat deposition in Laiwu pigs.

OBJECTIVE: The objective of this study was to measure the special expression pattern of lipid metabolism genes and investigate the molecular mechanisms underlying intramuscular fat (IMF) deposition in Longissimus dorsi muscle of Laiwu pigs. METHODS: Thirty-six pigs (Laiwu n = 18; Duroc×Landrace×Yorkshire n = 18) were used for the measurement of the backfat thickness, marbling score, IMF content, and expression of lipid metabolism genes. RESULTS: Significant correlations were found between IMF content and the mRNA expression of lipid metabolism genes. Of the 14 fat deposition genes measured, fatty acid synthase (FASN) showed the strongest correlation (r = 0.75, p = 0.001) with IMF content, and of the 6 fat removal genes, carnitine palmitoyl transferase 1B (CPT1B) exhibited the greatest negative correlation (r = -0.66, p = 0.003) with IMF content in Laiwu pig. Multiple regression analysis showed that CPT1B, FASN, solute carrier family 27 member 1 (SLC27A1), and fatty acid binding protein 3 (FABP3) contributed 38% of the prediction value for IMF content in Laiwu pigs. Of these four variables, CPT1B had the greatest contribution to IMF content (14%) followed by FASN (11%), SLC27A1 (9%), and FABP3 (4%). CONCLUSION: Our results indicate that the combined effects of an upregulation in fat deposition genes and downregulation in fat removal genes promotes IMF deposition in Laiwu pigs.

[Clinical efficacy of acupuncture combined with modified Xiangfu Decoction in treatment of menopausal insomnia cause by liver Qi stagnation].

To evaluate the efficacy and safety of acupuncture combined with modified Xiangfu Decoction in the treatment of menopausal insomnia case by liver Qi stagnation. Totally 120 cases were randomly divided into the control group(60 cases) and the treatment group(60 cases). Estazolam and acupuncture combined with modified Xiangfu Decoction were given for 16 weeks. Before and after treatment, Epworth sleepiness scale(ESS), Pittsburgh sleep quality index(PSQI), Hamilton anxiety scale(HAMA) and traditional Chinese medicine(TCM) syndrome score were compared between the two groups. Polysomnography monitor was used to monitor sleep progress and sleep structure. Serum LH, FSH and E_2 were determined. The clinical efficacy and incidence of adverse reactions were observed. Four cases were lost during the study. The total effective rate in the treatment group was 91.5%, which was higher than that in the control group 75.4%(P<0.05). After treatment, the scores of clinical symptoms(ESS, PSQI, HAMA, TCM symptoms) in the treatment group were significantly reduced(P<0.05), and lower than that in the control group(P<0.05). TST, SE in the treatment group were increased(P<0.05), while AWT, SL, AT in the treatment group were decreased(P<0.05), and the improvement was more significant than that in the control group(P<0.05). S_1 in the treatment group was decreased(P<0.05), whereas S_2, S_(3+4), REM in the treatment group were increased(P<0.05), and the improvement was more significant than that in the control group(P<0.05). The contents of LH and FSH in the treatment group were significantly reduced(P<0.05), while the content of E_2 was significantly increased(P<0.05), and the changes were more significant than those in the control group(P<0.05). The incidence of adverse reactions in the control group was 8.8%, which was higher than 1.7% in the treatment group(P<0.05). Acupuncture combined with modified Xiangfu Decoction could significantly improve the sleep status of menopausal insomnia cases caused by liver Qi stagnation, with a lower incidence of adverse reactions, and so is worthy of clinical promotion and application.

A new subset of small stem cells in bovine bone marrow stromal cell populations.

Bone marrow stromal cells (BMSCs) are a unique population of multipotent cells that exhibit pluripotent properties to a certain extent and are significantly heterogeneous in terms of the cell population. We isolate a small cell subpopulation from bovine BMSCs, bovine small stem cells (bSSCs), and herein characterize their properties. The bSSCs are smaller in size and express nuclear Oct-4 and other pluripotency markers. In addition, when cultured in suspension conditions, bSSCs form three-dimensional spheres and display a strong capability for self-renewal and differentiation into cells from three germ layers. Notably, bSSCs display neural features with Sox1 and Pax6 expression. Using bSSCs as donor nuclear cells for somatic cell nuclear transfer, we further demonstrate that the developmental potential of cloned embryos in vitro is significantly increased. Our study identifies a new bovine bone marrow stromal cell-derived stem cell subtype that could have broad importance for developmental biology as well as great potential for regenerative medicine.

[Ascending input from dorsal nuclei of lateral lemniscus mediates the plasticity of inferior colliculus neurons in mice].

