Two Ratiometric Fluorescent Probes Based on the Hydroxyl Coumarin Chalcone Unit with Large Fluorescent Peak Shift for the Detection of Hydrazine in Living Cells.

Hydrazine is widely used in industrial and agricultural production, but excessive hydrazine possesses a serious threat to human health and environment. Here two new ratiometric fluorescence probes, DDP and DDC, with the hydroxyl coumarin chalcone unit as the sensing site are developed, which can achieve colorimetric and ratiometric recognition for hydrazine with good sensitivity, excellent selectivity, and anti-interference. The calculated fluorescence limits of detections are 0.26 µM (DDC) and 0.14 µM (DDP). The ratiometric fluorescence response to hydrazine is realized through the adjustment of donor and receptor units in coumarin conjugate structure terminals, accompanied by fluorescence peak shift about 200 nm (DDC, 188 nm; DDP, 229 nm). Stronger electropositivity in the carbon-carbon double bond is helpful to the first phase addition reaction between the probe and hydrazine. Higher phenol activity in the hydroxyl coumarin moiety will facilitate the following dihydro-pyrazole cyclization reaction. In addition, both of these probes realized the convenient detection of hydrazine vapor. The probes were also successfully applied to detect hydrazine in actual water samples, different soils, and living cells.

Differences in verbal and spatial working memory in patients with bipolar II and unipolar depression: an MSI study.

BACKGROUND: Depressive symptoms could be similarly expressed in bipolar and unipolar disorder. However, changes in cognition and brain networks might be quite distinct. We aimed to find out the difference in the neural mechanism of impaired working memory in patients with bipolar and unipolar disorder. METHOD: According to diagnostic criteria of bipolar II disorder of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and assessments, 13 bipolar II depression (BP II), 8 unipolar depression (UD) patients and 15 healthy controls (HC) were recruited in the study. We used 2-back tasks and magnetic source imaging (MSI) to test working memory functions and get the brain reactions of the participants. RESULTS: Compared with HC, only spatial working memory tasks accuracy was significantly worse in both UD and BP II (p = 0.001). Pearson correlation showed that the stronger the FCs' strength of MFG-IPL and IPL-preSMA, the higher accuracy of SWM task within left FPN in patients with UD (r = 0.860, p = 0.006; r = 0.752, p = 0.031). However, the FC strength of IFG-IPL was negatively correlated with the accuracy of SWM task within left FPN in patients with BP II (r = - 0.591, p = 0.033). CONCLUSIONS: Our study showed that the spatial working memory of patients with whether UD or BP II was impaired. The patterns of FCs within these two groups of patients were different when performing working memory tasks.

Alleviation of cognitive deficits and high copper levels by an NMDA receptor antagonist in a rat depression model.

BACKGROUND: Major depressive disorder (MDD) is frequently associated with cognitive deficits and high copper levels. Dysfunction of N-methyl-d-aspartate (NMDA) receptors has been postulated to underlie MDD pathogenesis. This study sought to investigate the curative effect of the NMDA receptor antagonist memantine on cognitive deficits in depression and the underlying mechanisms. METHODS: Adult male Sprague-Dawley rats received corticosterone (CORT) (20 mg/kg) bi-weekly via subcutaneous injection and/or copper gluconate (7 mg/kg) via daily intragastric administration. After 3 weeks, sucrose preference tests and open field tests showed anhedonia and high anxiety in both the CORT and CORT+Cu groups. Memantine intervention (20 mg/kg daily via intragastric administration for 14 days) led to recovery of anhedonia and anxiety behaviors. Memantine also remarkably suppressed serum copper ion levels. Moreover, memantine treatment effectively rescued depression-related spatial memory deficits as shown by the Morris water maze task. RESULTS: Compared to the pre-memantine treatment results, the results of behavioral tests and cognitive function after memantine treatment were significantly normalized, and the copper concentration was decreased in all groups. CONCLUSIONS: Collectively, our findings suggest that the NMDA receptor antagonist memantine may improve symptoms of anhedonia and anxiety and the cognitive deficits associated with depression, likely be related to suppress serum copper ion levels.

