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New 2,3-disubstituted thieno[2,3- d ]pyrimidin-4(3 H )-ones were synthesized via a one-pot reaction from 2 H -thieno[2,3- d ] [1,3]oxazine-2,4(1 H )-diones, aromatic aldehydes, and benzylamine or 4-hydroxylbezylamine. The obtained compounds were tested in vitro for cancer cell growth inhibition. Compound 19 can inhibit all four types of tested cancer cells, i.e., MCF-7, A549, PC-9, and PC-3 cells. Most of the compounds inhibited the proliferation of A549 and MCF-7 cells. Compound 15 exhibited the strongest anti-proliferative effect against A549 cell lines with IC 50 values of 0.94 μM, and with no toxicity to normal human liver cells. Its potency was further proved by cell clone formation assay, Hoechst 33258 staining, and evaluation on the effects of apoptosis-related proteins.

Rice false smut fungus (teleomorph: Villosiclava virens ; anamorph: Ustilaginoidea virens ) can generate chlamydospores and survive winter under field conditions. The chlamydospore is considered as an important infection source of the disease. However, little is known about the regulatory mechanism of the chlamydospore production. In this study, we identified a defective homeobox transcription factor (designated as UvHOX2) gene in a U. virens random insertional mutant B-766 that could not form chlamydospores. To confirm the regulatory function of UvHOX2, an Agrobacterium tumefaciens mediated transformation- and CRISPR/Cas9- based targeted gene replacement method was developed. The UvHox2 deletion mutants completely failed to produce chlamydospores, showed reduced conidia production and decreased virulence, and was hyper-sensitive to oxidative, osmotic, and cell wall stresses. We confirmed that UvHOX2 is located in the nuclei of U. virens , and the expression of UvHox2 was the strongest during the early stage of chlamydospore and conidium formation. Global transcription pattern of UvHOX2 was also determined by RNA-seq in this study, and several genes that might be down-stream of UvHOX2 regulation were identified. The results will better our understanding of the molecular mechanism of chlamydospore formation in U. virens as a model fungus.

In this paper, a non-contact binocular vision profilometry method is proposed to measure a rough lens with aperture of around 300mm. A series of binarized band-limited pseudo-random patterns (BBPPs) are projected onto the rough lens, we utilize the temporal encoding method so that each pixel in the captured images has its specific code word. Homologous points could be matched via stereo matching procedure, then the surface of the rough lens will be reconstructed based on triangulation method according to the previous calibration data. Compared with the three coordinate measuring machine (CMM), this method achieves a fast and cheap measurement of the large-sized rough lens, which might be highly interesting for fast and overall measurement of metre-sized rough elements in the future.

The plant-pathogenic fungus Ustilaginoidea virens (Cooke) Takah causes rice false smut (RFS), which is responsible for significant quantitative and qualitative losses in rice industry. Propiconazole is a triazole fungicide which belongs to Demethylation inhibitors (DMIs). It is used to control RFS in China. We previously screened 158 isolates of U. virens collected in the fields in 2015 in Jiangsu province of China, and found two of them were highly resistant to propiconazole (named 82 and 88, respectively). In this study, we have analyzed the physiological and biochemical characters of six field-sensitive isolates and the two field-resistant isolates, including mycelial growth and cell wall integrity. We found there was cross-resistance between different DMIs fungicides, but was no cross-resistance between DMIs and QoIs fungicides. We also analyzed the fitness, and found the pathogenicity in 88 was stronger than the field-sensitive isolates, but was completely lost in 82. Sequence analyses of CYP51 and the 1000-bp upstream of CYP51 coding region showed no mutation in 82 compared to the field-sensitive strains, but two more bases CC were identified at 154-bp upstream of the coding region in the field-resistant isolate 88. Moreover, the expression of CYP51 gene in all tested isolates was significantly induced by propiconazole. However, the up-regulation expression level in both 82 and 88 was much higher than that in the field-sensitive isolates. We also found propiconazole could inhibit the ergosterol biosynthesis in the field-sensitive isolates, but stimulated it in both field-resistant isolates 82 and 88. Given the high level of U. virens developing propiconazole resistance and the good fitness of the field-resistant isolate 88, the resistance of U. virens to DMIs must be monitored and managed in rice fields., (Copyright © 2018. Published by Elsevier Inc.)

