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Unlike infectious peritonitis, non-infectious eosinophilic peritonitis (EP) in uremic patients on continuous ambulatory peritoneal dialysis (CAPD) still goes unrecognized, leading to inappropriate management. We report a 56-year-old male with uremia on CAPD exhibiting peritonitis with abdominal pain, fever, and turbid dialysate containing increasing WBCs with neutrophils predominant and growing Enterococcus faecalis. Intraperitoneal vancomycin 100 mg administration in each peritoneal dialysis (PD) bag exchange improved clinical and laboratory features initially. However, recurrent turbid dialysate with prominent eosinophils (25%) but negative culture appeared on the 5th day. Despite continuous intraperitoneal vancomycin, persistent turbid dialysate with prominent eosinophils (77%) was notable with peripheral eosinophilia (28%). With the cessation of intraperitoneal vancomycin and the use of oral steroid therapy, EP and eosinophilia completely resolved. Antibiotics (vancomycin)-induced eosinophilic peritonitis should be kept in mind as a cause of recurrent turbid dialysate with higher percentage of eosinophils and negative cultures to avoid unnecessary examination and complication.

The aims of this study were to investigate the efficacy of heart rate variability biofeedback (HRVBFB) intervention in terms of reducing craving, severity of dependence, and rate of positive methamphetamine urine testing in men taking part in a methamphetamine use disorder outpatient treatment program. Sixty-one adult men received either HRVBFB treatment plus treatment as usual (TAU) over four weeks or TAU only. Men receiving HRVBFB showed significantly greater reductions in craving, dependence severity, and the rate of positive methamphetamine urine testing at the end of the intervention and four weeks of follow-up. The analyses further showed that the levels of craving and dependence severity at treatment entry were predictive of changes in craving and dependence severity at the end of treatment and follow-up, respectively. The baseline status of a positive methamphetamine urine test only predicted a positive methamphetamine urine test at the end of treatment, not at the end of the follow-up period. Our results showed HRVBFB intervention has merits as an adjunct treatment to ameliorate cravings and reduce the severity of dependence experienced by persons with methamphetamine use disorder. An added value of HRVBFB intervention is the fact that it can be easily and affordably implemented in everyday life.

Sleep problems are common in Taiwan. Poor sleep may be associated with many illnesses, including substance use disorders. Ketamine use disorder has significantly increased in Taiwan in recent years and may lead to physical and cognitive problems. Craving for ketamine is a risk factor for ketamine use and relapse, and poor sleep quality may increase craving. This study aimed to explore the mediating effects of craving on the relationship between poor sleep quality and ketamine use. Demographic data, sleep quality, severity of dependence and craving were recorded for current ketamine users and abstinent ketamine users. Mediation analysis was used to examine the mediating effect of craving on the relationship between poor sleep and ketamine use. This study enrolled 414 current ketamine users with ketamine use disorder, 238 current ketamine users without ketamine use disorder, and 102 abstinent ketamine users with ketamine use disorder. Compared with healthy controls, all ketamine users had poor sleep quality. Poor sleep quality was associated with the initiation of and dependence on ketamine use. Craving can mediate the relationship between poor sleep quality and ketamine use. Poor sleep quality remains a problem for those abstaining from ketamine use. Poor sleep quality in ketamine users is an important issue because it is directly and indirectly through craving associated with ketamine use.

Context Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine that improves insulin sensitivity in animals. However, serum ANGPTL6 concentration was found to be higher in human participants with diabetes or metabolic syndrome in cross-sectional studies, implying that ANGPTL6 may be induced to counteract hyperglycemia. Objective To investigate whether serum ANGPTL6 can predict incident diabetes and explore whether glucose or insulin can regulate ANGPTL6 expression and secretion. Design This cohort study included adults without diabetes at baseline who were followed every 2 years for incident diabetes. Serum ANGPTL6 concentrations were measured at baseline and during oral glucose tolerance tests (OGTTs). A hepatic cell line, HepG2, and diet-induced obesity mouse model were used to evaluate the response of ANGPTL6 expression and secretion to hyperglycemia and the metabolic syndrome. Results We recruited 1103 participants without diabetes at baseline. During the 4.22-year follow-up, 113 (10.2%) participants developed incident diabetes. Serum ANGPTL6 was negatively associated with the incidence of diabetes (adjusted hazard ratio, 0.77; P = 0.042). However, serum ANGPTL6 level was higher in participants with prediabetes (P = 0.018) and was elevated during OGTT. In HepG2 cells, treatment with glucose, but not insulin, induced ANGPTL6 expression. Hepatic ANGPTL6 expression and serum ANGPTL6 concentrations were significantly higher in mice fed with a high-fat diet than in those fed with a standard chow (both P < 0.05). Conclusion A high serum ANGPTL6 level is associated with a low incidence of diabetes in humans. ANGPTL6 is expressed and secreted in response to hyperglycemia to maintain glucose homeostasis.

