A pan-cancer analysis of Dyskeratosis congenita 1 (DKC1) as a prognostic biomarker.

BACKGROUND: Dyskeratosis congenita 1 (DKC1), a critical component of telomerase complex, is highly expressed in a variety of human cancers. However, the association of DKC1 with cancer occurrence and development stages is not clear, making a pan-cancer analysis crucial. METHODS: We conducted a study using various bioinformatic databases such as TIMER, GEPIA, UALCAN, and KM plotter Analysis to examine the different expressions of DKC1 in multiple tissues and its correlation with pathological stages. Through KEGG analysis, GO enrichment analysis and Venn analysis, we were able to reveal DKC1-associated genes and signaling pathways. In addition, we performed several tests including the CCK, wound healing assay, cell cycle arrest assay, transwell assay and Sa-ß-gal staining on DKC1-deleted MDA-231 cells. RESULTS: Our study demonstrates that DKC1 has relatively low expression specificity in different tissues. Furthermore, we found that in ACC, KICH, KIRP and LIHC, the expression level of DKC1 is positively correlated with pathological stages. Conversely, in NHSC, KIRP, LGG, LIHC, MESO and SARC, we observed a negative influence of DKC1 expression level on the overall survival rate. We also found a significant positive correlation between DKC1 expression and Tumor Mutational Burden in 14 tumors. Additionally, we observed a significantly negative impact of DKC1 DNA methylation on gene expression at the promoter region in BRCA. We also identified numerous phosphorylation sites concentrated at the C-terminus of the DKC1 protein. Our GO analysis revealed a correlation between DKC1 and ribosomal biosynthesis pathways, and the common element UTP14A was identified. We also observed decreased rates of cell proliferation, migration and invasion abilities in DKC1-knockout MDA-MB-231 cell lines. Furthermore, DKC1-knockout induced cell cycle arrest and caused cell senescence. CONCLUSIONS: Our findings suggest that the precise expression of DKC1 is closely associated with the occurrence and developmental stages of cancer in multiple tissues. Depletion of DKC1 can inhibit the abilities of cancer cells to proliferate, migrate, and invade by arresting the cell cycle and inducing cell senescence. Therefore, DKC1 may be a valuable prognostic biomarker for the diagnosis and treatment of cancer in various tissues.

Mechanism of synergistic remediation of soil phenanthrene contamination in paddy fields by rice-crab coculture and bioaugmentation with Pseudomonas sp.

Polycyclic aromatic hydrocarbons (PAHs) are persistent and harmful pollutants with high priority concern in agricultural fields. This work constructed a rice-crab coculture and bioaugmentation (RCM) system to remediate phenanthrene (a model PAH) contamination in rice fields. The results showed that RCM had a higher remediation performance of phenanthrene in rice paddy compared with rice cultivation alone, microbial addition alone, and crab-rice coculture, reaching a remediation efficiency of 88.92 % in 42 d. The concentration of phenanthrene in the rice plants decreased to 6.58 mg/kg, and its bioconcentration effect was efficiently inhibited in the RCM system. In addition, some low molecular weight organic acids of rice root increased by 12.87 %∼73.87 %, and some amino acids increased by 140 %∼1150 % in RCM. Bioturbation of crabs improves soil aeration structure and microbial migration, and adding Pseudomonas promoted the proliferation of some plant growth-promoting rhizobacteria (PGPRs), which facilitated the degradation of phenanthrene. This coupling rice-crab coculture with bioaugmentation had favorable effects on soil enzyme activity, microbial community structure, and PAH degradation genes in paddy fields, enhancing the removal of and resistance to PAH contamination in paddy fields and providing new strategies for achieving a balance between production and remediation in contaminated paddy fields.

Effect of Lymph Node Dissection on the Prognosis of Thymic Carcinomas and Thymic Neuroendocrine Tumors.

