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Rong-Man Yuan,1,2 Wen-Ya Peng,1 Jiang Jiang1 1Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education (Beijing Normal University), Faculty of Psychology, Beijing Normal University, Beijing, People’s Republic of China; 2Mental Health Center, Beijing Youth Politics College, Beijing, People’s Republic of ChinaCorrespondence: Jiang Jiang, Email jjiang@bnu.edu.cnPurpose: Growth mindset and self-control, both recognized as pivotal qualities with significant impacts on personal success, possess respective robust predictive power for academic achievement and broader life outcomes. However, the bidirectional relationship between them remains largely unexplored. This study aims to investigate whether growth mindset, conceptualized as the belief that abilities can be developed through effort and support, prospectively predicts the development of self-control over time. Additionally, it endeavors to explore whether self-control, a crucial positive psychological trait, exerts an influence on the fostering of growth mindset. In summary, our research focuses on elucidating the bidirectional relationship between growth mindset and self-control among Chinese primary school students.Participants and Methods: The current research recruited a sample of 428 primary school students, aged 9– 12, from China (214 females, mean age = 9.64 ± 1.21) to participate in a longitudinal study. Participants underwent two follow-up assessments of growth mindset and self-control over a six-month period.Results: The correlation analysis revealed significant associations between growth mindset at T1 and self-control at T2, as well as between self-control at T1 and growth mindset at T2(r = 0.23 to 0.25, ps < 0.01). Cross-lagged analysis found that growth mindset at T1 positively predicted self-control at T2 (β = 0.11, p = 0.04), while self-control at T1 did not significantly predict growth mindset at T2.Conclusion: The results suggest that growth mindset exerts a direct impact on self-control among primary school students. This finding extends the scope of research concerning growth mindset and provides important theoretical inspiration and practical guidance for educators, parents and counselling professionals in assisting students to enhance self-control.Keywords: primary school students, growth mindset, self-control, longitudinal study, cross-lagged analysis

Aim: To examine the dynamic change in hepatic steatosis status during repeated assessments over time, and its potential impact on the risk of developing cardiovascular disease (CVD)., Methods: We assessed trajectories of hepatic steatosis and other metabolic disorders in 3134 middle-aged adults undergoing longitudinal assessment of ultrasonography during a pre-baseline period (1993-2009) in a population-based cohort study of liver health. Subsequently, we determined the association of hepatic steatosis trajectories with the incidence of CVD among 2185 CVD-free individuals, followed until 2021. Metabolic risk factors and cardiovascular events (including coronary heart disease and stroke) were determined through medical examination and linkage with nationwide health databases., Results: We identified three discrete trajectories of hepatic steatosis according to changing pattern over time through group-based trajectory modeling: "stable, non-steatosis" (n = 1298), "intermittent" (n = 921), and "persistent steatosis" (n = 915). During the pre-baseline period, hepatic steatosis trajectories were associated with trajectories of developing diabetes and hypertension, and persistent steatosis (vs. other trajectories) was associated with higher risks and rapidly progressive disease patterns. At a median 13.6 years of follow-up, 629 CVD events occurred. A persistent (vs. non-steatosis: HR 1.44, 95% CI 1.17-1.76), but not intermittent, steatosis pattern predicted the future risk of CVD, after adjustment for age, sex, smoking, and obesity. This association was independent of genetic background, and remained after accounting for pre-baseline body-mass index, other cardiometabolic risk factors, Framingham risk score, medications, and hepatic fibrosis score., Conclusions: The persistence of hepatic steatosis is associated with trajectories of metabolic disorder development and increased risk of CVD. These data have important implications for practice and further research., (© 2024 Japan Society of Hepatology.)

Aim of the Study: Our hypothesis is that nirmatrelvir can penetrate the blood‒brain barrier and reach effective concentrations in the brain. Furthermore, herbal formulations can help maintain nirmatrelvir levels in the body, suggesting potential interactions between these medications., Materials and Methods: To investigate this hypothesis, an animal model combining multisite microdialysis, ultrahigh-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) methods was developed to monitor nirmatrelvir levels in the blood and brain of rats., Results: The pharmacokinetic results showed that the area under the curve (AUC) of nirmatrelvir in the blood and brain was 798.3 ± 58.56 and 187.2 ± 23.46 min μg/mL, respectively, after the administration of nirmatrelvir alone (15 mg/kg, iv). When the Scutellaria baicalensis formulations were administered for five consecutive days prior to drug administration, the AUC of nirmatrelvir in the blood increased., Conclusions: These results provide constructive preclinical information that the concentrations of nirmatrelvir in the blood and brain were greater than the effective concentration (EC 90 ) for more than 6 h, and the Scutellaria baicalensis formulations had synergistic pharmacokinetic effects by increasing the concentration of nirmatrelvir in the blood., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.

