[HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems].

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Long non-coding RNA OR3A4 promotes metastasis of ovarian cancer via inhibiting KLF6.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA OR3A4 promotes metastasis of ovarian cancer via inhibiting KLF6, by F.-F. Guo, M.-M. Jiang, L.-L. Hong, B. Qiao, X.-M. Lin, W.-Y. Xu, X.-Q. Fu, published in Eur Rev Med Pharmacol Sci 2019; 23 (6): 2360-2365-DOI: 10.26355/eurrev_201903_17380-PMID: 30964160" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17380.

[The network investigation on knowledge, attitude and practice about COVID-19 of the residents in Anhui Province].

Objective: To analyze the current situation of the knowledge, attitudes and practice about COVID-19 of the residents in Anhui Province. Methods: Anonymous network sampling survey was carried out with an electronic questionnaire that designed by the questionnaire star, and a total of 4 016 subjects from Anhui province were investigated. The content of the survey includes that the basic information of subjects,the residents' knowledge, attitudes and practice about COVID-19, as well as their satisfaction with the prevention and control measures adopted by the government and health authorities and the suggestions on future prevention. The questionnaire doesn't involve any privacy information, and all questions were mandatory to ensure the response rate. Results: The M (P(25), P(75)) age the 4 016 subjects was 21 (19, 24) years old, and the ranging from 7 to 80 years old. The number of males was 1 431 (35.6%). Social networking tools such as WeChat and QQ were the main sources of epidemic information for residents (97.8%, 3 929 respondents). Residents had higher awareness rate of cough (99.5%,n=3 997) and fever (96.0%, n=3 857) symptoms, the transmission by droplets (99.5%, n=3 995), aerosol transmission (81.1%, n=3 258), and contact transmission (92.3%, n=3 708), but lower awareness of symptoms os muscle pain or fatigue (62.7%, n=2 518). 92.6% of the subjects (n=3 720) think that the outbreak was scary. In terms of psychological behavior scores, the results showed that female (9.38±4.81), the urban (9.37±5.02) and the medical workers (10.79±5.19) had a poorer mental health than the male (8.45±5.00), the rural (8.71±4.75) and the non-medical workers (the students: 8.85±4.83; public institude workers: 9.02±5.08; others: 8.97±5.39) (P<0.05). 71.9% of the residents (n=2 887) were satisfied with the local epidemic control measures. The residents took various of the measures to prevent and control the epidemic. The ratio of residents that could achieve "no gathering and less going out" , "wear masks when going out " and " do not go to crowded and closed places " was up to 97.4% (n=3 913), 93.6% (n=3 758) and 91.5% (n=3 673) respectively. Conclusion: The residents in Anhui province have a good KAP about COVID-19, yet it is necessary to strengthen the community publicity, the mental health maintenance of residents and students' health education.

[The network investigation on knowledge, attitude and practice about Novel coronavirus pneumonia of the residents in Anhui Province].

Objective: To analyze the current situation of the knowledge, attitudes and practice about Novelcoronavirus pneumonia (NCP) of the residents in Anhui Province. Methods: Anonymous network sampling survey was carried out with an electronic questionnaire that designed by the questionnaire star, and a total of 4016 subjects from Anhui province were investigated. The content of the survey includes that the basic information of subjects,the residents' knowledge, attitudes and practice about NCP, as well as their satisfaction with the prevention and control measures adopted by the government and health authorities and the suggestions on future prevention. The questionnaire doesn't involve any privacy information, and all questions were mandatory to ensure the response rate. Results: The M (P(25), P(75)) age the 4016 subjects was 21 (19, 24), and the ranging from 7 to 80 years old. The number of males was1431(35.6%). Social networking tools such as WeChat and QQ were the main sources of epidemic information for residents (97.8%, 3 929 respondents). Residents have a high awareness rate of the main symptoms, transmission routes, using of masks, hand washing and treatment information of NCP, while a low awareness rate of the atypical symptoms. 92.6% of the subjects (n=3 720) think that the outbreak was scary. In terms of psychological behavior scores, the results showed that female (9.38±4.81), the urban (9.37±5.02) and the medical workers (10.79±5.19) had a poorer mental health than the male (8.45±5.00) , the rural (8.71±4.75) and the non-medical workers (the students: 8.85±4.83; public institude workers: 9.02±5.08; others: 8.97±5.39) (P < 0.05). 71.9% of the residents (n=2 887)were satisfied with the local epidemic control measures. The residents took various of the measures to prevent and control the epidemic. The ratio of residents that could achieve "no gathering and less going out" , "wear masks when going out" and "do not go to crowded and closed places" was up to 97.4% (n=3 913), 93.6% (n=3758) and 91.5% (n=3 673) respectively. Conclusion: The residents in Anhui province have a good KAP about NCP, yet it is necessary to strengthen the community publicity, the mental health maintenance of residents and students' health education.

