Turn-on Persistent Luminescence Probe Based on Graphitic Carbon Nitride for Imaging Detection of Biothiols in Biological Fluids

Herein, we present a novel strategy based on a “turn-on” persistent luminescence imaging chemical system of graphitic carbon nitride for detecting biothiols in biological fluids. Graphitic carbon nitride (g-C₃N₄) as persistent luminescence probe is fabricated via a new procedure based on pyrolysis of guanidine hydrochloride under ambient atmospheric conditions. The prepared g-C₃N₄ nanosheets give intensively long-persistent luminescence that can avoid interference from biological media such as tissue autofluorescence and scattering light. The original persistent luminescence of g-C₃N₄ turns off due to the adsorption of silver ion (Ag⁺) onto g-C₃N₄ materials with an electron transfer process. The presence of biothiols induces the onset of persistent luminescence emission by interrupting the quenching interaction, thereby turning on the imaging probe. The approach exhibits high specificity and high sensitivity to biothiols with low detection limit for cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) with 6.4, 8.1, and 9.6 nM, respectively. It is also successfully applied for imaging detection of biothiols in human urine, plasma, and cell lysates, demonstrating its great value of practical application in biological systems

Improving the Signal-to-Background Ratio during Catalytic Hairpin Assembly through Both-End-Blocked DNAzyme

Catalyzed hairpin assembly (CHA) is an important DNA engineering tool for a variety of applications such as DNA nanotechnology and biosensing. Here we report a hairpin-type of both-end-blocked DNAzyme to improve the signal-to-background ratio during the CHA process. In the design, the DNAzyme activity can be blocked efficiently via locking both ends of the G-rich DNAzyme sequence in the loop and stem (blocking efficiency = 96%) and can be easily recovered during the CHA process (activation efficiency = 94%). The both-end-blocked DNAzyme is by far the most sensitive optical detection mode for monitoring the CHA process that can be used for determination of 0.05 fmol miRNA-21. The fabricated CHA-DNAzyme sensing system was also able to discriminate miRNA-21 from single-/three-base mismatch miRNA-21. The feasibility of real application was also tested via detection of miRNA-21 levels in tumor cell samples. Therefore, the sensing system with the advantages of convenience, high sensitivity, and selectivity is an appealing strategy for miRNA detection

Changes in the HRM metrics in the 12 patients with achalasia after POEM.

<p>Δ, decrease in the value of each metric after POME.</p><p>*<i>P</i> < 0.05.</p><p>HRM, high-resolution manometry; IRP, integrated relaxation pressure; LESP, resting lower esophageal sphincter pressure; LESL, lower esophageal sphincter length; DEP, mean distal esophageal pressure; PPR, panesophageal pressurization rate.</p><p>Changes in the HRM metrics in the 12 patients with achalasia after POEM.</p

Correlation between HRM metrics and Eckardt scores at the baseline.

<p>(A) Correlation between IRP and the total Eckardt score in all 30 patients, (B) correlation between IRP and the Eckardt score for regurgitation in all 30 patients, (C) correlation between IRP and the Eckardt score for weight loss in all 30 patients, (D) correlation between IRP and the Eckardt score for weight loss in type I achalasia patients.</p

Changes in the Eckardt score of patients with achalasia after POEM and its correlation with IRP.

<p>Changes in the Eckardt score of patients with type I (A, n = 10) and type II (B, n = 14) achalasia after POEM: correlation between IRP before POEM and changes in the total Eckardt score (C), correlation between IRP before POEM and changes in the Eckardt score for weight loss after POEM (D, n = 24), and (E) correlation between IRP changes and changes in the Eckardt score for weight loss after POEM (n = 12).</p

Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials

<div><p>Aim</p><p>We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT₃) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D).</p><p>Methods</p><p>We searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT₃ receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation. Meta- analysis was performed with Mantel Haenszel method using Revman 5.3 software.</p><p>Results</p><p>We included 21 RCTs; 16 were high quality (Jadad score ≥ 4). The pooled RR of global IBS symptoms improved by 5-HT₃ receptor antagonists versus placebo or mebeverine was 1.56 (95% CI: 1.43–1.71); alosetron, ramosetron, and cilansetron had similar treatment effects. The pooled RR of abdominal pain relieved by 5-HT₃ receptor antagonists versus placebo was 1.33 (95% CI: 1.26–1.39). The pooled RR showed that 5-HT₃ receptor antagonists improved abnormal bowel habits or stool consistency symptoms (RR = 1.63, 95% CI: 1.33, 1.99). The pooled RR of adverse events following 5-HT₃ receptor antagonist treatment was 1.15 (95% CI: 1.08, 1.22). Subgroup analysis indicated that alosetron had a high rate of adverse effects (RR = 1.16, 95% CI: 1.08, 1.25); adverse events following ramosetron treatment were not statistically significantly different. 5-HT₃ receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT₃ receptor antagonist versus placebo was 3.71 (95% CI: 2.98–4.61). However, constipation was likelier in patients with non-constipated IBS after taking 5-HT₃ receptor antagonists than in patients with IBS-D only (non-constipated IBS and IBS-D: RR = 5.28 [95% CI: 3.93, 7.08] vs. IBS-D only 3.24 [2.54, 4.12]).</p><p>Conclusions</p><p>Ramosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events.</p></div

Subgroup analyses of the efficacy endpoints.

<p>Subgroup analyses of the efficacy endpoints.</p

Characteristics of randomized controlled trials of 5-HT₃ receptor antagonists versus placebo in IBS.

<p>Characteristics of randomized controlled trials of 5-HT₃ receptor antagonists versus placebo in IBS.</p

Efficacy and Safety of Antidepressants for the Treatment of Irritable Bowel Syndrome: A Meta-Analysis

<div><p>Aim</p><p>The aim of this meta-analysis was to analyze the efficacy and safety of antidepressants for the treatment of irritable bowel syndrome.</p><p>Methods</p><p>We searched MEDLINE, EMBASE, Scopus and The Cochrane Library for randomized controlled trials investigating the efficacy and safety of antidepressants in the treatment of irritable bowel syndrome. Article quality was evaluated by Jadad score. RevMan 5.0 and Stata 12.0 were used for the meta-analysis.</p><p>Results</p><p>Twelve randomized controlled trials were included in this study and most of these trials were of high quality (Jadad score ≥4). Five articles focused on tricyclic antidepressants, six articles involved selective serotonin reuptake inhibitors, and one article investigated both types of treatment. The pooled risk ratio showed antidepressant treatment can improve global symptoms (RR = 1.38, 95% CI 1.08, 1.77). In the subgroup analysis, treatment with tricyclic antidepressants showed an improvement in global symptoms (RR = 1.36, 95% CI 1.07, 1.71), while treatment with selective serotonin reuptake inhibitors showed no statistically significant difference in global symptoms compared with the control groups (RR = 1.38, 95% CI 0.83, 2.28). The pooled risk ratio of dropout due to side effects following antidepressant treatment was 1.71 with 95% CI (0.98, 2.99). The subgroup analysis showed the pooled risk ratio of dropout in the tricyclic antidepressants group was 1.92 with 95% CI (0.89, 4.17). In the selective serotonin reuptake inhibitors group, the pooled risk ratio of dropout was 1.5 with 95% CI (0.67, 3.37). Selective serotonin reuptake inhibitors showed no benefit in alleviating abdominal pain and improving quality of life. There was no difference in the incidence of common adverse events between treatment and control groups.</p><p>Conclusions</p><p>TCAs can improve global symptoms of irritable bowel syndrome, while there was no strong evidence to confirm the effectiveness of SSRIs for the treatment of IBS.</p></div

Forest plot of the effects of antidepressants on global symptom relief.

<p>Nine articles were included. The random effect model (Mantel-Haenszel method) was applied. Abbreviation: CI confidence interval.</p