A Preliminary Comparison of Plasma Tryptophan Metabolites and Medium- and Long-Chain Fatty Acids in Adult Patients with Major Depressive Disorder and Schizophrenia.

Background and Objectives: Disturbance of tryptophan (Trp) and fatty acid (FA) metabolism plays a role in the pathogenesis of psychiatric disorders. However, quantitative analysis and comparison of plasma Trp metabolites and medium- and long-chain fatty acids (MCFAs and LCFAs) in adult patients with major depressive disorder (MDD) and schizophrenia (SCH) are limited. Materials and Methods: Clinical symptoms were assessed and the level of Trp metabolites and MCFAs and LCFAs for plasma samples from patients with MDD (n = 24) or SCH (n = 22) and healthy controls (HC, n = 23) were obtained and analyzed. Results: We observed changes in Trp metabolites and MCFAs and LCFAs with MDD and SCH and found that Trp and its metabolites, such as N-formyl-kynurenine (NKY), 5-hydroxyindole-3-acetic acid (5-HIAA), and indole, as well as omega-3 polyunsaturated fatty acids (N3) and the ratio of N3 to omega-6 polyunsaturated fatty acids (N3: N6), decreased in both MDD and SCH patients. Meanwhile, levels of saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) decreased in SCH patients, and there was a significant difference in the composition of MCFAs and LCFAs between MDD and SCH patients. Moreover, the top 10 differential molecules could distinguish the two groups of diseases from HC and each other with high reliability. Conclusions: This study provides a further understanding of dysfunctional Trp and FA metabolism in adult patients with SCH or MDD and might develop combinatorial classifiers to distinguish between these disorders.

Alterations in Plasma Lipidomic Profiles in Adult Patients with Schizophrenia and Major Depressive Disorder.

Background and Objectives: Lipidomics is a pivotal tool for investigating the pathogenesis of mental disorders. However, studies qualitatively and quantitatively analyzing peripheral lipids in adult patients with schizophrenia (SCZ) and major depressive disorder (MDD) are limited. Moreover, there are no studies comparing the lipid profiles in these patient populations. Materials and Method: Lipidomic data for plasma samples from sex- and age-matched patients with SCZ or MDD and healthy controls (HC) were obtained and analyzed by liquid chromatography-mass spectrometry (LC-MS). Results: We observed changes in lipid composition in patients with MDD and SCZ, with more significant alterations in those with SCZ. In addition, a potential diagnostic panel comprising 103 lipid species and another diagnostic panel comprising 111 lipid species could distinguish SCZ from HC (AUC = 0.953) or SCZ from MDD (AUC = 0.920) were identified, respectively. Conclusions: This study provides an increased understanding of dysfunctional lipid composition in the plasma of adult patients with SCZ or MDD, which may lay the foundation for identifying novel clinical diagnostic methods for these disorders.

Repetitive transcranial magnetic stimulation inhibits Sirt1/MAO-A signaling in the prefrontal cortex in a rat model of depression and cortex-derived astrocytes.

Repetitive transcranial magnetic stimulation (rTMS) is a useful monotherapy for depression or adjunctive therapy for resistant depression. However, the anti-depressive effects of different parameters and the underlying mechanisms remain unclear. Here, we aimed to assess the effect of rTMS with different parameters (1/5/10 Hz, 0.84/1.26 T) on the depressive-like behaviors, 5-hydroxytryptamine (5-HT), 5-HIAA (5-hydroxyindoleacetic acid) and DA and NE levels, and monoamine oxidase A (MAO-A) activity in chronic unpredictable stress-treated rats, along with the expression of sirtuin 1 (Sirt1) and MAO-A in the prefrontal cortex (PFC) and cortex-derived astrocytes from new-born rats. Moreover, the depressive-like behaviors were monitored following the transcranial injection of the Sirt1 inhibitor EX527 (1 mM) daily for 1 week. We found that rTMS treatment (5/10 Hz, 0.84/1.26 T) ameliorated depressive-like behaviors, increased 5-HT, DA and NE levels, decreased the 5-HIAA level and Sirt1 and MAO-A expression, and reduced MAO-A activity in the PFC. The depressive-like behaviors were also ameliorated after the transcranial injection of EX527. Importantly, rTMS (5/10 Hz, 0.84/1.26 T) inhibited Sirt1 and MAO-A expressions in astrocytes and Sirt1 knockdown with short hairpin RNA decreased MAO-A expression in astrocytes. These results suggest that the inhibition of Sirt1/MAO-A expression in astrocytes in the PFC may contribute to the different anti-depressive effects of rTMS with different parameters, and may also provide a novel insight into the mechanisms underlying major depressive disorder.

