Angelica sinensis polysaccharide suppresses the Wnt/ß-catenin-mediated malignant biological behaviors of breast cancer cells via the miR-3187-3p/PCDH10 axis.

Breast cancer (BC) is one of the most common malignant tumors in women. Angelica sinensis polysaccharide (ASP) is one of the main components extracted from the traditional Chinese medicine Angelica sinensis. Research has shown that ASP affects the progression of various cancers by regulating miRNA expression. This study aimed to explore the specific molecular mechanism by which ASP regulates BC progression through miR-3187-3p. After the overexpression or knockdown of miR-3187-3p and PDCH10 in BC cells, the proliferation, migration, invasion, and phenotype of BC cells were evaluated after ASP treatment. Bioinformatics software was used to predict the target genes of miR-3187-3p, and luciferase gene reporter experiments reconfirmed the targeted binding relationship. Subcutaneous tumor formation experiments were conducted in nude mice after the injection of BC cells. Western blot and Ki-67 immunostaining were performed on the tumor tissues. The results indicate that ASP can significantly inhibit the proliferation, migration, and invasion of BC cells. ASP can inhibit the expression of miR-3187-3p in BC cells and upregulate the expression of PDCH10 by inhibiting miR-3187-3p. A regulatory relationship exists between miR-3187-3p and PDCH10. ASP can inhibit the expression of ß-catenin and phosphorylated glycogen synthase kinase-3ß (p-GSK-3ß) proteins through miR-3187-3p/PDCH10 and prevent the occurrence of malignant biological behavior in BC. Overall, this study revealed the potential mechanism by which ASP inhibits the BC process. ASP mediates the Wnt/ß-catenin signaling pathway by affecting the miR-3187-3p/PDCH10 molecular axis, thereby inhibiting the proliferation, migration, invasion, and other malignant biological behaviors of BC cells.

Spatial and Temporal Abnormalities of Spontaneous Fixational Saccades and Their Correlates With Positive and Cognitive Symptoms in Schizophrenia.

BACKGROUND AND HYPOTHESIS: Visual fixation is a dynamic process, with the spontaneous occurrence of microsaccades and macrosaccades. These fixational saccades are sensitive to the structural and functional alterations of the cortical-subcortical-cerebellar circuit. Given that dysfunctional cortical-subcortical-cerebellar circuit contributes to cognitive and behavioral impairments in schizophrenia, we hypothesized that patients with schizophrenia would exhibit abnormal fixational saccades and these abnormalities would be associated with the clinical manifestations. STUDY DESIGN: Saccades were recorded from 140 drug-naïve patients with first-episode schizophrenia and 160 age-matched healthy controls during ten separate trials of 6-second steady fixations. Positive and negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Cognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB). STUDY RESULTS: Patients with schizophrenia exhibited fixational saccades more vertically than controls, which was reflected in more vertical saccades with angles around 90° and a greater vertical shift of horizontal saccades with angles around 0° in patients. The fixational saccades, especially horizontal saccades, showed longer durations, faster peak velocities, and larger amplitudes in patients. Furthermore, the greater vertical shift of horizontal saccades was associated with higher PANSS total and positive symptom scores in patients, and the longer duration of horizontal saccades was associated with lower MCCB neurocognitive composite, attention/vigilance, and speed of processing scores. Finally, based solely on these fixational eye movements, a K-nearest neighbors model classified patients with an accuracy of 85%. Conclusions: Our results reveal spatial and temporal abnormalities of fixational saccades and suggest fixational saccades as a promising biomarker for cognitive and positive symptoms and for diagnosis of schizophrenia.

Cool the Inflamed Brain: A Novel Anti-inflammatory Strategy for the Treatment of Major Depressive Disorder.

