History of suicidal behavior and clozapine prescribing among people with schizophrenia in China: a cohort study.

BACKGROUND: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia. METHODS: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates. RESULTS: The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08-17.83]) or during hospitalization (4.18[1.62-10.78]). CONCLUSION: The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.

Fusarium verticillioides Pex7/20 mediates peroxisomal PTS2 pathway import, pathogenicity, and fumonisin B1 biosynthesis.

Fusarium verticillioides, a well-known fungal pathogen that causes severe disease in maize and contaminates the grains with fumonisin B1 (FB1) mycotoxin, affects the yield and quality of maize worldwide. The intrinsic roles of peroxisome targeting signal (PTS)-containing proteins in phytopathogens remain elusive. We therefore explored the regulatory role and other biological functions of the components of PTS2 receptor complex, FvPex7 and FvPex20, in F. verticillioides. We found that FvPex7 directly interacts with the carboxyl terminus of FvPex20 in F. verticillioides. PTS2-containing proteins are recognized and bound by the FvPex7 receptor or the FvPex7-Pex20 receptor complex in the cytoplasm, but the peroxisome localization of the PTS2-Pex7-Pex20 complex is only determined by Pex20 in F. verticillioides. However, we observed that some putative PTS2 proteins that interact with Pex7 are not transported into the peroxisomes, but a PTS1 protein that interacts with Pex5 was detected in the peroxisomes. Furthermore, ΔFvpex7pex20 as well as ΔFvpex7pex5 double mutants exhibited reduced pathogenicity and FB1 biosynthesis, along with defects in conidiation. The PTS2 receptor complex mutants (ΔFvpex7pex20) grew slowly on minimal media and showed reduced sensitivity to cell wall and cell membrane stress-inducing agents compared to the wild type. Taken together, we conclude that the PTS2 receptor complex mediates peroxisome matrix proteins import and contributes to pathogenicity and FB1 biosynthesis in F. verticillioides. KEY POINTS: • FvPex7 directly interacts with FvPex20 in F. verticillioides. • vThe PTS2 receptor complex is essential for the importation of PTS2-containing matrix protein into peroxisomes in F. verticillioides. • Fvpex7/pex20 is involved in pathogenicity and FB1 biosynthesis in F. verticillioides.

First-principles study of polymer-passivated silicon nanowire outer-shell defects.

Highly effective defect passivation schemes are very important for the improvement of Si nanowire (SiNW) performances, because large numbers of outer-shell-defect states are caused by the high surface-to-volume ratios of nanowires. In this work, a polymer that can be fabricated by a simple, vacuum-free method at low temperatures, Nafion, was studied for the SiNW outer-shell defect passivation using first-principles calculations. Based on adsorption energy calculations, it was found that the Nafion molecule could firmly adsorb on the surfaces of SiNWs along the 〈112〉 direction. The Nafion-passivated SiNW outer-shell exhibited high stability to a chemical environment. Herein, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) were confined to the center of the SiNW due to being wrapped by the Nafion. The Nafion-passivated SiNWs exhibited an equivalent quantum confinement effect and a larger absorption coefficient compared with the H-passivated SiNWs. This work demonstrated a passivation strategy of SiNW shell defects using functional groups.

Giant optical absorption and ferroelectric polarization of BiCoO2S perovskite oxysulfide by first principles prediction.

Obtaining an ideal ferroelectric photovoltaic (FE-PV) material with a narrow bandgap and a large ferroelectric polarization value can enable us to achieve great practical FE-PV performance. By the introduction of sulfur into the tetragonal BiCoO3 perovskite with a C-type antiferromagnetic ordering, it is found that the bandgap of BiCoO2S decreases significantly (about 1.2 eV) while maintaining a large polarization value (about 1.86 C m-2) that is similar to the value of 1.793 C m-2 of BiCoO3. Most noteworthy is that the optical absorption of BiCoO2S is remarkably higher than those of BiCoO3 and other FE-PV materials. The decrease of the BiCoO2S bandgap originates from the movement of Co 3d states to a low-energy position due to the reduction of the Co ionicity when the less electronegative sulfur is introduced into BiCoO3 to substitute oxygen. The narrow bandgap and the high optical absorption of the BiCoO2S films grown on different substrates are favorable for FE-PV applications. In addition, the bandgap of BiCoO2S can be modulated by the doping amount of sulfur, which can help us fabricate multilayer FE-PV devices based on different bandgaps from different layers.