The auditory system has the ability to adjust its structure and function as the environment changes, which is called auditory plasticity. In the auditory system, inferior colliculus (IC) is an important relay station, which accepts the ascending inputs from dorsal nuclei of lateral lemniscus (DNLL). The present study was aimed to investigate the role of the DNLL in the formation of the plasticity of IC neurons. Here, we used extracellular single unit recording and electrical stimulation to investigate the plasticity of IC neurons in Kunming mice. The results showed that after the cessation of 30-minute electrical stimulation on contralateral DNLL, 95% of the inhibited IC neurons and 86% of the facilitated IC neurons showed plastic changes. Moreover, 1 h after the contralateral DNLL stimulation was stopped, the plastic changes in 74% of the inhibited IC neurons vanished, but still were maintained in 26% of the inhibited IC neurons. These results suggest that the contralateral DNLL ascending input can induce plastic changes of IC neurons, and this kind of effect can be maintained for a certain period of time, which is beneficial to enhance the sound intensity sensitivity of IC neurons.

Cytochrome P450 26A1 modulates natural killer cells in mouse early pregnancy.

Cytochrome P450 26A1 (CYP26A1) has a spatiotemporal expression pattern in the uterus, with a significant increase in mRNA and protein levels during peri-implantation. Inhibiting the function or expression of CYP26A1 can cause pregnancy failure, suggesting an important regulatory role of CYP26A1 in the maintenance of pregnancy. However, little is known about the exact mechanism involved. In this study, using a pCR3.1-cyp26a1 plasmid immunization mouse model and a Cyp26a1-MO (Cyp26a1-specific antisense oligos) knockdown mouse model, we report that the number of Dolichos biflorus agglutinin (DBA) lectin-positive uterine natural killer (uNK) cells was reduced in pCR3.1-cyp26a1 plasmid immunized and Cyp26a1-MO-treated mice. In contrast, the percentage of CD3- CD49b+ NK cells in the uteri from the treatment group was significantly higher than that of the control group in both models. Similarly, significantly up-regulated expression of CD49b (a pan-NK cell marker), interferon gamma, CCL2, CCR2 (CCL2 receptor) and CCL3 were detected in the uteri of pCR3.1-cyp26a1- and Cyp26a1-MO-treated mice. Transcriptome analysis suggested that CYP26A1 might regulate NK cells through chemokines. In conclusion, the present data suggest that silencing CYP26A1 expression/function can decrease the number of uNK cells and significantly increase the percentage of CD3- CD49b+ NK cells in the uteri of pregnant mice. These findings provide a new line of evidence correlating the deleterious effects of blocking CYP26A1 in pregnancy with the aberrant regulation of NK cells in the uterus.

[Preparation and evaluation of gastric adhesive-floating pellets for Bolo leaf phenols].

Gastric adhesive-floating pellets for Bolo leaf phenols (BLP) were prepared by extrusion-spheronization method, with chitosan as skeleton bioadhesive material, and stearyl alcohol as help-bleaching agent to evaluate its in vitro adhesivity, floatability and in vivo retention situation, and investigate its in vitro release characteristics. The in vitro adhesivity and floatability were evaluated respectively by in vitro tissue retention method and visual observation method. The retention of pellets in rats was investigated by in vivo tissue retention method and in vivo imaging of small animals. In addition, the in vitro release of p-coumaric acid and caffeic acid as the index components in pellets were evaluated. Results showed that the in vitro adhesivity of the prepared gastric adhesive-floating pellets reached (73.2±3.4)%, and the pellets could float immediately in simulated gastric fluid for more than 12 h; the retention rate of adhesive-floating pellets in rats reached more than 40% after 6 h, while the retention rate of common reference pellets was decreased by 15% as compared with the gastric adhesive-floating pellets, with significant difference (P<0.01); the drug in vitro release time can reach more than 6 h, and the drug release behaviors were lined with Higuchi equation. In vivo and in vitro studies showed that, the gastrointestinal bioadhesive and floating pellets prepared in this study have good bioadhesivity, floatability and good sustained release characteristics.

Potential role of microRNA-7 in the anti-neuroinflammation effects of nicorandil in astrocytes induced by oxygen-glucose deprivation.