Ketamine use has become of increasing concern because it has spread in many parts of the world during the past few years. Substance users usually have depression and a lower quality of life (QoL). The aim of this study was to explore depression and QoL in ketamine users, and to further examine the role of gender in relation to differences in depression and QoL in ketamine users. This study recruited 204 current ketamine users, 102 abstinent ketamine users and 102 healthy controls. The demographic data, severity of depression and QoL were recorded. Analysis of Variance (ANOVA) was employed to compare the associations of ketamine use status with depression and QoL. Gender differences were examined by moderator analysis. The current ketamine users with and without ketamine use disorder, in addition to the abstinent ketamine users with ketamine use disorder, have more severe depression and a lower QoL than healthy controls. There were significant gender differences in depression and QoL in abstinent ketamine users with ketamine use disorder. Ketamine users have more severe depression and a lower QoL. In particular, depression and a lower QoL are still prominent in abstinent ketamine users. The gender differences in depression and QoL are significant in abstinent ketamine users.

We present reference-quality genome assembly and annotation for the stout camphor tree (Cinnamomum kanehirae (Laurales, Lauraceae)), the first sequenced member of the Magnoliidae comprising four orders (Laurales, Magnoliales, Canellales and Piperales) and over 9,000 species. Phylogenomic analysis of 13 representative seed plant genomes indicates that magnoliid and eudicot lineages share more recent common ancestry than monocots. Two whole-genome duplication events were inferred within the magnoliid lineage: one before divergence of Laurales and Magnoliales and the other within the Lauraceae. Small-scale segmental duplications and tandem duplications also contributed to innovation in the evolutionary history of Cinnamomum. For example, expansion of the terpenoid synthase gene subfamilies within the Laurales spawned the diversity of Cinnamomum monoterpenes and sesquiterpenes.

Craving is a core feature of heroin use disorder. Craving for heroin is a conscious cognitive process. Recently, implicit (i.e., an implicit attitude toward heroin use) cognitive processes have been thought to be precursors of cravings. This study aimed to explore the associations of craving and implicit attitude toward heroin use with the level of heroin use disorder and adherence to methadone maintenance treatment (MMT). This study recruited 213 intravenous heroin users (196 males and 17 females) from MMT clinics of two hospitals. The mean age of participants was 42.3 years. They provided details of their severity of heroin use disorder and craving for heroin via questionnaires and also completed a computerized test to assess implicit attitude toward heroin use. The relationships between implicit attitude, craving, age, heroin use disorder, and MMT adherence were examined using path analysis. Craving was positively related to heroin use disorder (beta = 0.4). Implicit attitude directly and indirectly positively contributed to heroin use disorder (betas: 0.1 and 0.3). Craving was positively related to MMT adherence (beta: 0.2), whereas implicit attitude had an indirect effect on MMT adherence (beta: 0.03). Age was negatively associated with craving but was not associated with implicit attitude toward heroin. Methadone dosage was negatively associated with craving. Craving is significantly associated with the levels of heroin use disorder and MMT adherence. Meanwhile, craving mediates the relationship between implicit attitude and heroin use disorder, as well as MMT adherence. Implicit attitude also contributes to the level of heroin use disorder directly. For reducing craving, adequate dosage may be necessary.

Supplementary Tables for the manuscript "Serum Angiopoietin-like Protein 6, Risk of Type 2 Diabetes, and Response to Hyperglycemia: A Prospective Cohort Study".

BACKGROUND Methadone maintenance treatment (MMT) has been shown to be an effective therapeutic strategy for opioid users. This study aimed to investigate the predictive effect of clinically predominant sleep disturbance (CPSD) on the dose of methadone among opiate users receiving MMT during a follow-up period of 6 years in Taiwan. METHODS This retrospective study included 1,290 individuals with opioid dependence who visited our MMT clinic for the first time. Generalized estimating equations were used to analyze the effect of CPSD on the daily dose of methadone by controlling for the effects of demographic and MMT characteristics. RESULTS A total of 469 (36.4%) participants were comorbid with CPSD. After controlling for the effects of demographic and MMT characteristics, the participants comorbid with CPSD had a higher dose of daily methadone than those without CPSD (estimate: 7.03, p