Background and Objective: The effectiveness and long-term efficacy of edaravone, a recommended treatment for amyotrophic lateral sclerosis (ALS), has not been examined in real-world settings. This study aims to evaluate the effectiveness and long-term efficacy of edaravone., Methods: The OVID Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases were searched for articles published between January 1, 2000, and May 1, 2023. Two investigators independently screened the retrieved articles for randomized controlled trials (RCTs), cohort studies, or single-arm trials that evaluated the effect of edaravone on amyotrophic lateral sclerosis (ALS). The risk of bias was evaluated using the revised Cochrane Risk-of-Bias (RoB 2.0) tool for randomized controlled trials (RCTs) and the Risk-of-Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. The primary outcome was the ALSFRS-R score assessed at month 6, with secondary outcomes including the ALSFRS-R scores evaluated at months 9, 12, and 18, forced vital capacity (FVC), and adverse events. The certainty of evidence was assessed using the GRADE approach., Results: The analysis included 16 studies with a total of 4828 participants. Among these, four were randomized controlled trials (RCTs) and 12 were observational studies. Of the RCTs, four were rated as having a low risk of bias, while six of the observational studies were rated as having a low risk of bias. Edaravone was associated with slightly slower progression in the reduction of ALSFRS-R score at month 6 compared to placebo (mean difference 1.01, 95%CI -0.87 to 3.09, p = 0.293), as shown by evidence from RCTs. However, observational studies did not show any benefit of adding edaravone to routine practice (mean difference 1.85, 95%CI -2.05 to 5.75, p = 0.352). The change from baseline in ALSFRS-R score was -2.1, -4.04, -7.5, -6.82, and -7.9 at months 3, 6, 9, 12, and 18, respectively. The GRADE assessment indicated moderate certainty for evidence from RCTs, while evidence from observational studies had very low certainty., Conclusion: Due to the limited number of studies and confounding issues in observational studies, further examination of the added benefits of edaravone to routine practice is necessary through RCTs, particularly regarding its long-term efficacy., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background: Acupuncture showed better improvement than sham acupuncture in reducing attack frequency of tension-type headache (TTH), but its effectiveness relative to first-line drugs for TTH is unknown, which impedes the recommendation of acupuncture for patients who are intolerant to drugs for TTH. We aimed to estimate the relative effectiveness between acupuncture and tricyclic antidepressants (TCAs) through indirect treatment comparison (ITC) meta-analysis., Methods: We searched Ovid Medline, Embase, and Cochrane Library from database inception until April 13, 2023. Randomized controlled trials of TCAs or acupuncture in the prevention of TTH in adults were included. The primary outcome was headache frequency. The secondary outcomes were headache intensity, responder rate, and adverse event rate. Bayesian random-effect models were used to perform ITC meta-analysis, and confidence of evidence was evaluated by using the GRADE approach., Results: A total of 34 trials involving 4426 participants were included. Acupuncture had similar effect with TCAs in decreasing TTH frequency (amitriptyline: mean difference [MD] -1.29, 95% CI -5.28 to 3.02; amitriptylinoxide: MD -0.05, 95% CI -6.86 to 7.06) and reducing TTH intensity (amitriptyline: MD 2.35, 95% CI -1.20 to 5.78; clomipramine: MD 1.83, 95% CI -4.23 to 8.20). Amitriptyline had a higher rate of adverse events than acupuncture (OR 4.73, 95% CI 1.42 to 14.23)., Conclusion: Acupuncture had similar effect as TCAs in reducing headache frequency of TTH, and acupuncture had a lower adverse events rate than amitriptyline, as shown by very low certainty of evidence., (© 2024. The Author(s).)

Merkel cell polyomavirus (MCV or MCPyV) is an alphapolyomavirus causing human Merkel cell carcinoma and encodes four tumor (T) antigen proteins: large T (LT), small tumor (sT), 57 kT, and middle T (MT)/alternate LT open reading frame proteins. We show that MCV MT is generated as multiple isoforms through internal methionine translational initiation that insert into membrane lipid rafts. The membrane-localized MCV MT oligomerizes and promiscuously binds to lipid raft-associated Src family kinases (SFKs). MCV MT-SFK interaction is mediated by a Src homology (SH) 3 recognition motif as determined by surface plasmon resonance, coimmunoprecipitation, and bimolecular fluorescence complementation assays. SFK recruitment by MT leads to tyrosine phosphorylation at a SH2 recognition motif (pMT Y114 ), allowing interaction with phospholipase C gamma 1 (PLCγ1). The secondary recruitment of PLCγ1 to the SFK-MT membrane complex promotes PLCγ1 tyrosine phosphorylation on Y783 and activates the NF-κB inflammatory signaling pathway. Mutations at either the MCV MT SH2 or SH3 recognition sites abrogate PLCγ1-dependent activation of NF-κB signaling and increase viral replication after MCV genome transfection into 293 cells. These findings reveal a conserved viral targeting of the SFK-PLCγ1 pathway by both MCV and murine polyomavirus (MuPyV) MT proteins. The molecular steps in how SFK-PLCγ1 activation is achieved, however, differ between these two viruses., Competing Interests: Competing interests statement:The authors declare no competing interest.

Purpose: Corneal alkali burns can progress to corneal epithelial defects, inflammation, scarring, and angiogenesis, potentially leading to blindness. Therefore, we examined the therapeutic effects of a novel ophthalmic solution (ZK002) on wound healing in alkali-burned rat corneas., Methods: In this study, we attempted to treat alkali-exposed rat corneas using topical application of either an ophthalmic solution with ZK002 or an anti-vascular endothelial growth factor agent for 14 days. We evaluated corneal edema, corneal neovascularization area, and histological changes. We also assessed the inflammatory (MMP-9, MMP-2, and interleukin-1β) and angiogenic (vascular endothelial growth factor receptor 2, VEGFR2) markers. Levels of inflammatory (matrix metalloproteinase (MMP)-9, MMP-2, and interleukin-1β), profibrotic (α-smooth muscle actin, α-SMA; transforming growth factor-β2,TGF-β2), and angiogenic (vascular endothelial growth factor-receptor 2, VEGFR2) factors, as well as peroxisome proliferator-activated receptor γ (PPARγ) mRNA expression, were measured., Results: The analyses showed that alkali exposure caused an increase in corneal edema and fibrosis with corneal neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of transforming growth factor-β2 on the alkali-exposed corneas were noted on day 14. The mRNA expression levels of interleukin-1β, MMP-9, MMP-2, VEGFR2, and profibrotic factors were decreased in the ZK002 group compared with the control group during the early period of corneal alkali burns on day 14. However, the expression level of PPARγ mRNA was increased in the ZK002 group., Conclusions: ZK002 decreased the fibrotic reaction and prevented neovascularization in the cornea after an alkali burn. Therefore, the novel ophthalmic solution ZK002 could be a potentially promising therapeutic clinical treatment for corneal wound healing., (Copyright © 2023 Molecular Vision.)