We aimed to analyze the effect of lymph node dissection (LND) and accurate lymph node (LN) status on the survival and prognosis of patients with thymic carcinomas (TCs) and thymic neuroendocrine tumors (TNETs) undergoing surgical treatment. The Surveillance, Epidemiology, and End Results database was queried for patients who underwent surgical resection for TCs and TNETs during 1998-2016. LN status were defined as no LND (LND-), pathologically negative with LND (N0), and LN metastasis positive (N+). We investigated outcomes of LN status together with other clinicopathological features for overall survival (OS). Subgroup analyses were performed between LND-, N0, and N+ cohorts using propensity score matching, to analyze the significance of LND in prognosis. A total of 812 patients were enrolled, including 623 with TCs and 189 with TNETs. The proportion of LN metastasis positive in TNETs was 58.8% which was significantly higher than that in TCs (30%) (P < 0.001). In multivariable Cox analysis of OS, patients with LND- had a significantly worse prognosis than those with N0 (P = 0.018); there was no difference between N+ and LND- (P = 0.560). After propensity score matching, patients with N0 still had better survival than those with LND- and N+ in subgroup univariable and multivariable analyses of OS; however, the survival of patients with LND- and N+ was not significantly different in multivariable analysis. It was demonstrated that LND in TCs and TNETs can clarify the status of LN metastasis, to more accurately evaluate patients' long-term prognosis.

DHCR24 overexpression modulates microglia polarization and inflammatory response via Akt/GSK3ß signaling in Aß25-35 treated BV-2 cells.

Microglial phenotypic polarization, divided into pro-inflammatory "M1" phenotype and anti-inflammatory "M2" phenotype, played a crucial role in the pathogenesis of Alzheimer's disease (AD). Facilitating microglial polarization from M1 to M2 phenotype was shown to alleviate AD-associate pathologic damage, and modulator of the microglial phenotype has become a promising therapeutic approach for the treatment of AD. Previous little evidence showed that DHCR24 (3-ß-hydroxysteroid-Δ-24-reductase), also known as seladin-1 (selective Alzheimer's disease indicator-1), exerted potential anti-inflammatory property, however, the link between DHCR24 and microglial polarization has never been reported. Thus, the role of DHCR24 in microglial polarization in amyloid-beta 25-35 (Aß25-35) treated BV-2 cells was evaluated in this study. Our results demonstrated that Aß25-35 aggravated inflammatory response and facilitated the transition of microglia phenotype from M2 to M1 in BV-2 cells, by upregulating M1 marker (i-NOS, IL-1ß and TNF-α) and downregulating M2 marker (arginase-1, IL-4 and TGF-ß). DHCR24 overexpression by lentivirus transfection could significantly reverse these effects, meanwhile, activated Akt/GSK3ß signaling pathway via increasing the protein expression of P-Akt and P-GSK3ß. Furthermore, when co-treated with Akt inhibitor MK2206, the effect of DHCR24 was obviously reversed. The study exhibited the neuroprotective function of DHCR24 in AD-related inflammatory injury and provided a novel therapeutic target for AD in the future.

CdSe quantum dots labeled Staphylococcus aureus for research studies of THP-1 derived macrophage phagocytic behavior.

A simple biological strategy to couple intracellular irrelated biochemical reactions of staphylococcus aureus CMCC 26003 (S. aureus) with inorganic metal ions to synthesize cadmium selenide quantum dots (CdSe QDs) was demonstrated. Correspondingly, S. aureus as living matrices are internally generated and labeled with fluorescent QDs by the smart strategy. Several key factors in the process of biosynthesis were systematically evaluated. At the same time, ultraviolet-visible (UV-Vis), photo-luminescence (PL), inverted fluorescence microscopy and transmission electron microscopy (TEM) were utilized to study the characters of the as produced CdSe QDs. In addition, cytotoxicity and photostability of the QDs containing bacteria were also tested and evaluated as a whole. The results showed that intracellular CdSe nanocrystals had successfully formed in S. aureus living cells, which were less toxic, highly fluorescent and photostable. These fluorescent S. aureus bacteria were next applied as invading pathogens as well as fluorescent bioprobes for exploring the phagocytic behavior of THP-1-derived macrophage. Results proved that internal CdSe QDs labeling had no significantly adverse effects compared with the kind of infection reference, fluorescein isothiocyanate (FITC) stained S. aureus pathogen. Assuredly, the methods presented here provide researchers with a useful option to analyze the behavior of S. aureus as a type of infectious pathogen, which would also help understand the complex interplay between host cells and the invading bacteria on molecular level.