Switching from methadone to buprenorphine/naloxone remains a challenge for heroin users receiving methadone maintenance treatment (MMT). The present study aimed to investigate the predictors for failed switching from methadone to buprenorphine/naloxone among patients receiving MMT.This 5-year retrospective study included 168 individuals (138 males and 30 females) with opioid dependence who attempted to switch from methadone to buprenorphine/naloxone at our MMT clinics in Taiwan. We excluded patients with psychiatric comorbidity and other substance use disorders except nicotine. A univariate Cox proportional hazards regression model (Cox model) was used to estimate the potential factors of subsequent failed switching, followed by a multivariate Cox model to identify significant predictors after adjusting for other covariates.Seventy of the 168 participants (41.7%) failed switching from methadone to buprenorphine/naloxone. After forward selection in the Cox hazard regression model, a greater average dose of methadone (HR = 1.02; P = 0.01), greater maximal maintenance dose of MMT (HR = 1.02; P 0.001), greater average dose of buprenorphine (HR = 1.10; P = 0.021), and lower average attendance rate during the three months before switching (HR = 0.09; P = 0.002) were significantly associated with failed switching.This study with limited participants showed that dose of methadone, dose of buprenorphine, and attendance rates were significantly associated with failed switching. Clinicians should discuss with their patients about tapering the dose of methadone and improving their attendance if they want to switch from methadone to buprenorphine. Further studies are necessary to verify whether our findings generalize to other populations.

Many genes in the plastid genomes (plastomes) of plants are organized as gene clusters, in which genes are co-transcribed, resembling bacterial operons. These plastid operons are highly conserved, even among conifers, whose plastomes are highly rearranged relative to other seed plants. We have determined the complete plastome sequence of Sciadopitys verticillata (Japanese umbrella pine), the sole member of Sciadopityaceae. The Sciadopitys plastome is characterized by extensive inversions, pseudogenization of four tRNA genes after tandem duplications, and a unique pair of 370-bp inverted repeats involved in the formation of isomeric plastomes. We showed that plastomic inversions in Sciadopitys have led to shuffling of the remote conserved operons, resulting in the birth of four chimeric gene clusters. Our data also demonstrated that the relocated genes can be co-transcribed in these chimeric gene clusters. The plastome of Sciadopitys advances our current understanding of how the conifer plastomes have evolved toward increased diversity and complexity.

We present reference-quality genome assembly and annotation for the stout camphor tree (SCT;Cinnamomum kanehirae[Laurales, Lauraceae]), the first sequenced member of the Magnoliidae comprising four orders (Laurales, Magnoliales, Canellales, and Piperales) and over 9,000 species. Phylogenomic analysis of 13 representative seed plant genomes indicates that magnoliid and eudicot lineages share more recent common ancestry relative to monocots. Two whole genome duplication events were inferred within the magnoliid lineage, one before divergence of Laurales and Magnoliales and the other within the Lauraceae. Small scale segmental duplications and tandem duplications also contributed to innovation in the evolutionary history ofCinnamomum. For example, expansion of terpenoid synthase subfamilies within the Laurales spawned the diversity ofCinnamomummonoterpenes and sesquiterpenes.

We present reference-quality genome assembly and annotation for the stout camphor tree (Cinnamomum kanehirae (Laurales, Lauraceae)), the first sequenced member of the Magnoliidae comprising four orders (Laurales, Magnoliales, Canellales and Piperales) and over 9,000 species. Phylogenomic analysis of 13 representative seed plant genomes indicates that magnoliid and eudicot lineages share more recent common ancestry than monocots. Two whole-genome duplication events were inferred within the magnoliid lineage: one before divergence of Laurales and Magnoliales and the other within the Lauraceae. Small-scale segmental duplications and tandem duplications also contributed to innovation in the evolutionary history of Cinnamomum. For example, expansion of the terpenoid synthase gene subfamilies within the Laurales spawned the diversity of Cinnamomum monoterpenes and sesquiterpenes.

