Design, synthesis, and biological application of A-D-A-type boranil fluorescent dyes.

For the first time, three acceptor-donor-acceptor (A-D-A)-type boranil fluorescent dyes, CSU-BF-R (R = H, CH3, and OCH3), featuring phenothiazine as the donor, were designed and synthesized. CSU-BF-R exhibited remarkable photophysical characteristics, including large Stokes shifts (>150 nm), high fluorescence quantum yields (up to 40%), long-wavelength emissions, and strong red solid-state fluorescence. Moreover, these CSU-BF-R fluorescent dyes were demonstrated to function as highly selective and sensitive ratiometric fluorescent probes for detecting hypochlorous acid (HClO). The preliminary biological applications of CSU-BF-OCH3 for sensing intracellular HClO in living cells and zebrafish were demonstrated. Therefore, CSU-BF-R possess the potential to further explore the physiological and pathological functions associated with HClO and provide valuable insights into the design of high-performance A-D-A-type fluorescent dyes.

Tumor markers and depression scores are predictive of non-suicidal self-injury behaviors among adolescents with depressive disorder: A retrospective study.

Background: Non-suicidal self-injury (NSSI) is an important risk factor for suicide in adolescents with depressive disorders; therefore, it is important to predict NSSI occurrence as early as possible. Disturbances in biological rhythms are characteristic manifestations of depressive disorders and can lead to immune dysfunction, leading to changes in tumor markers. This study aimed to produce an index that utilizes tumor markers to predict NSSI behaviors among adolescents with depressive disorders. Methods: A total of 120 hospitalized adolescent patients with depressive disorders aged 14-24 years were included in this study. Participants were divided into NSSI and non-NSSI groups based on self-reports using the Ottawa Self-Injury Inventory. Demographics, tumor marker concentrations, other peripheral blood indices, Hamilton Depression Rating Scale (HDRS) scores, and Hamilton Anxiety Rating Scale (HAMA) scores were compared between the two groups. Logistic regression analysis was conducted to develop a joint index, and a receiver operating characteristic (ROC) curve was created to predict NSSI behaviors among adolescents with depressive disorders. Results: Compared with the non-NSSI group, the NSSI group had significantly higher insight, retardation, insomnia, hopelessness, psychiatric anxiety, total HDRS and HAMA scores, and significantly higher levels of cancer antigen 125 (CA-125), cancer antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). In addition, a joint index was developed by combining CA-125, CA19-9, CEA, HDRS total score, HAMA total score and age using multiple logistic regression to predict NSSI behaviors. The area under the curve was 0.831, with a sensitivity and specificity of 0.734 and 0.891, respectively. Conclusion: A combination of depression score, tumor marker levels, and age can identify NSSI behaviors among adolescents with depressive disorders.

Impact of depression on the quality of sleep and immune functions in patients with coronary artery disease.

Background: The risk of major depressive disorder (MDD) and insomnia is higher in patients with coronary heart disease (CHD) than in the general population. In addition, immune inflammation may be a shared aetiological factor for mental disorders and CHD. However, it is unclear whether MDD is associated with poor sleep quality and cell-mediated immune function in patients with CHD. Aims: This study investigated the impact of depression on sleep quality and cell-mediated immune functions in patients with CHD and examined discriminative factors in patients with CHD with and without MDD. Methods: This cross-sectional retrospective study was conducted at the Zhejiang University School of Medicine affiliated with Sir Run Run Shaw Hospital. The study population consisted of 84 patients with CHD assigned to two groups based on their Hamilton Depression Rating Scale (HAMD) score (CHD with MDD (HAMD score of ≥10) vs without MDD). Subjective sleep quality, systemic inflammatory response and cell-mediated immune functions were assessed in patients with CHD with (n=50) and without (n=34) MDD using the Pittsburgh Sleep Quality Index (PSQI), routine blood tests and flow cytometry. The relationships between variables were ascertained using Pearson's product-moment, and linear discriminant analysis was used to explore the discriminative factors between groups. Results: Patients with CHD with MDD had significantly poorer sleep quality than those without MDD (Z=-6.864, p<0.001). The Systemic Inflammation Index (SII) and CD4+/CD8+ T-cell ratios were higher in patients with CHD with MDD than in those without MDD (Z=-3.249, p=0.001). Patients with CHD with MDD had fewer CD3+CD8+ and CD3+ T cells (Z=3.422, p=0.001) than those without MDD (t=2.032, p=0.045). Furthermore, patients with CHD with MDD may be differentiated from those without MDD using the PSQI, SII and T-cell levels, as these variables correctly classified the depressed and non-depressed groups with an accuracy of 96.4%. Conclusions: MDD may be responsible for poor sleep quality, increased cell-mediated immunity and SII in patients with CHD, which are discriminative factors for CHD in the depressive state. Clinicians should be aware of these interactions, as treatment for depressive symptoms may also improve CHD prognosis.