Plasma profiling of amino acids distinguishes acute gout from asymptomatic hyperuricemia.

Gout and hyperuricemia are highly prevalent metabolic diseases caused by high level of uric acid. Amino acids (AAs) involve in various biochemical processes including the biosynthesis of uric acid. However, the role of AAs in discriminating gout from hyperuricemia remains unknown. Here, we report that the plasma AAs profile can distinguish acute gout (AG) from asymptomatic hyperuricemia (AHU). We established an LC-MS/MS-based method to measure the plasma AAs without derivatization for the AG and AHU patients, and healthy controls. We found that the plasma profiling of AAs separated the AG patients from AHU patients and controls visually in both principal component analysis and orthogonal partial least-squares discriminant analysis (OPLS-DA) models. In addition, L-isoleucine, L-lysine, and L-alanine were suggested as the key mediators to distinguish the AG patients from AHU and control groups based on the S-plot analysis and variable importance in the projection values in the OPLS-DA models, volcano plot, and the receiver operating characteristic curves. In addition, the saturation of monosodium urate in the AA solutions at physiologically mimic status supported the changes in plasma AAs facilitating the precipitation of monosodium urate. This study suggests that L-isoleucine, L-lysine, and L-alanine could be the potential markers to distinguish the AG from AHU when the patients have similar blood levels of uric acid, providing new strategies for the prevention, treatment, and management of acute gout.

Differentiating the acute phase of gout from the intercritical phase with ultrasound and quantitative shear wave elastography.

OBJECTIVES: To evaluate the value of ultrasound (US) in differentiating the acute phase of gout from the intercritical phase, particularly using shear wave elastography (SWE). METHODS: 57 gout patients were prospectively enrolled and divided into acute phase and intercritical phase groups. The patients underwent US and SWE examinations for the first metatarsophalangeal joints with the same protocol. Maximum synovial thickness was measured. US features were reviewed by two radiologists independently. The maximum (Emax) and mean (Emean) elastic moduli of synovium were calculated. Diagnostic performances of US, SWE and combined US and SWE were evaluated. RESULTS: US findings demonstrated that the colour Doppler flow signal grade in the acute phase was higher than that in the intercritical phase (p = 0.001), whereas no differences were found for B-mode US features between the two groups (all p > 0.05). For SWE, Emax and Emean were significantly higher in the intercritical phase than in the acute phase (both p < 0.001). The areas under the receiver operating characteristic curve (AUROCs) were 0.494-0.553 for B-mode US, 0.735 for colour Doppler US (CDUS), 0.887 for Emax and 0.882 for Emean. The combination of CDUS and SWE increased the AUROC, sensitivity and accuracy significantly in comparison with CDUS alone (all p < 0.001). However, the combined set did not show stronger diagnostic performance in comparison with SWE alone. CONCLUSION: SWE increases the diagnostic performance in differentiating the acute phase of gout from the intercritical phase in comparison with conventional US. KEY POINTS: • Colour Doppler flow signal grade is higher in acute phase of gout than in intercritical phase. • SWE demonstrates that synovium stiffness is higher in intercritical phase of gout than in acute phase. • SWE increases diagnostic performance in differentiating acute phase of gout from intercritical phase in comparison with conventional US.

A sensitive and accurate method to simultaneously measure uric acid and creatinine in human saliva by using LC-MS/MS.