Methadone maintenance treatment (MMT) has been shown to be an effective therapeutic strategy for opioid users. This study aimed to investigate the predictive effect of clinically predominant sleep disturbance (CPSD) on the dose of methadone among opiate users receiving MMT during a follow-up period of 6 years in Taiwan.This retrospective study included 1,290 individuals with opioid dependence who visited our MMT clinic for the first time. Generalized estimating equations were used to analyze the effect of CPSD on the daily dose of methadone by controlling for the effects of demographic and MMT characteristics.A total of 469 (36.4%) participants were comorbid with CPSD. After controlling for the effects of demographic and MMT characteristics, the participants comorbid with CPSD had a higher dose of daily methadone than those without CPSD (estimate: 7.03, p .001). Furthermore, younger age (estimate: -1.22, p .001), older age at initial MMT (estimate: .44, p .001), lower educational level (estimate: -.90, p = .003) and lower attendance rates (estimate: -.14, p = .033) are significantly related to higher doses of daily methadone.Our study provided a naturalistic observation of the cohort for long period, along with a large sample size which could reflect clinical practice in the real world. We reported that a higher daily dose of methadone was significantly associated with CPSD after controlling for the effects of other factors. CPSD should be routinely surveyed among heroin users receiving MMT. (Am J Addict 2018;27:225-230).

Techniques of a dual-path error amplifier and two capacitor multipliers for providing on-chip frequency compensation and soft-start function are proposed in this paper. The concept of the dual-path error amplifier is to use two currents to charge and discharge a compensation capacitor simultaneously. As a result, the equivalent capacitance is enlarged significantly with little additional power and silicon area. The dc-dc converter with the dual-path architecture also has great performance in transient response because the compensation capacitor is reduced significantly. For the soft-start function, the subtractive-type and time-average capacitor multipliers are used to relax the restriction of the capacitance and the charging current. Consequently, it is easy to integrate the soft-start capacitance into a chip and the output overshoot voltage can be suppressed. A prototype converter fabricated with TSMC 0.35-μm 2P4M CMOS process verifies the effectiveness of the techniques of a dual-path error amplifier and two capacitor multipliers. Experimental results demonstrate the converter stability, transient response, and soft-start function. The transient recovery time and transient ripple are less than 20 μs and 25 mV, respectively, for the load current swing from 50 to 500 mA. Moreover, the soft-start time is up to 8 ms. With the proposed techniques, the external pins of the dc-dc converters are minimized and their performance is improved significantly.

Background Craving is an important issue in substance use disorder. To achieve a better understanding of the cognitive processing systems of craving, the cognitive processes of craving have been considered as two distinct processes. One system, based on rule-based inferences and named explicit cognition, is more conscious and effortful. The other system, based on prior learned association and named implicit cognition, is unconscious and effortless. How explicit and implicit cognitions are associated with heroin use in patients with methadone maintenance treatment (MMT) is not clear. This study aimed to explore the relationship between explicit and implicit cognition and heroin use in patients undergoing MMT. Method This study recruited one-hundred forty intravenous heroin users. The participants were invited to provide social–demographic data, the severity of substance dependence and explicit cognition with regard to heroin. Then, participants completed a computerized test to assess implicit cognition with regards to heroin. Results This study found that explicit and implicit heroin-related cognitions were associated with the frequency of heroin use. There was an interaction effect between implicit and explicit cognition on the frequency of heroin use. This study also found that higher explicit heroin-related cognition was a risk factor for continuing heroin use. Conclusion Both explicit and implicit cognitions were associated with the frequency of heroin use in patients undergoing MMT, but only explicit cognition was associated with whether patients could stop using heroin during MMT. Therefore, the status of heroin use in patients undergoing MMT may be related to different cognitive processes.

Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. Objective: We investigated a 57-year-old woman with progressive low back pain. Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia.

Plastid-to-nucleus DNA transfer provides a rich genetic resource to the complexity of plant nuclear genome architecture. To date, the evolutionary route of nuclear plastid DNA (nupt) remain unknown in conifers. We have sequenced the complete plastomes of two yews, Amentotaxus formosana and Taxus mairei (Taxaceae of coniferales). Our comparative genomic analyses recovered an evolutionary scenario for plastomic reorganization from ancestral to extant plastomes in the three sampled Taxaceae genera, Amentotaxus, Cephalotaxus, and Taxus. Specific primers were designed to amplify nonsyntenic regions between ancestral and extant plastomes, and 12.6 kb of nupts were identified based on phylogenetic analyses. These nupts have significantly accumulated GC-to-AT mutations, reflecting a nuclear mutational environment shaped by spontaneous deamination of 5-methylcytosin. The ancestral initial codon of rps8 is retained in the T. nupts, but its corresponding extant codon is mutated and requires C-to-U RNA-editing. These findings suggest that nupts can help recover scenarios of the nucleotide mutation process. We show that the Taxaceae nupts we retrieved may have been retained because the Cretaceous and they carry information of both ancestral genomic organization and nucleotide composition, which offer clues for understanding the plastome evolution in conifers.