BACKGROUND: Abundant evidence suggests that inflammatory cytokines contribute to the symptoms of major depressive disorder (MDD) by altering neurotransmission, neuroplasticity, and neuroendocrine processes. Given the unsatisfactory response and remission of monoaminergic antidepressants, anti-inflammatory therapy is proposed as a feasible way to augment the antidepressant effect. Recently, there have been emerging studies investigating the efficiency and efficacy of anti-inflammatory agents in the treatment of MDD and depressive symptoms comorbid with somatic diseases. METHODS: In this narrative review, prospective clinical trials focusing on anti-inflammatory treatment for depression have been comprehensively searched and screened. Based on the included studies, we summarize the rationale for the anti-inflammatory therapy of depression and discuss the utilities and confusions regarding the anti-inflammatory strategy for MDD. RESULTS: This review included over 45 eligible trials. For ease of discussion, we have grouped them into six categories based on their mechanism of action, and added some other anti-inflammatory modalities, including Chinese herbal medicine and non-drug therapy. Pooled results suggest that anti-inflammatory therapy is effective in improving depressive symptoms, whether used as monotherapy or add-on therapy. However, there remain confusions in the application of anti-inflammatory therapy for MDD. CONCLUSION: Based on current clinical evidence, anti-inflammatory therapy is a promisingly effective treatment for depression. This study proposes a novel strategy for clinical diagnosis, disease classification, personalized treatment, and prognostic prediction of depression. Inflammatory biomarkers are recommended to be assessed at the first admission of MDD patients, and anti-inflammatory therapy are recommended to be included in the clinical practice guidelines for diagnosis and treatment. Those patients with high levels of baseline inflammation (e.g., CRP > 3 mg/L) may benefit from adjunctive anti-inflammatory therapy.

Direct and indirect effects of error monitoring on social functioning in a cohort with high-risk and first-episode psychosis.

Error monitoring plays a key role in people's adjustment to social life. This study aimed to examine the direct (DE) and indirect effects (IDE) of error monitoring, as indicated by error-related negativity (ERN), on social functioning in a clinical cohort from high-risk (APS) to first-episode psychosis (FEP). This study recruited 100 outpatients and 49 healthy controls (HC). ERN was recorded during a modified flanker task; social functioning was evaluated using the social scale of global functioning. The path analysis was executed using the "lavaan" package. When controlling for age and education, the clinical cohort had a smaller ERN than the HC group (F1, 145 = 19.58, p < 0.001, partial η2 = 0.12, 95%CI: 0.04-0.22). ERN demonstrated no substantial direct impact on current social functioning; however, it manifested indirect influences on social functioning via the disorganization factor of the Positive and Negative Syndrome Scale, both with (standardized IDE: -0.139, p = 0.009) and without (standardized IDE: -0.087, p = 0.018) accounting for the diagnosis, defined as a dummy variable (FEP = 1 and APS = 0) and included as a covariate. These findings suggest that error monitoring, as indicated by ERN, may serve as a potential prognostic indicator of social functioning in patients with psychosis.

The involvement of NLRP3 inflammasome in CUMS-induced AD-like pathological changes and related cognitive decline in mice.

BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.

The effect of initial antipsychotic treatment on hippocampal and amygdalar volume in first-episode schizophrenia is influenced by age.

BACKGROUND: Antipsychotic treatment has been shown to yield hippocampal and amygdalar volumetric changes in first-episode schizophrenia (FES). However, whether antipsychotic induced volumetric changes interact with age remains unclear. METHODS: The current study includes data from 120 medication naïve FES patients and 110 matched healthy controls (HC). Patients underwent MRI scans before (T1) and after (T2) antipsychotic treatment. HCs underwent MRI scans at baseline only. The hippocampus and amygdala were segmented via Freesurfer 7. General linear models were conducted to investigate the effect of age by diagnosis interaction on baseline volume. Linear mixed models (LMM) were used to detect the effect of age on volumetric changes from pre to post treatment in FES. RESULTS: GLM revealed a trending effect (F = 3.758, p = 0.054) of age by diagnosis interaction on the baseline volume of the left (whole) hippocampus, with older FES patients showing smaller hippocampal volumes, relative to HC, when controlled sex, education years, and ICV. LMM showed a significant age by time-point interaction effect (F = 4.194, estimate effect = -1.964, p = 0.043) on left hippocampal volume in all FES and significant time effect(F = 6.608,T1-T2(estimate effect) = 62.486, p = 0.011), whereby younger patients showed greater hippocampal volumetric decreases following treatment. At the subfield level, a significant time effect emerged in left molecular_layer_HP (F = 4.509,T1-T2(estimate effect) = 12.424, p = 0.032, FDR corrected) and left cornu ammonis(CA)4 (F = 4.800,T1-T2(estimate effect) = 7.527, p = 0.046, FDR corrected), implying volumetric reduction after treatment in these subfields. CONCLUSIONS: Our findings suggest that age plays an important role in the neuroplastic mechanisms of initial antipsychotics on the hippocampus and amygdala of schizophrenia.