Background: Bladder neuroendocrine carcinomas (BNECs) are relatively a rare type of tumor. The aim of this study was to examine the clinicopathological characteristics and predictors of survival outcomes of patients with BNECs based on the analysis of the national Surveillance, Epidemiology, and End Results (SEER) database., Materials and Methods: Kaplan-Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of different treatments on overall survival (OS) and cancer-specific survival (CSS)., Results: A total of 910 patients were identified between 2004 and 2014. Overall, 648 (71.2%) patients had small cell neuroendocrine carcinoma (SCNEC), 35 (3.8%) had large cell neuroendocrine carcinoma (LCNEC), 10 (1.1%) had carcinoid tumor (well-differentiated neuroendocrine tumor), 16 (1.8%) had paraganglioma/pheochromocytoma (PGL/PHEO), 619 (68.0%) had a poorly differentiated or undifferentiated histology grade, 214 (23.5%) presented with metastatic disease, 586 (64.4%) underwent transurethral ablation/destruction for bladder tumor, and 245 (26.9%) had partial/total cystectomy. Cystectomy+chemotherapy+radiotherapy (CCR) has the highest long-term survival rate among various treatments. The 1-, 3-, and 5-years CSS of CCR were 56%, 56%, and 56%, respectively. By using multivariable Cox proportional hazard model, age, histology, N stage, SEER stage, tumor size, radiotherapy, chemotherapy, and local treatment of the primary site were identified as independent predictors for OS and CSS; all P <0.05., Conclusion: In BNEC, SCNEC has an absolute advantage in number. SCNEC/LCNEC tend to be older men. PGL/PHEO and carcinoid tumors have younger mean ages, earlier tumor stages, and better prognosis than SCNEC/LCNEC. Surgery, radiotherapy and chemotherapy are better than conservative treatment. However, whatever cystectomy or bladder sparing, chemotherapy should be a major component of treatment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Forming solid solutions, as an effective strategy to improve thermoelectric performance, has a dilemma that alloy scattering will reduce both the thermal conductivity and carrier mobility. Here, an intuitive way is proposed to decouple the opposite effects, that is, using lanthanide contraction as a design factor to select alloying atoms with large mass fluctuation but small radius difference from the host atoms. Typical half-Heusler alloys, n-type (Zr,Hf)NiSn and p-type (Nb,Ta)FeSb solid solutions, are taken as paradigms to attest the validity of this design strategy, which exhibit greatly suppressed lattice thermal conductivity and maintained carrier mobility. Furthermore, by considering lanthanide contraction, n-type (Zr,Hf)CoSb-based alloys with high zT of ≈1.0 are developed. These results highlight the significance of lanthanide contraction as a design factor in enhancing the thermoelectric performance and reveal the practical potential of (Zr,Hf)CoSb-based half-Heusler compounds due to the matched n-type and p-type thermoelectric performance., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A high-efficiency polarization-independent wideband multilayer dielectric reflective bullet-alike cross-section (combination of trapezoidal-rectangular grating profile) fused-silica beam combining grating (BCG) used in the -1st order for spectral beam combining (SBC) is designed and fabricated. Exact grating profile parameters are optimized by using the rigorous coupled-wave analysis and simulated annealing algorithm. As a comparison, traditional pure trapezoidal and pure rectangular gratings are also designed. Numerical results show that such a bullet-alike cross-section BCG exhibits wide bandwidth with the lowest maximum electric field enhancement in the grating material, which is greatly beneficial for the promotion of the power scaling level of the grating-based SBC system. A two-step dry-etching procedure is developed to fabricate such a grating. The averaged diffraction efficiency of greater than 91% was experimentally demonstrated.