Background: The antiviral drug molnupiravir is an orally bioavailable prodrug of the nucleoside analog β-D-N4-hydroxycytidine (NHC), which is used to treat coronavirus disease 2019 (COVID-19). However, there is very little information on the barrier distribution of molnupiravir. Our hypothesis is that molnupiravir and NHC can penetrate the blood‒brain barrier (BBB) into brain tissue and that nucleoside transporters (equilibrative nucleoside transporters; ENT and concentrative nucleoside transporters; CNT) can modulate this process., Methods: To investigate the mechanism of molnupiravir transport through the BBB, multiple microdialyses coupled to a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC‒MS/MS) was developed to monitor dialysates, and nitrobenzylthioinosine (NBMPR; an inhibitor of ENT) was administered concomitantly with molnupiravir (100 mg/kg, i.v.) in the male rat., Results: Here, we show that molnupiravir is rapidly metabolized to NHC in the blood and crossed the BBB in 20 min. Furthermore, when NBMPR is concomitantly administered to inhibit efflux, the concentrations of molnupiravir and NHC in the brain increased significantly., Conclusions: In summary, molnupiravir rapidly transforms into NHC and crosses the BBB and reaches the brain at approximately 0.3-0.8% of the blood‒brain ratio. The maximum concentration of NHC in the blood and brain is above the average half maximal inhibitory concentration (IC50) of the drug required to treat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, suggesting a therapeutic effect. The penetration of NHC is modulated by NBMPR. These findings provide constructive information on brain disorders in clinical patients with COVID-19., (© 2023. Springer Nature Limited.)

The aim of this study was to explore the effects of herbal drug pharmacokinetic interactions on the biotransformation of molnupiravir and its metabolite β-D-N4-hydroxycytidine (NHC) in the blood and brain. To investigate the biotransformation mechanism, a carboxylesterase inhibitor, bis(4-nitrophenyl)phosphate (BNPP), was administered. Not only molnupiravir but also the herbal medicine Scutellaria formula-NRICM101 is potentially affected by coadministration with molnupiravir. However, the herb-drug interaction between molnupiravir and the Scutellaria formula-NRICM101 has not yet been investigated. We hypothesized that the complex bioactive herbal ingredients in the extract of the Scutellaria formula-NRICM101, the biotransformation and penetration of the bloodbrain barrier of molnupiravir are altered by inhibition of carboxylesterase. To monitor the analytes, ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLCMS/MS) coupled with the microdialysis method was developed. Based on the dose transfer from humans to rats, a dose of molnupiravir (100 mg/kg, i.v.), molnupiravir (100 mg/kg, i.v.) + BNPP (50 mg/kg, i.v.), and molnupiravir (100 mg/kg, i.v.) + the Scutellaria formula-NRICM101 extract (1.27 g/kg, per day, for 5 consecutive days) were administered. The results showed that molnupiravir was rapidly metabolized to NHC and penetrated into the brain striatum. However, when concomitant with BNPP, NHC was suppressed, and molnupiravir was enhanced. The blood-to-brain penetration ratios were 2% and 6%, respectively. In summary, the extract of the Scutellaria formula-NRICM101 provides a pharmacological effect similar to that of the carboxylesterase inhibitor to suppress NHC in the blood, and the brain penetration ratio was increased, but the concentration is also higher than the effective concentration in the blood and brain., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Molnupiravir is an orally bioavailable prodrug of the nucleoside analogue β-D-N4-hydroxycytidine (NHC) and is used to treat coronavirus disease 2019 (COVID-19). However, the pharmacokinetics and transplacental transfer of molnupiravir in pregnant women are still not well understood. In the present study, we investigated the hypothesis that molnupiravir and NHC cross the blood-placenta barrier into the fetus., Methods: A multisite microdialysis coupled with a validated ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC‒MS/MS) system was developed to monitor the dialysate levels of molnupiravir and NHC in maternal rat blood and conceptus (the collective term for the fetus, placenta, and amniotic fluid). Molnupiravir was administered intravenously (100 mg/kg, i.v.) on gestational day 16. To investigate the mechanism of transport of molnupiravir across the blood-placenta barrier, we coadministered nitrobenzylthioinosine (NBMPR, 10 mg/kg, i.v.) to inhibit equilibrative nucleoside transporter (ENT)., Findings: We report that molnupiravir is rapidly metabolized to NHC and then rapidly transformed in the fetus, placenta, amniotic fluid, and maternal blood. Our pharmacokinetics analysis revealed that the area under the concentration curve (AUC) for the mother-to-fetus ratio (AUC fetus /AUC blood ) of NHC was 0.29 ± 0.11. Further, we demonstrated that the transport of NHC in the placenta may not be subject to modulation by the ENT., Interpretation: Our results show that NHC is the predominant bioactive metabolite of molnupiravir and rapidly crosses the blood-placenta barrier in pregnant rats. The NHC concentration in maternal blood and conceptus was above the average median inhibitory concentration (IC 50 ) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), suggesting a therapeutic effect. These findings support the use of molnupiravir in pregnant patients infected with COVID., Funding: This study was supported in part by research grants from the National Science and Technology Council of Taiwan (NSTC 111-2113-M-A49-018 and NSTC 112-2321-B-A49-005)., Competing Interests: Declaration of interests The authors declare no conflicts of interest related to this study., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To investigate the effect and timing of subconjunctival bevacizumab injection on inhibiting corneal neovascularization (CorNV) in patients after chemical burns., Methods: Patients with CorNV secondary to chemical burns were involved. Two subconjunctival injections of bevacizumab (2.5 mg/0.1 mL per involved quadrant) with an interval of 4 weeks were administered, and followed up a year. The area occupied by neovascular vessels (NA), accumulative neovascular length (NL), mean neovascular diameter (ND), best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were evaluated. Complication was also recorded., Results: Eleven patients with CorNV were involved. Eight patients had a history of surgery (four had amniotic grafts, one had keratoplasty, and three had amniotic grafts and keratoplasty). Decreasing in NA, NL, and ND were statistically significant at each time point compared to the baseline ( p < 0.01). CorNV that developed within 1 month was considerably regressed, and vessels with fibrovascular membranes were found to be narrower and shorter than pretreatment. BCVA improved in five patients (from one to five lines), remained unchanged in five patients, and decreased in one patient compared to pretreatment., Conclusion: Subconjunctival bevacizumab injection has a particular potential for the regression of CorNV, especially newly formed within 1 month in patients after chemical burns., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peng, He, Yin, Zhou, Zhou and Zhou.)