Experimental continuous sludge microwave system to enhance dehydration ability and hydrogen production from anaerobic digestion of sludge.

Dehydrating large amounts of sludge produced by sewage treatment plants is difficult. Microwave pretreatment can effectively and significantly improve the dewaterability and hydrogen production of sludge subjected to anaerobic digestion. The aim of this study was to investigate the effects of different microwave conditions on hydrogen production from anaerobic digestion and dewaterability of sludge. Based on an analysis of the electric field distribution, a spiral reactor was designed and a continuous microwave system was built to conduct intermittent and continuous experiments under different conditions. Settling Volume, Capillary Suction Time, particle size, and moisture content of the sludge were measured. The results show that sludge pretreatment in continuous experiments has equally remarkable dehydration performance as in intermittent experiments; the minimum moisture content was 77.29% in the intermittent experiment under a microwave power of 300W and an exposure time of 60sec, and that in the continuous experiment was 77.56% under a microwave power of 400W and an exposure time of 60sec. The peak measured by Differential Scanning Calorimeter appeared earliest under a microwave power of 600W and an exposure time of 180sec. The heat flux at the peak was 4.343W/g, which is relatively small. This indicates that microwave pretreatment induced desirable effects. The maximum yield of hydrogen production was 7.967% under the conditions of microwave power of 500W, exposure time of 120sec, and water bath at 55°C. This research provides a theoretical and experimental basis for the development of a continuous microwave sludge-conditioning system.

Mixed lineage leukemia 5 (MLL5) protein regulates cell cycle progression and E2F1-responsive gene expression via association with host cell factor-1 (HCF-1).

Trithorax group proteins methylate lysine 4 of histone 3 (H3K4) at active gene promoters. MLL5 protein, a member of the Trithorax protein family, has been implicated in the control of the cell cycle progression; however, the underlying molecular mechanism(s) have not been fully determined. In this study, we found that the MLL5 protein can associate with the cell cycle regulator "host cell factor" (HCF-1). The interaction between MLL5 and HCF-1 is mediated by the "HCF-1 binding motif" (HBM) of the MLL5 protein and the Kelch domain of the HCF-1 protein. Confocal microscopy showed that the MLL5 protein largely colocalized with HCF-1 in the nucleus. Knockdown of MLL5 resulted in reduced cell proliferation and cell cycle arrest in the G1 phase. Moreover, down-regulation of E2F1 target gene expression and decreased H3K4me3 levels at E2F1-responsive promoters were observed in MLL5 knockdown cells. Additionally, the core subunits, including ASH2L, RBBP5, and WDR5, that are necessary for effective H3K4 methyltransferase activities of the Trithorax protein complexes, were absent in the MLL5 complex, suggesting that a distinct mechanism may be used by MLL5 for exerting its H3K4 methyltransferase activity. Together, our findings demonstrate that MLL5 could associate with HCF-1 and then be recruited to E2F1-responsive promoters to stimulate H3K4 trimethylation and transcriptional activation, thereby facilitating the cell cycle G1 to S phase transition.

Effects of microbubble pretreatment on physiochemical and microbial properties of excess activated sludge.