Reduction of miR­132­3p contributes to gastric cancer proliferation by targeting MUC13.

Abnormal expression of epidermal growth factor receptor (EGFR) signaling and microRNAs (miRNAs) has been widely seen in gastric cancer. The present study focused on the miRNAs that regulate human epidermal growth factor receptor (HER) activation through mucin 13 (MUC13). The protein level of MUC13 was demonstrated to be significantly increased in gastric cancer tissues compared with normal tissues by western blot analysis and immunohistochemistry. TargetScan bioinformatic predictions indicated that miRNA (miR)­212­3p and miR­132­3p may bind to the 3'­untranslated region of MUC13. Further investigation revealed that miR­132­3p was significantly decreased in gastric cancer tissues compared with normal tissues, whereas miR­212­3p expression was unaffected. Luciferase assays and western blot confirmed MUC13 as a target gene of miR­132­3p. Inhibition of miR­132­3p enhanced gastric cancer cell migration through activation of HER2, extracellular signal­regulated kinase (ERK) and Akt serine/threonine kinase (Akt) signaling, which was a similar effect to that of MUC13 overexpression. In summary, reduction of miR­132­3p may contribute to gastric cancer proliferation by targeting MUC13.

Targeting of the ß6 gene to suppress degradation of ECM via inactivation of the MAPK pathway in breast adenocarcinoma cells.

Integrin ανß6 has emerged as a potential novel target for anticancer and plays a major role in promoting malignant tumor progression. Recent studies indicate that integrin ανß6 occurs in many cancers. However, whether and how ανß6 is regulated by genetic and epigenetic mechanisms in breast cancer remain unknown. In the present study, two different short hairpin RNAs (shRNAs) targeting the ß6 gene were designed and constructed into pSUPER, respectively, which were transfected into the MCF-7 human breast adenocarcinoma cell line. The ß6-shRNA stably transfected cells were successfully established, and significant lower levels of ανß6 mRNA and protein expression were confirmed. Furthermore, inhibition of integrin ανß6 markedly downregulated the expression of matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-3 (MMP-3) and urokinase plasminogen activator (uPA) in tumor conditioned medium. Furthermore, ß6-shRNA-mediated silencing of the ανß6 gene obviously decreased the expression of ERK1/2. In particular, supression of integrin ανß6 caused significant downregulation of the degradation of basement membrane type IV collagen secretion via modulation of the plasminogen activation cascade. Our results thus indicate that ανß6 plays a fundamental role in promoting invasion and growth of breast adenocarcinoma cells. Taken together, this study revealed that targeting of the ß6 gene by RNA interference (RNAi) could efficiently downregulate ανß6 expression and suppress the ERK1/2-dependent extracellular matrix degradation in vitro, which is dependent upon inactivation of the mitogen-activated protein kinase (MAPK) pathway. These findings may offer a useful therapeutic approach to block invasion and migration of breast cancer cells.

Bioaccumulation of heavy metals in plant leaves from Yan׳an city of the Loess Plateau, China.

Urban plants are capable of reducing environmental pollutions through bioaccumulation contaminants in their tissues. The accumulation of heavy metals (Pb, Cu, Cd, Cr, and Zn) in leaves of nine tree species and five shrub species from Yan׳an city of China were investigated, and total metal accumulation capacities of different plants were evaluated using the metal accumulation index (MAI). The results indicated that plants in polluted environments are enriched in heavy metals relative to those in pristine environments, this is mainly caused by traffic emissions and coal combustion. Species with the highest accumulation of a single metal did not have the highest total metal accumulation capacity, the MAI should be an important indicator for tree species selection in phytoextraction and urban greening. Considering total accumulation capacities, Sabina chinensis, Juniperus formosana, Ailanthus altissima and Salix matsudana var. matsudana could be widely used in the Loess Plateau.

Simultaneous determination of aminomethylbenzoic acid, cefminox sodium and etamsylate in human urine by capillary electrophoresis.