Background: Telocytes (TCs), a novel interstitial cell type in the reproductive tract, participating in pathophysiology of intrauterine adhesions (IUA). This study further investigates the hypothesis that TCs, a source of Wnt, promote the regeneration and repair of IUA., Methods: RNA sequencing datasets of IUA patient (GSE160633) and mouse intestine mesenchymal cells (GSE94072) in GEO database were analyzed for differentially expressed genes (DEGs), and quantitative real-time PCR (qRT-PCR) measured indicated gene expression in TC-educated endometrial stromal cells (ESCs) and noneducated ESCs and verified the results of data mining from GEO database., Results: The expression levels of Wnt genes were downregulated in IUA compared to the control and were upregulated in TCs. In particular, the changes of Wnt5a expression level were the most significant (logFC = 4.0314 and adjusted P value = 0.0023), and the relative Wnt5a expression level was remarkably higher in TC-educated ESCs than noneducated ESCs verified by qRT-PCR ( P = 0.0027)., Conclusions: TCs may enhance the regeneration and repair of IUA through the Wnt signaling pathway., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2022 Cai-zhen Zhao et al.)

Background: Probiotic and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet are two commonly used management approaches for patients with irritable bowel syndrome (IBS). We aimed to evaluate the most effective combinations and components among different probiotics or low FODMAP diet through component network meta-analysis (NMA). Methods: We searched Embase, Ovid Medline, and Web of Science from inception to 21 January 2021. Randomized controlled trials (RCTs) examining the efficacy of probiotics and low FODMAP diet for IBS were included, with placebo, sham diet, or conventional treatments as controls. Binary outcomes were compared among treatments using the relative ratio (RR). A minimally contextualized framework recommended by the GRADE group was used to evaluate the certainty of evidence. The primary efficacy outcome was the relief of global IBS symptoms, and the secondary efficacy outcome was the reduction in IBS symptom scores or abdominal pain scores. Key Results: We included 76 RCTs (n = 8058) after screening 1940 articles. Eight RCTs were classified as low risk of bias. Standard network meta-analysis (NMA) showed that Lactobacillus (RR 1.74, 95% CI 1.22-2.48) and Bifidobacterium (RR 1.76, 95% CI 1.01-3.07) were the most effective for the primary efficacy outcome (high certainty evidence); component NMA showed that Bacillus (RR 5.67, 95% CI 1.88 to 17.08, p = 0.002) and Lactobacillus (RR 1.42, 95% CI 1.07 to 1.91, p = 0.017) were among the most effective components. The results of standard NMA and CNMA analysis of the improvement of overall IBS symptom scores or abdominal pain scores were consistent with this finding. Conclusion: Lactobacillus was the most effective component for the relief of IBS symptoms; Bifidobacterium and Bacillus were possibly effective and need further verification. Systematic Review Registration: website, identifier registration number., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Tang, Shi, Peng, Ye, Tao, Yu, Zheng and Chen.)

Background: Previous studies suggested an association of sleep disorders with inflammatory bowel disease (IBD) and indicated that using pharmacological treatments for the modulation of circadian rhythms might prevent IBD pathogenesis or aggravation, but whether the effect of sleep traits on IBD was causal is inconclusive and, therefore, prevents drug repurposing based on the previous studies. We aimed to examine the causal effect of different sleep traits on the pathogenesis of IBD. Methods: Genetic instruments for sleep traits were selected from the largest GWAS studies available in the UK Biobank ( n = 449,734) and the 23andMe Research ( n = 541,333). A two-sample Mendelian randomization (MR) study was conducted to examine the association of the genetic instruments with IBD (12,882 cases and 21,770 controls), ulcerative colitis (6,968 cases, 20,464 controls), and Crohn's disease (5,956 cases and 14,927 controls). We applied the inverse-variance weighted (IVW) method to estimate causal effects, and we used the weighted median and MR-Egger method for sensitivity analyses. Results: We found that sleep duration (OR, 1.00, 95% CI 1.00-1.01), short sleep duration (OR, 1.07, 95% CI 0.41-2.83), morningness (OR, 1.05, 95% CI 0.87-1.27), daytime napping (OR, 1.64, 95% CI 0.62-4.4), frequent insomnia (OR, 1.17, 95% CI 0.8-1.72), any insomnia (OR, 1.17, 95% CI 0.69-1.97), and snoring (OR, 0.31, 95% CI 0.06-1.54) had no causal effect on IBD, and these sleep traits had no causal effect on ulcerative colitis and Crohn's disease either. Most of the sensitivity analyses showed consistent results with those of the IVW method. Conclusion: Our MR study did not support the causal effect of sleep traits on IBD. Pharmacological modulation of circadian rhythms for the prevention of IBD pathogenesis was unwarranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Peng, Tang and Zheng.)