A number of 2-aroyl-3-arylquinoline derivatives was synthesized and evaluated for their anti-Dengue virus activity. Both 2-(hydroxyphenylmethyl)-3-(4-methoxyphenyl)quinoline (13a) and 2-(4-hydroxybenzoyl)-3-(4-hydroxyphenyl)quinoline (17) were found to significantly inhibit the DENV2 RNA expression in Huh-7-DV-Fluc cells with a potency approximately equal to that of ribavirin and the inhibition is in a dose-dependent manner. Compounds 13a and 17 reduced DENV replication in both viral protein and mRNA levels, and no significant cell cytotoxicity was detected, with greater than 50% viability of Huh-7-DV-Fluc cells at a concentration of 100 μM. However, significant cytotoxicity was detected for the positive ribavirin. In addition, we performed infectious assay to further verify the inhibitory activity of 13a and 17 on DENV replication in protein and RNA levels. On the other hand, compounds 19a-19c exhibited IC50 values ranged from 4.47 to 8.68 μM against A549, H1299, MCF-7, and Huh-7 which were approximately equal potent to the positive topotecan. Structural optimization of lead compounds, 13a and 17, and their detailed molecular mechanism of action are ongoing.

Patients with schizophrenia suffer from symptoms such as hallucination and delusion. There are currently a number of publications that discuss the treatment, diagnosis, prognosis, and damage in schizophrenia. This study utilized joint independent component analysis to process the images of GMV and WMV and incorporated the Wisconsin card sorting test (WCST) and the positive and negative syndrome scale (PANSS) to examine the correlation of obtained brain characteristics. We also used PANSS score to classify schizophrenic patients into acute and subacute cases, to analyze the brain structure differences. Finally, we used brain structure images and the error rate of the WCST as eigenvalues in support vector machine learning and classification. The results of this study showed that the frontal and temporal lobes of a normal brain are more apparent than those of a schizophrenia brain. The highest level of classification recognition reached 91.575%, indicating that the WCST error rate and characteristic changes in brain structure volume can be used to effectively distinguish schizophrenia and normal brains. Similarly, this result confirmed that the WCST and brain structure volume are correlated with the differences between schizophrenia and normal participants.

We report a novel means for chiral separation and stacking of amino acids by MEKC with LED-induced fluorescence detection. Naphthalene-2,3-dicarboxaldehyde, hydroxypropyl-beta-cyclodextrin (Hp-beta-CD), SDS, and poly(ethylene oxide) (PEO) serve as a derivatized agent, chiral selector, pseudostationary phase, and concentrated medium, in sequence. To improve speed, resolution, and stacking efficiency, the analysis of chiral amino acids was performed under discontinuous conditions--the capillary was filled with a solution of 100 mM Tris-borate, 150 mM SDS, and 50 mM Hp-beta-CD, whereas buffer vials contain 20 mM Tris-borate, 150 mM SDS, 50 mM Hp-beta-CD, and 0.5% w/v PEO. A solution of nonionic PEO enters the capillary with the help of EOF during the separation. Through interaction of SDS micelles/Hp-beta-CD and chiral amino acid, the negatively charged complexes migrated into the PEO solution and stacked at the boundary between the sample zone and the PEO solution. Compared with normal sample injection (10 nL sample volume), a several hundred-fold sensitivity improvement for chiral amino acids was obtained under the injection of 270 nL sample volume (30% of the capillary volume). Meanwhile, the LOD at S/N of three for DL-amino acids were in the range of 0.18-0.22 nM. The proposed method has been applied for the determination of DL-leucine in urine and plasma samples.

Objective: Prior early prediction models for antipsychotic treatment response demonstrate good specificity but poor sensitivity (i.e., high false-negative rates). The purpose of this study was to refine the early prediction model in schizophrenia patients taking an atypical antipsychotic agent, zotepine. Method: 135 acutely ill inpatients with DSM-IV-defined schizophrenia received 4 weeks of 150 mg/day zotepine treatment. Psychopathology severity was assessed weekly with the Brief Psychiatric Rating Scale (BPRS) and subscales for positive, negative, and general symptoms. Clinical response was defined as a reduction of 20% or more in the BPRS total score at week 4. A logistic regression model was used to obtain early predictors. The receiver operating characteristic curve was employed to determine the optimal cutoff points of the variables for predicting response. The study was conducted from June 2004 to April 2005. Results: The most significant early predictors for ultimate response at week 4 were BPRS positive subscale score changes at week 1 and, better, at week 2 (p

