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Ying-Hui Zhou,1,* Yue Guo,1,2,* Fang Wang,3,* Ci-La Zhou,1 Chen-Yi Tang,1 Hao-Neng Tang,4 De-Wen Yan,5 Hou-De Zhou1 1National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of China; 2Department of Stomatology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People’s Republic of China; 3Department of Endocrinology and Metabolism, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, 046000, People’s Republic of China; 4Department of Laboratory Medicine, The Second XiangYa Hospital of Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Endocrinology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hou-De ZhouNational Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, People’s Republic of China, Tel +86-731-85292223, Fax +86-731-85533525, Email houdezhou@csu.edu.cnPurpose: Although several studies have explored the association of sex hormones with glucose metabolism, the association between sex hormones and body fat distribution, which is closely related to insulin resistance, has not been fully elucidated. We have tried to explore the relationship of testosterone (T) and estradiol (E2) with visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) mass in Chinese men with different obese and metabolic statuses.Patients and Methods: A total of 128 men from the Health Management Center of the Second Xiangya Hospital, Central South University were collected and grouped in accordance with their obese and metabolic syndrome (MS) statuses: metabolically healthy non-overweight/obese men (MHNO), metabolically healthy overweight/obese men (MHO) and metabolically unhealthy overweight/obese men (MUO). Multiple regression analyses were performed to estimate contributions of sex hormones levels to the variations of body fat distribution and the contributions of body fat distribution to the variations of sex hormone levels.Results: With fat mass parameters as independent variables, SAT had a strong negative association with T in MHNO (β = − 2.772, P = 0.034), VAT was positively correlated with E2 in MHO (β = 22.269, P = 0.009), and SAT was negatively associated with T in MUO (β = − 3.315, P = 0.010). With sex hormones as independent variables, E2 positively correlated with VAT (β = − 176.259, P = 0.048), while T negatively correlated with VAT in MHO (β = 183.150, P = 0.029). In MUO, an inverse association of T with SAT was observed (β = − 213.689, P = 0.021).Conclusion: E2 and VAT had a mutual influence, thus resulting in a vicious circle, and the negative correlation between T and VAT may be related to the decrease of the MS occurrence in the MHO group. There were bi-directional relationships between sex hormones and fat distribution in men with different obese and metabolic statuses.Trial Registration: Chinese Clinical Trial Registry, ChiCTR-EOC-16010194. Retrospectively registered.Keywords: sex hormone, body fat distribution, metabolic syndrome, obesity, Chinese

Susu kedelai terbuat dari hasil ekstraksi kedelai. Susu kedelai memiliki komposisi yang mirip dengan susu sapi yaitu 3,5% protein, 2% lemak, dan 2,9% karbohidrat, sehingga susu kedelai dapat digunakan sebagai pengganti susu sapi bagi orang yang alergi terhadap protein hewani. Masalah yang dihadapi UKM mitra (pengusaha susu kedelai) yaitu pada proses pengolahan, pendinginan dan pengemasan. Selama ini proses pengadukan dilakukan secara konvensional yaitu menggunakan pengaduk manual sehingga karyawan mudah capek dan tangan terasa panas karena terkena uap panas. Selain itu, suhu yang digunakan harus tepat (80-90 oC) karena jika suhunya >90 oC maka susu kedelai akan pecah dan jika suhunya < 80 oC maka susu kedelai akan menggumpal. Masalah berikutnya yaitu pada proses pendinginan membutuhkan waktu yang lama (30 menit) dan kurang higenis karena dibiarkan di udara terbuka. Sedangkan untuk proses pengemasan memerlukan 2 orang sehingga waktu yang diperlukan untuk mengemas juga relatif lebih lama (60 menit). Tujuan dalam kegiatan PKMT ini yaitu meningkatkan efektivitas produksi susu kedelai dengan indikator: proses pengadukan dilakukan mesin dengan penggerak motor listrik, proses pendinginan menjadi 5 kali lebih cepat, dan proses pengemasan menjadi 2 kali lebih cepat. Metode pelaksanaan dalam kegiatan ini yaitu merancang, manufaktur, assembly, ujicoba mesin, serah terima mesin, pelatihan pengoperasian dan perawatan mesin serta pemantauan secara berkala. Hasil penerapan mesin pengolah dan pengemas susu kedelai semi otomatis diperoleh bahwa proses pengadukan menjadi lebih praktis karena dilakukan mesin dengan penggerak motor listrik, mempercepat proses pendinginan menjadi 4 menit, dan mempercepat proses pengemasan menjadi 21 menit maka dapat disimpulkan bahwa permasalahan UKM mitra dapat teratasi karena proses pengolahan, pendinginan dan pengemasan dapat dilakukan dalam satu mesin.

Emisi gas buang merupakan zat/unsur dari pembakaran didalam ruang bakar yang dilepas ke udara yang ditimbulkan oleh kendaraan bermotor, sehingga dapat menimbulkan dampak terhadap lingkungan, terutama dapat menyebabkan polusi udara, lingkungan, dan perubahan iklim global. Untuk mengatasi permasalahan tersebut diperlukan cara lain agar dapat menghemat bakar yang sederhana, bahan relatif murah, dan mudah didapatkan. Salah satu caranya menggunakan ferrite magnet untuk mengurangi emisi gas buang yang dihasilkan. Metode yang digunakan dalam penelitian ini berdasarkan standar SNI 19-7118.3-2005 dengan pengukuran emisi gas buang pada kendaraan berbahan bakar bensin yang dilakukan pada kondisi idle. Namun untuk penelitian dapat juga dilakukan pengujian pada bukaan katup (throttle) yang berubah yang menggunakan metode pengujian kecepatan berubah dengan katup (throttle) terbuka penuh. Dari penelitian ini diperoleh bahwa pemasangan ferrite magnet pada kendaraan four stroke engine 125 cc dapat mempengaruhi emisi gas buang kendaraan yang dihasilkan saat menggunakan bahan bakar pertalite maupun pertamax. Kadar emisi gas buang yang didapat adalah 562 ppm vol (ferrite pertalite) untuk gas HC, 8,53% untuk gas CO (pertalite/pertamax), 10,8% untuk gas CO2 (ferrite pertamax), dan untuk gas O2 kadar emisinya sebesar 14,91% (ferrite pertalite).

Tumor necrosis factor α (TNFα) exhibits diverse biological functions; however, its regulatory roles in myogenesis are not fully understood. In the present study, we explored the function of TNFα in myoblast proliferation, differentiation, migration, and myotube fusion in primary myoblasts and C2C12 cells. To this end, we constructed TNFα muscle-conditional knockout ( TNFα -CKO) mice and compared them with flox mice to assess the effects of TNFα knockout on skeletal muscles. Results indicated that TNFα -CKO mice displayed phenotypes such as accelerated muscle development, enhanced regenerative capacity, and improved exercise endurance compared to flox mice, with no significant differences observed in major visceral organs or skeletal structure. Using label-free proteomic analysis, we found that TNFα -CKO altered the distribution of several muscle development-related proteins, such as Hira, Casz1, Casp7, Arhgap10, Gas1, Diaph1, Map3k20, Cfl2, and Igf2, in the nucleus and cytoplasm. Gene set enrichment analysis (GSEA) further revealed that TNFα deficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling. These findings suggest that TNFα -CKO positively regulates muscle growth and development, possibly via these newly identified targets and pathways.