Purpose: To investigate the safety and efficacy of femtosecond laser-assisted penetrating keratoplasty (FLAK) versus conventional penetrating keratoplasty (CPK)., Methods: A literature search of PubMed, Cochrane, Embase, Web of Science, and Clinicaltrials.gov was conducted for comparative studies published from January 2007 to October 2019. Studies that involved both FLAK and CPK groups and reported on the relevant efficacy and/or safety parameters were included. The Newcastle-Ottawa quality assessment scale was used to analyse the methodological quality of these studies. Further, weighted mean differences (WMDs) with 95% confidence intervals (CIs) were calculated., Results: From the screened articles, a total of 1991 eyes from nine comparative studies were included. FLAK was not statistically superior for twelve-month postoperative best corrected visual acuity (WMD = - 0.06; 95% CI [- 0.16, 0.04]; P = 0.22), corneal astigmatism (WMD = - 0.81; 95% CI [- 1.63, 0.01]; P = 0.05) or six-month postoperative uncorrected visual acuity (WMD = - 0.11; 95% CI [- 0.27, 0.06]; P = 0.21). There were no significant differences in corneal graft rejection rate and the graft failure between FLAK and CPK at twelve months postoperative. However, best-corrected visual acuity (BCVA) and corneal astigmatism corrected with FLAK were better than those with CPK six months postoperative after elimination of data heterogeneity., Conclusion: Visual outcomes improvement in FLAK was better than that in CPK at six months postoperative, but not twelve months postoperative. This review recommends selecting a technique based on patients' work demands and economic burdens., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Chinese herbal medicine (CHM) is an important complementary and alternative therapy for the management of irritable bowel syndrome (IBS). Previous meta-analyses suggested that CHM is effective for IBS; nonetheless, its effectiveness is inconclusive owing to repeated significance testing. We aimed to examine the efficacy and safety of CHM for IBS through a meta-analysis and trial sequential analysis (TSA). Methods: We searched OVID Medline, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from January 1, 1980, to September 20, 2020. The primary outcome was adequate relief of global IBS symptoms. The secondary outcomes included relief of abdominal pain and treatment-related adverse events. The relative ratio (RR) and required information size (RIS) were calculated for each outcome. Results: Ten trials recruiting 2,501 participants were included. Seven (70%) trials were at low risk of bias (RoB). Compared with placebo, CHM was associated with a significantly higher proportion of adequate relief of global IBS symptoms [RR 1.76 (95% confidence interval (95%CI), 1.33-2.33); I 2 = 81.1%; p < 0.001]. The RIS was 1,083 for the primary outcome, and the accrued information size was 1,716. The analysis of the relief of abdominal pain (three trials with 916 participants) showed similar results compared with placebo [RR 1.85 (95%CI, 1.59-2.14); I 2 = 0%; p < 0.001; RIS = 197 participants]. CHM was associated with a higher proportion of adverse events compared with placebo [RR 1.51 (95%CI, 1.14-2); I 2 = 0%; p = 0.004]. Conclusion: CHM was effective in relieving IBS symptoms but caused a higher adverse event rate than placebo. TSA analysis confirmed the findings with sufficient information size., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Jin, Shen, Peng, Ye, Tang, Zhao, Chen and Li.)

Lovastatin is a standard therapy for dyslipidemia. Alternatively, some ethnomedicines, such as Coptidis preparation, have been used for the treatment of dyslipidemia. Statins and complementary and alternative medicines may possess individual mechanisms of action against dyslipidemia. We hypothesize that the combination of Coptidis preparation and lovastatin may have synergistic effects for the treatment of dyslipidemia. To investigate this hypothesis, we developed a validated ultra-high-performance liquid chromatography-tandem mass spectrometry method to monitor lovastatin and its metabolites for pharmacokinetic studies in rats. This study was divided into four groups: lovastatin (10 mg/kg, p.o.) alone and lovastatin (10 mg/kg, p.o.) + Coptidis preparation (0.3, 1, or 3 g/kg, p.o.) for five consecutive days. In pharmacodynamic studies, a high-fat diet (HFD) was used to induce dyslipidemia in experimental rat models. The HFD rats were divided into four groups: treatment with HFD, HFD + lovastatin (100 mg/kg, p.o.), HFD + Coptidis preparation (1 g/kg, p.o.), and HFD + lovastatin (50 mg/kg, p.o.) + Coptidis preparation (1 g/kg, p.o.) for 28 consecutive days. The pharmacokinetic results demonstrated that Coptidis preparation significantly augmented the conversion of lovastatin into its main metabolite lovastatin acid in vivo. The pharmacodynamic results revealed that the Coptidis preparation and half-dose lovastatin group reduced the body weight, liver weight, and visceral fat in HFD rats. These findings provide constructive preclinical pharmacokinetic and pharmacodynamic applications of Coptidis preparation on the benefit of hyperlipidemia., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Ethnopharmacological Relevance: Ambroxol elevates glucocerebrosidase (GCase) activity and reduces nigrostriatal alpha-synuclein burden to better ameliorate motor function in Parkinson's disease (PD). Polygala tenuifolia is a potential alternative botanical medicine for the treatment of many nonmotor symptoms of PD commonly used in Taiwanese patients. Co-administration of these two medicines pose potential herb-drug interaction., Aim of the Study: Our hypothesis is that ambroxol and P. tenuifolia may potentially possess herbal drug synergetic effects in the blood and brain., Materials and Methods: To investigate this hypothesis, a multiple microdialysis system coupled with validated ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for rat blood and brain samples. Experimental rats were divided into three groups: low-dose and high-dose ambroxol alone (10 mg/kg, i.v. and 30 mg/kg, i.v., respectively) and ambroxol (10 mg/kg, i.v.) pretreated with P. tenuifolia extract (1 g/kg, p.o. for 5 consecutive days)., Results: Ambroxol easily penetrated into the brain and reached a maximum concentration in the striatum at approximately 60 min after low- and high-dose treatment. The area under the concentration curve (AUC) ratio increased proportionally at the doses of 10 and 30 mg/kg, which suggested a linear pharmacokinetic manner of ambroxol. The brain penetration of ambroxol was approximately 30-34%, which was defined as the ambroxol AUC blood-to-brain distribution ratio (AUC brain /AUC blood ). The P. tenuifolia extract did not significantly alter the pharmacokinetics of ambroxol in the blood and brain of rats., Conclusion: The present study suggests that it is safety without pharmacokinetic interactions for this dosing regimen to use P. tenuifolia extract and ambroxol together., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to explore the efficacy, safety, and tolerability of a novel cyclosporine formulation for dry eye disease (DED)., Methods: This is an exploratory, multicenter, single-blind, randomized, positive-controlled Phase II clinical trial between cyclosporine ophthalmic gel (CyclAGel) and an open-label comparator (Restasis, positive control). A total of 240 eligible patients with moderate to severe DED were randomized to 4 study groups: CyclAGel 0.05%/once daily (QD) (n = 59), CyclAGel 0.05%/BID (n = 60), CyclAGel 0.1%/QD (n = 60), and Restasis 0.05%/BID (n = 61). After receiving BID dosing of hypromellose eye drops during a 2-week run-in period, patients were randomized to the respective treatment group and dosed QD or BID for 12 weeks. Efficacy was assessed based on a number of sign and symptom end points, including eye dryness score (visual analog scale), 6 other parameters of symptoms for dryness (burning/stinging, itching, foreign body sensation, discomfort, sensitivity to light, and pain), and corneal fluorescein staining. The Schirmer test was used to assess dry eye symptoms (visual analog scale severity) at visit 3 (week 2), visit 4 (week 6), and visit 5 (week 12)., Findings: CyclAGel showed a consistent improvement in eye dryness score and the 6 other parameters of symptoms for dryness, corneal fluorescein staining, breakup time, and Schirmer test scores compared with Restasis over the 12-week treatment period. However, there were no statistically significant differences between CyclAGel and Restasis after baseline corrections were made, and the results of the full analysis set remained consistent with those of the per-protocol set (P > 0.05). Moreover, each CyclAGel-treated group (0.05%/QD, 0.05%/BID, and 0.1%/QD) exerted better effects than the Restasis group, and CyclAGel 0.05%/QD showed the most significant improvement. The number of ocular-related treatment-emergent adverse events was low in all treatment groups, with no serious drug-related treatment-emergent adverse events., Implications: CyclAGel showed excellent safety, tolerability, and comfort profiles at 2 concentrations and frequency in moderate to severe DED., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To facilitate the cell-based experiment for pulsed electromagnetic field biological effect study, a novel TEM-cell-integrated CO 2 incubator was developed. The integrated experimental system could simultaneously meet the requirement of standard cell culture condition and the various Transient Electromagnetic Field (TEF) exposure, which made it possible to study the relationship between different electromagnetic pulse exposure and the cellular responses in a reliable way. During the research, a comparison experiment was carried out to evaluate the necessity of the integrated incubator system: firstly, two different types of cell lines, which are the human prostate cancer cell line (PC3) and the pancreatic β cell line (MIN6) were chosen and exposed in the TEM-cell which located in the open area and the integrated system, respectively, with the same EFT radiation conditions; then, the cells' viability, the cellular ROS level and the mitochondrial membrane potential (MMP) were detected, respectively. The results showed that in the same parameter of the EFT radiation, the processes of the cells had a significant difference and even opposite in the incubator and open area, and all the results could be reproducible. The phenomenon indicated the stability of the TEM-cell-integrated CO 2 incubator, and also demonstrated the necessity to strictly control the cell culture condition when carrying out the precise mechanism study of the TEF bioresponse at the cellular levels.

