Targeted metabolomics-based understanding of the sleep disturbances in drug-naïve patients with schizophrenia.

BACKGROUND: Sleep disturbances are a common occurrence in patients with schizophrenia, yet the underlying pathogenesis remain poorly understood. Here, we performed a targeted metabolomics-based approach to explore the potential biological mechanisms contributing to sleep disturbances in schizophrenia. METHODS: Plasma samples from 59 drug-naïve patients with schizophrenia and 36 healthy controls were subjected to liquid chromatography-mass spectrometry (LC-MS) targeted metabolomics analysis, allowing for the quantification and profiling of 271 metabolites. Sleep quality and clinical symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Positive and Negative Symptom Scale (PANSS), respectively. Partial correlation analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) model were used to identify metabolites specifically associated with sleep disturbances in drug-naïve schizophrenia. RESULTS: 16 characteristic metabolites were observed significantly associated with sleep disturbances in drug-naïve patients with schizophrenia. Furthermore, the glycerophospholipid metabolism (Impact: 0.138, p<0.001), the butanoate metabolism (Impact: 0.032, p=0.008), and the sphingolipid metabolism (Impact: 0.270, p=0.104) were identified as metabolic pathways associated with sleep disturbances in drug-naïve patients with schizophrenia. CONCLUSIONS: Our study identified 16 characteristic metabolites (mainly lipids) and 3 metabolic pathways related to sleep disturbances in drug-naïve schizophrenia. The detection of these distinct metabolites provide valuable insights into the underlying biological mechanisms associated with sleep disturbances in schizophrenia.

Sex- and age-specific prevalence and risk factors of depressive symptoms in Parkinson's disease.

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50-80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50-59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50-59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70-80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression.

Exploring specific associations of childhood maltreatment with social cognition in drug-naive first-episode major depressive disorder: a sex-centric approach.

Childhood maltreatment (CM) has been linked to social cognition deficits in major depressive disorder (MDD), but little is known about sex-specific effects. This study aimed to investigate the sex-specific associations of CM with social cognition in first-episode drug-naive patients with MDD. A total of 117 first-episode drug-naive patients with MDD and 134 healthy controls (HCs) were recruited and assessed for demographic and clinical characteristics. All participants completed the Childhood Trauma Questionnaire (CTQ), Toronto Alexithymia Scale (TAS-20), Interpersonal Reactivity Index-C (IRI), and Facial Emotion Recognition Test. Partial correlation analysis was used to explore the sex-specific association of CM with social cognition. Our findings revealed significant differences in the associations of CM with social cognition between males and females in MDD patients. In comparison to HCs, the associations of CM with social cognition displayed distinct and even contrasting sex-specific patterns in MDD patients. Specifically, male MDD patients exhibited unique imbalanced associations between emotional neglect and alexithymia, while both female and male MDD patients shared imbalanced associations of childhood abuse with empathy. These results emphasize the importance of considering the sex-specific associations of CM with social cognition in MDD and highlight the need for personalized interventions and treatments based on sex for MDD patients with a history of CM.

Visualized lateral flow assay for logic determination of co-existing viral RNA fragments.

Different types of pathogenic viruses that have common transmission path can be co-infected, inducing distinct disease procession in comparison to that infection of one. Also, in the post COVID-19 time, more types of respiratory infectious virus are becoming prevalent and are concurrent. Those bring an urgent need for detection of co-existing viruses. Here, we propose a visualized lateral flow assay for logic determination of co-existing viral RNA fragments. In the presence of specific viral RNA inputs, DNAzyme is de-blocked according to defined logic, and catalyzes the hydrolysis of hairpin-structural substrate. One of cleaved substrates contains DNAzyme domain to realize dual signal amplification, which obtains copious of the other cleaved substrates. The cleaved substrates act as linking strands for bridging DNA-modified gold nanoparticles onto lateral flow strip to induce coloration on test line. "AND", "OR" and "INHIBIT" controlled lateral flow assays are respectively demonstrated for co-existing viral RNA detection, and the visual results can be obtained by the same kind of prepared strip, without need of re-fabricating strips according to logic systems. The work provides a flexible, convenient, visual and logic-processing strategy for simultaneous analysis of co-existing viruses.