Jasmonic acid (JA) signaling plays a pivotal role in plant development and defense. MYC2 is a master transcription factor in JA signaling, and was found to be phosphorylated and negatively regulated by MAP kinase and receptor-like kinase. However, the kinases that positively regulate MYC2 through phosphorylation and promote MYC2-mediated activation of JA response have not been identified. Here, we identified CK2 as a kinase that phosphorylates MYC2 and thus regulates the JA signaling. CK2 holoenzyme can interact with MYC2 using its regulatory subunits and phosphorylate MYC2 at multiple sites with its catalytic subunits. Inhibition of CK2 activity in a dominant-negative plant line, CK2mut, repressed JA response. On the other hand, increasing CK2 activity by overexpression of CKB4, a regulatory subunit gene of CK2, enhanced JA response in a MYC2-dependent manner. Substitution of the Ser and Thr residues at phosphorylation sites of MYC2 by CK2 with Ala impaired MYC2 function in activating JA response. Further investigations evidenced that CK2 facilitated the JA-induced increase of MYC2 binding to the promoters of JA-responsive genes in vivo. Our study demonstrated that CK2 plays a positive role in JA signaling, and reveals a previously undiscovered mechanism that regulates MYC2 function., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Osteoporosis is a growing public health concern worldwide. To avoid extra surgeries, developing biodegradable bone cement is critical for the treatment of osteoporosis. Herein, we designed calcium phosphate/calcium sulfate cement reinforced with sodium carboxymethyl cellulose (CMC/OPC). It presents an appropriate physicochemical performance for clinical handling. Meanwhile, CMC/OPC bone cement promotes osteogenic differentiation in vitro . Results of the immune response in vitro and in vivo confirmed that increasing the cellulose content triggered macrophage switching into the M2 phenotype and CMC/OPC exhibited significant anti-inflammation. Furthermore, in vitro and in vivo degradation demonstrated that cellulose tailors the degradation rate of composite bone cement, which achieved a linear degradation process and could degrade by more than 90% for 12 weeks. In summary, the composite bone cement CMC/OPC is a promising candidate for bone repair applications.

Introduction: The study aims to present the potential benefits and challenges of incorporating communication technology (CT), namely synchronous computer-mediated communication (SCMC) (e.g., Zoom Video Communications), computer-mediated communication (CMC) (e.g., WhatsApp), and social networking sites (SNS) (e.g., Instagram) into the tertiary classroom based on the honest account of four English as a Second Language (ESL) teachers during the pandemic. The authors intend to explore the efficacy of SCMC in lowering language anxiety and in fostering closer teacher-student relationship as suggested by the previous literature (Abraham in Comput Assist Lang Learn 21:199-226, 2008; Aristika and Juandi in Emerg Sci J 5:443-456, 2021; Darhower in Synchronous computer-mediated communication in the intermediate foreign language class: a sociocultural case study, University of Pittsburgh, 2000; Hagenauer and Volet in Oxf Rev Educ 40:370-388, 2014)., Method: Qualitative data collected from the authors' teaching reflections over a 13-week period were analyzed from a third-person perspective. The above collaborative autoethnography (CAE) approach was adopted in face of the then difficulties in data collection given factors such as social-distancing during the pandemic. The authors selected and agreed on the key observations, feelings, and anecdotes worth-examining in their first-time online teaching experience at informal group interviews facilitated by SCMC., Findings: It was identified by the authors that learners' text-based production in the target language increased possibly due to the novelty of online learning platforms, lower affective variables, and a closer teacher-student relationship fostered by teachers' increased self-disclosure and the reduced formality in communication technology. Despite the above potential benefits of CT in ESL, challenges, such as an increasingly blurred teacher-student professional distance, students' increased code-mixed production in their L1 and L2, and the resultant 'teacher burnout' due to the obscured concept of standard office hours, were observed. The incorporation of CT into English Language Teaching (ELT) is desirable for its potential benefits in the affective domain of both teachers and students. However, it is recommended that teachers should establish guidelines in the use of CMC and SNSs both inside and outside class to avoid boundary and privacy issues as well as deviation from the initial lesson objectives., Competing Interests: Conflict of interestAll authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: MicroRNAs (miRNAs) are abundant in tumor-derived extracellular vesicles (EVs) and the functions of extracellular miRNA to recipient cells have been extensively studied with tumorigenesis. However, the role of miRNA in EV secretion from cancer cells remains unknown., Methods: qPCR and bioinformatics analysis were applied for determining extracellular let-7a expression from CRC patient serum and cells. Nanosight particle tracking analysis was performed for investigating the effect of let-7a on EV secretion. Luciferase reporter assays was used for identifying targeted genes synaptosome-associated protein 23 (SNAP23). In vitro and in vivo assays were used for exploring the function of let-7a/SNAP23 axis in CRC progression. Bioenergetic assays were performed for investigating the role of let-7a/SNAP23 in cellular metabolic reprogramming., Results: let-7a miRNA was elevated in serum EVs from CRC patients and was enriched in CRC cell-derived EVs. We determined that let-7a could suppress EV secretion directly targeting SNAP23. In turn, SNAP23 promotes EV secretion of let-7a to downregulate the intracellular let-7a expression. In addition, we found a novel mechanism of let-7a/SNAP23 axis by regulating mitochondrial oxidative phosphorylation (OXPHOS) through Lin28a/SDHA signaling pathway., Conclusions: Let-7a plays an essential role in not only inhibiting EV secretion, but also suppressing OXPHOS through SNAP23, resulting in the suppression of CRC progression, suggesting that let-7a/SNAP23 axis could provide not only effective tumor biomarkers but also novel targets for tumor therapeutic strategies.