Microglial NLRP3 inflammasome activation mediates diabetes-induced depression-like behavior via triggering neuroinflammation.

BACKGROUND: Abundant evidence suggests that the prevalence and risk of depression in people with diabetes is high. However, the pathogenesis of diabetes-related depression remains unclear. Since neuroinflammation is associated with the pathophysiology of diabetic complications and depression, this study aims to elucidate the neuroimmune mechanism of diabetes-related depression. METHODS: Male C57BL/6 mice were injected with streptozotocin to establish a diabetes model. After screening, diabetic mice were treated with the NLRP3 inhibitor MCC950. Then, metabolic indicators and depression-like behaviors were evaluated in these mice, as well as their central and peripheral inflammation. To explore the mechanism of high glucose-induced microglial NLRP3 inflammasome activation, we performed in vitro studies focusing on its canonical upstream signal I (TLR4/MyD88/NF-κB) and signal II (ROS/PKR/P2X7R/TXNIP). RESULTS: Diabetic mice exhibited depression-like behaviors and activation of NLRP3 inflammasome in hippocampus. In vitro high-glucose (50 mM) environment primed microglial NLRP3 inflammasome by promoting NF-κB phosphorylation in a TLR4/MyD88-independent manner. Subsequently, high glucose activated the NLRP3 inflammasome via enhancing intracellular ROS accumulation, upregulating P2X7R, as well as promoting PKR phosphorylation and TXNIP expression, thereby facilitating the production and secretion of IL-1ß. Inhibition of NLRP3 with MCC950 significantly restored hyperglycemia-induced depression-like behavior and reversed the increase in IL-1ß levels in the hippocampus and serum. CONCLUSION: The activation of NLRP3 inflammasome, probably mainly in hippocampal microglia, mediates the development of depression-like behaviors in STZ-induced diabetic mice. Targeting the microglial inflammasome is a feasible strategy for the treatment of diabetes-related depression.

Diagnosis of Alzheimer's disease using hypergraph p-Laplacian regularized multi-task feature learning.

Multimodal data-based classification methods have been widely used in the diagnosis of Alzheimer's disease (AD) and have achieved better performance than single-modal-based methods. However, most classification methods based on multimodal data tend to consider only the correlation between different modal data and ignore the inherent non-linear higher-order relationships between similar data, which can improve the robustness of the model. Therefore, this study proposes a hypergraph p-Laplacian regularized multi-task feature selection (HpMTFS) method for AD classification. Specifically, feature selection for each modal data is considered as a distinct task and the common features of multimodal data are extracted jointly by group-sparsity regularizer. In particular, two regularization terms are introduced in this study, namely (1) a hypergraph p-Laplacian regularization term to retain higher-order structural information for similar data, and (2) a Frobenius norm regularization term to improve the noise immunity of the model. Finally, using a multi-kernel support vector machine to fuse multimodal features and perform the final classification. We used baseline sMRI, FDG-PET, and AV-45 PET imaging data from 528 subjects in the Alzheimer's Disease Neuroimaging Initiative (ADNI) to evaluate our approach. Experimental results show that our HpMTFS method outperforms existing multimodal-based classification methods.

Symptom-circuit mappings of the schizophrenia connectome.