Oxalate decarboxylase (OxDC), catalyzing the degradation of oxalic acid, is widely distributed in varieties of organisms. In this study, an oxalate decarboxylase gene from Bacillus subtilis strain BS-916, Bacisubin, was transformed into rice variety Nipponbare to generate transgenic rice with increased OxDC activity. Pathogenicity test revealed that the transgenic rice showed enhanced resistance to rice blast and sheath blight. Further RNA-seq analysis between Nipponbare WT (wild type) and transgenic rice identified 1764 DEGs (Differentially expressed genes) including 723 up-regulated unigenes and 1041 down-regulated unigenes. Five GO terms including single-organism process and oxidation-reduction process were significantly enriched in the up-regulated genes. Interestingly, five genes encoding glutaredoxin and one gene encoding MADS box were up- and down-regulated in the transgenic rice, respectively. Collectively, our study advances the understanding of OxDC in resistance to rice disease and its possible mechanisms. Our results also suggest that OxDC would be an effective antifungal protein preventing fungal infection in transgenic rice., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Multifocal spots in high numerical-aperture (NA) objectives has emerged as a rapid, parallel, and multi-location method in a multitude of applications. However, the typical method used for forming three-dimensional (3D) multifocal spots based on iterative algorithms limits the potential applications. We demonstrate a non-iterative method using annular subzone phases (ASPs) that are composed of many annular subareas in which phase-only distributions with different 3D displacements are filled. The dynamic 3D multifocal spots with controllable position of each focal spot in the focal volume of the objective are created using the ASPs. The experimental results of such dynamic tunable 3D multifocal spots offer the possibility of versatile process in laser 3D fabrication, optical trapping, and fast focusing scanned microscopic imaging.

MicroRNAs, a class of small noncoding RNAs, are implicated in controlling a variety of biological processes. We have shown that leucine deprivation suppresses lipogenesis by inhibiting fatty acid synthase (FAS) expression in the liver previously; the aim of our current study is to investigate which kind of microRNA is involved in the regulation of FAS expression in response to leucine deprivation. Here, we indicated that microRNA-212-5p specifically binds to mouse FAS 3'UTR and inhibits its activity. Leucine deficiency significantly increased the mRNA levels of miR-212-5p in the livers of mice. Further studies proved that miR-212-5p also directly binds to the 3'UTR of stearoyl-CoA desaturase-1 (SCD1) to inhibit its activity. Overexpression of miR-212-5p decreases the protein levels of FAS and SCD1 in vitro and in vivo , and silencing of miR-212-5p has the opposite effects in mouse primary hepatocytes. Moreover, overexpression of miR-212-5p significantly decreases triglyceride (TG) accumulation in primary hepatocytes and in the livers of mice injected with adenovirus-mediated overexpressing of miR-212-5p (Ad-miR-212). Interestingly, inhibition of miR-212-5p reverses the suppressive effects of leucine deficiency on FAS and SCD1 expression, as well as TG accumulation in mouse primary hepatocytes. Finally, we demonstrate that leucine deficiency induces the expression of miR-212-5p in a GCN2/ATF4-dependent manner. Taken together, our results demonstrate a novel function of hepatic miR-212-5p in the regulation of lipid metabolism which represents a potential therapeutic target for the treatment of non-alcohol fatty liver diseases (NAFLD)., (© 2017 Society for Endocrinology.)

Purpose: We performed this meta-analysis to evaluate the efficacy and safety of artery preserving versus artery non-preserving in laparoscopic varicocelectomy., Methods: All publications up until October 2015 were searched in PubMed, EMBASE, Ovid, Web of Science, and Cochrane library. Randomized controlled trials (RCTs) and cohort studies (CSs) that compared the difference in two operative approaches in laparoscopic varicocelectomy were included. Statistical analysis was performed using Stata version 12.0., Results: A total of four RCTs and ten CSs involving 503 cases with artery preserving and 911 cases with artery non-preserving met our inclusion criteria. Meta-analysis showed that artery preserving had higher recurrence rate [risk ratio (RR) = 2.91, 95 % confidence interval (CI) 1.83-4.61; P = 0.000], lower incidence of hydrocele formation (RR = 0.18; 95 % CI 0.08-0.42; P = 0.000), and prolonged operating time [standard mean difference (SMD) = 1.27; 95 % CI 0.17-2.37; P = 0.023], compared with artery non-preserving in laparoscopic varicocelectomy. The results were similar in postoperative catch-up growth (RR = 1.00; 95 % CI 0.86-1.17; P = 0.985) and testicular atrophy (RR = 0.36; 95 % CI 0.09-1.54; P = 0.169). Besides, no significant difference was found in sperm concentration, motility, and normal morphology between two groups, as well as on postoperative pregnancy rate (RR = 0.95; 95 % CI 0.65-1.40; P = 0.809)., Conclusion: With the advantages of less recurrence, easier operating and less time spending, and comparable results in other respects, artery non-preserving is preferable to artery preserving in laparoscopic varicocelectomy, although there is a relatively high incidence of hydrocele formation. Considering the limitation of included studies, more large-scaled RCTs are required to confirm the present findings.