Background: Atypical clinical symptoms of juvenile hereditary hemochromatosis (JHH) often leads to misdiagnosis and underdiagnosis bringing ominous outcomes, even death., Methods: The whole exome was sequenced and interpreted. A literature review assisted to analyze and verify the phenotype-genotype relationships. We revealed the entire process of diagnosis, treatments, and outcome of two diabetic onset of JHH families to provide new insights for genotype-phenotype relation with novel compound heterozygous mutations in the hepcidin antimicrobial peptide (HAMP, OMIM: 606464)., Results: Two probands were diagnosed and treated as type 1 diabetes initially because of specific symptoms and positive islet autoantibodies. Poor control of hyperglycemia and progressive symptoms occurred. Sequencing informed that the compound heterozygous and homozygous mutations c.166C>G and c.223C>T in HAMP caused type 1 diabetic-onset JHH. The two patients accessed irregular phlebotomy treatments, and then, experienced poor prognosis. We summarized the process of overall clinical management of reported 26 cases comparing to our novel atypical diabetic onsets Juvenile Hereditary Hemochromatosis cases., Conclusion: It was first reported that positive pancreatic islet autoantibodies diabetes onset of JHH resulted from loss-of-function mutations of HAMP, of which the atypical JHH should be differentially diagnosed with type 1 diabetes at the onset. Early administration of phlebotomy and vital organs protection and surveillance might be important for the treatment of atypical JHH., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we used 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly the EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67 , which underwent positive selection in three of the domestic mammals. Our data provide an insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway., (© The Author(s) 2020. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Background: Natural meroterpenes derived from phloroglucinols and β-caryophyllene have shown high inhibitory activity against α-glucosidase or cancer cells, however, the chemical diversity of this type of skeletons in Nature is limited., Methods: To expand the chemical space and explore their inhibitory activities against α-glucosidase (EC 3.2.1.20), we employed β-caryophyllene and some natural moieties (4-hydroxycoumarins, lawsone or syncarpic acid) to synthesize new types of meroterpene-like skeletons. All the products (including side products) were isolated and characterized by NMR, HR-MS, and ECD., Results: In total, 17 products (representing seven scaffolds) were generated through a one-pot procedure. Most products (12 compounds) showed more potential activity (IC 50 < 25 μM) than the positive controls (acarbose and genistein, IC 50 58.19, and 54.74 μM, respectively). Compound 7 exhibited the most potent inhibition of α-glucosidase (IC 50 3.56 μM) in a mixed-type manner. The CD analysis indicated that compound 7 could bind to α-glucosidase and influence the enzyme's secondary structure., Conclusions: Compound 7 could serve as a new type of template compound to develop α-glucosidase inhibitors. Full investigation of a biomimic reaction can be used as a concise strategy to explore diverse natural-like skeletons and search for novel lead compounds., Competing Interests: The authors declare no conflict of interest.

Cancer chemotherapy can cause significant damage to the bone marrow (BM) microvascular (sinusoidal) system. Investigations must now address whether and how BM sinusoidal endothelial cells (SECs) can be protected during chemotherapy. Herein we examined the potential protective effects of genistein, a soy-derived flavonoid, against BM sinusoidal damage caused by treatment with methotrexate (MTX). The groups of young adult rats were gavaged daily with genistein (20 mg/kg) or placebo. After 1 week, rats also received daily injections of MTX (0.75 mg/kg) or saline for 5 days and were killed after a further 4 days. Histological analyses showed that BM sinusoids were markedly dilated ( p < 0.001) in the MTX-alone group but were unaffected or less dilated in the genistein+MTX group. In control rats, genistein significantly enhanced expression of vascular endothelial growth factor (VEGF; p < 0.01), particularly in osteoblasts, and angiogenesis marker CD31 ( p < 0.001) in bone. In MTX-treated rats, genistein suppressed MTX-induced apoptosis of BM SECs ( p < 0.001 vs MTX alone group) and tended to increase expression of CD31 and VEGF ( p < 0.05). Our in vitro studies showed that genistein in certain concentrations protected cultured SECs from MTX cytotoxic effects. Genistein enhanced tube formation of cultured SECs, which is associated with its ability to induce expression of endothelial nitric oxide synthase and production of nitric oxide. These data suggest that genistein can protect BM sinusoids during MTX therapy, which is associated, at least partially, with its indirect effect of promoting VEGF expression in osteoblasts and its direct effect of enhancing nitric oxide production in SECs., (© 2018 Wiley Periodicals, Inc.)

Type 2 diabetic patients are becoming younger and having a tendency to family aggregation, they are easily suspected as maturity-onset diabetes of young (MODY) in the outpatient clinic and send to genetic testing. 9 diabetic families were compared in our outpatient clinic who met the primary diagnosis criteria of MODY. Detailed clinical features and laboratory data including gene sequence were collected and analyzed. The patients met the primary clinical diagnostic criteria of MODY for genetic testing at the first look. However, members of families A1 to A3 had normal Body mass index (BMI) and a lower C-peptide level which indicated impaired pancreatic islet function. In contrast, the members with diabetes of families B1 to B6 had normal or increased C-peptide level which indicated insulin resistance and were overweight with BMI. Genetic testing showed that the mutations in HNF1A, INS, KCNJ11 and so on in families A were consistent with the diagnosis of MODY. No pathogenic mutation was found in the members of families B which were diagnosed with familial T2D. Before the clinical laboratory testing and the further gene test, BMI and the concentration of C-peptide are important for the promptly differential diagnosis of MODY from familial type 2 diabetes and medication instruction in the outpatient clinic which could help to alleviate the burden of genetic testing for them.

Oxidative stress induced by long-term glucocorticoid (GC) use weakens the repair capacity of bone tissue. Nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) oxidase (NOX) is a superoxide-generating enzyme that plays an important role in regulating bone metabolism. To clarify the role of nonphagocytic NOX isoforms in osteoblast reactive oxygen species (ROS) generation and apoptosis, dexamethasone was used to establish a high-dose GC environment in vitro . A dose-dependent increase in intracellular ROS generation was demonstrated, which was accompanied by increased osteoblastic MC3T3-E1 cell apoptosis. Addition of the ROS inhibitor NAC ( N -acetyl-L-cysteine) or NOX inhibitor DPI (diphenyleneiodonium) reversed this effect, indicating that NOX-derived ROS can induce osteoblast apoptosis under high-dose dexamethasone stimulation. NOX1, NOX2, and NOX4 are NOX homologs recently identified in bone tissue. To clarify the NOX isoforms that play a role in osteoblast ROS generation, Nox1 , Nox2 , and Nox4 mRNA expression and NOX2 and NOX4 protein expression were analyzed. Nox1 and Nox4 mRNA expression was elevated in a dose-dependent manner after culture in 100 nM, 250 nM, 500 nM, or 1000 nM dexamethasone, and the increased expression of NOX1 mRNA was more significant compared with NOX4 mRNA. Small interfering RNAs (siRNAs) were used to confirm the role of NOX1 and NOX4 in ROS generation. To clarify the signaling pathway in ROS-induced osteoblast apoptosis, mitogen-activated protein kinase (MAPK) signaling molecules were analyzed. Phosphorylated ASK1 and p38 levels were significantly higher in the 1000 nM dexamethasone group, which NAC or DPI markedly attenuated. However, the total mRNA and protein levels of ASK1 and p38 between the dexamethasone group and control were not significantly different. This is related to ROS regulating the posttranslational modification of ASK1 and p38 in MC3T3-E1 cell apoptosis. Altogether, NOX1- and NOX4-derived ROS plays a pivotal role in high-dose dexamethasone-induced preosteoblast apoptosis by increasing phosphorylated ASK1 and p38 and may be an important mechanism in steroid-induced avascular necrosis of the femoral head (SANFH).

Meroterpenoids isolated from guava (Psidium guajava) and Rhodomyrtus tomentosa possess special skeletons which incorporate terpenoids with phloroglucinol derivatives. Most of these meroterpenoids showed high cytotoxicity against cancer cell lines. However, their chemical diversity is very limited. Herein, we employed a biomimetic hetero-cycloaddition starting from ortho-quinone methides and an abundant natural product, β-caryophyllene, to generate meroterpene-like compounds. Considering that the source plant has hyperglycemic functions, α-glucosidase was selected as a target for bioassay. Nine compounds were screened out for promising activities (IC50 < 15 μM), which were better than the positive controls genistein and acarbose. The best inhibitor 12 (IC50 2.73 μM) possesses two caryophyllene moieties. They represented a new type of skeleton possessing activities against α-glucosidase. The kinetic study exhibited that these inhibitors belong to a non-competitive type. All these inhibitors may provide an opportunity to develop a new class of antidiabetic agents.