OBJECTIVE: This paper aims to model the anatomical circuits underlying schizophrenia symptoms, and to explore patterns of abnormal connectivity among brain networks affected by psychopathology. METHODS: T1 magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), and resting-state functional MRI (rsfMRI) were obtained from a total of 126 patients with schizophrenia who were recruited for the study. The images were processed using the Omniscient software (https://www.o8t. com). We further apply the use of the Hollow-tree Super (HoTS) method to gain insights into what brain regions had abnormal connectivity that might be linked to the symptoms of schizophrenia. RESULTS: The Positive and Negative Symptom Scale is characterised into 6 factors. Each symptom is mapped with specific anatomical abnormalities and circuits. Comparison between factors reveals co-occurrence in parcels in Factor 1 and Factor 2. Multiple large-scale networks are involved in SCZ symptomatology, with functional connectivity within Default Mode Network (DMN) and Central Executive Network (CEN) regions most frequently associated with measures of psychopathology. CONCLUSION: We present a summary of the relevant anatomy for regions of the cortical areas as part of a larger effort to understand its contribution in schizophrenia. This unique machine learning-type approach maps symptoms to specific brain regions and circuits by bridging the diagnostic subtypes and analysing the features of the connectome.

The Effect of Brief Mindfulness Meditation on Suicidal Ideation, Stress and Sleep Quality.

OBJECTIVES: Suicide is the fourth leading cause of death for individuals aged 15-29 years, and early intervention on suicidal ideation and risk factors should be priortized. Brief mindfulness meditation (BMM) is convenient and cost-effective in improving physical and mental well-being, but less is known about its efficacy for suicidal ideation, stress and sleep quality. We investigated the effects of BMM on suicidal ideation, stress, and sleep quality for individuals with suicide risk. METHODS: Sixty-four college students with high suicidal ideation (aged 18-30 years) were randomly allocated to either a BMM (n = 32) or control group (n = 32). The BMM was based on Anapanasati and core mindfulness concepts. Sixty participants completed all scheduled sessions including pretest, one month of intervention or waiting, and posttest. Suicidal ideation was measured with the Beck Scale for Suicidal Ideation. Stress was evaluated using the Perceived Stress Scale and salivary cortisol levels. Sleep was measured using the Pittsburgh Sleep Quality Index and actigraphy accompanied with 7-day sleep diaries. RESULTS: Post-intervention, the BMM group showed significant decrease in suicidal ideation with a large effect size; the decrease showed a medium effect size in the control group. The BMM group, but not the control group, showed significant decrease in morning salivary cortisol and sleep latency, and improved sleep efficiency. CONCLUSIONS: BMM could help reduce suicidal ideation, stress, and sleep disturbance for individuals with high suicidal ideation and it may implicate effective suicide prevention strategy.

Immunological characteristics of human umbilical cord mesenchymal stem cells after hepatogenic differentiation.

BACKGROUND: Acute liver failure is one of the most intractable clinical problems. The use of bioartificial livers may solve donor shortage problems. Human umbilical cord mesenchymal stem cells (hUCMSCs) are an excellent seed cell choice for artificial livers because they change their characteristics to resemble hepatocyte-like cells (HLCs) following artificial liver transplantation. OBJECTIVE: This study aimed to determine whether the immunological characteristics of hUCMSCs are changed after being transformed into hepatocyte-like cells. METHODS: HUCMSCs were isolated by the adherent method. The following hUCMSC surface markers were detected using flow cytometry: CD45, CD90, CD105, CD34, and octamer-binding transcription factor 4 (OCT-4). Functional detection of adipogenic differentiation was performed. The hUCMSCs were cultured in complete medium (control group) or induction medium (induction group), and flow cytometry was used to detect cell surface markers. Peritoneal lavage fluid was collected after intraperitoneal injection of 1 × 106 cells/mouse over 40 minutes. The leukocyte count, labeled CD45, CD3, CD4 and CD8 antibodies, and flow detection of T lymphocyte subsets were determined using the peritoneal lavage fluid. RESULTS: Using phenotypic and functional identification, hUCMSCs were successfully isolated using a two-step induction method. The surface markers of the hUCMSCs cells changed after HLC induction. In vivo immune results showed that hUCMSCs and HLsC induced leukocyte production. CONCLUSION: Hepatic induction of hUCMSCs changes their cell surface markers. Both HLCs and hUCMSCs cause leukocytosis in vivo, but the immune response induced by HLCs is slightly stronger.

Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia.

BACKGROUND: Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported. METHODS: Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts. RESULTS: Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)-left inferior temporal gyrus (ITG), right IFG-left ITG, right IFG-left middle frontal gyrus (MFG), and right IFG-right MFG in the FES group. CONCLUSION: Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

Reduced interpersonal neural synchronization in right inferior frontal gyrus during social interaction in participants with clinical high risk of psychosis: An fNIRS-based hyperscanning study.

BACKGROUND: Clinical high risk (CHR) of psychosis is characterized by cognitive impairment in social interaction. However, research investigating the neurobiological underpinnings of social interactions and interpersonal relationships in CHR participants is sparse. METHODS: 21 CHR and 54 healthy controls (HCs) participated in the study. Dyads were formed between one CHR, one sex-matched HC, and two sex-matched HCs comprising 19 CHR-HC dyads and 19 HC-HC dyads. The concentration changes of oxyhemoglobin and deoxyhemoglobin were examined during a two-block button-press "cooperation" and "competition" task using functional near-infrared spectroscopy(fNIRS) hyperscanning technology. CHR diagnosis and psychopathological assessments were performed by Structured Interview for Prodromal Syndromes (SIPS) and Scale of Prodromal Symptoms (SOPS). Neural synchronizations were compared between CHR-HC dyads and HC-HC dyads. Correlation analyses were performed to identify the relationship between neural synchronization, clinical syndrome and cognition. RESULTS: During the cooperation, but not the competition task, the CHR-HC dyads showed reduced inter-brain neural synchronization (INS) in the right inferior frontal gyrus (IFG) compared to the HC-HC dyads. INS also showed a positive correlation with the average cooperation rate. Moreover, the reduced INS in the CHR-HC group was significantly correlated with symptoms score of suspiciousness/persecutory ideas and movement disorders. CONCLUSIONS: The decreased INS in right IFG during cooperation could account for CHR's cognitive impairment of social interaction. Our findings provide evidence that inter-brain neural synchronization potentially represents a biomarker of social interaction deficits of CHR.

Reduced temporal activation during a verbal fluency test in clinical high risk of psychosis: a functional near-infrared spectroscopy-based study.

Background: Clinical high risk (CHR) of psychosis is a state in which positive symptoms cause the subjects distress but do not approach a severity level that fulfils the criteria for a psychotic episode. CHR exhibits cognitive deficits; however, the underlying neurobiological mechanisms remain unclear. This study aimed to investigate whether brain activation measured by the levels of oxygenated hemoglobin (oxy-Hb) in CHR subjects could be correlated with cognitive deficits. Methods: Fifty-eight CHR individuals who fulfilled the criteria for attenuated positive syndrome as specified in the Structured Interview for Prodromal Syndrome (SIPS) and the Scale of Prodromal Syndrome (SOPS) and 58 age- and sex-matched healthy participants were included in the study. All subjects completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) that includes tests measuring attention, verbal memory, verbal fluency, executive function, and general intelligence. Functional near-infrared spectroscopy (fNIRS) was used to measure the level of oxy-Hb in the dorsolateral prefrontal and frontotemporal cortices. Results: We observed significantly decreased oxy-Hb levels in channel 32 (located in the right superior temporal gyrus, rSTG)) within the CHR individuals compared with that in the healthy controls (HCs) (t=-3.44, Bonferroni-corrected p=0.002), indicating lower brain activity. A significant positive correlation was observed between task-related ß values and working memory in the CHR group (r=0.35, p=0.008). Conclusions: The brain activation of rSTG is abnormal among subjects at clinicial high risk for psychosis. This abnormality is probably associated with the neural mechanisms of deficits in the working memory during the early stage of psychosis.

Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants.

Background: Disrupted white matter (WM) microstructure has been commonly identified in youth at clinical high risk (CHR) for psychosis. Several lines of evidence suggest that fatty acids, especially unsaturated fatty acids (UFAs), might play a crucial role in the WM pathology of early onset psychosis. However, evidence linking UFA and WM microstructure in CHR is quite sparse. Aims: We investigated the relationship between the plasma UFA level and WM microstructure in CHR participants and healthy controls (HC). Methods: Plasma fatty acids were assessed and diffusion tensor imaging (DTI) data were performed with tract-based spatial statistics (TBSS) analysis for 66 individuals at CHR for psychosis and 70 HC. Results: Both the global and regional diffusion measures showed significant between-group differences, with decreased fractional anisotropy (FA) but increased mean diffusivity (MD) and radial diffusivity (RD) found in the CHR group compared with the HC group. On top of that, we found that in the HC group, plasma arachidic acid showed obvious trend-level associations with higher global FA, lower global MD and lower global RD, which regionally spread over the corpus callosum, right anterior and superior corona radiata, bilateral anterior and posterior limb of the internal capsule, and bilateral superior longitudinal fasciculus. However, there were no associations between global WM measures and any UFA in the CHR group. Conversely, we even found negative associations between arachidic acid levels and regional FA values in the right superior longitudinal fasciculus and right retrolenticular part of the internal capsule in the CHR group. Conclusions: Compared with the HC group, CHR subjects exhibited a different pattern of association between WM microstructure and plasma UFA, with a neuroprotective effect found in the HC group but not in the CHR group. Such discrepancy could be due to the excessively upregulated UFAs accumulated in the plasma of the CHR group, highlighting the role of balanced plasma-membrane fatty acids homeostasis in WM development.

Effect of cognitive insight on clinical insight from pre-morbid to early psychosis stages.

Poor cognitive insight, including low self-reflectiveness and high self-certainty, contributes to poor clinical insight, which includes awareness of illness, relabelling of specific symptoms, and treatment compliance. However, inconsistent results regarding cognitive insight among individuals at clinical high risk of psychosis (CHR) have been reported. This study investigated the difference in cognitive insight among groups with different severity of positive symptoms and analysed the effect of cognitive insight on clinical insight in each group. All participants, including CHR individuals with 3 or 4 points (L-Pitem, n = 85) and 5 points (H-Pitem, n = 37) on any positive-symptom item of the Scale of Prodromal Syndromes, and patients with first-episode psychosis (FEP, n = 59), were measured cognitive and clinical insight using the Beck Cognitive Insight Scale and the Schedule of Assessment of Insight, respectively. The self-reflectiveness of cognitive insight was highest in the L-Pitem group and lowest in the FEP group. Self-reflectiveness was positively associated with awareness of illness in the L-Pitem and FEP groups; both self-reflectiveness and self-certainty was positively associated with treatment compliance in the L-Pitem group. Improving self-reflectiveness of cognitive insight may conduce to good clinical insight. Self-certainty may have different implication to individuals with mild prodromal symptoms.

Thalamo-hippocampal dysconnectivity is associated with serum cholesterol level in drug-naïve patients with first-episode schizophrenia.

Hippocampal deficits and metabolic dysregulations such as dyslipidemia have been frequently reported in schizophrenia and are suggested to contribute to the pathophysiology of schizophrenia. Hippocampus is particularly susceptible to environmental challenges including metabolism and inflammation. However, evidence linking hippocampal alterations and metabolic dysregulations are quite sparse in drug-naïve schizophrenia. A total of 166 drug-naïve patients with first-episode schizophrenia (FES) and 78 healthy controls (HC) underwent measures for several serum metabolic markers, structural and resting-state functional magnetic resonance imaging (rs-fMRI), as well as diffusion tensor imaging (DTI). Seed-to-voxel functional connectivity (FC) and probabilistic tractography were performed to assess the functional and microstructural connectivity of the bilateral hippocampi. Clinical symptoms were evaluated with Positive and Negative Syndrome Scale (PANSS). Patients with FES showed significantly decreased total cholesterol (Chol) level. Patients showed elevated FC between the left hippocampus and bilateral thalami while showing decreased microstructural connectivity between the left hippocampus and bilateral thalami. Multiple regression analyses showed that FC from the left hippocampus to the right superior frontal gyrus (SFG), bilateral frontal pole (FP), and right thalamus were negatively associated with the Chol level, while no association was observed in the HC group. Our study validated alterations in both functional and microstructural thalamo-hippocampal connectivities, and abnormal cholesterol level in FES. Moreover, decreased cholesterol level is associated with elevated thalamo-hippocampal functional connectivity in patients with FES, suggesting that dyslipidemia may interact with the hippocampal dysfunction in FES.