AIM: To establish a method to simultaneously measure uric acid (UA) and creatinine (Cr) in human saliva. MATERIALS & METHODS: By using HPLC-MS/MS, we developed and validated a fast, sensitive and accurate method to simultaneously determine UA and Cr in human saliva. The determination range for Cr and UA is of 10-5000 ng/ml with the R2 for both calibration curves over 0.999. The accuracy, precision and recovery of Cr and UA were all acceptable. By using the established method, the Cr and UA levels in saliva from 28 healthy volunteers were measured as 2.9 ± 0.8 µM and 46.8 ± 18.2 µM, respectively. CONCLUSION: This method can simultaneously determine Cr and UA in saliva for clinical and translational study.

A hearing self-reported survey in people over 80 years of age in China by hearing handicap inventory for the elderly-complete version vs screening version.

CONCLUSION: HHIE-S can be a useful tool in investigating hearing loss among people over 80 years old, with the same validity as HHIE. OBJECTIVE: To investigate the effect of hearing loss on the quality-of-life in people over 80 years of age in China, and to compare the results of the Chinese mandarin version Hearing Handicap Inventory for the Elderly (HHIE) and its screening version (HHIE-S). METHODS: Eighty-four people over 80 years participated in the study. Both HHIE and HHIE-S were completed, and the hearing handicap degrees were rated according to HHIE scores and HHIE-S scores, respectively. Results obtained by HHIE and HHIE-S were compared. Multi-factor analysis of variance was used to analyze the impact of eight factors on hearing handicap in the oldest old people over 80 years of age, including age, noise exposure, ear surgery, infection, ototoxic drugs use, cardiovascular and cerebrovascular diseases, diabetes, and tumors. RESULTS: Both HHIE and HHIE-S revealed 48 subjects (57.1%) with no self-perceived hearing problem, and 36 subjects (42.9%) with hearing handicap. No statistical difference was found between results of the functional hearing handicap rating by HHIE and HHIE-S (Chi-square = 1.532, p = 0.465). The HHIE and HHIE-S were in agreement with each other (kappa = 0.772, p < 0.001). All the eight factors had no significance on both HHIE and HHIE-S scores (p > 0.05), except noise exposure on S-score of HHIE-S (p = 0.032), and the R-squares of these factors were less than 5%.

Construction of photodynamic-effect immunofluorescence probes by a complex of quantum dots, immunoglobulin G and chlorin e6 and their application in HepG2 cell killing.

In this study, tri-functional immunofluorescent probes (Ce6-IgG-QDs) based on covalent combinations of quantum dots (QDs), immunoglobulin G (IgG) and chlorin e6 (Ce6) were developed and their photodynamic ability to induce the death of cancer cells was demonstrated. Strategically, one type of second-generation photosensitizer, Ce6, was first coupled with anti-IgG antibody using the EDC/NHS cross-linking method to construct the photosensitive immunoconjugate Ce6-IgG. Then, a complex of Ce6-IgG-QDs immunofluorescent probes was obtained in succession by covalently coupling Ce6-IgG to water soluble CdTe QDs. The as-manufactured Ce6-IgG-QDs maintained the bio-activities of both the antigen-antibody-based tumour targeting effects of IgG and the photodynamic-related anticancer activities of Ce6. By way of polyclonal antibody interaction with rabbit anti-human epidermal growth factor receptor (anti-EGFR antibody, N-terminus), Ce6-IgG-QDs were labelled indirectly onto the surface of human hepatocarcinoma (HepG2) cells in cell recognition and killing experiments. The results indicated that the Ce6-IgG-QDs probes have excellent tumour cell selectivity and higher photosensitivity in photodynamic therapy (PDT) compared with Ce6 alone, due to their antibody-based specific recognition and location of HepG2 cells and the photodynamic effects of Ce6 killed cells based on efficient fluorescence resonance energy transfer between QDs and Ce6. Copyright © 2015 John Wiley & Sons, Ltd.