We previously demonstrated that fermitin family member 1 (FERMT1) was significantly overexpressed in colon cancer (CC) and associated with poor metastasis-free survival. This study aimed to investigate the precise role of FERMT1 in CC metastasis and the mechanism by which FERMT1 is involved in the epithelial-mesenchymal transition (EMT). Correlations between FERMT1 and EMT markers (E-cadherin, Slug, N-cadherin and β-catenin) were examined via immunohistochemistry in a cohort of CC tissues and adjacent normal colon mucosae. A series of in vitro and in vivo assays were performed to elucidate the function of FERMT1 in CC metastasis and underlying mechanisms. The upregulated expression of FERMT1 in CC tissues correlated positively with that of Slug, N-cadherin and β-catenin, but correlated inversely with E-cadherin expression. Altered FERMT1 expression led to marked changes in the proliferation, migration, invasion and EMT markers of CC cells both in vitro and in vivo. Investigations of underlying mechanisms found that FERMT1 interacted directly with β-catenin and activated the Wnt/β-catenin signaling pathway by decreasing the phosphorylation level of β-catenin, enhancing β-catenin nuclear translocation and increasing the transcriptional activity of β-catenin/TCF/LEF. Activation of the Wnt/β-catenin pathway by CHIR99021 reversed the effect of FERMT1 knockdown, whereas inhibition of the Wnt/β-catenin pathway by XAV939 impaired the effect of FERMT1 overexpression on EMT and cell motility. In conclusion, findings of this study suggest that FERMT1 activates the β-catenin transcriptional activity to promote EMT in CC metastasis.

The aim of this study was to investigate the association between CYP1A1 gene polymorphism and ischaemic stroke (IS) risk, and the impact of gene-gene interaction on IS risk based on a Chinese Han case-control study. A total of 1162 subjects (612 men and 550 women), with a mean age of 63.1 ± 12.5 years old, were selected, including 580 IS patients and 582 normal controls. Logistic regression was performed to investigate association between single-nucleotide polymorphisms (SNP) and IS risk, and generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interaction. Logistic regression analysis showed that the frequency for rs4646903 minor alleles was lower in cases than that in normal controls, and C allele of rs4646903 was 20.7 % in ischemic stroke cases and 27.1 % in controls subjects (p < 0.001). Logistic analysis showed the significant association between genotypes of variants in rs4646903 and decreased ischemic stroke risk. GMDR analysis indicated that there was a significant two-locus model (p = 0.0107) involving rs4646903 and rs1048943, indicating a potential gene-gene interaction between rs4646903 and rs1048943. Overall, the two- locus models had a cross-validation consistency of 9 of 10, and had the testing accuracy of 60.72 %. Subjects with TC or CC of rs4646903 and AG or GG of rs1048943 genotype have lowest ischemic stroke risk, compared to subjects with TT of rs4646903 and AA of rs1048943 genotype, and OR (95 % CI) was 0.63 (0.42-0.89). rs4646903 minor alleles and interaction between rs4646903 and rs1048943 were associated with decreased IS risk.

Series of catalysts made of Pt nanoparticles supported on reduced graphene oxides (Pt/RGO) were synthesized and tested in methanol oxidation reaction, aiming for optimizing the mass-specific activity of prepared Pt/RGO composites. The loading amount of Pt is controlled through setting different reaction time and determined precisely by atomic absorption spectrophotometer. The structure of Pt/RGO composites is characterized by X-ray diffraction, transmission electron microscopy and Raman spectroscopy. The electrochemical testing data reveal that the Pt/RGO-mass-specific activity, judged by current density and long-term stability, is maximized in the sample in which cooperation of the Pt loading amount and electrochemical active surface area (ECSA) per amount of Pt is best optimized. The performance of the catalyst with smallest Pt particles or highest Pt loading amount is dragged down by either too less Pt loading or poor ECSA per amount of Pt. The results in this research demonstrate that the mass-normalized activity of whole catalyst, which is associated with the anticipated power output per amount of catalyst, could be enhanced significantly by deliberate tuning of fabrication process.

Colon cancer is one of the most frequently diagnosed cancer and the third most fatal malignancy worldwide. HOTAIR, a cancer-associated long non-coding RNA (lncRNA), is a powerful biomarker of metastasis and poor prognosis in a diverse group of cancers. Nevertheless, an understanding of how HOTAIR is involved in colon cancer progression is limited. In the present study, we hypothesized that HOTAIR plays a crucial role in colon cancer development. We evaluated the expression of HOTAIR in 120 colon cancer samples, matched adjacent non-tumor mucosa and 32 lymph node metastasis tissues by real-time PCR. Increased HOTAIR expression was significantly correlated with the depth of tumor invasion, lymph node metastasis, organ metastasis, histological differentiation, vascular invasion and advanced tumor stage. Patients with high HOTAIR expression had higher recurrence rates and reduced metastasis-free and overall survival than patients with low HOTAIR expression. Moreover, our findings revealed that HOTAIR had a limited effect on cell proliferation but significantly promoted colon cancer cell migration and invasion in vitro. Depletion of HOTAIR increased the expression of E-cadherin while concomitantly decreasing expression of vimentin and MMP9. Hence, HOTAIR may be another pleiotropic modulator participating in epithelial-mesenchymal transition (EMT). These results indicate that HOTAIR may also be a valuable predictor for colon cancer management; furthermore, this lncRNA may be a potential target for cancer prevention and treatment.

Cip1-interacting zinc-finger protein1 (Ciz1) is a nuclear matrix protein associated DNA replication factor which has been implicated in breast and lung cancer progression. However, the clinical significance of Ciz1 expression in colon cancer has not been determined. This study aimed to examine Ciz1 expression pattern and its potential as a biomarker of prognosis in colon cancer. Using quantitative PCR, tissue microarray (TMA), and ELISA, we evaluated Ciz1 mRNA and protein levels in tumor tissues from patients with colon cancer and in paired adjacent normal tissues. Ciz1 mRNA expression was significantly upregulated in 22 of 39 paired samples (P < 0.001). Immunohistochemistry on TMA-containing samples from 203 colon cancer patients indicated that Ciz1 protein expression was significantly higher in tumor tissues than in adjacent normal tissues (Stuart-Maxwell test, P < 0.001). Elevated expression of Ciz1 protein was significantly correlated with T stage (P < 0.001), N stage (P = 0.005), M stage (P = 0.021), and AJCC stage (P = 0.002). Multivariate Cox proportion hazard model analysis revealed that Ciz1 expression is an independent prognostic factor for overall time (OS; hazard ratio (HR): 1.76; 95% confidence interval (CI): 1.04-2.98; P = 0.034) and disease-free survival (DFS; HR: 2.02; 95% CI: 1.14-3.58; P = 0.017) of patients with colon cancer after colectomy. Our data suggested that Ciz1 may be involved in colon cancer progression and could serve as a novel predictor of survival for colon cancer patients., (© 2014 by the Society for Experimental Biology and Medicine.)