Misophonia is related to stress but not directly with traumatic stress.

The relationship between misophonia, stress, and traumatic stress has not been well characterized scientifically. This study aimed to explore the relationships among misophonia, stress, lifetime traumatic events, and traumatic stress. A community sample of adults with self-reported misophonia (N = 143) completed structured diagnostic interviews and psychometrically validated self-report measures. Significant positive correlations were observed among perceived stress, traumatic stress, and misophonia severity. However, multivariate analyses revealed that perceived stress significantly predicted misophonia severity, over and above traumatic stress symptoms. The number of adverse life events was not associated with misophonia severity. Among symptom clusters of post-traumatic stress disorder, only hyperarousal was associated with misophonia severity. These findings suggest that transdiagnostic processes related to stress, such as perceived stress and hyperarousal, may be important phenotypic features and possible treatment targets for adults with misophonia.

Association between cognitive impairments and aberrant dynamism of overlapping brain sub-networks in unmedicated major depressive disorder: A resting-state MEG study.

OBJECTIVE: Little is known about the pathogenesis underlying cognitive impairment in major depressive disorder (MDD). We aimed to explore the mechanisms of cognitive impairments among patients with MDD by investigating the dynamics of overlapping brain sub-networks. METHODS: Forty unmedicated patients with MDD and 28 healthy controls (HC) were enrolled in this study. Cognitive function was measured using the Chinese versions of MATRICS Consensus Cognitive Battery (MCCB). All participants were scanned using a whole-head resting-state magnetoencephalography (MEG) machine. The dynamism of neural sub-networks was analyzed based on the detection of overlapping communities in five frequency bands of oscillatory brain signals. RESULTS: MDD demonstrated poorer cognitive performance in six domains compared to HC. The difference in community detection (functional integration mode) in MDD was frequency-dependent. MDD showed significantly decreased community dynamics in all frequency bands compared to HC. Specifically, differences in the visual network (VN) and default mode network (DMN) were detected in all frequency bands, differences in the cognitive control network (CCN) were detected in the alpha2 and beta frequency bands, and differences in the bilateral limbic network (BLN) were only detected in the beta frequency band. Moreover, community dynamics in the alpha2 frequency band were positively correlated with verbal learning and reasoning problem solving abilities in MDD. CONCLUSIONS: Our study found that decreasing in the dynamics of overlapping sub-networks may differ by frequency bands. The aberrant dynamics of overlapping neural sub-networks revealed by frequency-specific MEG signals may provide new information on the mechanism of cognitive impairments that result from MDD.

The Effectiveness of Eye Movement Desensitization and Reprocessing Toward Adults With Major Depressive Disorder: A Meta-Analysis of Randomized Controlled Trials.

The practice-based evidence suggests that it is possible to use eye movement desensitization and reprocessing (EMDR) to treat major depressive disorder (MDD), but its specific efficacy is unknown. A systematic search was carried out for randomized controlled trials comparing EMDR with a control condition group in MDD patients. Two meta-analyses were conducted, with symptom reduction as primary outcome and remission as exploratory outcome. Eight studies with 320 participants were included in this meta-analysis. The first meta-analysis showed that EMDR outperformed "No Intervention" in decreasing depressive symptoms (standardized mean difference [SMD] = -0.81, 95% CI = -1.22 to -0.39, p < 0.001, low certainty), but statistically significant differences were not observed in improving remission (risk ratio = 1.20, 95% CI = 0.87-1.66, p = 0.25, very low certainty). The second showed the superiority of EMDR over CBT in reducing depressive symptoms (mean difference [MD] = -7.33, 95% CI = -8.26 to -6.39, p < 0.001, low certainty), and improving remission (risk ratio = 1.95, 95% CI = 1.24-3.06, p = 0.004, very low certainty). Besides, anxiety symptoms and level of functioning could not be included as secondary outcome due to the lack of data. The present meta-analysis suggests that EMDR is more effective in treating MDD than "No Intervention" and CBT, particularly in individuals who have traumatic experience. However, this result should be considered with caution due to small sample size and low quality of trails.