[A clinical performance study of modified CT angiography in detecting bronchial artery-pulmonary artery fistula].

Objective: To evaluate the clinical value of modified computed tomography angiography(CTA) in detecting bronchial artery-pulmonary artery fistula(BPF). Methods: Retrospective analysis was performed on 246 patients with hemoptysis admitted to the First Affiliated Hospital of Wenzhou Medical University from July 2017 to December 2018, who underwent modified CTA and DSA examination at the same time. CT was performed with Toshiba Aquilion one 320 row 640-slice spiral CT scanner. All modified CTA images were read blindly by two radiologists above the attending doctors. The sensitivity, specificity and accuracy of the modified CTA in diagnosing BPF were calculated with the DSA results as the reference,and the consistency of the two tests was analyzed. Results: DSA detected 186 cases of positive and 60 cases of negative, modified CTA detected 160 cases of positive and 86 cases of negative. The sensitivity,specificity and accuracy of modified CTA for BPF diagnosis was 85.5%(159/186),98.3%(59/60), 88.6%(218/246) respectively, and they were with high consistency with DSA examination results (kappa=0.73,P<0.01). Conclusion: Modified CTA has high diagnostic specificity for BPF,which can be used as the preferred method for non-invasive screening of suspected BPF patients.

[Preliminary application of transjugular intrahepatic portosystemic shunt in individualized treatment of patients with cirrhotic portal hypertension complicated with refractory ascites and variceal hemorrhage].

Objective: To investigate the feasibility, efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in the individualized treatment of patients with refractory ascites and variceal hemorrhage caused by portal hypertension. Methods: Prospective study of clinical data of 47 patients with portal hypertension and refractory ascites and variceal bleeding admitted to the Affiliated Hospital of Xuzhou Medical University from August 2017 to December 2018, 26 males and 21 females, aged 23-75 (52±14) years old. The Viabahn stent was used to control the diameter of the shunt and the preoperative interval of PPG after individualized TIPS was determined according to the preoperative liver function Child-Pugh classification. The PPG of the Child A and B patients was <10 mm Hg (1 mmHg=0.133 kPa), Child-Pugh C grade patients with postoperative PPG interval values of 12 to 15 mmHg. The success rate, hemostasis rate, ascites remission rate, and complication rate were recorded. Results: Forty-seven patients were with a success rate of 100%, and there was no surgically related fatal complications. The portal pressure gradients of patients with Child-Pugh A, B and Child-Pugh C were reduced from preoperative (22.5±5.4), (24.4±2.6) mm Hg to postoperative (8.8±2.5), (13.2±1.1) mm Hg (all P<0.05). All the patients were followed up for 6 to 24 months, with a median follow-up of 13 months. The success rate of hemostasis in patients with upper gastrointestinal bleeding was 93.5% (29/31), the remission rate of patients with refractory ascites was 14/16, the postoperative rebleeding rate was 6.5% (2/31), the incidence of hepatic encephalopathy was 8.5% (4/47), and the shunt disorder was 2.1% (1/47). Conclusion: The use of Viabahn stent for individualized TIPS in the treatment of portal hypertension with refractory ascites and variceal hemorrhage is feasible, and the clinical efficacy is affirmative, which can reduce the incidence of postoperative hepatic encephalopathy and shunt dysfunction.

Long non-coding RNA OR3A4 promotes metastasis of ovarian cancer via inhibiting KLF6.

OBJECTIVE: Recently, long noncoding RNAs (lncRNAs) have attracted much attention for their roles in tumor progression. The aim of this study was to investigate the exact role of lncRNA OR3A4 in the development of ovarian cancer (OC), and to explore the possible underlying mechanism. PATIENTS AND METHODS: OR3A4 expression in OC tissue samples was detected by Real-time quantitative polymerase chain reaction (qRT-PCR). Moreover, wound healing assay and transwell assay were performed to evaluate the effect of OR3A4 on the metastasis of OC. Furthermore, the underlying mechanism was explored by RT-qPCR and Western blot assay. RESULTS: The expression level of OR3A4 in OC samples was significantly higher than that of adjacent tissues. Moreover, cell migration and invasion were significantly repressed after OR3A4 knockdown in vitro. Moreover, the mRNA and protein expressions of kruppel-like factor 6 (KLF6) were remarkably upregulated after knockdown of OR3A4. Furthermore, the expression level of KLF6 was negatively correlated with the expression of OR3A4 in OC tissues. CONCLUSIONS: Our results showed that OR3A4 could enhance OC cell metastasis and invasion via suppressing KLF6. Moreover, OR3A4 might be a potential therapeutic target for OC.