Although numerous functions of extracellular signal-regulated kinase 1/2 (ERK1/2) are identified, a direct effect of ERK1/2 on liver steatosis has not been reported. Here, we show that ERK1/2 activity is compromised in livers of leptin receptor-deficient (db/db) mice. Adenovirus-mediated activation of mitogen-activated protein kinase kinase 1 (MEK1), the upstream regulator of ERK1/2, significantly ameliorated liver steatosis in db/db mice, increased expression of genes related to fatty acid β-oxidation and triglyceride (TG) export and increased serum β-hydroxybutyrate (3-HB) levels. Opposite effects were observed in adenovirus-mediated ERK1/2 knockdown C57/B6J wild-type mice. Furthermore, autophagy and autophagy-related protein 7 (ATG7) expression were decreased or increased by ERK1/2 knockdown or activation, respectively, in primary hepatocytes and liver. Blockade of autophagy by the autophagy inhibitor chloroquine or adenovirus-mediated ATG7 knockdown reversed the ameliorated liver steatosis in recombinant adenoviruses construct expressing rat constitutively active MEK1 Ad-CA MEK1 db/db mice, decreased expression of genes related to fatty acid β-oxidation and TG export, and decreased serum 3-HB levels. Finally, ERK1/2 regulated ATG7 expression in a p38-dependent pathway. Taken together, these results identify a novel beneficial role for ERK1/2 in liver steatosis via promoting ATG7-dependent autophagy, which provides new insights into the mechanisms underlying liver steatosis and important hints for targeting ERK1/2 in treating liver steatosis., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Insulin resistance is one of the major factors contributing to metabolic diseases, but the underlying mechanisms are still poorly understood. As an important cofactor, B-cell translocation gene 1 (BTG1) is involved in many physiologic processes; however, the direct effect of BTG1 on insulin sensitivity has not been described. In our study, BTG1 overexpression or knockdown improved or impaired insulin signaling in vitro, respectively. In addition, adenovirus-mediated BTG1 overexpression improved insulin sensitivity in wild-type (WT) and insulin-resistant leptin-receptor mutated (db/db) mice. In addition, transgenic BTG1-overexpressing mice were resistant to high-carbohydrate diet-induced insulin resistance. Adenovirus-mediated BTG1 knockdown consistently impaired insulin sensitivity in WT and insulin-sensitive leucine-deprived mice. Moreover, hepatic BTG1 expression was increased by leucine deprivation via the mammalian target of rapamycin/ribosomal protein S6 kinase 1 pathway. Furthermore, c-Jun expression was up-regulated by BTG1, and adenovirus-mediated c-Jun knockdown blocked BTG1-improved insulin signaling and insulin sensitivity in vitro and in vivo. Finally, BTG1 promoted c-Jun expression via stimulating c-Jun and retinoic acid receptor activities. Taken together, these results identify a novel function for BTG1 in the regulation of hepatic insulin sensitivity and provide important insights into the nutritional regulation of BTG1 expression.- Xiao, F., Deng, J., Yu, J., Guo, Y., Chen, S., Guo, F. A novel function of B-cell translocation gene 1 (BTG1) in the regulation of hepatic insulin sensitivity in mice via c-Jun., (© FASEB.)

Objective: As the obesity pandemic continues to expand, novel molecular targets to reduce obesity-related insulin resistance and Type 2 Diabetes (T2D) continue to be needed. We have recently shown that obesity is associated with reactivated liver Notch signaling, which, in turn, increases hepatic insulin resistance, opening up therapeutic avenues for Notch inhibitors to be repurposed for T2D. Herein, we tested the systemic effects of γ-secretase inhibitors (GSIs), which prevent endogenous Notch activation, and confirmed these effects through creation and characterization of two different adipocyte-specific Notch loss-of-function mouse models through genetic ablation of the Notch transcriptional effector Rbp-Jk (A-Rbpj) and the obligate γ-secretase component Nicastrin (A-Nicastrin)., Methods: Glucose homeostasis and both local adipose and systemic insulin sensitivity were examined in GSI-treated, A-Rbpj and A-Nicastrin mice, as well as vehicle-treated or control littermates, with complementary in vitro studies in primary hepatocytes and 3T3-L1 adipocytes., Results: GSI-treatment increases hepatic insulin sensitivity in obese mice but leads to reciprocal lowering of adipose glucose disposal. While A-Rbpj mice show normal body weight, adipose development and mass and unchanged adipose insulin sensitivity as control littermates, A-Nicastrin mice are relatively insulin-resistant, mirroring the GSI effect on adipose insulin action., Conclusions: Notch signaling is dispensable for normal adipocyte function, but adipocyte-specific γ-secretase blockade reduces adipose insulin sensitivity, suggesting that specific Notch inhibitors would be preferable to GSIs for application in T2D.