Background: The aim of this study was to compare the changes in primary (heroin use-related) and secondary (depressive symptoms and quality of life, QOL) outcome indicators of 3-month methadone maintenance treatment (MMT) between heroin users with and without HIV infection. Methods: A total of 242 intravenous heroin-dependent individuals (30 with and 212 without HIV infection) receiving MMT were recruited. Primary (severity of heroin dependence, harm caused by heroin use and current heroin use) and secondary (depressive symptoms and QOL) outcome indicators were determined before and after receiving 3-month MMT. Changes in primary and secondary outcome indicators between the two groups were compared using mixed-model analysis. Results: Heroin users both with and without HIV infection showed significant improvement in three primary outcome indicators after 3-month MMT, and there was no difference in the changes of these primary outcome indicators between the two groups. However, improvements in depressive symptoms and the physical domain of QOL among HIV-infected heroin users were poorer than in those without HIV infection. Conclusions: The results of this study indicated that heroin users with HIV infection did improve in the primary but not the secondary outcomes after 3-month MMT.

A number of 3-phenylquinolinylchalcone derivatives were synthesized and evaluated in vitro for their antiproliferative activities against three breast cancer cell lines (MCF-7, MDA-MB-231, and SKBR-3), and a non-cancer normal epithelial cell line (H184B5F5/M10). Among them, (E)-3-[3-(4-methoxyphenyl)quinolin-2-yl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (7) was active against the growth of MCF-7, MDA-MB-231, and SKBR-3 with IC50 values of 1.05, 0.75, and 0.78 μM respectively without significant cytotoxicity to the normal H184B5F5/M10 cell line and therefore, was selected as a new lead for further mechanism studies. Results indicated that compound 7 inhibited the polymerization of tubulins, induced G2/M cell cycle arrest via modulation of the cyclin B1, cdk1 and CDC25. Compound 7 ultimately induced cell apoptosis by the increase of apoptotic protein Bax and the decrease of anti-apoptotic protein Bcl-2. In addition, PARP was cleaved while caspase-3 and -8 activities were induced after the treatment of compound 7 for 24 h in a concentration-dependent manner. Thus, compound 7 induces cell cycle arrest at G2/M phase via cleavage of PARP, induces caspase-3 and -8 activities and consequently to cause the cell death. Further study on the structure optimization of 7 is ongoing.

Background Craving for substance use has been added as one of the diagnostic criteria of substance use disorders in DSM-5 . However, further research is necessary to examine and expand the clinical potential of craving in the assessment and treatment for heroin users. This study aimed to examine the psychometrics of the Desire for Drug Questionnaire–Chinese Mandarin version (DDQ-CM) and its clinical utility of assessing craving for heroin measured among heroin users with methadone maintenance treatment (MMT). Method Self-reported craving for heroin use was measured on the DDQ-CM and visual analog scale among 314 intravenous heroin users receiving MMT. Self-reported heroin dependence, attitude toward heroin use, readiness to change heroin use, and depression were collected. Results The results found that although the original three-factor model was acceptable for applying the DDQ-CM for heroin users with MMT, only the concurrent validity of the subscales of Desire and Intention and Negative Reinforcement was supported but not that of Control. Meanwhile, the levels of craving on the subscales of Desire and Intention and of Negative Reinforcement on the DDQ-CM were positively associated with the levels of heroin dependence, positive and negative attitudes toward heroin use, and depression, but negatively associated with readiness to change heroin use. Conclusions This study supported the application of the subscales of Desire and Intention and Negative Reinforcement on the DDQ-CM to measure heroin craving in Taiwanese-Chinese heroin users and supported the clinical implication of craving in heroin users with MMT.

This study reports the complete plastome sequence of Gnetum ula, a gymnosperm species of Gnetaceae (Gnetophyta). The plastome is 113 249 bp long. It has a quadripartite structure containing a pair of large inverted repeat regions of 19 772 bp each, a large single-copy region of 64 914 bp, and a small single-copy region of 8791 bp. One hundred sixteen genes were predicted in the plastome, including 68 protein-coding genes, eight ribosomal RNA genes, and 40 transfer RNA genes. The gene density is 1.024 (genes/kb). Similar to other known Gnetum plastomes, the G.ula plastome has lost 20 protein-coding genes commonly present in other seed plant plastomes. Our phylogenetic analyses indicate that the four sampled Gnetum species are monophyletic and that G. ula is close to the two other lianas rather than the only small tree species, G. gnemon. Our phylogenetic trees also indicate that gnetophytes have the fastest evolutionary rates among gymnosperms.