Clinical efficacy of sequential therapy with voriconazole on COPD patients in acute phase with pulmonary aspergillosis and effects on cytokines and pulmonary functions.

OBJECTIVE: To explore the clinical efficacy of sequential therapy with voriconazole on chronic obstructive pulmonary disease (COPD) patients in acute phase with pulmonary aspergillosis and its effects on cytokines and pulmonary functions. PATIENTS AND METHODS: A total of 110 COPD patients in acute phase with pulmonary aspergillosis who were admitted to the hospital between February 2015 and November 2016 were enrolled. We divided them randomly into two groups, i.e., the control group (n = 55) and the treatment group (n = 55). Patients in the control group took itraconazole capsules orally (200 mg/time, twice per day for three days followed by once per day). Patients in treatment group underwent sequential treatment with voriconazole through intravenous infusion at a dose of 5 mg/kg/time twice a day for 3 days followed by a dose of 4 mg/kg/time, twice a day for 8 days. Then, patients took voriconazole orally at a dose of 150 mL/time, twice a day for 6 days. Patients in two groups received the treatment for a total of 14 days. After treatment, we evaluated the levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-8. The total lung capacity (TLC), diffusing capacity of the lung for carbon monoxide (DLco), and arterial oxygen saturation (SaO2), were measured as well. RESULTS: The total effectiveness rates of the treatment group and the control group were 83.63% and 61.82%. The differences had statistical significance (p < 0.01). After treatment, the incidence of chest pain, cough, sputum-coughing, hemoptysis, cyanosis, and dyspnea in the treatment group was significantly fewer than that in the control group (p < 0.05). TCL, DLco, and SaO2 in the two groups were significantly ameliorated by treatment (p < 0.05). The amelioration in the treatment group was more prominent than that in the control group (p < 0.05). The levels of TNF-α, IL-8, and IL-6 in the two groups were decreased dramatically by the treatments. The decrease in the treatment group was significantly lower than those in the control group (p < 0.05). Occurrence of adverse reactions in treatment group and control group were 8.33% and 6.25%, respectively; (p > 0.05). CONCLUSIONS: Sequential therapy with voriconazole exhibits promising clinical efficacy in COPD patients in acute phase with pulmonary aspergillosis. The treatment ameliorated the clinical symptoms and vital signs of patients significantly. It also improved the pulmonary functions and inhibited the inflammatory responses of patients with evident clinical efficacy.

The correlation between children's status asthmatics and interstitial lung disease.

OBJECTIVE: Investigating the correlation between children's status asthmatics and interstitial lung disease (ILD). PATIENTS AND METHODS: We continuously selected 20 cases of children's status asthmatics combined with ILD (group A), 20 cases of pure status asthmatics (group B), 20 cases of pure ILD (group C) and 20 cases of healthy children (group D). We measured Th1/Th2 by flow cytometry as well as the level of expression of hs-CRP, IL-7 cytokines (TSLP), monocyte chemoattractant protein-1 (MCP-1) and anti-Jo-1 antibody by ELISA method. RESULTS: Th1 and Th1/Th2 of groups A and B were significantly lower than those of group C and D. Th2 was significantly (p<0.05) higher than that of groups C and D. The level of expression of hs-CRP, TSLP, MCP-1 and anti-Jo-1 antibody in the groups A and B were all significantly higher (p<0.05) than those of groups C and D. There were differences of the above index of the comparison between groups A and B, but no difference between groups C and D. CONCLUSIONS: Children's status asthmatics and ILD may correlate with the abnormal expression of Th1/Th2, hs-CRP, TSLP, MCP-1 and anti-Jo-1 antibody.

Lasing mode regulation and single-mode realization in ZnO whispering gallery microcavities by the Vernier effect.

The wide direct bandgap and strong exciton binding energy of ZnO have inspired examinations of ultraviolet lasing over the previous decades. However, regulation of the lasing mode, especially the realization of single mode lasing, is still a challenge. In this study, a ZnO comb-like structure with an array of microrods was selected to design coupled whispering-gallery-mode cavities, wherein the naturally varied air-gap between the adjacent microrods created a flexible condition for optical field coupling without any complicated micromanipulation. Spectral behaviour of lasing and coupling interaction between coupled ZnO microrods were systematically investigated. By regulating the nano-scale inter-space of dual coupled microrods, stable single-mode lasing with a higher Q factor and lower threshold was obtained successfully based on the Vernier effect. The formation conditions and the mechanism of single-mode lasing derived from the coupled ZnO microrods were discussed in detail. It also demonstrated an approach to construct high quality single-mode lasing by tuning the diameters of the coupled ZnO microrods.