Multiherbal preparation of Coptidis rhizoma , Scutellariae radix , and Rhei rhizoma is a well-known herbal formula, which is widely used in the prescription for relieving heat toxicity, inflammation of the intestine, and eczema. However, little is known about the characteristics of the physical and chemical qualities of industrial pharmaceutical products. The aim of the study is to develop a liquid chromatography system to examine the quality and quantity of pharmaceutical products. Besides scanning electron microscopy, light microscopy photographs with Congo red staining and iodine-KI staining were used for physical examination of the quality of the pharmaceutical products. A reverse-phase C18 column was used to separate the analytes of baicalin, berberine, rhein, and p -hydroxybenzoate (internal standard) with a gradient eluent mobile phase of acetonitrile and 10 mM NaH 2 PO 4 (pH 3.0, adjusted by orthophosphoric acid). The results demonstrated that a large variety of content range presents among the testing herbal pharmaceutical products. The contents of rhein, baicalin, and berberine were around 0.22-22.46, 0.44-50.79, and 0.41-2.48 mg/g, respectively. The physical examination data demonstrated that different brands of industrial pharmaceutical products have different shapes of granules or rods. In summary, to ensure the clinical efficacy of complicated herbal medicine, both quality and quantity controls are all very important. This study provides a reference standard operating procedure guide for the quality control (QC) with chemical and physical examination for the Chinese herbal pharmaceutical products of San-Huang-Xie-Xin-Tang (SHXXT)., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

This article describes a novel surgical technique for successful repair of intractable corneoscleral necrosis caused by severe ocular burns. In this prospective case series, 19 eyes of 15 consecutive patients with sectional scleral necrosis and persistent corneal epithelial defects were treated with tenonplasty and amniotic membrane transplantation. The main outcome measure was the stability of the ocular surface after reepithelialization and repair of defects. All patients underwent successful combined surgery involving tenonplasty and amniotic membrane transplantation, in which the conjunctival and corneal surfaces were reconstructed. The interval from injury to surgery was 37.4 ± 24.5 days (3-91 days), and the ocular surfaces became stabilized in 82.2 ± 35.4 days (26-156 days, median 87 days). At the final visit, all cases presented with corneal opacity and neovascularization to various degrees. The best-corrected visual acuity decreased from 2.83 ± 1.02 LogMAR preoperatively to 2.87 ± 1.31 LogMAR postoperatively. The results imply that tenonplasty combined with amniotic membrane transplantation could provide vascular supply to the ischemic sclera, repair defects in the conjunctiva, and promote corneal reepithelialization, thus facilitating ocular surface stabilization after burns., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Burn Association.)