[Correlation between suicidal ideation and polysomnography parameters in late-life depression patients].

OBJECTIVE: To investigate the relationship between sleep parameters and suicidal ideation in patients with late-life depression (LLD). METHODS: Seventy-seven LLD patients over 60 years old from Sir Run Run Shaw Hospital of Zhejiang University during July 2017 and July 2018 were included in the study. All patients were assessed with Hamilton Depression Rating Scale (HAMD) and polysomnography (PSG) overnight. The suicidal score of item 3 in HAMD (HAM-D3)was used to define whether there was a suicidal ideation. Participants were subsequently grouped according to endorsement of presence (HAM-D3 score ≥1, n=46) versus absence (HAM-D3 score=0, n=31) of suicidal ideation symptoms. The sleep efficiency, total sleep time, wakefulness after sleep onset, rapid eye movement percent/latency, and non-rapid eye movement sleep stages 1-3 (N1-N3) were assessed. ANOVA analyses were conducted to explore the correlation of sleep parameters with suicidal ideation between the groups with and without suicidal ideation. In model 1, the HAM-D3 constituted the independent variable in separate ANOVA tests; in model 2 the impact of depressive symptoms were assessed as a covariate with sleep parameters. RESULTS: There was less stage N3 [(55±41)min, t=-4.731, P<0.05] and the reduced percentage of N3 [(15±11)%, t=-4.194, P<0.05] in LLD patients with suicidal ideation, compared with the LLD patients without suicidal ideation [(104±49) min, (26±11)%]. Correlation analyses revealed that there was a significant correlation between the suicidal ideation and the percentage of stage N3 and sleep time of stage N3 (both P<0.05). CONCLUSIONS: Suicidal ideation is associated with less N3 sleep in LLD patients.

Neuroprotective Effect of DAHP via Antiapoptosis in Cerebral Ischemia.

Aberrant production of nitric oxide following inducible nitric oxide synthase (iNOS) expression has been implicated in cell death and contributes to ischemic brain injury. Tetrahydrobiopterin (BH4) is an essential cofactor of NOS activity. Herein, we evaluated antiapoptotic and anti-inflammatory effects of diamino-6-hydroxypyrimidine (DAHP), a guanosine 5'-triphosphate cyclohydrolase 1 (GTPCH1) inhibitor on focal cerebral ischemia-reperfusion injury by middle cerebral artery occlusion and reperfusion (MCAO) and investigated the underlying mechanism. Sprague-Dawley rats were divided into five groups. Experimental groups were subjected to 1.5 h transient MCAO. T2-weighted imaging was performed to evaluate brain edema lesions in the stroke rats. Infarct volume was estimated by 2,3,5-triphenyltetrazolium chloride (TTC) staining after 24 h reperfusion. Western blotting and immunohistochemistry were performed to detect iNOS, caspase-3, Bcl-2, COX-2, and TNF-α protein expressions. Apoptosis was determined by TUNEL staining. T2 hyperintensity changes were observed in primary ischemic region. DAHP pretreatment significantly suppressed iNOS overexpression, caspase-3, and TNF-α. There was also attenuation of neuronal apoptosis with decrement in proteins Bcl-2 and COX-2 expressions. On the basis of our results, we hypothesize DAHP to have a neuroprotective function against focal cerebral ischemia and might attenuate brain injury by decreasing reactive oxygen species (ROS) production, subsequently inhibiting apoptosis.

Spatiotemporal, metabolic, and therapeutic characterization of altered functional connectivity in major depressive disorder.

Although imbalanced functional integration has been increasingly reported in major depressive disorder (MDD), there still lacks a general framework to characterize common characteristic and origin shared by the integrative disturbances. Here we examined spatial selectivity, temporal uniqueness, metabolic basis, and therapeutic response of altered functional connectivity (FC) in MDD by analyzing both cross-sectional and longitudinal multimodal functional magnetic resonance imaging data from 35 patients and 34 demographically matched healthy controls. First, based on a voxel-wise, data-driven, graph-based degree centrality approach, the bilateral anterior cingulate gyri, middle frontal gyri and superior frontal gyri, and the right parahippocampal gyrus were robustly identified to show decreased FC in MDD. Further spatiotemporal analyses revealed that these regions exhibited hub-like features and were selectively located in limbic and default mode networks spatially and, relative to other areas in the brain, exhibited unique, frequency-dependent oscillation power (stronger within 0.01-0.027 Hz and weaker within 0.027-0.073 Hz) and less dynamical variability of whole-brain FC profiles temporally. Moreover, a cross-modality fusion analysis showed that all MDD-related FC impairments were associated with reduced cerebral blood flow (CBF); however, there existed multiple regions that showed reduced CBF but had intact FC in the patients, which resulted in a decreased FC-CBF coupling and implied an earlier emergence of reduced CBF than impaired FC in MDD. Finally, the disrupted FC in MDD gradually recovered over the course of drug treatment (2 and 12 weeks). Altogether, these findings could help establish a general framework to provide mechanistic insights into integrative dysfunctions in MDD.