Fast increased amount of excess activated sludge (EAS) from wastewater treatment plants has aroused universal concerns on its environmental risks and demands for appropriate treatments, while effective treatment is dependent upon proper pretreatment. In this study, air-supplied microbubbles (air-MBs) with generated size of 25.18 to 28.25 µm were used for EAS pretreatment. Different durations (30, 60, 90, and 120 s) yielded sludge with varied physiochemical conditions, and 60 s decreased sludge oxidation status and significantly increased adenosine triphosphate (ATP) content. Soluble, loosely-bound, and tightly-bound extracellular polymeric substances (SEPS, LB-EPS, and TB-EPS) were extracted from the sludge through a stepwise approach and examined through three-dimensional excitation-emission matrix (3D-EEM) and quantitative analysis. The results showed that 60- and 120-s treatments generated stronger fluorescence intensities on dissolved organic matters (DOMs) of protein-like and fulvic acid in LB-EPS and TB-EPS, which indicated the decrease of counterparts in EAS, and therefore facilitated sludge dewaterability and reduction. The dominant microbial communities in EAS, including Proteobacteria, Bacteroidota, Chloroflexi, and Actinobacteriota, were not significantly affected by MB pretreatment. The results collectively revealed the effects of MB pretreatment on EAS and indicated that MBs could be an effective pretreatment technique for EAS treatment process.

Electroacupuncture intervention alleviates depressive-like behaviors and regulates gut microbiome in a mouse model of depression.

Electroacupuncture (EA) is a neuroregulatory therapy for depression. Nonetheless, the effects of EA on the gut microbiome in mice models of depression are not well established. Here, using a chronic unpredictable mild stress (CUMS) model in mice, we evaluated the antidepressant effects of EA and changes in gut microbiota with behavioral tests and 16S rRNA gene sequencing. The results found that EA increased the time spent in the center area of the open-field test and the percentage of sucrose preference and reduced the immobility time in the tail suspension test in CUMS-treated mice. Furthermore, the genus Lachnoclostridium, Ruminococcaceae_UCG-002 and Rikenellaceae_RC9_gut_group were enriched in the CUMS group, which was positively correlated with depressive-like behaviors. Whereas phylum Actinobacteria and genus Allobaculum, Bifidobacterium, Dubosiella, Rikenella and Ileibacterium were enriched in the EA and CUMS + EA groups, all of which were negatively correlated with depressive-like behaviors. This study characterizes gut microbiota under EA treatment and provides new insights into the association of anti-depressive-like effects of EA and gut microbiota.

Effects of esketamine and fluoxetine on depression-like behaviors in chronic variable stress: a role of plasma inflammatory factors.

Mounting evidence has identified the rapid and sustained antidepressive and anxiolytic-like effects of esketamine. However, the underlying mechanism of this no-monoamine target rapid-onset antidepressant is still underexplored. Immune-inflammatory pathways and cell-mediated immune activation, mainly including inflammatory cytokines in plasma, play a pivotal role in the pathogenesis of major depressive disorder and are also a potential therapeutic target for MDD. The current study was designed to clarify the role of esketamine on the expression of plasma cytokines in a depressive-like model introduced by chronic variable stress (CVS). In this study, a 21-day consecutive CVS protocol was applied to produce depressive- and anxiety-like behaviors. After the single dose or 7-day repeated administration of esketamine or fluoxetine, the depressive- and anxiety-like behaviors and the expression of inflammatory cytokines in plasma were examined. Both a single dose of esketamine and 7-days repeated fluoxetine administration elicited anti-depressive and anxiolytic effects in mice exposed to CVS. Additionally, CVS produced significant changes in the plasma inflammatory factors, notably increasing the expression of IL-1ß, IL-6, IL-8, IL-17A, TNFα, IL-4, IL-9, IL-24, IL-37, IFN-ß, and CXCL12, while reducing IL-10 and IL-33. With the administration of esketamine and fluoxetine, CVS-produced inflammatory disturbances were partially normalized. Together, our findings provide a novel insight that acute esketamine treatment could rescue CVS-produced depressive-like and anxiety-like behaviors in mice by normalizing the expression of inflammatory cytokines; this effect was similar to the repeated administration of fluoxetine. These results contributed to the understating of rapid anti-depressant effects elicited by esketamine.