Ghrelin and depressive symptoms in patients with first-episode drug-naïve major depressive disorder: The mediating role of hypothalamic-pituitary-adrenal axis.

BACKGROUND: Major depressive disorder (MDD) is one of the global burdens of disease, and its pathogenesis remains unclear. An increasing amount of research indicates that ghrelin regulates mood in patients with MDD. Still, current results are inconsistent, and the mechanisms underlying how ghrelin modulates depressive symptoms are inconclusive, especially in first-episode drug-naïve MDD patients. Therefore, this study aims to investigate the relationship and potential mechanism between ghrelin and first-episode drug-naïve MDD. METHODS: Ninety first-episode drug-naïve MDD patients and 65 healthy controls (HCs) were included. Hamilton Depression Scale (HAMD-17) as a measure of depressive symptoms. Plasma levels of ghrelin and hypothalamic-pituitary-adrenal axis (HPA-axis) hormones were measured in all participants. RESULTS: Compared to HCs, the ghrelin levels were higher in the MDD (p < .001) and still showed significance after covarying for sex, age, and Body Mass Index (BMI). Ghrelin was positively related to corticotropin-releasing-hormone (CRH) levels (r = .867, p < .001), adrenocorticotropic hormone (ACTH) levels (r = .830, p < .001), and cortisol levels (r = .902, p < .001) in partial correlation analysis. In addition, there was a positive correlation between HAMD total score and ghrelin levels (r = .240, p = .026). Other than that, the HAMD total score also had a positive correlation with the CRH (r = .333, p = .002) and cortisol (r = .307, p = .004) levels. Further mediation analysis demonstrated that the relationship between ghrelin and HAMD total score was mediated by CRH (ab-path; ß = .4457, 95% CI = 0.0780-1.0253, c-path; ß = .2447, p = .0260, c'-path; ß = -.2009, p = .3427). CONCLUSIONS: These findings revealed that plasma ghrelin provides a pivotal link to depressive symptoms in first-episode drug-naive MDD patients. CRH mediated the relationship between ghrelin and HAMD total score. It might provide new insights into understanding the pathogenesis of MDD, contributing to intervention and treatment from this approach.

Association between peripheral plasma cytokine levels and suicidal ideation in first-episode, drug-naïve major depressive disorder.

BACKGROUND: Inflammatory processes could potentially impact both mood and suicide risk, however, the relationship between cytokines and suicidal ideation remains unclear. This study aimed to investigate the association between plasma levels of cytokines and suicidal ideation in population with major depressive disorders (MDD). METHODS: A cross-sectional study was performed to assess the peripheral plasma levels of interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α) in 88 Chinese Han first-episode drug-naïve MDD patients. Suicidal ideation in the past week were identified using the Beck Scale for Suicide Ideation-Chinese Version (BSI-CV). The Hamilton Depression Rating Scale-17 (HAMD-17), the Hamilton Anxiety Rating Scale-14 (HAMA-14) and the Childhood Trauma Questionnaire (CTQ) was used to assess depression, anxiety and childhood trauma. Multivariable logistic regression models were used to estimate the association between cytokines and suicidal ideation. Interaction and stratified analyses were conducted according to age, sex, marital status, education, smoking status, BMI and physical activity. RESULTS: Among the 88 participants, 42 individuals (47.7%) reported suicidal ideation within the past week. In the fully adjusted model, a statistically significant trend was observed in the association between IL-2 level and suicidal ideation (OR: 1.40, 95% CI: 1.00-1.97). The stratified analysis showed a statistically significant association between IL-6 level and suicidal ideation among younger people (OR: 1.17, 95% CI: 1.01-1.36) and a significant positive association between IL-8 (OR: 1.59, 95% CI: 1.03-2.44) and IL-10 (OR: 2.51, 95% CI: 1.27-4.96) levels and suicide ideation among higher educated populations. LIMITATIONS: The cross-sectional design, residual confounding effects and small sample size CONCLUSION: Our findings indicate a significant positive association between plasma IL-2 level and suicidal ideation in MDD patients. IL-2 has the potential to be a biomarker of suicidal ideation in patients with depression.