Underdetermined Wideband DOA Estimation for Off-Grid Sources with Coprime Array Using Sparse Bayesian Learning.

Sparse Bayesian learning (SBL) is applied to the coprime array for underdetermined wideband direction of arrival (DOA) estimation. Using the augmented covariance matrix, the coprime array can achieve a higher number of degrees of freedom (DOFs) to resolve more sources than the number of physical sensors. The sparse-based DOA estimation can deteriorate the detection and estimation performance because the sources may be off the search grid no matter how fine the grid is. This dictionary mismatch problem can be well resolved by the SBL using fixed point updates. The SBL can automatically choose sparsity and approximately resolve the non-convex optimizaton problem. Numerical simulations are conducted to validate the effectiveness of the underdetermined wideband DOA estimation via SBL based on coprime array. It is clear that SBL can obtain good performance in detection and estimation compared to least absolute shrinkage and selection operator (LASSO), simultaneous orthogonal matching pursuit least squares (SOMP-LS) , simultaneous orthogonal matching pursuit total least squares (SOMP-TLS) and off-grid sparse Bayesian inference (OGSBI).

Quantifying the effects of LUCCs on local temperatures, precipitation, and wind using the WRF model.

Land use/cover changes (LUCCs) are an important cause of regional climate changes, but the contribution of LUCCs to regional climate changes is not clear. In this study, the Weather Research and Forecasting (WRF) model and statistical methods were used to investigate changes in meteorologic variables in January, April, July, and October 2013 due to local LUCCs from 1990 to 2010 in southern Shandong province, China. The results indicate that the WRF model simulates temperatures in the region well, with high correlation coefficients (0.86-0.97, p < 0.001) between the modeled and measured values. The model simulates precipitation less well, with correlation coefficients of 0.41-0.91, but they are all at statistically significant levels, with p < 0.05. During the 20-year period, the LUCCs in the study area consisted mainly of conversions from dry land to urbanized land (747.3 km2) and bare/sparse vegetation (132.4 km2). The LUCCs caused a 0.16 °C temperature increase in January and October and 0.01 and 0.18 °C temperature decreases in April and July, respectively. The range of temperature changes over mixed forest and water bodies due to the LUCCs was wide (0.39-1.31 °C) and was narrower over deciduous broadleaf forest and wetland (0.01 to 0.06 °C). The LUCCs did not change the precipitation greatly in January, April, and October but did affect the precipitation in July substantially, causing a decrease of 23.71 mm. The LUCCs did not affect wind speed and direction substantially during these four months: average wind speeds increased by 0.02 and 0.01 m/s in January and October, respectively, and decreased by 0.02 and 0.05 m/s in April and July, respectively. Overall, The LUCCs affected spring temperatures the least and summer precipitation the most.

Separation of phenolic acids and flavonoids from Trollius chinensis Bunge by high speed counter-current chromatography.

In this work, eleven compounds were successfully separated from Trollius chinensis Bunge by using a two-step high-speed counter-current chromatography (HSCCC) method. NRTL-SAC (nonrandom two-liquid segment activity coefficient) method, a newly developed solvent system selection strategy, was applied to screening the suitable biphasic liquid systems. Hexane/ethyl acetate/ethanol/water (3:7:3:7, v/v) solvent system was used in the first step, while the hexane/ethyl acetate/methanol/water (1:2:1:2, 1:4:1:4, 1:9:1:9, v/v) systems were employed in the second step. The chemical structures of the separated compounds were identified by UV, high resolution ESI-MS and MS/MS data. The separated compounds are 3,4-dihydroxyphenylethanol (1), vanillic acid (2), orientin (3), vitexin (4), veratric acid (5), 2″-O-(3‴, 4‴-dimethoxybenzoyl) orientin (6), 2″-O-feruloylorientin (7), 2″-O-feruloylvitexin (8), 2″-O-(2‴-methylbutyryl) vitexin (9), 2″-O-(2‴-methylbutyryl) isoswertiajaponin (10), 2″-O-(2‴-methylbutyryl) isoswertisin (11). The results demonstrate that HSCCC is a powerful tool for the separation of compounds from extremely complex samples.

Systematic and practical solvent system selection strategy based on the nonrandom two-liquid segment activity coefficient model for real-life counter-current chromatography separation.