Study Design: Systematic review with meta-analysis., Objectives: To evaluate the effects of enhanced recovery after surgery (ERAS) on the postoperative recovery of patients who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA)., Methods: The PubMed, Embase, Cochrane and ISI Web of Science databases were searched to identify literature including randomised controlled trials (RCTs), cohort studies and case-control studies through 2 May 2018. The analysed outcomes were mortality rate, transfusion rate, range of motion (ROM), 30-day readmission rate, postoperative complication rate and in-hospital length of stay (LOS)., Results: A total of 25 studies involving 16 699 patients met the inclusion criteria and were included in the meta-analysis. Compared with conventional care, ERAS was associated with a significant decrease in mortality rate (relative risk (RR) 0.48, 95% CI 0.27 to 0.85), transfusion rate (RR 0.43, 95% CI 0.37 to 0.51), complication rate (RR 0.74, 95% CI 0.62 to 0.87) and LOS (mean difference (MD) -2.03, 95% CI -2.64 to -1.42) among all included trials. However, no significant difference was found in ROM (MD 7.53, 95% CI -2.16 to 17.23) and 30-day readmission rate (RR 0.86, 95% CI 0.56 to 1.30). There was no significant difference in complications of TKA (RR 0.84, 95% CI 0.34 to 2.06) and transfusion rate in RCTs (RR 0.66, 95% CI 0.15 to 2.88) between the ERAS group and the control group., Conclusions: This meta-analysis showed that ERAS significantly reduced the mortality rate, transfusion rate, incidence of complications and LOS of patients undergoing TKA or THA. However, ERAS did not show a significant impact on ROM and 30-day readmission rate. Complications after hip replacement are less than those of knee replacement, and the young patients recover better., Level of Evidence: Level 1., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The development and demonstration of a four-color single-ended mid-infrared tunable laser-absorption sensor for simultaneous measurements of H 2 O, CO 2 , CO, and temperature in combustion flows is described. This sensor operates by transmitting laser light through a single optical port and measuring the backscattered radiation from within the combustion device. Scanned-wavelength-modulation spectroscopy with second-harmonic detection and first-harmonic normalization (scanned-WMS-2f/1f) was used to account for variable signal collection and nonabsorption losses in the harsh environment. Two tunable diode lasers operating near 2551 and 2482 nm were utilized to measure H 2 O concentration and temperature, while an interband cascade laser near 4176 nm and a quantum cascade laser near 4865 nm were used for measuring CO 2 and CO, respectively. The lasers were modulated at either 90 or 112 kHz and scanned across the peaks of their respective absorption features at 1 kHz, leading to a measurement rate of 2 kHz. A hybrid demultiplexing strategy involving both spectral filtering and frequency-domain demodulation was used to decouple the backscattered radiation into its constituent signals. Demonstration measurements were made in the exhaust of a laboratory-scale laminar methane-air flat-flame burner at atmospheric pressure and equivalence ratios ranging from 0.7 to 1.2. A stainless steel reflective plate was placed 0.78 cm away from the sensor head within the combustion exhaust, leading to a total absorption path length of 1.56 cm. Detection limits of 1.4% H 2 O, 0.6% CO 2 , and 0.4% CO by mole were reported. To the best of the authors' knowledge, this work represents the first demonstration of a mid-infrared laser-absorption sensor using a single-ended architecture in combustion flows.

We report measured line intensities and temperature-dependent broadening coefficients of NH 3 with Ar, N 2 , O 2 , CO 2 , H 2 O, and NH 3 for nine sQ( J , K ) transitions in the ν 2 fundamental band in the frequency range 961.5-967.5 cm -1 . This spectral region was chosen due to the strong NH 3 absorption strength and lack of spectral interference from H 2 O and CO 2 for laser-based sensing applications. Spectroscopic parameters were determined by multi-line fitting using Voigt lineshapes of absorption spectra measured with two quantum cascade lasers in thermodynamically-controlled optical cells. The temperature dependence of broadening was measured over a range of temperatures between 300 and 600 K. These measurements aid the development of mid-infrared NH 3 sensors for a broad range of gas mixtures and at elevated temperatures.

Manual editing of a metro map is essential because many aesthetic and readability demands in map generation cannot be achieved by using a fully automatic method. In addition, a metro map should be updated when new metro lines are developed in a city. Considering that manually designing a metro map is time-consuming and requires expert skills, we present an interactive editing system that considers human knowledge and adjusts the layout to make it consistent with user expectations. In other words, only a few stations are controlled and the remaining stations are relocated by our system. Our system supports both curvilinear and octilinear layouts when creating metro maps. It solves an optimization problem, in which even spaces, route straightness, and maximum included angles at junctions are considered to obtain a curvilinear result. The system then rotates each edge to extend either vertically, horizontally, or diagonally while approximating the station positions provided by users to generate an octilinear layout. Experimental results, quantitative and qualitative evaluations, and user studies show that our editing system is easy to use and allows even non-professionals to design a metro map.

Powdery mildew and rust fungi are obligate parasites that cannot live without host organisms. They are difficult to culture in synthetic medium in the laboratory. Genomic DNA extraction is one of the basic molecular techniques used to study the genetic structure of populations. In this study, 2 different DNA extraction methods, Chelex-100 and cetyltrimethylammonium bromide (CTAB), were used to extract DNA from euonymus powdery mildew and Puccinia striiformis f. sp Tritici. Polymerase chain reaction was carried out with a race-specific-marker rDNA-internal transcribed spacer sequence. Both DNA extraction methods were compared and analyzed. The results showed that both Chelex-100 and CTAB were effective for extracting genomic DNA from infected plant tissue. However, less DNA was required for the Chelex-100 method than for the CTAB method, and the Chelex-100 method involved fewer steps, was simpler and safer, and did not require organic solvents compared to the CTAB method. DNA quality was evaluated by polymerase chain reaction, and the results showed that genomic DNA extracted using the Chelex-100 method was better than that using CTAB method, and was sufficient for studying the genetic structure of population.

Field experiments were conducted in 2006-2008 to study the effects of no-tillage on the spatiotemporal dynamics of soil water content and related soil physical properties in spring corn fields in Beijing region during growth season. In study period, the water storage in 0-100 cm soil layer in tillage and no-tillage treatments had the same variation trend with time and precipitation, but the water storage at different time periods and under different precipitations was 2.7%-30.3% higher in no-tillage treatment than in tillage treatment. When the precipitation was relatively abundant, the increment of soil water storage was somewhat increased, but no-tillage was still worth to be popularized in the regions relatively deficit in precipitation. Under no-tillage, the average water storage in 0-100 cm soil layer during the three growth seasons in 2006-2008 was 3.4%-12.8% higher than that under conventional tillage, and the increment of the water storage in 0-20 cm and 80-100 cm soil layers under no-tillage was higher than that in intermediate layer, with the highest increment reached 22.2%. No-tillage improved soil water-holding capacity and water use efficiency via decreasing soil bulk density, increasing soil porosity, and promoting the formation of soil water-stable aggregates, and thereby, promoted crop yielding. After 3 years no-tillage, the soil water use efficiency and spring corn yield were increased by 13.3% and 16.4%, respectively, compared with those under conventional tillage.