Quercus dentata Thunb. leaves extract inhibits CaOx crystallization and ameliorates ethylene glycol-induced CaOx kidney stones via the OPN/CD44 and NLRP3 pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Quercus dentata Thunb. (QD), a member of the Fagaceae family and genus Quercus, with distributions in China, Japan, Korea, and other regions. As recorded in the Ben Cao Gang Mu (Compendium of Materia Medica) and other classical Chinese medical texts, QD has been traditionally employed in Traditional Chinese Medicine (TCM) for their hemostatic and diuretic effects and has been used to treat urinary stones (Lin Zheng). It is also the main ingredient of the Mishitong capsule (MST), a Chinese patent drug, used for kidney stones and ureteral stones. Nonetheless, the specific active ingredients and the mechanisms of QD in treating kidney stones remain to be elucidated, which is crucial for advancing the scientific understanding and clinical application of this traditional medicine. AIM OF STUDY: This study aimed to identify the active constituents of QD water extract (QDWE), explore its inhibitory effects on kidney stones through in vitro and in vivo studies, and elucidate the underlying mechanisms of the OPN/CD44 axis and the NLRP3 signaling pathway to provide a full understanding of its potential as a novel treatment approach against kidney stones. MATERIALS AND METHODS: The micromolecular components in the supernatant of QDWE (QDS) were analyzed by UPLC-Q-Exactive-Orbitrap-MS and the monosaccharide composition of the macromolecular polysaccharide components in the crude polysaccharide (QDP) was determined by pre-column derivatization in HPLC. The effects of QDWE, QDS and QDP on the shape, size, and structure of calcium oxalate (CaOx) crystals in vitro were explored by XRD, FTIR and SEM. The effects of QDWE, QDS and QDP on CaOx kidney stones in SD rats induced by ethylene glycol and VD3 were compared in vivo. Furthermore, the underlying mechanisms of OPN/CD44 and NLRP3 pathways were investigated by Western blot analysis. RESULTS: There were 32 compounds identified in QDS. The monosaccharide composition ratio of QDP was Man: L-Rha: D-GlcA: D-GalA: D-Glc: D-Gal: L-Ara = 1.01: 22.52: 8.27: 38.61: 3.43: 17.80: 6.38, indicating a mixture of pectin-type acidic heteropolysaccharides. QDP had a more significant inhibitory effect on CaOx crystals in vitro than QDWE, which can inhibit the formation of CaOx monohydrate crystals (COM) and convert them into thermodynamically unstable CaOx dihydrate (COD) crystals. The high dose of QDWE exhibited significant in vivo efficacy (P < 0.05), including anti-calculus, diuretic effects, and kidney protection, marked by decreased calcification and stone formation, alongside improved kidney vitality. Furthermore, the protective effects of QDWE were demonstrated to be associated with the OPN/CD44 and NLRP3 pathways. CONCLUSION: The studies identified and analyzed the active constituents of QDWE. Among these, QDP significantly inhibited CaOx crystal generation in vitro and could be a potential component for the treatment of urinary stones in QDWE. Moreover, the results indicated that QDWE had a remarkable therapeutic effect on CaOx stones by modulating the OPN/CD44 axis to affect stone formation and the NLRP3 signaling pathway to mediate inflammation, providing an experimental basis for the mechanism of anti-urinary stone and deep development of QD.

Specific correlation between childhood trauma and social cognition in Chinese Han first-episode, drug-naïve major depressive disorder.