Solvent system selection is the first step toward a successful counter-current chromatography (CCC) separation. This paper introduces a systematic and practical solvent system selection strategy based on the nonrandom two-liquid segment activity coefficient (NRTL-SAC) model, which is efficient in predicting the solute partition coefficient. Firstly, the application of the NRTL-SAC method was extended to the ethyl acetate/n-butanol/water and chloroform/methanol/water solvent system families. Moreover, the versatility and predictive capability of the NRTL-SAC method were investigated. The results indicate that the solute molecular parameters identified from hexane/ethyl acetate/methanol/water solvent system family are capable of predicting a large number of partition coefficients in several other different solvent system families. The NRTL-SAC strategy was further validated by successfully separating five components from Salvia plebeian R.Br. We therefore propose that NRTL-SAC is a promising high throughput method for rapid solvent system selection and highly adaptable to screen suitable solvent system for real-life CCC separation.

Relationship between personality disorder functioning styles and the emotional states in bipolar I and II disorders.

BACKGROUND: Bipolar disorder types I (BD I) and II (BD II) behave differently in clinical manifestations, normal personality traits, responses to pharmacotherapies, biochemical backgrounds and neuroimaging activations. How the varied emotional states of BD I and II are related to the comorbid personality disorders remains to be settled. METHODS: We therefore administered the Plutchick - van Praag Depression Inventory (PVP), the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32), and the Parker Personality Measure (PERM) in 37 patients with BD I, 34 BD II, and in 76 healthy volunteers. RESULTS: Compared to the healthy volunteers, patients with BD I and II scored higher on some PERM styles, PVP, MDQ and HCL-32 scales. In BD I, the PERM Borderline style predicted the PVP scale; and Antisocial predicted HCL-32. In BD II, Borderline, Dependent, Paranoid (-) and Schizoid (-) predicted PVP; Borderline predicted MDQ; Passive-Aggressive and Schizoid (-) predicted HCL-32. In controls, Borderline and Narcissistic (-) predicted PVP; Borderline and Dependent (-) predicted MDQ. CONCLUSION: Besides confirming the different predictability of the 11 functioning styles of personality disorder to BD I and II, we found that the prediction was more common in BD II, which might underlie its higher risk of suicide and poorer treatment outcome.

Using nonrandom two-liquid model for solvent system selection in counter-current chromatography.

Selection of an appropriate solvent system is of great importance for a successful counter-current chromatography separation. In this work, the nonrandom two-liquid (NRTL) model, a thermodynamic method, was used for predicting the partition coefficient based on a few measured partition coefficients. The NRTL method provides quite satisfactory results for model solutes in first correlating measured partition coefficient in a few representative biphasic liquid systems and then successfully predicting partition coefficient in other two-phase liquid systems. According to the predicted partition coefficient, a suitable solvent system can be screened. Assisted with the NRTL method, the solvent system composed of hexane/ethyl acetate/methanol/water (1:4:1:4, v/v) was rapidly screened for the successful separation of two major compounds with high purity from Malus hupehensis leaves. The results demonstrated that the NRTL model can offer a simple and practical strategy to estimate partition coefficients in support of CCC solvent system selection, which will significantly minimize the experimental efforts and cost involved in solvent system selection.

Separation of nine compounds from Salvia plebeia R.Br. using two-step high-speed counter-current chromatography with different elution modes.

Nine compounds were successfully separated from Salvia plebeia R.Br. using two-step high-speed counter-current chromatography with three elution modes. Elution-extrusion counter-current chromatography was applied in the first step, while classical counter-current chromatography and recycling counter-current chromatography were used in the second step. Three solvent systems, n-hexane/ethyl acetate/ethanol/water (4:6.5:3:7, v/v), methyl tert-butyl ether/ethyl acetate/n-butanol/methanol/water (6:4:1:2:8, v/v) and n-hexane/ethyl acetate/methanol/water (5:5.5:5:5, v/v) were screened and optimized for the two-step separation. The separation yielded nine compounds, including caffeic acid (1), 6-hydroxyluteuolin-7-glucoside (2), 5,7,3',4'-tetrahydroxy-6-methoxyflavanone-7-glucoside (3), nepitrin (4), rosmarinic acid (5), homoplantaginin (6), nepetin (7), hispidulin (8), and 5,6,7,4'-tertrahydroxyflavone (9). To the best of our knowledge, 5,7,3',4'-tetrahydroxy-6-methoxyflavanone-7-glucoside and 5,6,7,4'-tertrahydroxyflavone have been separated from Salvia plebeia R.Br. for the first time. The purities and structures of these compounds were identified by high-performance liquid chromatography, electrospray ionization mass spectrometry, (1)H and (13)C NMR spectroscopy. This study demonstrates that high-speed counter-current chromatography is a useful and flexible tool for the separation of components from a complex sample.