Roots play important roles in plant survival and productivity as they not only anchor the plants in the soil but are also the primary organ for the uptake of nutrients from the outside. The growth and development of roots depend on the specification and maintenance of the root meristem. Here, we report a previously unknown role of TIME FOR COFFEE (TIC) in controlling root meristem size in Arabidopsis. The results showed that loss of function of TIC reduced root meristem length and cell number by decreasing the competence of meristematic cells to divide. This was due to the repressed expression of PIN genes for decreased acropetal auxin transport in tic-2, leading to low auxin accumulation in the roots responsible for reduced root meristem, which was verified by exogenous application of indole-3-acetic acid. Downregulated expression of PLETHORA1 (PLT1) and PLT2, key transcription factors in mediating the patterning of the root stem cell niche, was also assayed in tic-2. Similar results were obtained with tic-2 and wild-type plants at either dawn or dusk. We also suggested that the MYC2-mediated jasmonic acid signalling pathway may not be involved in the regulation of TIC in controlling the root meristem. Taken together, these results suggest that TIC functions in an auxin-PLTs loop for maintenance of post-embryonic root meristem.

T-box2 (TBX2) plays a critical role in embryonic development. Recently, deregulated expression of TBX2 has been implicated in several malignancies. However, the expression and the role of TBX2 in colorectal cancer (CRC) remain unclear. In this study, we found that TBX2 was obviously up-regulated in CRC in comparison with the corresponding normal mucosa at transcriptional and protein level. Up-expression of TBX2 was significantly associated with depth of tumor invasion (P = 0.006), distant metastasis (P = 0.038), advanced AJCC stage (P = 0.008), and relapse (P = 0.003). TBX2 was a significantly prognostic factor for decreased survival and increased disease recurrence independent of tumor stage(II, III stage) and functioned as a biomarker to identify prognosis of patients with CRC (OS: HR 2.154; 95% CI 1.019-4.551; P = 0.044, DFS: HR 2.253; 95% CI 1.109-4.575; P = 0.025). Furthermore, TBX2 could serve as a potential target of cancer drug therapy.

Tripartite motif-containing 29 (TRIM29), also known as ataxia-telangiectasia group D, is structurally a member of the tripartite motif family of proteins, which characterized by the conserved RING finger, B-box, and coiled-coil domains. TRIM29 functions as an oncogene or a tumor suppressor depending on the tumor types. In this study, we aim to evaluate whether TRIM29 affects the tumorigenesis and progression of colorectal cancer. The expression of TRIM29 was investigated using real-time PCR in 40 pairs of colorectal cancer tissues and immunohistochemistry on a tissue microarray containing 203 cases of primary colorectal cancer paired with non-cancerous tissues. Down-regulation of TRIM29 was achieved by transient transfection in RKO cell lines, and the effects of TRIM29 on tumor proliferation were evaluated by MTT and plate colony formation assays. Results indicated that TRIM29 expression was much higher in colorectal cancer tissues and significantly associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion, ki-67 index, and advanced tumor stage. Patients with TRIM29-positive tumors had a higher recurrence rate and poorer survival than patients with TRIM29-negative tumors. In multivariate analyses, the TRIM29 expression was an independent factor for determining colorectal cancer prognosis after surgery. Moreover, down-regulation of TRIM29 inhibited tumor cell proliferation in vitro. In conclusion, TRIM29 plays an important role in promoting colorectal cancer progression. Our findings suggest that TRIM29 may serve as a novel biomarker for tumor recurrence and survival for colorectal cancer patients.

Selective oxygen (O2) removal from wood-derived syngas was investigated over three types of ceria-modified alumina supported metal catalysts (i.e., Pt, Pd, and Cu). Complete O2 removal was observed with the Pt and Pd catalysts at a lower temperature than with the Cu catalyst. Gas hourly space velocity (GHSV) was another critical parameter affecting O2 removal, substantially reducing O2 conversion by all three catalysts at 4000 h(-1) or above. The Cu catalyst appeared to be most sensitive to GHSV. Among three catalysts, the Pd catalyst had the best performance on O2 removal. In addition to reaction conditions, CO2 and water vapor in the syngas also influenced O2 removal, both of which had adverse effects on O2 conversion. Stability tests indicated that both Pt and Pd catalysts were quite stable over a 300 h testing period while the Cu catalyst was deactivated after 50h and regenerated by elevating reaction temperature., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Auxin regulates a variety of physiological processes via its downstream factors included Aux/IAAs. In this study, one of these Aux/IAAs, IAA8 is shown to play its role in Arabidopsis development with transgenic plants expressing GFP-mIAA8 under the control of IAA8 promoter, in which IAA8 protein was mutated by changing Pro170 to Leu170 in its conserved domain II. These transgenic dwarfed plants had more lateral branches, short primary inflorescence stems, decreased shoot apical dominance, curled leaves and abnormal flower organs (short petal and stamen, and bent stigmas). Further experiments revealed that IAA8::GFP-mIAA8 plants functioned as gain-of-function mutation to increase GFP-mIAA8 amount probably by stabilizing IAA8 protein against proteasome-mediated protein degradation with IAA8::GFP-IAA8 plants as control. The searching for its downstream factors indicated its interaction with both ARF6 and ARF8, suggesting that IAA8 may involve in flower organ development. This was further evidenced by analyzing the expression of jasmonic acid (JA) biosynthetic genes and JA levels because ARF6 and ARF8 are required for normal JA production. These results indicated that in IAA8::GFP-mIAA8 plants, JA biosynthetic genes including DAD1 (AT2G44810), AOS (AT5G42650) and ORP3 (AT2G06050) were dramatically down-regulated and JA level in the flowers was reduced to 70 % of that in wild-type. Furthermore, exogenous JA application can partially rescue short petal and stamen observed IAA8::GFP-mIAA8 plants. Thus, IAA8 plays its role in floral organ development by changes in JA levels probably via its interaction with ARF6/8 proteins.

Aux/IAAs interact with auxin response factors (ARFs) to repress their transcriptional activity in the auxin signaling pathway. Previous studies have focused on gain-of-function mutations of domain II and little is known about whether the expression level of wild-type Aux/IAAs can modulate auxin homeostasis. Here we examined the perturbation of auxin homeostasis by ectopic expression of wild-type IAA15. Root gravitropism and stem cell differentiation were also analyzed. The transgenic lines were less sensitive to exogenous auxin and exhibited low-auxin phenotypes including failures in gravity response and defects in stem cell differentiation. Overexpression lines also showed an increase in auxin concentration and reduced polar auxin transport. These results demonstrate that an alteration in the expression of wild-type IAA15 can disrupt auxin homeostasis.

Cullin 4B (CUL4B), a scaffold protein of the Cullin4B-RING E3 ligase complex, functions in proteolysis. The present study aims to investigate its expression pattern and evaluate whether CUL4B expression was associated with histopathological and prognosis in the patients with colon cancer. Real-time PCR and western blot were used to identify CUL4B expression in tumor tissue and the paired adjacent normal mucosa from patients with colon cancer. Immunohistochemistry on a tissue microarray containing 203 cases of colon cancer was performed to analyze the association between CUL4B expression and clinicopathological features. Results indicated that CUL4B mRNA and protein levels in tumor tissues were both higher than that in normal mucosae (P < 0.001). Immunohistochemical study displayed that high CUL4B expression was significantly associated with the depth of tumor invasion, lymph node metastasis, distant metastasis, histological differentiation, vascular invasion, and advanced tumor stage. Patients with CUL4B-positive tumors had a higher recurrence rate and poorer survival than patients with CUL4B-negative tumors. In multivariate analyses, CUL4B expression was an independent factor for determining colon cancer prognosis after surgery. In conclusion, CUL4B might promote the progression of colon cancer and can be served as a novel independent prognostic marker for the prediction of recurrence in colon cancer.

