Deletion of the Feeding-Induced Hepatokine TSK Ameliorates the Melanocortin Obesity Syndrome.

Work in recent decades has established that metabolic hormones released by endocrine cells and diverse other cell types serve to regulate nutrient intake and energy homeostasis. Tsukushi (TSK) is a leucine-rich repeat-containing protein secreted primarily by the liver that exerts an inhibitory effect on brown fat sympathetic innervation and thermogenesis. Despite this, physiological regulation of TSK and the mechanisms underlying its effects on energy balance remain poorly understood. Here we show that hepatic expression and plasma concentrations of TSK are induced by feeding and regulated by melanocortin-4 receptor (MC4R) signaling. We generated TSK and MC4R-double-knockout mice to elucidate the nature of cross talk between TSK and the central regulatory circuit of energy balance. Remarkably, TSK inactivation restores energy balance, ameliorates hyperphagia, and improves metabolic health in MC4R-deficient mice. TSK ablation enhances thermogenic gene expression in brown fat, dampens obesity-association inflammation in the liver and adipose tissue, and protects MC4R-null mice from diet-induced nonalcoholic steatohepatitis. At the cellular level, TSK deficiency augments feeding-induced c-Fos expression in the paraventricular nucleus of the hypothalamus. These results illustrate physiological cross talk between TSK and the central regulatory circuit in maintaining energy balance and metabolic homeostasis.

Reduction of phonetic mismatch negativity may depict illness course and predict functional outcomes in schizophrenia.

Schizophrenia (SZ) is characterized by a series of cognitive impairments, including automatic processing impairment of basic auditory information, indexed by mismatch negativity (MMN). Existing studies mainly focus on MMN induced by deviant of single acoustic features, and relatively few studies have focused on complex acoustic stimuli, especially speech-induced MMN. Many cognitive impairments in SZ are related to speech function. Thus, the present study aimed to examine the reduction of phonetic MMN in SZ as a potential biomarker and its relationship with illness course and functional outcomes. Electroencephalogram (EEG) signals were recorded from 32 SZ and 32 healthy controls (HC) in a double oddball paradigm, with /da/ as the standard stimulus and /ba/ and /du/ as the deviant stimuli. MMN was computed for vowel and consonant deviants separately. Clinical symptoms were assessed using the Positive and Negative Symptom Rating Scale (PANSS). Illness duration and illness relapse were acquired by combining clinical interviews and electronic medical records. Functional outcomes were assessed using the Global Assessment of Functioning scale (GAF). Compared with HC, SZ showed lower amplitudes of phonetic MMN, especially for vowel deviants. In addition, the MMN amplitude of the vowel deviant was significantly correlated with illness duration, illness relapse, and functional outcomes among patients with SZ. These findings indicate that the pre-attentive automatic phonetic processing of SZ was impaired for both consonants and vowels, while the vowel processing deficit may be the key speech processing deficit in SZ, which could depict the illness course and predict the functional outcomes.

Shifting Perceptual Weights in L2 Vowel Identification after Training.

Difficulties with second-language vowel perception may be related to the significant challenges in using acoustic-phonetic cues. This study investigated the effects of perception training with duration-equalized vowels on native Chinese listeners' English vowel perception and their use of acoustic-phonetic cues. Seventeen native Chinese listeners were perceptually trained with duration-equalized English vowels, and another 17 native Chinese listeners watched English videos as a control group. Both groups were tested with English vowel identification and vowel formant discrimination before training, immediately after training, and three months later. The results showed that the training effect was greater for the vowel training group than for the control group, while both groups improved their English vowel identification and vowel formant discrimination after training. Moreover, duration-equalized vowel perception training significantly reduced listeners' reliance on duration cues and improved their use of spectral cues in identifying English vowels, but video-watching did not help. The results suggest that duration-equalized English vowel perception training may improve non-native listeners' English vowel perception by changing their perceptual weights of acoustic-phonetic cues.

English vowel identification and vowel formant discrimination by native Mandarin Chinese- and native English-speaking listeners: The effect of vowel duration dependence.

The purpose of this study was to examine the relationship between English vowel identification and English vowel formant discrimination for native Mandarin Chinese- and native English-speaking listeners. The identification of 12 English vowels was measured with the duration cue preserved or removed. The thresholds of vowel formant discrimination on the F2 of two English vowels,/Λ/and/i/, were also estimated using an adaptive-tracking procedure. Native Mandarin Chinese-speaking listeners showed significantly higher thresholds of vowel formant discrimination and lower identification scores than native English-speaking listeners. The duration effect on English vowel identification was similar between native Mandarin Chinese- and native English-speaking listeners. Moreover, regardless of listeners' language background, vowel identification was significantly correlated with vowel formant discrimination for the listeners who were less dependent on duration cues, whereas the correlation between vowel identification and vowel formant discrimination was not significant for the listeners who were highly dependent on duration cues. This study revealed individual variability in using multiple acoustic cues to identify English vowels for both native and non-native listeners.