Ultraviolet Lasers Realized via Electrostatic Doping Method.

P-type doping of wide-bandgap semiconductors has long been a challenging issue for the relatively large activation energy and strong compensation of acceptor states in these materials, which hinders their applications in ultraviolet (UV) optoelectronic devices drastically. Here we show that by employing electrostatic doping method, hole-dominant region can be formed in wide bandgap semiconductors, and UV lasing has been achieved through the external injection of electrons into the hole-dominant region, confirming the applicability of the p-type wide bandgap semiconductors realized via the electrostatic doping method in optoelectronic devices.

Identification and expression analysis of YABBY family genes associated with fruit shape in tomato (Solanum lycopersicum L.).

YABBY family genes play important roles in the development of leaf, flower, and fruit. The purpose of this research was to integrate all the YABBY genes and analyze the correlation between gene expression and fruit shape in tomato. Scanning of 24 genomes of sequenced species demonstrated that YABBY genes were very normal and stable in flowering plants except the seedless plants. Nine YABBY genes in tomato were computationally and experimentally characterized. The phylogeny was constructed based on whole proteins or the YABBY domain, and five distinct clades were observed as described in other angiosperms. A comparison of the expression patterns in tomatoes with large differences in fruit shape and/or size suggested that during the fruit development, YABBY genes had both negative and positive functions. The obtained information could provide a deeper understanding of the evolution of YABBY genes and can also be useful for tomato yield and shape breeding.

High gain Ga2O3 solar-blind photodetectors realized via a carrier multiplication process.

Ga2O3 photodetectors with interdigitated electrodes have been designed and fabricated, and the Ga2O3 area exposed to illumination acts as the active layer of the photodetector, while the area covered by Au interdigital electrode provide an arena for carrier multiplication. The photodetectors show a maximum responsivity at around 255 nm and a cutoff wavelength of 260 nm, which lies in the solar-blind region. The responsivity of the photodetector reaches 17 A/W when the bias voltage is 20 V, which corresponds to a quantum efficiency of 8228%, amongst the best value ever reported in Ga2O3 film based solar-blind photodetectors.

Studies on different iron source absorption by in situ ligated intestinal loops of broilers.

The objective of this study was to investigate the iron source absorption in the small intestine of broiler. In situ ligated intestinal loops of 70 birds were poured into one of seven solutions, including inorganic iron (FeSO4, Fe2(SO4)3), organic Fe glycine chelate (Fe-Gly(II), Fe-Gly(III)), the mixtures (FeSO4 with glycine (Fe+Gly(II)), Fe2(SO4)3 with glycine (Fe+Gly(III)), and no Fe source (control). The total volume of 3-mL solution (containing 1 mg of elemental Fe) was injected into intestinal loops, and then 120-min incubation was performed. Compared with inorganic iron groups, in which higher FeSO4 absorption than Fe2(SO4)3 was observed, supplementation with organic Fe glycine chelate significantly increased the Fe concentration in the duodenum and jejunum (P < 0.05), however, decreased DMT1 and DcytB messenger RNA (mRNA) levels (P < 0.05). Organic Fe glycine chelate (Fe-Gly(II), Fe-Gly(III)) increased serum iron concentration (SI), compared with inorganic 3 valence iron groups (Fe2(SO4)3 and Fe+Gly(III)) (P < 0.05); moreover, lower TIBC value was observed for the chelate (P < 0.05); however, mixture of inorganic iron and glycine did not have a positive role at DMT1 and DcytB mRNA levels, SI and Fe concentrations in the small intestine. Those results indicated that the absorption of organic Fe glycine chelate was more effective than that of inorganic Fe, and the orders of iron absorption in the small intestine were: Fe-Gly(II), Fe-Gly(III) > FeSO4, Fe+Gly(II) > Fe2(SO4)3, Fe+Gly(III). Additionally, the simple mixture of inorganic iron and glycine could not increase Fe absorption, and the duodenum was the main site of Fe absorption in the intestines of broilers and the ileum absorbed iron rarely.

Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model.