A sensitive and selective capillary electrophoresis method is developed, for the first time, for effective separation and simultaneous determination of aminomethylbezoic acid (PAMBA), cefminox sodium (CMNX) and etamsylate (ETM). The electrophoresis conditions were investigated and optimized. A 25 mM phosphate solution (pH 8.5) was used as a buffer and the peak area was determined with UV detection at 216 nm wavelength under 18 kV separation voltage. Under optimal conditions, the three drugs can be separated effectively. Good linearity was achieved in 3.13-150 microg/mL for PAMBA, 6.25-150 microg/mL for CMNX and 3.13-150 microg/mL for ETM, with the correlation coefficients of >0.999. The limit of detection (LOD) for PAMBA, CMNX and ETM was 1.04, 2.08 and 1.04 microg/mL, respectively. Their recoveries in human urine were in the range from 90.2% to 101% with the RSD (n=5) of 0.7-3.1%. The proposed method is simple, rapid and accurate, and provides the sensitivity and linearity necessary for analysis of the test drugs in human urine at clinically relevant concentrations.

Transcriptional modulation of BCRP gene to reverse multidrug resistance by toremifene in breast adenocarcinoma cells.

Breast cancer resistance protein (BCRP/ABCG2), an ATP-binding cassette half transporter, confers multidrug resistance (MDR) to a series of antitumor agents such as mitoxantrone, daunorubicin, SN-38, and topotecan, and often limits the efficacy of chemotherapy. Recent studies have indicated that a putative estrogen response element (ERE) is located in the promoter region of the BCRP gene. However, whether and how BCRP is regulated transcriptionally by toremifene (TOR) remains unknown. In the present study, two plasmid vectors have been designed to express the wild-type full-length BCRP cDNA enforced driven by its endogenous promoter containing a functional ERE and a constitutive cytomegalovirus (CMV) promoter as control, respectively, which were transfected into estrogen-responsive MCF-7 and estrogen-independent MDA-MB-231 human breast adenocarcinoma cell lines. We showed that toremifene alone significantly downregulated BCRP mRNA and protein levels in estrogen receptor α (ERα)-positive MCF-7 cells in a dose-dependent manner, and the inhibitory effect was partially reversed by estrone (E(1)). Furthermore, gel shift assays demonstrated that specific binding of ERα to the ERE in the BCRP promoter is essential for transcriptional inhibition of BCRP by toremifene. Interestingly, toremifene alone increased the cellular accumulation of mitoxantrone in BCRP-transfected cells, suggesting that TOR indeed inhibits BCRP-mediated drug efflux and overcome drug resistance. To the best of our knowledge, this is the first report describing a direct effect of toremifene on BCRP. Our results thus indicate that toremifene by itself downregulates BCRP expression to reverse BCRP-mediated atypical multidrug resistance via a novel transcriptionally mechanism, which might be involved in TOR-ER complexes binding to the ERE of BCRP promoter to repress transcription of BCRP gene.

A novel modification of tunical plication by plaque thinning: long-term results in treating penile curvature of Peyronie's disease.

OBJECTIVE: To investigate the efficacy of a novel modified tunical plication procedure in correcting penile curvature of patients with Peyronie's disease. METHODS: Penile tunical plication was performed, combined with plaque thinning with carbide burs, and 18 patients were available for a long-term follow-up. Preoperative deformity and erectile capacity were accessed, and postoperative cosmetic and functional results were evaluated by physical examination, subjective satisfaction rate, and International Index of Erectile Function-5 questionnaire (IIEF-5). RESULTS: During the initial assessment after 6 months since surgery, complete straightening was achieved in 83.3% patients, and the residual curvatures in the three patients were within 20°. Satisfaction rate was 94.4% while one patient was partly dissatisfied with penile shortening, although the penile shortening occurred in 66.7% patients. No de novo erectile dysfunction was observed, and sexual function was significantly improved with the IIEF-5 scores increasing from 17.3 ± 4.1 to 20.9 ± 3.3 (P = 0.008). After a mean of 50.5-month follow-up (range from 29 to 72 months), although 22.2% patients reported curvature recurrence, neither the recurrence nor the penile shortening affected coitus, and 100% patients were satisfied with the results of the operation. CONCLUSIONS: The plication procedure modified by plaque thinning with carbide burs is safe and effective in treating penile deformity due to Peyronie's disease, which characterized in improving the life quality of patients.