The utility of lymph node ratio (LNR) in predicting outcomes has been reported previously. In current study, we further subgroup by LNR in subjects with lymph nodes metastasis of colorectal cancer, breast cancer, and head and neck cancer. Cancers with pathological lymph node metastasis (pN+) at time of diagnosis between 2004 and 2012 were identified from the cancer registry database of the Dalin Tzu Chi General Hospital. The Kaplan–Meier method with log-rank test and the Cox proportional hazards model were used to compare the disease-specific survival (DSS) rates for different LNR after adjusting for possible confounding risk factors. A total of 431 cancer patients with pN+ were eligible in the current study: 149 patients with colorectal cancer; 141 patients with breast cancer; and 141 patients with head and neck cancer. High LNR was associated with poor DSS rates with the mean 24–45 months of follow-up period. In the multivariate analysis, high LNR was an independent poor prognostic factor in colorectal cancer (LNR ≥ 0.5; HR 4.10; p

Remission seems achievable for a portion of schizophrenic patients. This study aimed to identify the early predictors for remission and to establish an optimal prediction model. One hundred thirty-five acutely ill schizophrenic inpatients received 150-mg/d zotepine treatment for 4 weeks. Psychopathologic severity was assessed weekly using the Brief Psychiatric Rating Scale (BPRS). Symptomatic remission was defined according to the consensus criteria proposed by Andreasen et al. Backward stepwise logistic regression model was used to obtain the early predictors. The receiver operating characteristic curve was used to determine the cutoff point of predictors. The study was conducted from June 2004 to April 2005. Twenty-one (21.0%) of 100 completers remitted after 4 weeks of treatment. The most influential predictors for ultimate remission were percentage of BPRS score reduction at week 2 and BPRS remission-items score at week 2. Brief Psychiatric Rating Scale score reduction at week 2 of 35% and BPRS remission-items score of 18 at week 2 seemed to be the optimal cutoff points. They provided a sensitivity of 62% and 84% and a specificity of 86% and 65%. Patients with less than a 35% BPRS score reduction and a BPRS remission-items score larger than 18 during the first 2 weeks of treatment were unlikely to reach a final remission. Whether the finding can be extrapolated to other validated assessment scales and other antipsychotics require further studies.

Certain 3-phenylquinolinylchalcone derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-3-(3-(4-methoxyphenyl)quinolin-2-yl)-1-phenylprop-2-en-1-one (6a) and (E)-1-(5-bromothiophen-2-yl)-3-(3-(4-methoxyphenyl)quinolin-2-yl)prop-2-en-1-one (11) were identified as potential lead compounds for further development. Compound 6a was active against the growth of H1299 and SKBR-3 with IC50 values of 1.41 and 0.70 μM respectively which was more active than the positive topotecan (IC50 values of 6.02 and 8.91 μM respectively). Compound 11 exhibited an IC50 value of less than 0.10 μM against the growth of MDA-MB231, and non-cytotoxic to the normal mammary epithelial cell (H184B5F5/M10). Mechanism studies indicated that compound 11 induced cell cycle arrest at G2/M phase followed by activation of caspase-3, cleavage of PARP, and consequently caused the cell death.

Three-dimensional integrated circuits (3D ICs) have many advantages over traditional integrated circuits. Although 3D ICs have such advantages, there are many difficulties to be overcome. Testing for 3D ICs is regarded as the most difficult challenge. High power density in 3D ICs causes rising temperature, which may cause test yield loss. In this paper, we propose a thermal-aware test scheduling technique for 3D ICs. Our experimental results show that the maximum temperature in the test schedule of our proposed technique is under the temperature limit while the test length overhead is only 19%.

Toona sinensis (Chinese Mahogany; Meliaceae), a subtropical deciduous tree, has a tangy scent resembling a mix of shallots and garlic. T. sinensis has long been known for its medicinal efficacy for treating enteritis, dysentery, itch and some cancers. However, its volatile components and their biosynthesis remain unexamined. In this study, we identified the spectrum of volatile compounds, isolated and functionally characterized two terpene synthase genes, Tstps1 and Tstps2, responsible for terpenoid synthesis in T. sinensis leaflets. TsTPS1 and TsTPS2 afford multiple products upon incubation with geranyl and farnesyl diphosphate respectively and mainly regulate the biosynthesis of (+) limonene and β- elemene in vitro, respectively. Headspace analyses show that 98% of leaflet volatiles were sesquiterpenoids and the developing leaflets released a greater diversity and quantity of volatiles than the mature leaflets did, and that β-elemene was the dominant component in both of them. These data suggested that tangy scent of T. sinensis consists of a combination of terpenoids and that Tstps2 was the major gene involved in the terpenoid biosynthesis in T. sinensis. In situ hybridization revealed that glandular cells of the leaf rachises accumulated abundant Tstps1 mRNA transcripts. Our GFP-based assay further unprecedentedly demonstrated that the transit-peptide of TsTPS1 targets specifically to the mitochondria.