OBJECTIVE: The major complaint of Osteoarthritis (OA) patients is pain. However, due to the nature of clinical studies and the limitation of animal studies, few studies have linked function impairment and behavioral changes in OA animal models to cartilage loss and histopathology. Our objective was to study surrogate markers of functional impairment in relation to cartilage loss and pathological changes in a post-traumatic mouse model of OA. METHOD: We performed a battery of functional analyses in a mouse model of OA generated by cruciate ligament transection (CLT). The changes in functional analyses were linked to histological changes graded by OARSI standards, histological grading of synovitis, and volumetric changes of the articular cartilage and osteophytes quantified by phase contrast micro-computed tomography (µCT). RESULTS: OA generated by CLT led to decreased time on rotarod, delayed response on hotplate analysis, and altered gait starting from 4 weeks after surgery. Activity in open field analysis did not change at 4, 8, or 12 weeks after CLT. The magnitude of behavioral changes was directly correlated with higher OARSI histological scores of OA, synovitis in the knee joints, cartilage volume loss, and osteophyte formation. CONCLUSION: Our findings link functional analyses to histological grading, synovitis, comprehensive three-dimensional assessment of cartilage volume and osteophyte formation. This serves as a reference for a mouse model in predicting outcomes of OA treatment.

Inhibition of ß-catenin signaling by nongenomic action of orphan nuclear receptor Nur77.

Dysregulation of ß-catenin turnover due to mutations of its regulatory proteins including adenomatous polyposis coli (APC) and p53 is implicated in the pathogenesis of cancer. Thus, intensive effort is being made to search for alternative approaches to reduce abnormally activated ß-catenin in cancer cells. Nur77, an orphan member of the nuclear receptor superfamily, has a role in the growth and apoptosis of cancer cells. Here, we reported that Nur77 could inhibit transcriptional activity of ß-catenin by inducing ß-catenin degradation via proteasomal degradation pathway that is glycogen synthase kinase 3ß and Siah-1 independent. Nur77 induction of ß-catenin degradation required both the N-terminal region of Nur77, which was involved in Nur77 ubiquitination, and the C-terminal region, which was responsible for ß-catenin binding. Nur77/ΔDBD, a Nur77 mutant lacking its DNA-binding domain, resided in the cytoplasm, interacted with ß-catenin, and induced ß-catenin degradation, demonstrating that Nur77-mediated ß-catenin degradation was independent of its DNA binding and transactivation, and might occur in the cytoplasm. In addition, we reported our identification of two digitalis-like compounds (DLCs), H-9 and ATE-i2-b4, which potently induced Nur77 expression and ß-catenin degradation in SW620 colon cancer cells expressing mutant APC protein in vitro and in animals. DLC-induced Nur77 protein was mainly found in the cytoplasm, and inhibition of Nur77 nuclear export by the CRM1-dependent nuclear export inhibitor leptomycin B or Jun N-terminal kinase inhibitor prevented the effect of DLC on inducing ß-catenin degradation. Together, our results demonstrate that ß-catenin can be degraded by cytoplasmic Nur77 through their interaction and identify H-9 and ATE-i2-b4 as potent activators of the Nur77-mediated pathway for ß-catenin degradation.

Ethanol hypersensitivity and olfactory discrimination defect in mice lacking a homolog of Drosophila neuralized.

Neurogenic genes in the Notch receptor-mediated signaling pathway play important roles in neuronal cell fate specification as well as neuronal differentiation. The Drosophila neuralized gene is one of the neurogenic genes. We have cloned a mouse homolog of Drosophila neuralized, m-neu1, and found that the m-neu1 transcript is expressed in differentiated neurons. Mice deficient for m-neu1 are viable and morphologically normal, but exhibit specific defects in olfactory discrimination and hypersensitivity to ethanol. These findings reveal an essential role of m-neu1 in ensuring proper processing of certain information in the adult brain.

Mouse numb is an essential gene involved in cortical neurogenesis.

During neurogenesis of the mammalian neocortex, neural progenitor cells divide to generate daughter cells that either become neurons or remain as progenitor cells. The mouse numb (m-numb) gene encodes a membrane-associated protein that is asymmetrically localized to the apical cell membrane of dividing cortical progenitor cells and may be segregated to only the apical daughter cell that has been suggested to remain as a progenitor cell. To examine m-numb function during neural development, we generated a loss-of-function mutant allele of m-numb. Mice homozygous for this mutation exhibit severe defects in cranial neural tube closure and precocious neuron production in the forebrain and die around embryonic day 11.5 (E11. 5). These findings suggest that m-numb is an essential gene that plays a role in promoting progenitor cell fate during cortical neurogenesis.