In this report, we demonstrate that sodium hydrosulfide (NaHS), a hydrogen sulfide (H(2)S) donor, promoted adventitious root formation mediated by auxin and nitric oxide (NO). Application of the H(2)S donor to seedling cuttings of sweet potato (Ipomoea batatas L.) promoted the number and length of adventitious roots in a dose-dependent manner. It was also verified that H(2)S or HS(-) rather than other sulfur-containing components derived from NaHS could be attributed to the stimulation of adventitious root formation. A rapid increase in endogenous H(2)S, indole acetic acid (IAA) and NO were sequentially observed in shoot tips of sweet potato seedlings treated with HaHS. Further investigation showed that H(2)S-mediated root formation was alleviated by N-1-naphthylphthalamic acid (NPA), an IAA transport inhibitor, and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), an NO scavenger. Similar phenomena in H(2)S donor-dependent root organogenesis were observed in both excised willow (Salix matsudana var. tortuosa Vilm) shoots and soybean (Glycine max L.) seedlings. These results indicated that the process of H(2)S-induced adventitious root formation was likely mediated by IAA and NO, and that H(2)S acts upstream of IAA and NO signal transduction pathways.

The purpose of the present study was to examine the kinetic process of hemoglobin (Hb) carrying and releasing oxygen. Under the standard conditions (pH 7.4, Po(2) 20 mmHg, 20 °C) the blood samples of chicken, rabbit, frog and carp were equilibrated in oxygen content analyzer with calibrated gas mixture A (0.5% CO(2) and 99.5% N(2)). Then the blood samples were exposed to gas mixture B (21% O(2), 0.5% CO(2) and 78.5% N(2)). After equilibration, the blood samples were exposed to gas mixture A again. During the whole process, Po(2) of blood samples was detected in real-time. The time spent in blood Po(2) changing from 0 to 21 kPa was recorded carefully. The results indicated that the kinetic curve of Hb carrying oxygen presented a shape of "S". It was similar to the Hb oxygen dissociation curve (Hb ODC). Based on the curve, T(50), a new kinetic parameter, was established. T(50) is the time of 50% O(2) saturation of Hb. It can reflect the efficiency of Hb carrying oxygen. Through comparing of T(50), the efficiency of Hb carrying oxygen among 4 species of animals was: frog < carp < rabbit < chicken. In the phase I of Hb carrying and releasing oxygen kinetic curve, the slope in carp was much larger than that in rabbit; the time [(1 411±6) s] of Hb releasing oxygen in chicken was longer than that in other 3 animals. These differences reflected the variety of efficiency of Hb carrying and releasing oxygen. In addition, the kinetic features of Hb carrying oxygen were likely to become an important index to evaluate the function of Hb carrying oxygen, especially in evaluating the ability of artificial blood substitute. On the basis of the analysis of the kinetic curve of Hb carrying oxygen and Hb ODC, another new important efficacy parameter E(50) was proposed. E(50) reflects the relationship between the time of 50% O(2) saturation of Hb and environmental Po(2). E(50) can be used as a synthetic index to assess the efficiency of Hb carrying oxygen.

Rice bifunctional alpha-amylase/subtilisin inhibitor (RASI) can inhibit both alpha-amylase from larvae of the red flour beetle (Tribolium castaneum) and subtilisin from Bacillus subtilis. The synthesis of RASI is up-regulated during the late milky stage in developing seeds. The 8.9 kDa molecular-weight RASI from rice has been crystallized using the hanging-drop vapour-diffusion method. According to 1.81 angstroms resolution X-ray diffraction data from rice RASI crystals, the crystal belongs to space group P2(1)2(1)2, with unit-cell parameters a = 79.99, b = 62.95, c = 66.70 angstroms. Preliminary analysis indicates two RASI molecules in an asymmetric unit with a solvent content of 44%.

This study was aimed to determine organotin concentrations in the muricids Thais clavigera, Thais tuberosa and Morula granulata on an island wide scale and to find an adequate bioindicator species for long-term monitoring purpose. Samples were collected from the coast of Taiwan and vicinity islands with organotin analysis by graphite furnace atomic absorption spectrophotometry. Because triphenyltin (TPT) could not be discriminated from tributyltin (TBT) by the extraction method, organotins were measured as TBT + TPT and total hexane extractable organotins. Severity of imposex in the muricid population samples expressed as relative penis size (RPS) indices were calculated and compared to determine a suitable bioindicator species. In T. clavigera, T. tuberosa and M. granulata, TBT + TPT were 17-157, 1-44 and 117-1343 ng Sn g(-1) dry wt, respectively. And total organotins varied in the range of 181 to 1125, 23 to 44 and 229 to 1402 ng Sn g(-1) dry wt, respectively. A positive correlation was found between TBT + TPT and total organotins in M. granulata (TBT + TPT = Total organotins x 1.01-110.79; R2=0.97; p<0.001). At the site of Dapaisha, total organotins in M. granulata was 10 times higher than in T. tuberosa (i.e. 242 versus 23 ng Sn g(-1) dry wt). No signs of imposex were found in T. tuberosa (a single site in two subsequent years) and in M. granulata (seven collection sites). The degree of imposex (RPS) of T. clavigera varied from 0.2 to 38.1%. The RPS indices from fishing harbors were not higher than from rocky shores and oyster culture sites. No correlation was found between RPS indices and concentrations of TBT + TPT or total organotins. M. granulata seemed to be insensitive to organotin pollution although organotins were also detected. Our results indicate that organotin pollution is wide spread in coastal waters of Taiwan and pollutants at least include butyltins and phenyltins. As a bioindicator species, T. clavigera is more appropriate than T. tuberosa and M. granulata to monitor organotin contamination.