BACKGROUND: It is generally recognized that the inflammatory reaction in glia is one of the important pathological factors in brain ischemic injury. Our previous study has revealed that opening ATP-sensitive potassium (K-ATP) channels could attenuate glial inflammation induced by ischemic stroke. However, the detailed mechanisms are not well known. METHODS: Primary cultured astrocytes separated from C57BL/6 mice were subjected to oxygen-glucose deprivation (OGD); cellular injuries were determined via observing the changes of cellular morphology and cell viability. MicroRNA (miR) and messenger RNA (mRNA) level was validated by real-time PCR. The interaction between microRNA and the target was confirmed via dual luciferase reporter gene assay. Expressions of proteins and inflammatory cytokines were respectively assessed by western blotting and enzyme-linked immunosorbent assay. RESULTS: OGD resulted in astrocytic damage, which was prevented by K-ATP channel opener nicorandil. Notably, we found that OGD significantly downregulated miR-7 and upregulated Herpud2. Our further study proved that miR-7 targeted Herpud2 3'UTR, which encoded endoplasmic reticulum (ER) stress protein-HERP2. Correspondingly, our results showed that OGD increased the levels of ER stress proteins along with significant elevations of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß). Pretreatment with nicorandil could remarkably upregulate miR-7, depress the ER-related protein expressions including glucose-regulated protein 78 (GRP78), C/EBP-homologous protein (CHOP), and Caspase-12, and thereby attenuate inflammatory responses and astrocytic damages. CONCLUSIONS: These findings demonstrate that opening K-ATP channels protects astrocytes against OGD-mediated neuroinflammation. Potentially, miR-7-targeted ER stress acts as a key molecular brake on neuroinflammation.

Synthesis, crystal structures, molecular docking, and in vitro biological activities of transition metals with 4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid.

Four novel mononuclear complexes, [Cd(L)2·2H2O] (1), [Ni(L)2·2H2O] (2) [Cu(L)2·H2O] (3), and [Zn(L)2·2H2O] (4) (CCDC numbers: 1444630-1444633 for complexes 1-4) (HL=4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid) were synthesized, and have been characterized by IR spectroscopy, elemental analysis, and X-ray crystallography. Molecular docking study preliminarily revealed that complex 1 had potential telomerase inhibitory activity. In accordance with the result of calculation, in vitro tests of the inhibitory activities of complex 1 against telomerase showed complex 1 (IC50=8.17±0.91µM) had better inhibitory activities, while complexes 2, 3 and 4 showed no inhibitory activities. Antiproliferative activity in human cancer cell line HepG2 was further determined by MTT assays. The IC50 value (6.5±0.2µM) for the complex 1 having good inhibitory activity against HepG2 was at the same micromolar concentrations with cis-platinum (2.2±1.2µM). While the IC50 value for the metal-free ligand, complex 2, 3 and 4 was more than 100µM. These results indicated that telomerase was potentially an anticancer drug target and showed that complex 1 was a potent inhibitor of human telomerase as well as an antiproliferative compound.

[Response characteristics of neurons to tone in dorsal nucleus of the lateral lemniscus of the mouse].

The dorsal nucleus of lateral lemniscus (DNLL) is a nucleus in the auditory ascending pathway, and casts inhibitory efferent projections to the inferior colliculus. Studies on the DNLL are less than studies on the auditory brain stem and inferior colliculus. To date, there is no information about response characteristics of neurons in DNLL of albino mouse. Under free field conditions, we used extracellular single unit recording to study the acoustic signal characteristics of DNLL neurons in Kunming mice (Mus musculus). Transient (36%) and ongoing (64%) firing patterns were found in 96 DNLL neurons. Neurons with different firing patterns have significant differences in characteristic frequency and minimal threshold. We recorded frequency tuning curves (FTCs) of 87 DNLL neurons. All of the FTCs exhibit an open "V" shape. There is no significant difference in FTCs between transient and ongoing neurons, but among the ongoing neurons, the FTCs of sustained neurons are sharper than those of onset plus sustained neurons and pauser neurons. Our results showed that the characteristic frequency of DNLL neurons of mice was not correlated with depth, supporting the view that the DNLL of mouse has no frequency topological organization through dorsal-ventral plane, which is different from cats and some other animals. Furthermore, by using rate-intensity function (RIF) analysis the mouse DNLL neurons can be classified as monotonic (60%), saturated (31%) and non-monotonic (8%) types. Each RIF type includes transient and ongoing firing patterns. Dynamic range of the transient firing pattern is smaller than that of ongoing firing ones (P < 0.01), suggesting that the inhibitory inputs may underlie the formation of transient firing pattern. Multiple firing patterns and intensity coding of DNLL neurons may derive from the projections from multiple auditory nuclei, and play different roles in auditory information processing.

Biotechnological potential of a rhizosphere Pseudomonas aeruginosa strain producing phenazine-1-carboxylic acid and phenazine-1-carboxamide.