Phosphoserine aminotransferase 1 (PSAT1) is an enzyme participating in serine synthesis. A role of PSAT1 in the regulation of insulin sensitivity, however, is unknown. In this study, we showed that hepatic PSAT1 expression and liver serine levels are reduced in genetically engineered leptin receptor-deficient (db/db) mice and high-fat diet (HFD)-induced diabetic mice. Additionally, overexpression of PSAT1 by adenovirus expressing PSAT1 improved insulin signaling and insulin sensitivity in vitro and in vivo under normal conditions. Opposite effects were observed when PSAT1 was knocked down by adenovirus expressing small hairpin RNA specific for PSAT1 (Ad-shPSAT1). Importantly, overexpression of PSAT1 also significantly ameliorated insulin resistance in diabetic mice. In addition, PSAT1 inhibited the expression of hepatic tribbles homolog 3 (TRB3) in vitro and in vivo, and adenoviruses expressing small hairpin RNA against TRB3-mediated inhibition of TRB3 reversed the attenuated insulin sensitivity in Ad-shPSAT1 mice. Interestingly, we found that serine mediates PSAT1 regulation of TRB3 expression and insulin signaling in vitro. These results identify a novel function for hepatic PSAT1 in regulating insulin sensitivity and provide important insights in targeting PSAT1 for treating insulin resistance and type 2 diabetes. Our results also suggest that nonessential amino acid serine may play an important role in regulating insulin sensitivity., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Aims/hypothesis: Recent studies have revealed the crucial role of the central nervous system (CNS), especially the hypothalamus, in the regulation of insulin sensitivity in peripheral tissues. The aim of our current study was to investigate the possible involvement of hypothalamic prolactin receptors (PRLRs) in the regulation of hepatic insulin sensitivity., Methods: We employed overexpression of PRLRs in mouse hypothalamus via intracerebroventricular injection of adenovirus expressing PRLR and inhibition of PRLRs via adenovirus expressing short-hairpin RNA (shRNA) specific for PRLRs in vivo. Selective hepatic vagotomy was employed to verify the important role of the vagus nerve in mediating signals from the brain to peripheral organs. In addition, a genetic insulin-resistant animal model, the db/db mouse, was used in our study to investigate the role of hypothalamic PRLRs in regulating whole-body insulin sensitivity., Results: Overexpression of PRLRs in the hypothalamus improved hepatic insulin sensitivity in mice and inhibition of hypothalamic PRLRs had the opposite effect. In addition, we demonstrated that hypothalamic PRLR-improved insulin sensitivity was significantly attenuated by inhibiting the activity of signal transducer and activator of transcription 5 (STAT5) in the CNS and by selective hepatic vagotomy. Finally, overexpression of PRLRs significantly ameliorated insulin resistance in db/db mice., Conclusions/interpretation: Our study identifies a novel central pathway involved in the regulation of hepatic insulin sensitivity, mediated by hypothalamic PRLR/STAT5 signalling and the vagus nerve, thus demonstrating an important role for hypothalamic PRLRs under conditions of insulin resistance.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid (ASA), improve glucose metabolism in diabetic subjects, although the underlying mechanisms remain unclear. In this study, we observed dysregulated expression of cyclooxygenase-2, prostacyclin biosynthesis, and the I prostanoid receptor (IP) in the liver's response to diabetic stresses. High doses of ASA reduced hepatic prostaglandin generation and suppressed hepatic gluconeogenesis in mice during fasting, and the hypoglycemic effect of ASA could be restored by IP agonist treatment. IP deficiency inhibited starvation-induced hepatic gluconeogenesis, thus inhibiting the progression of diabetes, whereas hepatic overexpression of IP increased gluconeogenesis. IP deletion depressed cAMP-dependent CREB phosphorylation and elevated AKT phosphorylation by suppressing PI3K-γ/PKC-ζ-mediated TRB3 expression, which subsequently downregulated the gluconeogenic genes for glucose-6-phosphatase (G6Pase) and phosphoenol pyruvate carboxykinase 1 in hepatocytes. We therefore conclude that suppression of IP modulation of hepatic gluconeogenesis through the PKA/CREB and PI3K-γ/PKC-ζ/TRB3/AKT pathways contributes to the effects of NSAIDs in diabetes., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