Intracellular Biosynthesis of Fluorescent CdSe Quantum Dots in Bacillus subtilis: A Strategy to Construct Signaling Bacterial Probes for Visually Detecting Interaction Between Bacillus subtilis and Staphylococcus aureus.

In this work, fluorescent Bacillus subtilis (B. subtilis) cells were developed as probes for imaging applications and to explore behaviorial interaction between B. subtilis and Staphylococcus aureus (S. aureus). A novel biological strategy of coupling intracellular biochemical reactions for controllable biosynthesis of CdSe quantum dots by living B. subtilis cells was demonstrated, through which highly luminant and photostable fluorescent B. subtilis cells were achieved with good uniformity. With the help of the obtained fluorescent B. subtilis cells probes, S. aureus cells responded to co-cultured B. subtilis and to aggregate. The degree of aggregation was calculated and nonlinearly fitted to a polynomial model. Systematic investigations of their interactions implied that B. subtilis cells inhibit the growth of neighboring S. aureus cells, and this inhibition was affected by both the growth stage and the amount of surrounding B. subtilis cells. Compared to traditional methods of studying bacterial interaction between two species, such as solid culture medium colony observation and imaging mass spectrometry detection, the procedures were more simple, vivid, and photostable due to the efficient fluorescence intralabeling with less influence on the cells' surface, which might provide a new paradigm for future visualization of microbial behavior.

[Impacts of genetically modified soybean leaf residues on Folsomia candida.] / è½¬åŸºå› å¤§è±†å¶ç‰‡æ®‹ä½“å¯¹ç™½ç¬¦è·³çš„å½±å“.

When the genetically modified soybean is planted in the field, the expression product of exogenous gene could be exposed in the soil ecosystem and bring potential risk to the soil fauna, with the form of leaves and other debris. A few of genetically modified soybeans developed by China independently were used in our study as materials. They were Phytophthora-resistant soybean harboring hrpZm gene (B4J8049), leaf-feeding insect-resistant soybean harboring Cry1C gene (A2A8001) and Leguminivora glycinivorella-resistant soybean harboring Cry1Iem gene (C802). By feeding Folsomia candida with the three genetically modified soybeans for continuous 60 days, the surviving rate, reproductive rate and changes on the body length of F. candida were studied. The results showed that all the three genetically modified soybeans of B4J8049, A2A8001 and C802 had no significant adverse effects on the growth of F. candida, as an environmental indicator organism. It was initially inferred that they were environmentally safe under short-term exposure, which provided basic data of ecological safety for their wide cultivation.

Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease.

PURPOSE: To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method. MATERIALS AND METHODS: 79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis. RESULTS: Normal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P < 0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P < 0.05). CONCLUSION: Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.

Diagnostic value of quantitative contrast-enhanced ultrasound (CEUS) for early detection of renal hyperperfusion in diabetic kidney disease.

PURPOSE: To investigate the diagnostic value of quantitative contrast-enhanced ultrasound (CEUS) for early detection of renal hyperperfusion in diabetic kidney disease (DKD). MATERIALS AND METHODS: 55 DKD patients with estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m(2) and 26 normal controls (NCs) were enrolled. Clinical data was well documented. Blood samples were drawn for evaluation of renal function including blood urea nitrogen (BUN), serum creatinine (SCr) and serum uric acid (SUA), and urine samples were assayed for total protein quantification, and various microprotein markers. According to eGFR level, DKD patients were divided into early-stage DKD (eGFR ≥90 ml/min/1.73 m(2), n = 18) and middle-stage DKD (eGFR 30-90 ml/min/1.73 m(2), n = 37). Based on urinary microalbumin/creatinine ratio (MALB/UCR), early-stage DKD patients were further classified into two groups: MALB/UCR <10 g/mol (n = 11) and MALB/UCR ≥10 g/mol (n = 7). Then, CEUS was performed to observe the real-time renal perfusion, and low acoustic power contrast-specific imaging was used for quantitative analysis. RESULTS: The renal perfusion images of CEUS were well developed successively. The corresponding perfusion curves based on echo-power signals in time series were constructed. Quantitative analysis showed that area under the descending curve (AUC2) was significantly increased in early-stage DKD compared to middle-stage DKD (p < 0.05), but AUC showed no significant difference. Further comparison between different MALB/UCR levels of early-stage DKD showed that patients with MALB/UCR ≥10 g/mol had significantly increased levels of AUC, AUC2 and proteinuria than patients with low MALB/UCR (p < 0.05). Also, high MALB/UCR DKD patients had increased proteinuria but similar eGFR compared to low MALB/UCR patients. CONCLUSION: Renal microvascular hyperperfusion may be responsible for overt proteinuria until decline of renal filtration in DKD. AUC2 could be an early and sensitive marker for early renal injury and renal microvascular hyperperfusion in DKD.