Bacterial phenazine metabolites belong to a group of nitrogen-containing heterocyclic compounds with antimicrobial activities. In this study, a rhizosphere Pseudomonas aeruginosa strain PA1201 was isolated and identified through 16S rDNA sequence analysis and fatty acid profiling. PA1201 inhibited the growth of various pathogenic microorganisms, including Rhizotonia solani, Magnaporthe grisea, Fusarium graminearum, Xanthomonas oryzae pv. oryzae, Xanthomonas oryzae pv. oryzicola, and Staphylococcus aureus. High Performance Liquid Chromatography showed that PA1201 produced high levels of phenazine-1-carboxylic acid (PCA), a registered green fungicide 'Shenqinmycin' with the fermentation titers of 81.7 mg/L in pigment producing medium (PPM) and 926.9 mg/L in SCG medium containing soybean meal, corn steep liquor and glucose. In addition, PA1201 produced another antifungal metabolite, phenazine-1-carboxaminde (PCN), a derivative of PCA, with the fermentation titers of 18.1 and 489.5 mg/L in PPM and SCG medium respectively. To the best of our knowledge, PA1201 is a rhizosphere originating P. aeruginosa strain that congenitally produces the highest levels of PCA and PCN among currently reported P. aeruginosa isolates, which endows it great biotechnological potential to be transformed to a biopesticide-producing engineering strain.

Synthesis, crystal structures, molecular docking, and urease inhibitory activity of transition metal complexes with 2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid.

Two novel mononuclear complexes, [Cu(L)(2)(H(2)O)]·(2)H(2)O (1) and [Ni(L)(2)(H(2)O)(2)] (2) (HL = 2-[4-(4-fluorophenyl)piperazin-1-yl]acetic acid) were synthesized and structurally determined by single-crystal X-ray diffraction. Their inhibitory activities were tested in vitro against jack bean urease. Molecular docking was investigated to determine the probable binding mode. The experimental values and docking simulation exhibited that complex 1 had better inhibitory activity than the positive reference aceto hydroxamic acid (AHA), showing IC(50) value of 0.15 ± 0.08 µM, while 2 showed no inhibitory activity.

Iptakalim protects against ischemic injury by improving neurovascular unit function in the mouse brain.

It has been reported that the novel ATP-sensitive potassium (K-ATP) channel opener iptakalim (IPT) decreases ischemic neuronal damage in rats. However, the mechanisms underlying neuroprotection are still to be fully elucidated. The results of this study showed that mice with ischemia induced by middle cerebral artery occlusion exhibited higher mortality and more neurological deficits, as well as larger infarct volume, compared with sham mice. Moreover, it was found that ischemia activated astrocytes surrounding CA1 neurons with an increased expression of D-serine, induced greater microglial activation accompanied by higher tumor necrosis factor alpha (TNF-α) production, and caused higher expressions of matrix metalloproteinase 9 (MMP-9) in the endothelial cells of mice. Pretreatment with IPT significantly attenuated the neurological deficits and decreased the infarct volume in mice. IPT treatment could decrease MMP-9 secretion, inhibit astrocytic activation with decreasing D-serine and elevating connexin43 expression. Microglial activation was also inhibited and TNF-α production was decreased by IPT. Taken together, a K-ATP channel opener may improve the function of neurovascular unit and protect against ischemic injury. These findings suggest that targeting K-ATP channels provides a promising therapeutic approach for stroke.

Isolation and characterization of OsMY1, a putative partner of OsRac5 from Oryza sativa L.

OsRac5 belongs to the rice Rho of plants family, and acts as the molecular switch in the signal pathway which is pivotally involved in the rice fertility control. One of its putative partners, OsMY1, was isolated by yeast two-hybrid screening from rice panicle cDNA library. Bioinformatics analysis shows that OsMY1 contains a coiled-coil domain which generally appeared in the partners of Rho GTPases. By yeast two-hybrid assay, it is confirmed that OsMY1 binds both the wild type (WT) and constitutively active (CA) OsRac5, but does not interact with dominantly negative OsRac5. In addition, the interactions between OsMY1 and WT-OsRac5 or CA-OsRac5 in vivo are demonstrated by bimolecular fluorescence complementation assay. Using PCR-mediated sequence deletion and point mutation of OsMY1, the interaction between OsMY1 and OsRac5 was identified to be mediated by the coiled-coil domain in OsMY1, and their binding was quantified by O-nitro-phenyl-ß-D-galactopyranoside assay. Real-time PCR shows that OsMY1 and OsRac5 are coordinately expressed in rice leaves and panicles with similar expression patterns. Our results suggest that OsMY1 is an important target of OsRac5 and that these two genes are involved in the same biological processes in rice growth and development.