A number of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-6-{4-[3-(dimethylamino)propoxy]phenyl}-2-fluoro-9-hydroxy-11H-indeno[1,2-c]quinolin-11-one O-3-(dimethylamino)propyl oxime (23a) was the most active, exhibited GI(50) values of 0.64, 0.39, 0.55, 0.67, and 0.65μM against the growth of Hep G2, Hep 3B, A549, H1299, and MDA-MB-231, respectively. Compound 23a inhibited the growth of hepatoma cell lines in a dose- and time-dependent manner. The proportion of cells was decreased in the G1 and accumulated in G2/M phase after 12h treatment of 23a, while the hypodiploid (sub-G0/G1 phase) cells increased. Further investigations have shown that 23a induced cell cycle arrest at G2/M phase and induce apoptosis via activation of p53, Bax, and caspase-8 which consequently cause cell death.

As the largest and the basal-most family of conifers, Pinaceae provides key insights into the evolutionary history of conifers. We present comparative chloroplast genomics and analysis of concatenated 49 chloroplast protein-coding genes common to 19 gymnosperms, including 15 species from 8 Pinaceous genera, to address the long-standing controversy about Pinaceae phylogeny. The complete cpDNAs of Cathaya argyrophylla and Cedrus deodara (Abitoideae) and draft cpDNAs of Larix decidua, Picea morrisonicola, and Pseudotsuga wilsoniana are reported. We found 21- and 42-kb inversions in congeneric species and different populations of Pinaceous species, which indicates that structural polymorphics may be common and ancient in Pinaceae. Our phylogenetic analyses reveal that Cedrus is clustered with Abies–Keteleeria rather than the basal-most genus of Pinaceae and that Cathaya is closer to Pinus than to Picea or Larix–Pseudotsuga. Topology and structural change tests and indel-distribution comparisons lend further evidence to our phylogenetic finding. Our molecular datings suggest that Pinaceae first evolved during Early Jurassic, and diversification of Pinaceous subfamilies and genera took place during Mid-Jurassic and Lower Cretaceous, respectively. Using different maximum-likelihood divergences as thresholds, we conclude that 2 (Abietoideae and Larix–Pseudotsuga–Piceae–Cathaya–Pinus), 4 (Cedrus, non-Cedrus Abietoideae, Larix–Pseudotsuga, and Piceae–Cathaya–Pinus), or 5 (Cedrus, non-Cedrus Abietoideae, Larix–Pseudotsuga, Picea, and Cathaya–Pinus) groups/subfamilies are more reasonable delimitations for Pinaceae. Specifically, our views on subfamilial classifications differ from previous studies in terms of the rank of Cedrus and with recognition of more than two subfamilies.

This paper tackles a simple and efficient method for the simultaneous separation and stacking of neurotransmitters in capillary electrophoresis with UV detection. By using poly(diallyldimethylammonium chloride) (PDDAC) as a buffer additive, the high and reversed EOF are observed. Moreover, the mobility of indolamines and catecholamines decreases as the PDDAC concentration increases. Based on the difference in mobility in the presence and absence of PDDAC, the analytes were simply stacked between the boundary of the sample zone and the background electrolyte containing PDDAC. The separation of 14 analytes including indolamines, catecholamines, and metanephrines was accomplished within 33 min under optimal conditions (1.2% PDDAC and 5 mM formic acid at pH 4.0), and the values of relative standard deviation of their migration time were less than 3.1%. By applying stacking methods for fourteen analytes, we observed: (a) the sample injection volume of sample is up to 216 nL, (b) the limits of detection at signal-to-noise of 3 range from 15.4 to 122.1 nM, and (c) the sensitivity enhancements, compared to normal injection (12 nL), range from 110- to 220-fold. Under the optimal stacking conditions, the present method has been applied to analyze of vanillomandelic acid, 5-hydroxyindole-3-acetic acid, dopamine, tryptamine, and 3-indoxyl sulfate in urine samples.