[Mn2Ga4Sn4S20](8-) T3 supertetrahedral nanocluster directed by a series of transition metal complexes.

With different transition metal (TM) complexes as structure directing agents or building units, three new multinary chalcognidometalates based on T3 supertetrahedral nanocluster of [Mn2Ga4Sn4S20](8-) have been solvothermally synthesized and structurally characterized. In compound Mn2Ga4Sn4S20[Mn2(en)5]2·4H2O (, en = ethylenediamine), the neighboring [Mn2Ga4Sn4S20](8-) cores were bridged by two pairs of [Mn2(en)5](4+) complex cations via Mn-S bonds to form one-dimensional (1D) neutral chains. Compound Mn2Ga4Sn4S20[Mn(dien)2]4·2H2O (, dien = diethylenetriamine) contained discrete [Mn2Ga4Sn4S20](8-) cores separated by [Mn(dien)2](2+) cations. In compound Mn2Ga4Sn4S20[Mn(teta)]4 (, teta = triethylenetetramine), each [Mn2Ga4Sn4S20](8-) core was covalently attached by four [Mn(teta)](2+) complexes via terminal Mn-S bonds to form a neutral isolated cluster. The photocatalytic experiments indicate that compound was able to degrade rhodamine B (RhB) and crystal violet (CV) under visible irradiation. Furthermore, the luminescence properties and thermal stabilities of the title compounds, as well as the second-order nonlinear optical property of were also studied.

[Investigation of metabolites of Triptergium wilfordii on liver toxicity by LC-MS].

In this paper, biomarkers of liver toxicity of Triptergium wilfordii based on metabolomics was screened, and mechanism of liver toxicity was explored to provide a reference for the clinical diagnosis for liver toxicity of Triptergium wilfordii. MS method was carried on the analysis to metabolic fingerprint spectrum between treatment group and control group. The potential biomarkers were compared and screened using the multivariate statistical methods. As well, metabolic pathway would be detailed description. Combined with PCA and OPLS-DA pattern recognition analysis, 20 metabolites were selected which showed large differences between model group and blank group (VIP > 1.0). Seven possible endogenous biomarkers were analyzed and identified. They were 6-phosphate glucosamine, lysophospholipid, tryptophan, guanidine acetic acid, 3-indole propionic acid, cortisone, and ubiquinone. The level changes of above metabolites indicated that the metabolism pathways of amino acid, glucose, phospholipid and hormone were disordered. It is speculated that liver damage of T. wilfordii may be associated with the abnormal energy metabolism in citric acid cycle, amino acid metabolism in urea cycle, and glucose metabolism. It will be helpful to further research liver toxicity ingredients of Triptergium wilfordii.

Prognostic value of circulating microRNA-21 in digestive system cancers: a meta-analysis.