The characteristic of cognitive impairments in patients with bipolar II depression and its association with N-acetyl aspartate of the prefrontal white matter.

BACKGROUND: Cognitive deficit is acknowledged as a core feature of clinical manifestations of bipolar disorder (BD). However, the underlying mechanism of cognitive impairment in bipolar II depression has remained uncertain. We aim to determine the association of cognitive impairments with biochemical metabolism using proton magnetic resonance spectroscopy (1H-MRS) and a battery of neuropsychological testing. METHODS: The current study was designed to assess four cognitive domains in a sample of 110 patients with bipolar II depression and 110 healthy controls, using a battery of 6 cognitive tests, including the Digit Symbol Substitution Test (DSST), Wisconsin Cart Sorting Test (WCST), Trail Making Test Part B (TMT-B), Digit Span Test (DST), TMT-part A (TMT-A) and Verbal Fluency Test (VFT). Metabolite levels were obtained in the following brain regions of interest: bilateral prefrontal white matter (PWM), bilateral anterior cingulate cortex (ACC), bilateral lenticular nucleus (LN), and bilateral thalamus. N-acetyl aspartate (NAA)/creatine (Cr) and choline-containing compounds (Cho)/Cr ratios are analyzed. RESULTS: Patients with bipolar II depression performed significantly worse on DSST (score), TMT (completion time), DSB (score), and VFT (valid word number) when compared with healthy controls. In the bilateral PWM, NAA/Cr ratios in the PWM were significantly reduced (bilaterally) than those in healthy controls. Correlation analysis was conducted with data from patients with bipolar II depression, we found that the NAA/Cr ratio of the left PWM was positively correlated with the score of DS and DSB, and the NAA/Cr ratio of the right PWM was negatively correlated with the completion time of TMT-B. CONCLUSIONS: Our findings suggested that psychomotor speed, executive function, working memory, and verbal fluency are impaired in patients with BD II depression. Hypoactivity NAA/Cr in bilateral PWM may be associated with BD II depression's pathophysiology and results in cognitive dysfunction.

Altered biochemical metabolism and its lateralization in the cortico-striato-cerebellar circuit of unmedicated bipolar II depression.

OBJECTIVES: Evidence of the relationship between neurometabolic changes in the cortico-striato-cerebellar (CSC) circuit and bipolar disorder (BD) is still limited. To elucidate the pathogenesis of BD, we investigated the underlying neurometabolic changes and their effect on CSC lateralization circuits in unmedicated patients with bipolar II depression. METHODS: Forty unmedicated participants with bipolar II depression and forty healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS). We obtained bilateral metabolic ratios of N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr in the prefrontal white matter (PWM), anterior cingulate cortex (ACC), basal ganglia (BG) and the cerebellum. Metabolic ratios were characterized using a laterality index (LI) for left-right asymmetry. RESULTS: Overall, aberrant lateralization in the CSC circuit was characteristic in patients with bipolar II depression. Patients with bipolar II depression showed significantly lower NAA/Cr ratios in the left PWM, right ACC, left BG and left cerebellum when compared with the healthy controls. For bipolar II depression, we found lower NAA/Cr LI in the PWM, BG, and cerebellum, higher NAA/Cr LI in the ACC, and higher Cho/Cr LI in the BG and cerebellum when compared to the standard value (1.0). For healthy controls, we found lower NAA/Cr LI only in the BG and higher Cho/Cr LI in the cerebellum when compared to 1.0. LIMITATIONS: As a cross-sectional study with a small sample size, progressive changes and complex metabolic interactions with treatment were not observed. CONCLUSIONS: Our findings suggest that abnormal biochemical metabolism with aberrant lateralization in the CSC circuit may be an underlying pathophysiology of bipolar II depression.

Cyanide and biothiols recognition properties of a coumarin chalcone compound as red fluorescent probe.