Objective: To explore the expression of gut-enriched Kruppel-like factor 4(KLF4) in gastric cancer, and its association with prognosis., Methods: Surgical specimens were collected from 264 patients undergoing radical surgery between 2004 and 2009 in the Affiliated Qianfoshan Hospital, Shandong University. KLF4 mRNA level of specimens was detected by real-time PCR. KLF4 protein expression was measured by immunohistochemistry on tissue microarray, which contained primary gastric cancer, corresponding para-cancerous tissue, and paired lymph node metastases., Results: Real-time PCR revealed that mRNA level of KLF4 was down-regulated in gastric cancer compared with paired normal gastric mucosa. Immunohistochemistry on tissue microarray showed gastric cancer tissues had significantly lower KLF4 levels compared with paired normal gastric tissues. By univariate and multivariate analysis, KLF4 was a significant predictor of survival and recurrence., Conclusion: KLF4 expression is significantly down-regulated in gastric cancer, and is an independent predictor of survival and recurrence.

Purpose: Downregulation of metallothionein (MT) genes has been reported in several tumors with discrepant results. This study is to investigate molecular mechanism of MT gene regulation in colon cancer which is characterized by tumor suppressor gene alterations., Experimental Design: Integral analysis of microarray data with loss of heterozygosity (LOH) information was employed. Quantitative real-time PCR and immunohistochemistry were used to validate MT isoform expression in colon cancer tissues and cell lines. The effects of MT1F expression on RKO cell survival and tumorigenesis was analyzed. Bisulphite sequencing PCR (BSP) and methylation-specific PCR were employed to detect the methylation status of the MT1F gene in colon cancer tissues and cell lines. DNA sequencing was used to examine the LOH at the MT1F locus., Results: MT1F, MT1G, MT1X, and MT2A gene expression was significantly downregulated in colon cancer tissue (p<0.05). Exogenous MT1F expression increased RKO cell apoptosis and inhibited RKO cell migration, invasion and adhesion as well as in vivo tumorigenicity. Downregulation of MT1F gene in majority of human colon tumor tissues is mainly through mechanism by loss of heterozygosity (p=0.001) while CpG island methylation of MT1F gene promoter region was only observed in poorly differentiated, MSI-positive RKO and LoVo colon cancer cell lines., Conclusions: MT1F is a putative tumor suppressor gene in colon carcinogenesis that is downregulated mainly by LOH in colon cancer tissue. Further studies are required to elucidate a possible role for MT1F downregulation in colon cancer initiation and/or progression., (© 2012 Elsevier B.V. All rights reserved.)

Expression microarrays are widely used for investigating the candidate molecular targets in human cancer. While genome-wide expression signatures screened by gene set enrichment analysis (GSEA) were not performed in Chinese gastric cancer (GC). To gain new molecular targets for GC, GSEA analysis was performed. In the present study, GSEA were used to pick out differentially expressed gene sets of our database. Total RNA of paired tissue samples (n = 48) and a tissue microarray containing 132 paired tissues were used to further validate expression levels of INHBA and its correction with clinicopathological factors. Upregulated INHBA expression in gastric cancer was screened and further confirmed by qPCR and immunostaining analysis. Increased INHBA expression was significantly correlated with the diameter of cancer and depth of tumor invasion. Patients with higher expression levels of INHBA had a shorter disease-free survival rate. It was effective to gain new molecular targets for GC by GSEA analysis. INHBA may be a poor survival indicator of GC.

Biglycan, a member of the small leucine-rich proteoglycan family, has been implicated in the development and progression of human cancers. However, the clinical significance of biglycan expression in gastric cancer has not been determined. In the present study, biglycan mRNA and protein concentrations were analyzed using quantitative realtime reverse transcription polymerase chain reaction and Western blot in 69 gastric cancer and adjacent non-tumorous tissues, respectively. Biglycan expression was further assessed using immunohistochemistry in tissue microarrays that contained 264 cases of gastric cancer, and others containing normal or metastasized lymph node tumor tissues. Biglycan was upregulated at the transcriptional and translational levels and there was a correlation between the expression of biglycan mRNA and protein (P = 0.000, κ = 0.769). Over-expression of biglycan was strongly associated with lymph node metastasis, tumor (T) classification, metastasis (M) classification, vascular invasion and Union for International Cancer Control (UICC) stage. Patients with biglycan-positive tumors had a significantly higher disease recurrence rate and poorer survival than patients with biglycan-negative tumors after the radical surgery. Multivariate analysis revealed that biglycan expression is an independent prognostic indicator for survival of patients with gastric cancer. The data from the current study demonstrate that elevated expression of biglycan may play an important role in the development and progression of gastric cancer, and could be further evaluated as a biomarker for predication of a poor clinical outcome.

Background and Objectives: It is important to identify and validate the differentially expressed genes in gastric cancer to screen diagnostic and/or prognostic tumor markers., Methods: cDNA expression microarray, gene set enrichment analysis, and bioinformatics approaches were used to screen the differentially expressed genes between gastric cancer tissues and adjacent non-cancerous mucosa. A novel candidate prognostic marker, Kallikrein-related peptidase 11 (KLK11), was validated in 400 Chinese gastric cancer patients. KLK11 expression in gastric cancer tissues was detected using real-time PCR and Western blot. KLK11 protein expression was further analyzed by immunostaining on tissue microarray, followed with clinicopathological significance and survival analysis., Results: KLK11 expression was significantly decreased in gastric cancer compared with that in normal gastric mucosa (P<0.001). Furthermore, KLK11 expression was much lower in poorly differentiated cancer samples than that in well-differentiated group (P<0.01). Survival analysis showed that negative KLK11 expression was associated with nearly fivefold increased risk of distant metastasis after curative gastrectomy (HR 4.65, P<0.01). Multivariate Cox regression analysis showed that KLK11 expression emerged as a significant independent prognostic factor for disease-free survival and overall survival (P<0.05)., Conclusions: The results indicated that KLK11 expression was decreased in gastric cancer and might serve as a novel independent prognostic marker., (Copyright © 2011 Wiley-Liss, Inc.)

To assess the genetic diversity between randomly and selectively bred populations, we sequenced 438 bp of the mitochondrial DNA control region from 102 pigs. These samples represented four native pig breeds, one nucleus and one conservation herd from Yunnan, China. Twenty haplotypes with sixteen polymorphic sites were identified. The number of haplotypes in the nucleus herd of Saba pig and the conservation herd of Banna miniature pig were restricted to three and one, respectively, while the randomly bred pig populations exhibited over six haplotypes. Notably, haplotype diversity in randomly bred populations was significantly greater than the selectively bred populations (h=0.732 vs. 0.425 and 0, exact test, P<=0.0036). These findings demonstrate that selective breeding generated low genetic diversity compared to randomly bred pig breeds. A timely intervention and well programmed breeding approach would stop further genetic diversity reduction in the nucleus and conservation herds of native pig breeds. Otherwise, selective breeding would dramatically reduce genetic diversity in only several years, indicating that sharp contradictions exist between breeding, conservation and genetic diversity. Genetic relationships are discussed based on net genetic distances among pig populations.