BACKGROUND: Childhood trauma (CT) is a significant factor affecting social cognition in major depressive disorder (MDD). However, the relationship between CT, social cognition, and MDD is still not well-understood. METHODS: A total of 251 Han Chinese participants, comprising 117 first-episode drug-naïve MDD patients and 134 healthy controls (HCs), were recruited. The Childhood Trauma Questionnaire (CTQ), Toronto Alexithymia Scale (TAS-20), Interpersonal Reactivity Index-C (IRI), and Facial Emotion Recognition Test were used to measure CT and social cognition. Partial correlations were conducted to analyze the association between CT and social cognition. RESULTS: Our results showed that no significant correlation was observed between CTQ total score and social cognition in MDD (p > 0.05), while it was different in HCs (TAS-20 total score: r = 0.21, p = 0.016; difficulty identifying feelings (DIF): r = 0.219, p = 0.012; perspective-taking (PT): r = -0.214, p = 0.014; recognizing neutral facial emotions: r = -0.4, p < 0.001). CTQ subtyping analysis revealed that CTQ subscale scores in MDD were significantly correlated with PT, personal distress (PD), and recognizing angry facial emotions. Interestingly, physical abuse score was positively correlated with PT in MDD (r = 0.219, p = 0.019) but negatively with PT in HCs (r = -0.276, p = 0.001). LIMITATIONS: Insufficient sample size and cross-sectional designs. CONCLUSION: The correlation between CT and social cognition in MDD was weakened or reversed compared to HCs, highlighting the need for further investigation to determine the cause of this specific correlation.

The attenuation effect of licorice on the hepatotoxicity of Euodiae Fructus by inhibiting the formation of protein conjugates and GSH depletion.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine and food, Euodiae Fructus (EF) is widely used in clinics to relieve pain and prevent vomiting and for making tea for more than a thousand years. In recent years, hepatotoxic reactions to EF have been reported. The intermediates produced by evodiamine and rutaecarpine metabolism in vitro were captured by glutathione (GSH), suggesting that the toxicity of EF may be related to metabolic activation. Whether licorice can inhibit the metabolic activation of EF has not been reported, which needed an effective strategy to clarify the correlation between protein conjugates and hepatotoxicity and the attenuation mechanism of licorice processing. AIM OF THE STUDY: This study aimed to explore the toxic components and mechanisms of EF based on metabolic activation and the detoxification of licorice. MATERIALS AND METHODS: The content and toxicity index of protein conjugates in the liver were determined by orally administering mice and rats with EF. The attenuation mechanism of licorice was examined in cell and enzymology experiments. RESULTS: The change in evodiamine-cysteinylglycine (EVO-Cys-Gly) and evodiamine-cysteine (EVO-Cys) levels was consistent with the change in hepatotoxicity. Licorice inhibited the formation of the protein conjugates of EF and increased the content of GSH in L02 cells. CONCLUSION: EF mediated by P450 enzymes produced toxic intermediates, which combined with cysteine residues in animal liver and inactivate them, leading to hepatotoxicity. Interestingly, licorice can alleviate the GSH depletion caused by EF and inhibit the production of protein conjugates by inhibiting P450 enzymes.

Feasibility study on solidification of municipal solid waste incinerator fly ash with circulating fluidized bed combustion coal fly ash.

The objective of this study was to assess the feasibility of solidification of municipal solid waste incinerator (MSWI) fly ash with circulation fluidized bed combustion (CFBC) fly ash, which is unsuitable as a cement replacement due to its high amounts of carbon, lime and anhydrite. The solidification process was conducted on samples prepared from MSWI fly ash, binders (cement clinkers and CFBC fly ash were mixed at two replacement ratios) and water (water/solid weight ratio = 0.4), among which the MSWI fly ash replaced each binder at the ratio of 0, 20, 40, 60 and 80% by dry weight. The samples were subjected to compressive strength tests and Toxicity Characteristic Leaching Procedure and the results showed that all solidified MSWI fly ash can meet the landfill standard imposed by US EPA after 28 days of curing. Micro-analysis (X-ray diffraction, scanning electron microscopy and Fourier transform infrared spectrophotometry) revealed that the main hydrate products were C-S-H gel and ettringite, which have a positive effect on heavy metals retention. Therefore, this method provides a possibility to achieve a cheap and effective solution for MSWI fly ash management and use for CFBC fly ash.