Impact of laparoscopic surgery on efficacy in the treatment of gastrointestinal stromal tumors in different anatomical locations / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the efficacy of laparoscopic surgery in the treatment of gastrointestinal stromal tumors (GIST) in different anatomical locations.</p><p><b>METHODS</b>Clinical data of 133 patients with primary gastric GIST undergoing laparoscopic resection at our department from January 2006 to December 2014 were retrospectively analyzed. These patients were divided into favorable site group (F group, 90 cases), including gastric fundus, anterior wall and greater curvature of gastric body, and unfavorable site group (UF group, 43 cases),including gastroesophageal junction, posterior wall and lesser curvature of gastric body,antrum and pylorus, according to the 2014 version National Comprehensive Cancer Network Clinical Guidelines. Short-term and long-term efficacy between the two groups was compared.</p><p><b>RESULTS</b>There were no significant differences between the two groups in the general clinicopathological parameters (all P>0.05). The operation time of F group and UF group was (107.3±52.3) min and (119±53.4) min respectively (P=0.21). The blood loss in F group and UF group was (35.2±34.2) ml and (35.2±31.2) ml respectively (P=1.00). In addition, there were no significant differences in time to first fluid diet, time to first flatus, postoperative hospital stay and hospitalization expenses between the two groups(all P>0.05). In F group and UF group, morbidity of postoperative complication was 6.7%(6/90) and 4.7%(2/43) respectively (P=0.72), morbidity of category I(-II( complication was 4.4%(4/90) and 2.3%(1/43) respectively (P=0.66),and morbidity of category III(-IIII( complication was 2.2%(2/90) and 2.3% (1/43) respectively (P=1.00). Median follow-up time of all the cases was 36(1 to 84) months. The 5-year overall survival rates of F group and UF group were 93.8% and 95.2% respectively, and 5-year relapse-free survival rates were 81.1% and 89.4% respectively, without significant differences(both P>0.05).</p><p><b>CONCLUSION</b>Laparoscopic operation for gastric GIST in unfavorable sites can yield similar short- and long-term outcomes compared with those in favorable sites.</p>

Interaction of 14-3-3σ with KCMF1 suppresses the proliferation and colony formation of human colon cancer stem cells.

AIM: To investigate the biological function of 14-3-3σ protein and to look for proteins that interact with 14-3-3σ protein in colon cancer stem cells. METHODS: Reverse transcription polymerase chain reaction was performed to amplify the 14-3-3σ gene from the mRNA of colon cancer stem cells. The gene was then cloned into the pGEM-T vector. After being sequenced, the target gene 14-3-3σ was cut from the pGEM-T vector and cloned into the pGBKT7 yeast expression plasmid. Then, the bait plasmid pGBKT7-14-3-3σ was transformed into the yeast strain AH109. After the expression of the pGBKT7-14-3-3σ fusion protein in the AH109 yeast strain was accomplished, a yeast two-hybrid screening assay was performed by mating AH109 with Y187 that contained a HeLa cDNA library plasmid. The interaction between the 14-3-3σ protein and the proteins obtained from positive colonies was further confirmed by repeating the yeast two-hybrid screen. After extracting and sequencing the plasmids from the positive colonies, we performed a bioinformatics analysis. A coimmunoprecipitation assay was performed to confirm the interaction between 14-3-3σ and the proteins obtained from the positive colonies. Finally, we constructed 14-3-3σ and potassium channel modulatory factor 1 (KCMF1) siRNA expression plasmids and transfected them into colon cancer stem cells. RESULTS: The bait plasmid pGBKT7-14-3-3σ was constructed successfully, and the 14-3-3σ protein had no toxic or autonomous activation effect on the yeast. Nineteen true-positive colonies were selected and sequenced, and their full-length sequences were obtained. We searched for homologous DNA sequences for these sequences from GenBank. Among the positive colonies, four coding genes with known functions were obtained, including KCMF1, quinone oxidoreductase (NQO2), hydroxyisobutyrate dehydrogenase (HIBADH) and 14-3-3σ. For the subsequent coimmunoprecipitation assay, the plasmids PCDEF-Flag-14-3-3σ, PCDEF-Myc-KCMF1, PCDEF-Myc-NQO2 and PCDEF-Myc-HIBADH were successfully constructed, and the sequences were further confirmed by DNA sequencing. The Fugene 6 reagent was used to transfect the plasmids, and fluorescence-activated cell sorting analysis showed the transfection efficiency was 97.8% after 48 h. The HEK 293FT cells showed the stable expression of the PCDEF-Flag-14-3-3σ, PCDEF-Myc-KCMF1, PCDEF-Myc-NQO2 and PCDEF-Myc-HIBADH plasmids. After anti-Myc antibody immunoprecipitation with Myc-KCMF1, Myc-NQO2 and Myc-HIBADH from cell lysates, the presence of Flag-14-3-3σ protein in the immunoprecipitated complex was determined by western blot analysis. The knock-down expression of the 14-3-3σ and KCMF1 proteins significantly inhibited cell proliferation and colony formation of SW1116csc. CONCLUSION: Genes of the proteins that interacted with 14-3-3σ were successfully screened from a HeLa cDNA library. KCMF1 and 14-3-3σ protein may affect the proliferation and colony formation of human colon cancer stem cells.

English vowel identification in long-term speech-shaped noise and multi-talker babble for English and Chinese listeners.

The identification of 12 English vowels was measured in quiet and in long-term speech-shaped noise (LTSSN) and multi-talker babble for English-native (EN) listeners and Chinese-native listeners in the U.S. (CNU) and China (CNC). The signal-to-noise ratio was manipulated from -15 to 0 dB. As expected, EN listeners performed significantly better in quiet and noisy conditions than CNU and CNC listeners. Vowel identification in LTSSN was similar between CNU and CNC listeners; however, performance in babble was significantly better for CNU listeners than for CNC listeners, indicating that exposing non-native listeners to native English may reduce informational masking of multi-talker babble.