The aim of this study was to detect the expression of the Forkhead box M1 (FOXM1) protein in human hepatocellular carcinoma (HCC) and to associate FOXM1 expression with clinicopathological features of the patients, and predict the prognosis of patients with FOXM1 expression. Surgical tissue specimens from 151 HCC patients were subjected to a tissue microarray construction and immunohistochemistry analysis of FOXM1 and the proliferation marker proliferating cell nuclear antigen (PCNA). The data showed that the FOXM1 protein was expressed in 59.3% of the HCC tissues, which was significantly higher compared to that of the surrounding non-tumorous tissues (23.8%; P<0.001). Moreover, FOXM1 expression was positively correlated with the labeling index of PCNA (P<0.001) in HCC and with aggressive tumor phenotypes, such as larger tumor size, multiple tumors, bilobar involvement, poor tumor cell differentiation, advanced stage and macrovascular invasion (P<0.05). In addition, HCC patients with FOXM1-positive tumors had a poorer recurrence-free and overall survival after hepatectomy than those with FOXM1-negative tumors. Multivariate Cox regression analysis demonstrated that FOXM1 expression was an independent predictor of unfavorable outcome (P<0.05). The data from the current study suggest that FOXM1 may play an important role in HCC progression and could be further evaluated as a prognostic biomarker and potential therapeutic target.

Photorespiration-associated production of H(2) O(2) accounts for the majority of total H(2) O(2) in leaves of C(3) plants and is mainly eliminated by catalases. In Arabidopsis, lack of CAT2, but not CAT1 or CAT3, results in growth suppression and a marked accumulation of H(2) O(2) in leaves. To evaluate the contribution of individual catalase genes and their promoters to catalase function, we investigated the growth suppression and H(2) O(2) accumulation phenotypes of Arabidopsis derivatives expressing catalase genes from heterologous CAT promoters in a cat2 mutant background. The expression of CAT2 from the CAT2 promoter restored the wild-type phenotype in a cat2-1 mutant, while CAT1 and CAT3 promoter-driven expression of CAT2 did not. Ectopic expression of CAT3 from the CAT2 promoter also restored the normal phenotype, unlike that of CAT1 which required replacement of the CAT1 3'-untranslated region (UTR) with that of CAT2. These results demonstrated that the photorespiratory role of CAT2 is determined mainly by the regulation of its promoter activity. The 3'-UTR of CAT2 was vital for controlling CAT2 protein levels under photorespiratory conditions. Identification of component of heterotetramers catalase isoforms suggested that there is some functional redundancy between CAT2 and CAT1 and CAT3., (© 2010 Blackwell Publishing Ltd.)

Background: Our recent study observed that the expression of ubiquitin D (UBD), a member of ubiquitin-like modifier family, was upregulated in colon cancer parenchymal cells. The present study further investigated the clinical signicance of UBD in colon cancer., Methods: Using quantitative PCR, tissue microarray (TMA), western blot analysis and immunohistochemical stain, we evaluated UBD mRNA and protein levels in tumour tissues from patients with colon cancer at different stages and in paired adjacent normal epithelium., Results: Immunohistochemical detection of UBD on a TMA containing 203 paired specimens showed that increased cytoplasmic UBD was signicantly associated with depth of cancer invasion, lymph node metastasis, distant metastasis, tumour histologic grade, advanced clinical stage and Ki-67 proliferative index. Patients with UBD-positive tumours had a significantly higher disease recurrence rate and poorer survival than patients with UBD-negative tumours after the radical surgery. Stratification analysis according to tumour stage revealed UBD as an independent predictor for tumour recurrence in patients with stage II and III tumours., Conclusion: UBD may contribute to the progression of colon carcinogenesis and function as a novel prognostic indicator of forecasting recurrence of stage II and III patients after curative operations.

Purpose: To investigate the clinicopathologic significance and predictive value of Bmi-1 expression in patients with colon cancer., Methods: Bmi-1 expression was assessed by immunohistochemistry, PCR, and western blotting in specimens from 203 patients and by immunohistochemistry in 66 specimens of lymph node metastasis (LNM)., Results: Positive staining of Bmi-1 occurred in 7.9% (16/203), 66.5% (135/203), and 86.4% (57/66) of specimens from normal tissue, colon cancer, and LNM, respectively. Staining was significantly correlated with clinical stage, depth of invasion, nodal involvement, distant metastasis, and Ki67 level. Bmi-1 was upregulated at the transcriptional and translational levels. Patients with Bmi-1-positive localized tumors had a much lower 5-year disease-free survival (relative risk 2.919, P < 0.0001) and overall survival (relative risk 5.056, P < 0.0001). Bmi-1 immunoreactivity emerged as an independent prognostic factor in the multivariate analysis., Conclusions: We have shown that expression of Bmi-1 was elevated in colon cancer and might serve as an independent prognostic marker.

A series of 3-alkoxy(phenyl)thiophosphorylamido-2-(per-O-acetylglycosyl-1'-imino)thiazolidine-4-one derivatives were prepared by the reaction of 1-alkoxy(phenyl)thiophosphoryl-4-(per-O-acetylglycosyl) thiosemicarbazides with ethyl bromoacetate. (1)H/(13)C HMBC measurements corroborated by X-ray crystallographic results revealed the exclusive regioselectivity of these ring closures toward the N-2 position of the thiosemicarbazide moiety. The bioactivity data of 3a-k suggest that the thiazolidine-4-one ring is critical for the herbicidal and fungicidal activities.

Objective: To investigate insulin resistance in type 1 diabetes (T1DM) with euglycemic-hyperinsulinemic clamp., Methods: Eight cases of newly diagnosed T1DM and 8 cases of newly diagnosed type 2 diabetes (T2DM) were selected. Their insulin sensitivity index (ISI) was evaluated with euglycemic-hyperinsulinemic clamp after 2 week insulin intensive treatment and compared with that of 10 healthy volunteers (normal control group, NC group)., Results: Age, BMI, fasting insulin (FIns), fasting C-peptide in the T1DM group were significantly lower than those in the NC group, while waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, HDL-C were not significantly different between the T1DM and NC groups. Age, BMI, WHR, FIns, fasting C-peptide, SBP, TC, TG in the T1DM group were significantly lower than those in the T2DM group. The ISI of the NC, T1DM and T2DM groups were 12. 83 +/- 1.09, 9.95 +/-0.50, 3.80 +/- 0.20, respectively. There was significant difference among the three groups (P < 0.05)., Conclusion: The ISI in T1DM was significantly lower than that in NC group, but higher than that in T2DM.