Effects of (S)-ketamine on depression-like behaviors in a chronic variable stress model: a role of brain lipidome.

Introduction: Compelling evidence indicates that a single sub-anesthetic dose of (S)-ketamine elicits rapid and robust antidepressant effects. However, the underlying mechanisms behind the antidepressant effects of (S)-ketamine remain unclear. Methods: Here, using a chronic variable stress (CVS) model in mice, we analyzed changes inthe lipid compositions of the hippocampus and prefrontal cortex (PFC) with a mass spectrometry-based lipidomic approach. Results: Similar to previous research outcomes, the current study also showed that (S)-ketamine reversed depressive-like behaviors in mice produced by CVS procedures. Moreover, CVS induced changes inthe lipid compositions of the hippocampus and PFC, notably in the contents of sphingolipids, glycerolipids, and fatty acyls. With the administration of (S)-ketamine, CVS-induced lipid disturbances were partially normalized, particularly in the hippocampus. Conclusion: Altogether, our results indicated that (S)-ketamine could rescue CVS-induced depressive-like behaviors in mice through region-specific modulation of the brain lipidome, contributing to the understanding of (S)-ketamine's antidepressant effects.

Electroacupuncture treatment ameliorates depressive-like behavior and cognitive dysfunction via CB1R dependent mitochondria biogenesis after experimental global cerebral ischemic stroke.

Introduction: This study aimed to identify the effect of electroacupuncture (EA) treatment on post-stroke depression (PSD) and explore whether cannabinoid receptor 1 (CB1R)-mediated mitochondrial biogenesis accounts for the treatment effect of EA. Methods: The PSD mouse model was induced by a consecutive 14-day chronic unpredictable stress operation after 7 days of recovery from the bilateral common carotid artery occlusion surgery. Either EA treatment or sham stimulation was performed for 14 consecutive days from Day 7 after the BCCAO operation. Subjects' PSD-like behaviors were tested via open field test, sucrose preference test, novelty suppressed feeding test, tail suspension test, and forced swim test, and subjects' cognitive function was examined using Y-maze and novelty object recognition test. In addition, the levels of CB1R, mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), proteins related to mitochondrial function (Cytochrome C, Cyto C; AIF, COX IV), and mitochondrial DNA were measured. To elucidate the role of CB1R in EA treatment, CB1R antagonists AM251 and CB1R-shRNA were given to mice before EA treatment. Likewise, subjects' depressive-like behaviors, cognitive function, mitochondrial function, and mitochondrial biogenesis were examined after the PSD procedure. Results: It has been showed that EA successfully ameliorated depressive-like behaviors, improved cognitive dysfunctions, and upregulated CB1R, NRF1 and TFAM expressions. However, the supplementation of AM251 and CB1R-shRNA blocked the antidepressant-like effects generated by EA, and EA failed to improve cognitive dysfunction, upregulate CB1R protein expression, and increase mitochondrial function and biogenesis. Conclusion: Altogether, these results indicated that EA ameliorated PSD-like behaviors in mice, improved cognitive dysfunctions after PSD, and promoted mitochondrial biogenesis by activating CB1R, a novel mechanism underlying EA's antidepressant-like effects in treating PSD.

Gut microbial signatures and differences in bipolar disorder and schizophrenia of emerging adulthood.