UNLABELLED: Circulating microRNAs show aberrant expression in patients with cancer. The aim of this study was to investigate the prognostic value of circulating microRNA-21 (miR-21) in digestive system cancers. METHODS: All the eligible studies were searched by Medline and EMBASE. The hazard ratios (HRs) for overall survival (OS), which compared the expression levels of circulating miR-21 in patients with digestive cancer was extracted and estimated. Pooled HRs and 95% confidence intervals (CI) were calculated. Then a meta-analysis was performed to clarify the prognostic value of the miR-21. RESULTS: A total of seven studies involving 907 subjects were included. The results suggested that higher circulating miR-21 could predict worse OS outcome with the pooled HR of 2.19 (95% CI 1.01-4.75, P = 0.05) in digestive system cancers. Subgroup analysis by ethnicity indicated circulating miR-21 was associated with OS in patients with digestive cancer among Asians with the pooled HR of 2.90 (95% CI 1.30-6.45, P = 0.009). However, subgroup analysis by digestive system site revealed that there is no associated with OS in patients with colorectal cancer with the pooled HR of 1.34 (95% CI 0.45-4.00, P = 0.60). CONCLUSION: The present findings suggest that circulating miR-21 is associated with poor survival in patients with digestive cancer and could be a prognostic biomarker for those patients.

The DREAM protein negatively regulates the NMDA receptor through interaction with the NR1 subunit.

Glutamate-induced excitotoxicity has been implicated in the etiology of stroke, epilepsy, and neurodegenerative diseases. NMDA receptors (NMDARs) play a pivotal role in excitotoxic injury; however, clinical trials testing NMDAR antagonists as neuroprotectants have been discouraging. The development of novel neuroprotectant molecules is being vigorously pursued. Here, we report that downstream regulatory element antagonist modulator (DREAM) significantly inhibits surface expression of NMDARs and NMDAR-mediated current. Overexpression of DREAM showed neuroprotection against excitotoxic neuronal injury, whereas knockdown of DREAM enhanced NMDA-induced toxicity. DREAM could directly bind to the C0 domain of the NR1 subunit. Although DREAM contains multiple binding sites for the NR1 subunit, residues 21-40 of the N terminus are the main binding site for the NR1 subunit. Thus, 21-40 residues might relieve the autoinhibition conferred by residues 1-50 and derepress the DREAM core domain by a competitive mechanism. Intriguingly, the cell-permeable TAT-21-40 peptide, constructed according to the critical binding site of DREAM to the NR1 subunit, inhibits NMDAR-mediated currents in primary cultured hippocampal neurons and has a neuroprotective effect on in vitro neuronal excitotoxic injury and in vivo ischemic brain damage. Moreover, both pretreatment and posttreatment of TAT-21-40 is effective against excitotoxicity. In summary, this work reveals a novel, negative regulator of NMDARs and provides an attractive candidate for the treatment of excitotoxicity-related disease.

Characterization of a novel wheat NAC transcription factor gene involved in defense response against stripe rust pathogen infection and abiotic stresses.

Proteins encoded by the NAC gene family constitute one of the largest plant-specific transcription factors, which have been identified to play many important roles in both abiotic and biotic stress adaptation, as well as in plant development regulation. In the current paper, a full-length cDNA sequence of a novel wheat NAC gene, designated as TaNAC4, was isolated using in silico cloning and the reverse transcription PCR (RT-PCR) methods. TaNAC4 sharing high homology with rice OsNAC4 gene was predicted to encode a protein of 308 amino acid residues, which contained a plant-specific NAC domain in the N-terminus. Transient expression analysis indicated that the deduced TaNAC4 protein was localized in the nucleus of onion epidemical cells. Yeast one-hybrid assay revealed that the C-terminal region of the TaNAC4 protein had transcriptional activity. The expression of TaNAC4 was largely higher in the wheat seedling roots, than that in leaves and stems. TaNAC4 transcript in wheat leaves was induced by the infection of strip rust pathogen, and also by exogenous applied methyl jasmonate (MeJA), ABA and ethylene. However, salicylic acid (SA) had no obvious effect on TaNAC4 expression. Environmental stimuli, including high salinity, wounding, and low-temperature also induced TaNAC4 expression. These results indicate that this novel TaNAC4 gene functions as a transcriptional activator involved in wheat response to biotic and abiotic stresses.