Background: As a model for both multistep and multipathway carcinogenesis, colorectal neoplastic progression provides paradigms for researching both oncogenes and tumor suppressor genes (TSGs). However, the mechanism of colorectal cancer (CRC) is not completely understood, and many genes may be involved in the colorectal carcinogenesis. The purpose of this study was to screen for the potential TSGs on chromosome 1q31.1-32.1 in Chinese patients with sporadic colorectal cancer, to explore whether colorectal cancer in the Chinese population has unique genetic alterations and determine whether other putative TSGs exist and contribute to colon carcinogenesis., Methods: Six polymorphic microsatellite markers, at a density of approximately one marker in every 1.6 cM, were chosen for refined loss of heterozygosity (LOH) mapping of 1q31.1-32.1. Eighty-three colorectal cancer patients' tumor and normal DNA were analyzed via polymerase chain reaction (PCR) for these microsatellite markers. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. On the basis of refined LOH mapping results, we undertook a microarray-based expression screening to identify tumor association genes in 19 of the CRC cases., Results: The average LOH frequency of 1q31.1-32.1 was 24.41%, with the highest frequency of 36.73% (18/49) at D1S2622, and the lowest of 16.42% (11/67) at D1S412. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622. There was no significant association between LOH of any marker in the studied regions and the clinicopathological data (patient sex, age, tumor size, growth pattern, or Dukes stage). On the basis of refined mapping results, we chose 25 genes located in the D1S413-D1S2622 (1q31.3-32.1) region and presented a microarray-based high throughput screening approach in 19 sporadic CRC cases to identify candidate CRC related tumor suppressor genes. This study found 4 significantly down-expressed genes, including CSRP1, LMOD1, PPP1R12B and CFHL3. There was no significant association between expression levels of CFHL3, CSRP1, LMOD1, PPP1R12B and the clinicopathological data. By database searching, CSRP1 was hypothesized to be a colorectal cancer related tumor suppressor gene., Conclusions: Through detailed deletion mapping, we found that the 1q31.3-32.1 region might harbor one or more colorectal cancer related tumor suppressor gene (s). And by microarray-based high-throughput screening of candidate genes located in this region and by subsequent database searching, we present the first evidence that CSRP1 might be involved in the progression of CRC.

The phytohormone abscisic acid (ABA) regulates plant growth and development as well as stress tolerance. To gain more insights into ABA signalling, a population of chemical-inducible activation-tagged Arabidopsis mutants was screened on the basis of the ABA effect on the inhibition of seed germination. Two novel ABA supersensitive mutants ABA supersensitive during germination1 (absg1) and absg2 were characterized as alleles of Dicer-like1 (DCL1) and HEN1, respectively, as microRNA biogenesis genes, and accordingly, these two mutants were renamed dcl1-11 and hen1-16. The dcl1-11 mutant was an ABA hypersensitive mutant for seed germination and root growth. Reverse transcriptase polymerase chain reaction assays revealed that the expression of ABA- and stress-responsive genes was increased in dcl1-11, as compared with the wild type (WT). Furthermore, the germination assay showed that dcl1-11 was also more sensitive to salt and osmotic stress. The hen1-16 mutant also showed supersensitive to ABA during seed germination. Further analysis showed that, among the microRNA biogenesis genes, all the other mutants were not only enhanced in sensitivity to ABA, salt and osmotic stress, but also enhanced the expression of ABA-responsive genes. In addition to the mutants in the microRNA biogenesis, the interruption of the production of crucial components of other small RNA pathways such as dcl2, dcl3 and dcl4 also caused ABA supersensitive during germination.

We report a facile hydrothermal synthetic approach to selectively produce 1-dimensional, 2-dimensional, or 3-dimensional MnO2 nanomaterials reliably and conveniently. The influences of reaction conditions on the morphology and crystallographic forms and the formation mechanism of the as-obtained MnO2 nanostructures have been studied in this work. And the materials produced by this method have excellent crystalline nature. Preliminary electrochemical study indicates that the as-prepared 2-dimensional MnO2 nanomaterials are excellent cathode materials using in lithium batteries.

Objective: To investigate the state of insulin secretion and insulin resistance in patients of Graves disease (GD) with impaired glucose tolerance (IGT) by hyperglycemic clamp., Methods: Six cases of Graves disease with IGT were selected as GD + IGT group and ten healthy volunteers as normal control group (NC group). All the subjects were required to fast for 12 hours and then underwent hyperglycemic clamp to assay insulin secretion and insulin sensitivity. Glutamic acid decarboxylase antibody (GAD-A) was tested in all the subjects., Results: Insulin secretion in GD + IGT group was significantly higher than that in NC group. The 1st phase insulin secretion (1PH) was (636.31 +/- 105.54) mIU/L vs (233.56 +/- 21.33) mIU/L, P = 0.001. The 2nd phase insulin secretion (2PH) was (146.68 +/- 25.00) mIU/L vs (67.06 +/- 6.23) mIU/L, P = 0.03. The maximal insulin secretion during 120 - 150 minutes (Ins(120 - 150)) was (195.05 +/- 32.94) mIU/L vs (87.64 +/- 9.78) mIU/L, P = 0.04. The hyperglycemic clamp insulin sensitivity index (average glucose metabolic rate during 120 - 150 minutes/Ins(120 - 150)) was significantly lower in GD + IGT group than that in NC group (11.52 +/- 1.90 vs 21.72 +/- 3.25, P = 0.04). GAD-A was negative in all subjects., Conclusion: Cases of GD with IGT show significant insulin resistance with compensated elevated insulin secretion.

Objective: To evaluate the function of the first phase of insulin secretion of pancreatic B cells in newly diagnosed type 2 diabetics using nateglinide-intravenous glucose insulin release test (NG-IVGIRT)., Methods: NG-IVGIRT and intravenous glucose insulin release test (IVGIRT) were done in 8 patients with newly diagnosed type 2 diabetes mellitus and NG-IVGIRT was done in 8 normal people. Insulin and glucose of blood were determined at - 15, 0, 2, 4, 6, 8 and 10 min in NG-IVGIRT or IVGIRT., Results: The response of 0 - 10 min insulin to NG-IVGIRT was significantly higher than that to IVGIRT in the diabetics. The response of insulin to NG-IVGIRT in the normal controls was much higher than that in the diabetics. The area under curve (AUC) of insulin to NG-IVGIRT was apparently elevated and the AUC of glucose to NG-IVGIRT reduced in the normal controls as compared with those in the diabetics., Conclusion: The results indicated that the reserve of first phase insulin secretion in newly diagnosed type 2 diabetics could be provoked in some degree by NG-IVGIRT and there was a big difference in the reserve of the first phase of insulin secretion provoked by NG-IVGIRT between newly diagnosed type 2 diabetics and normal people.

MicroRNAs (miRNAs) are important regulators in the development of plants and animals. Several hundred have been identified from animals, and about a dozen have been cloned from plants, mainly Arabidopsis thaliana (L.) Heynh. We have identified nine miRNAs in Oryza sativa L., an important food crop that has been sequenced in recent years. The nine miRNAs include miRNA171 and miRNA167, which were also identified in Arabidopsis. These had the typical properties of miRNAs, including short length, an ability to form a stem-loop structure with a flanking genomic sequence and they could be identified by northern blot analyses. In addition, m-fold program and computational analyses indicted that the potential targets of six of the nine miRNAs are four known gene families and two unknown protein families, which comprise 16 unique genes.