MicroRNAs (miRNAs) are endogenous, noncoding, short, single-stranded RNAs that are evolutionarily conserved and believed to play a role in controlling a variety of biological processes. The roles of miRNAs in insulin resistance and liver steatosis, however, are largely unknown. The objective of this study was to evaluate the roles of miR-130a in the regulation of insulin sensitivity and liver steatosis. In our current study, we observed that overexpression of miR-130a-3p increases insulin signaling in both HepG2 cells and primary mouse hepatocytes, and silencing of miR-130a-3p has the opposite effects. However, miR-130a-5p has no effect in the regulation of insulin signaling. Consistently, whole-body and hepatic insulin sensitivity are improved in mice injected with adenoviruses that overexpress miR-130a-3p. Furthermore, we provided evidence showing that growth factor receptor-bound protein 10 is required for miR-130a-3p-regulated insulin sensitivity. On the other hand, we observed that expression of miR-130a-3p is decreased in the livers of db/db mice and that adenovirus-mediated overexpression of miR-130a-3p reverses insulin resistance and liver steatosis, the latter of which is achieved via suppressing fatty acid synthase expression in these mice. This study identifies a novel function for hepatic miR-130a-3p in the regulation of insulin sensitivity and liver steatosis., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: To assess the effects of warm ischaemia time (WIT) on renalfunction after laparoscopic partial nephrectomy (LPN) for renal masses in patients., Methods: From January 2010 to December 2012, 39 patients treated with LPN for a single T1 renal tumor were enrolled in this prospective study. There were 24 male and 15 female patients. Their age was (58 ± 10) years old, and their body mass index was (27 ± 3) kg/m(2). The mean operation time was (132 ± 12) minutes, and the mean WIT was (29 ± 8) minutes. Clinical parameters, the single glomerular filtration rates (sGFR) were compared before the operation and after 3 and 12 months in order to observer the effects on renal function and find the factors predicting the renal function impairment., Results: There were significant differences between 3, 12 months after the operation ((26.8 ± 5.6) ml/min and (28.6 ± 5.6) ml/min, respectively) and preoperation ((31.9 ± 6.3) ml/min) in sGFR (F = 4.882 and 5.511, both P < 0.05). And there were significant negative correlations between the sGFR in 3 and 12 months after the operation and WIT (r = -0.569, P = 0.000 and r = -0.448, P = 0.004) . The preoperative sGFR (β = 0.260, 95%CI:0.089-0.431) and WIT (β = 0.369, 95%CI:0.189-0.555) were independent predictors for function decline of the operated kidney (both P < 0.05). The analysis showed that the effects of WIT within 30 minutes on renal function is relatively small. Longer WIT was associated with lower postoperative sGFR values (F = 22.128 and 20.552, both P = 0.000) ., Conclusions: For the LPN operation, the longer of the WIT, the more serious of renal function damage. sGFR is an accurate measurement to assess the renal damage. Every effort should be made to minimise WIT during LPN, and the limit of 30 minutes should be not exceeded.

microRNAs (miRNAs) are a class of small non-coding RNAs that can post-transcriptionally regulate gene expression and play critical roles in many important biological processes. The role of miRNAs in prostate cancer (PCa) development and pathogenesis remains largely unknown. In the present study, we showed that miR-200b was downregulated in clinical prostatic tumors when compared to normal prostate tissue and in advanced PCa cell lines when compared to normal epithelial prostatic cells. Enforced miR-200b expression suppressed PCa cell proliferation and migration and enhanced chemosensitivity to docetaxel by targeting B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1). Bmi-1 was detected at higher levels in PCa, and knockdown of Bmi-1 showed similar effects as miR-200b overexpression in PCa cells. Moreover, we confirmed that these effects were correlated with increased levels of E-cadherin and P16 and a reduction in vimentin expression and expression of stem cell markers (CD44 and OCT4). These findings suggest that miR-200b plays vital roles as a tumor-suppressor by targeting Bmi-1 and may be a promising therapeutic target for PCa treatment.