Study on the Role of Salicylic Acid in Watermelon-Resistant Fusarium Wilt under Different Growth Conditions.

BACKGROUND: Fusarium wilt disease is leading threat to watermelon yield and quality. Different cultivation cropping systems have been reported as safe and efficient methods to control watermelon Fusarium wilt. However, the role of salicylic acid (SA) in watermelon resistance to Fusarium wilt in these different cultivation systems remains unknown. METHODS: in this experiment, we used RNA-seq and qRT-PCR to study the effect of SA biosynthesis on improving watermelon health, demonstrating how it may be responsible for Fusarium wilt resistance under continuous monocropping and oilseed rape rotation systems. RESULTS: the results revealed that the expression of the CIPALs genes was key to SA accumulation in watermelon roots. We observed that the NPR family genes may play different roles in responding to the SA signal. Differentially expressed NPRs and WRKYs may interact with other phytohormones, leading to the amelioration of watermelon Fusarium wilt. CONCLUSIONS: further understanding of gene expression patterns will pave the way for interventions that effectively control the disease.

Antipsychotics Effects on Network-Level Reconfiguration of Cortical Morphometry in First-Episode Schizophrenia.

Cortical thickness reductions are evident in schizophrenia (SZ). Associations between antipsychotic medications (APMs) and cortical morphometry have been explored in SZ patients. This raises the question of whether the reconfiguration of morphological architecture by APM plays potential compensatory roles for abnormalities in the cerebral cortex. Structural magnetic resonance imaging was obtained from 127 medication-naive first-episode SZ patients and 133 matched healthy controls. Patients received 12 weeks of APM and were categorized as responders (n = 75) or nonresponders (NRs, n = 52) at follow-up. Using surface-based morphometry and structural covariance (SC) analysis, this study investigated the short-term effects of antipsychotics on cortical thickness and cortico-cortical covariance. Global efficiency was computed to characterize network integration of the large-scale structural connectome. The relationship between covariance and cortical thinning was examined by SC analysis among the top-n regions with thickness reduction. Widespread cortical thickness reductions were observed in pre-APM patients. Post-APM patients showed more reductions in cortical thickness, even in the frontotemporal regions without baseline reductions. Covariance analysis revealed strong cortico-cortical covariance and higher network integration in responders than in NRs. For the NRs, some of the prefrontal and temporal nodes were not covariant between the top-n regions with cortical thickness reduction. Antipsychotic effects are not restricted to a single brain region but rather exhibit a network-level covariance pattern. Neuroimaging connectomics highlights the positive effects of antipsychotics on the reconfiguration of brain architecture, suggesting that abnormalities in regional morphology may be compensated by increasing interregional covariance when symptoms are controlled by antipsychotics.

Life in the flame: Inflammation sounds the alarm for suicide risk.

As suicide became a critical issue in mental healthcare, the World Health Organization (WHO) presented a Mental Health Action Plan in 2013. Particularly, the plan set an explicit goal for suicide prevention, which called for 10% reduction in the suicide rate in member countries by 2020. Now the tough year of 2020 has passed by, many valuable breakthroughs on suicide research have emerged during these recent years. To some extent, a multi-stage system for the prediction and prevention of suicide is taking shape. Inflammatory biomarkers may have a promising future within this field.