INTRODUCTION: Gut microbial disturbance has been established as potential pathogenesis of mental disorders. However, the signatures and differences regarding patients with schizophrenia (SCH) or bipolar disorder (BD) in emerging adulthood as well as their subtypes have been poorly addressed. METHODS: In the present study, stool samples obtained from 63 emerging adult patients with schizophrenia (SCH), 50 with bipolar disorder (BD), and 40 healthy controls (HC) were analyzed by 16 S rRNA gene sequencing; psychiatric symptoms and psychological, social, and professional functioning were also assessed. RESULTS: We found that gut microbiota composition was remarkably changed in the patients with SCH and BD. Moreover, the distinct gut microbiome signatures and their potential function in bipolar depression (BP-D) and SCH with predominantly negative symptoms (SCH-N) as well as bipolar mania (BP-M) and SCH with predominantly positive symptoms (SCH-P) were also observed. Furthermore, we identified diagnostic potential biomarkers that can distinguish BD from HC (38 genera, AUC = 0.961), SCH from HC (32 genera, AUC = 0.962), and BD from Scheme (13 genera, AUC = 0.823). Potential diagnostic biomarkers that can distinguish BD-D from SCH-N (16 genera, AUC = 0.969) and BD-M from SCH-P (31 genera, AUC = 0.938) were also identified. CONCLUSION: This study provides further understanding of abnormal gut microbiome in emerging adulthood patients with SCH and BD and lay the potential foundation for the development of microbe-based clinical diagnosis for BD and SCH.

rTMS ameliorates depressive-like behaviors and regulates the gut microbiome and medium- and long-chain fatty acids in mice exposed to chronic unpredictable mild stress.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a clinically useful therapy for depression. However, the effects of rTMS on the metabolism of fatty acids (FAs) and the composition of gut microbiota in depression are not well established. METHODS: Mice received rTMS (15 Hz, 1.26 T) for seven consecutive days after exposure to chronic unpredictable mild stress (CUMS). The subsequent depressive-like behaviors, the composition of gut microbiota of stool samples, as well as medium- and long-chain fatty acids (MLCFAs) in the plasma, prefrontal cortex (PFC), and hippocampus (HPC) were evaluated. RESULTS: CUMS induced remarkable changes in gut microbiotas and fatty acids, specifically in community diversity of gut microbiotas and PUFAs in the brain. 15 Hz rTMS treatment alleviates depressive-like behaviors and partially normalized CUMS induced alterations of microbiotas and MLCFAs, especially the abundance of Cyanobacteria, Actinobacteriota, and levels of polyunsaturated fatty acids (PUFAs) in the hippocampus and PFC. CONCLUSION: These findings revealed that the modulation of gut microbiotas and PUFAs metabolism might partly contribute to the antidepressant effect of rTMS.

High-frequency repetitive transcranial magnetic stimulation regulates neural oscillations of the hippocampus and prefrontal cortex in mice by modulating endocannabinoid signalling.

BACKGROUND: Neural oscillations play a role in the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS). However, the effects of high-frequency rTMS on the neural oscillations of the medial prefrontal cortex (mPFC) and hippocampus (HPC) and its molecular mechanism have not been fully clarified. METHODS: The depressive-like behaviours, local field potentials (LFPs) of the ventral HPC (vHPC)-mPFC, and alternations of endocannabinoid system (ECS) in the HPC and mPFC were observed after rTMS treatment. Meanwhile, depressive-like behaviours and LFPs were also observed after cannabinoid type-1 receptor (CB1R) antagonist AM281 or monoacylglycerol lipase inhibitor JZL184 injection. Moreover, the antidepressant effect of rTMS was further assessed in glutamatergic-CB1R and gamma-amino butyric acid (GABA)-ergic -CB1R knockout mice. RESULTS: Alternations of endocannabinoids and energy value and synchronisation of mPFC-vHPC, especially the decrease of theta oscillation induced by CUMS, were alleviated by rTMS. JZL184 has similar effects to rTMS and AM281 blocked the effects of rTMS. GABAergic-CB1R deletion inhibited CUMS-induced depressive-like behaviours whereas Glutaminergic-CB1R deletion dampened the antidepressant effects of rTMS. LIMITATIONS: The immediate effect of rTMS on field-potential regulation was not observed. Moreover, the role of region-specific regulation of the ECS in the antidepressant effect of rTMS was unclear and the effects of cell-specific CB1R knockout on neuronal oscillations of the mPFC and vHPC should be further investigated. CONCLUSION: Endocannabinoid system mediated the antidepressant effects and was involved in the regulation of LFP in the vHPC-mPFC of high-frequency rTMS.