Insulin resistance is one of the major contributing factors in the development of metabolic diseases. The mechanisms responsible for insulin resistance, however, remain poorly understood. Although numerous functions of the prolactin receptor (PRLR) have been identified, a direct effect on insulin sensitivity has not been previously described. The aim of our current study is to investigate this possibility and elucidate underlying mechanisms. Here we show that insulin sensitivity is improved or impaired in mice injected with adenovirus that overexpress or knock down PRLR expression, respectively. Similar observations were obtained in in vitro studies. In addition, we discovered that the signal transducer and activator of transcription-5 pathway are required for regulating insulin sensitivity by PRLR. Moreover, we observed that PRLR expression is decreased or increased under insulin-resistant (db/db mice) or insulin-sensitive (leucine deprivation) conditions, respectively, and found that altering PRLR expression significantly reverses insulin sensitivity under both conditions. Finally, we found that PRLR expression levels are increased under leucine deprivation via a general control nonderepressible 2/mammalian target of rapamycin/ribosomal protein S6 kinase-1-dependent pathway. These results demonstrate a novel function for hepatic PRLR in the regulation of insulin sensitivity and provide important insights concerning the nutritional regulation of PRLR expression.

Objective: We have previously shown that serum insulin levels decrease threefold and blood glucose levels remain normal in mice fed a leucine-deficient diet, suggesting increased insulin sensitivity. The goal of the current study is to investigate this possibility and elucidate the underlying cellular mechanisms., Research Design and Methods: Changes in metabolic parameters and expression of genes and proteins involved in regulation of insulin sensitivity were analyzed in mice, human HepG2 cells, and mouse primary hepatocytes under leucine deprivation., Results: We show that leucine deprivation improves hepatic insulin sensitivity by sequentially activating general control nonderepressible (GCN)2 and decreasing mammalian target of rapamycin/S6K1 signaling. In addition, we show that activation of AMP-activated protein kinase also contributes to leucine deprivation-increased hepatic insulin sensitivity. Finally, we show that leucine deprivation improves insulin sensitivity under insulin-resistant conditions., Conclusions: This study describes mechanisms underlying increased hepatic insulin sensitivity under leucine deprivation. Furthermore, we demonstrate a novel function for GCN2 in the regulation of insulin sensitivity. These observations provide a rationale for short-term dietary restriction of leucine for the treatment of insulin resistance and associated metabolic diseases.

Objective: To compare the effectiveness of dressing by a combination of traditional Chinese medicine (TCM)-Western medicine (WM) after TCM bath and by the silver sulfadiazine cream (SD-Ag) in treating residual deep burn wound., Methods: A total of 128 cases of residual deep burn wound between July 2003 and December 2009 were randomly divided into the TCM-WM treatment group (70 cases) and the WM control group (58 cases). In the treatment group, there were 45 males and 25 females with an average age of 38.6 years (range, 18-60 years), including 34 cases of flame burns, 28 cases of molten steel burns, and 8 cases of chemical burns with an average burn area of 57.6% total body surface area (TBSA) and an average residual wound of 7.4% TBSA. In the control group, there were 50 males and 8 females with an average of 37.9 years (range, 20-59 years), including 26 cases of flame burns, 12 cases of hot water burns, 16 cases of molten steel burns, and 4 cases of chemical burns with an average burn area of 56.5% TBSA and an average residual wound of 6.9% TBSA. There was no significant difference in general data between 2 groups (P > 0.05), so the clinical data of 2 groups had comparability. In the treatment group, the patients had a bath with TCM, and then the wounds were treated with dressing change of combined TCM-WM. In the control group, the wounds were treated with SD-Ag after cleaning the wounds with chlorhexidine solution. The pain, wound healing time, and the rate of scar formation were observed in 2 groups after treatment., Results: According to wound pain classification after medication, the results were excellent in 23 cases, good in 30 cases, fair in 17 cases in the treatment group; were excellent in 17 cases, good in 20 cases, fair in 13 cases, poor in 5 cases, and fairly poor in 3 cases in the control group. The wound healing time of the treatment group (13.45 +/- 4.74) days was significantly shorter than that of the control group [(23.87 +/- 14.45) days, P < 0.05)]. After 2 weeks of treatment, scar occurred in 15 patients (21.4%) of the treatment group and 35 patients (60.3%) of the control group, showing significant difference (P < 0.05)., Conclusion: Based on TCM bath, a combination of TCM-WM for the residual burn wounds is obviously superior to SD-Ag. It has the advantages of rapid healing, light pain, no obvious scar, and short hospitalization time.