A novel coumarin chalcone derivative 1 was designed, synthesized and characterized by nuclear magnetic resonance spectra and high resolution mass spectrum. The photophysical and recognition properties of the compound as red fluorescent probe for cyanide and biothiols including cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) have been discussed systematically. Red fluorescence probe 1 was able to achieve rapid and selective identification for cyanide anion and biothiols in aqueous solutions with red fluorescence quench. In addition, the recognition mechanism of 1 was demonstrated by in situ 1H NMR. The compound has two potential nucleophilic sensing sites including carbon-carbon double bond and 4-position of coumarin. The results indicate that cyanide anions can be bonded to these two sites to afford 2:1 bonding product. But biothiols only are bonded to carbon-carbon double bond by Michael addition reaction. The bonding of both cyanide and biothiols to the probe disrupts intramolecular charge transfer and leads to fluorescence quench.

Correlations between working memory impairment and neurometabolites of prefrontal cortex and lenticular nucleus in patients with major depressive disorder.

BACKGROUND: The mechanism of working memory (WM) impairment in MDD remains unclear. We aimed to find out the mechanism by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS). METHODS: 31 MDD patients and 31 healthy controls were recruited in our study. The WM performance and neurometabolite ratios of prefrontal cortex (PFC) and lenticular nucleus (LN) between two groups were evaluated and compared. And the correlations between abnormal neurometabolite ratios and WM dysfunction were computed. RESULTS: Scores of SDMT, DST(forwards), VRS and 2-back Task(accuracy rate) in MDD were lower than HCs. NAA/Cr ratios of bilateral PFC in MDD were significantly lower than HCs, while no significant differences showed in NAA/Cr ratios of LN and Cho/Cr, mI/Cr values of the bilateral PFC and LN between two groups. And for MDD patients, NAA/Cr ratios in the right PFC were positively correlated with scores of DST (Forwards). CONCLUSIONS: Our findings suggest that depressed patients may have impairments in working memory, including phonological loop, visual-spatial sketchpad, episodic buffer and central executive. And the impairment of verbal WM and WM capacity may be associated with the abnormal neurometabolites in the right PFC.

Several hemicyanine dyes as fluorescence chemosensors for cyanide anions.

Four hemicyanine dyes as chemosensors for cyanide anions were synthesized easily. Their photophysical properties and recognition properties for cyanide anions were investigated. The results indicate that all the dyes can recognize cyanide anions with obvious color, absorption and fluorescence change. The recognition mechanism analysis basing on in situ (1)H NMR and Job plot data indicates that to the compounds with hydroxyl group, the recognition mechanism is intramolecular hydrogen bonding interaction. However, to the compounds without hydroxyl group, cyanide anion is bonded to carbon-carbon double bond in conjugated bridge and induces N(+)CH3 to neutral NCH3. Fluorescence of the compounds is almost quenched upon the addition of cyanide anions.

Coumarin benzothiazole derivatives as chemosensors for cyanide anions.

Four coumarin benzothiazole derivatives, N-(benzo[d]thiazol-2-yl)-2-oxo-2H-chromene-3-carboxamide (1), (Z)-N-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-2-oxo-2H-chromene-3-carboxamide (2), 7-(diethylamino)-N-(benzo[d]thiazol-2-yl)-2-oxo-2H-chromene-3-carboxamide (3) and (Z)-7-(diethylamino)-N-(3-methylbenzo[d]thiazol-2(3H)-ylidene)-2-oxo-2H-chromene-3-carboxamide) (4), have been synthesized. Their crystal structures, photophysical properties in acetonitrile and recognition properties for cyanide anions have been investigated. All the compounds are generally planar, especially compound 1 exhibits perfect planarity with dihedral angle between benzothiazolyl group and coumarin group being only 3.63°. Coumarin benzothiazole compounds 1 and 3 can recognize cyanide anions by Michael addition reaction and compound 3 exhibits color change from yellow to colorless and green fluorescence was quenched completely, which can be observed by naked eye. Coumarin benzothiazolyliden compound 4 can recognize cyanide anions with fluorescence turn-on response based on the copper complex ensemble displacement mechanism.