The heme oxygenase-1 inhibitor ZnPPIX induces non-canonical, Beclin 1-independent, autophagy through p38 MAPK pathway.

Zinc protoporphyrin IX (ZnPPIX), a heme oxygenase-1 enzyme inhibitor, has been reported to induce apoptosis and to have antitumor properties. Here, we report that ZnPPIX triggers autophagy and causes defective autophagy flux in HeLa cells. Autophagosome formation was independent of Beclin 1, indicating non-canonical autophagy activity in ZnPPIX-treated cells. Furthermore, western blot results indicated that p38 MAPK (mitogen-activated protein kinase) was phosphorylated in treated cells. Consistently, SB203580 (a p38 inhibitor) obviously inhibited the accumulation of autophagosomes. Our results indicated that p38 MAPK may be a key regulator for non-canonical Beclin1-independent autophagy.

The Impact of Electroacupuncture Early Intervention on the Brain Lipidome in a Mouse Model of Post-traumatic Stress Disorder.

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.

Alterations of Plasma Lipids in Adult Women With Major Depressive Disorder and Bipolar Depression.

Lipidomics has been established as a potential tool for the investigation of mental diseases. However, the composition analysis and the comparison of the peripheral lipids regarding adult women with major depressive depression (MDD) or bipolar depression (BPD) has been poorly addressed. In the present study, age-matched female individuals with MDD (n = 28), BPD (n = 22) and healthy controls (HC, n = 25) were enrolled. Clinical symptoms were assessed and the plasma samples were analyzed by comprehensive lipid profiling based on liquid chromatography-mass spectrometry (LC/MS). We found that the composition of lipids was remarkably changed in the patients with MDD and BPD when compared to HC or compared to each other. Moreover, we identified diagnostic potential biomarkers comprising 20 lipids that can distinguish MDD from HC (area under the curve, AUC = 0.897) and 8 lipids that can distinguish BPD from HC (AUC = 0.784), as well as 13 lipids were identified to distinguish MDD from BPD with moderate reliability (AUC = 0.860). This study provides further understanding of abnormal lipid metabolism in adult women with MDD and BPD and may develop lipid classifiers able to effectively discriminate MDD from BPD and HC.

An improved bimolecular fluorescence complementation tool based on superfolder green fluorescent protein.

Bimolecular fluorescence complementation (BiFC) has been widely used in the analysis of protein-protein interactions (PPIs) in recent years. There are many notable advantages of BiFC such as convenience and direct visualization of PPI in cells. However, BiFC has one common limitation: the separated non-fluorescent fragments can be spontaneously self-assembled into an intact protein, which leads to false-positive results. In this study, a pair of complementary fragments (sfGFPN and sfGFPC) was constructed by splitting superfolder GFP (sfGFP) between the 214 and 215 amino acid residue, and sfGFPC was mutated by site-directed gene mutagenesis to decrease the signal of negative control. Our results showed that mutations in sfGFPC (sfGFPC(m12)) can effectively decrease the signal of negative control. Thus, we provide an improved BiFC tool for the analysis of PPI. Further, since the self-assembly problem is a common shortcoming for application of BiFC, our research provides a feasible strategy for other BiFC candidate proteins with the same problem.

A two-stage amplified PZT sensor for monitoring lung and heart sounds in discharged pneumonia patients.

Assessment of lung and heart states is of critical importance for patients with pneumonia. In this study, we present a small-sized and ultrasensitive accelerometer for continuous monitoring of lung and heart sounds to evaluate the lung and heart states of patients. Based on two-stage amplification, which consists of an asymmetric gapped cantilever and a charge amplifier, our accelerometer exhibited an extremely high ratio of sensitivity to noise compared with conventional structures. Our sensor achieves a high sensitivity of 9.2 V/g at frequencies less than 1000 Hz, making it suitable to use to monitor weak physiological signals, including heart and lung sounds. For the first time, lung injury, heart injury, and both lung and heart injuries in discharged pneumonia patients were revealed by our sensor device. Our sound sensor also successfully tracked the recovery course of the discharged pneumonia patients. Over time, the lung and heart states of the patients gradually improved after discharge. Our observations were in good agreement with clinical reports. Compared with conventional medical instruments, our sensor device provides rapid and highly sensitive detection of lung and heart sounds, which greatly helps in the evaluation of lung and heart states of pneumonia patients. This sensor provides a cost-effective alternative approach to the diagnosis and prognosis of pneumonia and has the potential for clinical and home-use health monitoring.

The Effects of Repetitive Transcranial Magnetic Stimulation on Cognitive Impairment and the Brain Lipidome in a Cuprizone-Induced Mouse Model of Demyelination.

The protective effects of repetitive transcranial magnetic stimulation (rTMS) on myelin integrity have been extensively studied, and growing evidence suggests that rTMS is beneficial in improving cognitive functions and promoting myelin repair. However, the association between cognitive improvement due to rTMS and changes in brain lipids remains elusive. In this study, we used the Y-maze and 3-chamber tests, as well as a mass spectrometry-based lipidomic approach in a CPZ-induced demyelination model in mice to assess the protective effects of rTMS on cuprizone (CPZ)-induced cognitive impairment and evaluate changes in lipid composition in the hippocampus, prefrontal cortex, and striatum. We found that CPZ induced cognitive impairment and remarkable changes in brain lipids, specifically in glycerophospholipids. Moreover, the changes in lipids within the prefrontal cortex were more extensive, compared to those observed in the hippocampus and striatum. Notably, rTMS ameliorated CPZ-induced cognitive impairment and partially normalized CPZ-induced lipid changes. Taken together, our data suggest that rTMS may reverse cognitive behavioral changes caused by CPZ-induced demyelination by modulating the brain lipidome, providing new insights into the therapeutic mechanism of rTMS.

A double-blind, randomized, sham-controlled study of cranial electrotherapy stimulation as an add-on treatment for tic disorders in children and adolescents.

AIM: The aim of this study was to determine the efficacy and safety of cranial electrotherapy stimulation (CES) as an add-on treatment for TD. METHODS: A randomized, double-blind, sham-controlled trial was conducted at an outpatient, single-center academic setting. A total of 62 patients aged 6-17 years with TD and lack of clinical response to 4 weeks' pharmacotherapy were enrolled. Patients were divided randomly into 2 groups and given 4 weeks' treatment, including 30 min sessions of active CES (500 µA-2 mA) or sham CES (lower than 100 µA) per day for 40 d on weekdays. Change in Yale Global Tic Severity Scale (YGTSS), Clinical Global Impression-severity of illness-severity (CGI-S) and Hamilton Anxiety Scale-14 items (HAMA-14) were performed at baseline, week 2, week 4. Adverse events (AEs) were also evaluated. RESULTS: 53 patients (34 males and 9 females) completed the trial, including 29 in the active CES group and 24 in the sham CES group. Both groups showed clinical improvement in tic severities compared to baseline respectively at week 4. Participants receiving active CES showed a reduction of 31.66 % in YGTSS score, compared with 23.96 % in participants in sham CES group, resulting in no significant difference between the two groups (t = 1.54, p = 0.13). CONCLUSION: Four-week's treatment of CES for children and adolescents with TD is effective and safe, but the improvement for tic severity may be related to placebo effect.