Changes in Mental Health and EEG Biomarkers of Undergraduates Under Different Patterns of Mindfulness.

The effects of short-term mindfulness are associated with the different patterns (autonomic, audio guided, or experienced and certified mindfulness instructor guided mindfulness). However, robust evidence for reported the impacts of different patterns of mindfulness on mental health and EEG biomarkers of undergraduates is currently lacking. Therefore, we aimed to test the hypotheses that mindfulness training for undergraduates would improve mental health, and increase alpha power over frontal region and theta power over midline region at the single electrode level. We also describe the distinction among frequency bands patterns in different sites of frontal and midline regions. 70 participants were enrolled and assigned to either 5-day mindfulness or a waiting list group. Subjective questionnaires measured mental health and other psychological indicators, and brain activity was recorded during various EEG tasks before and after the intervention. The 5-day mindfulness training improved trait mindfulness, especially observing (p = 0.001, d = 0.96) and nonreactivity (p = 0.03, d = 0.56), sleep quality (p = 0.001, d = 0.91), and social support (p = 0.001, d = 0.95) while not in affect. Meanwhile, the expected increase in the alpha power of frontal sites (p < 0.017, d > 0.84) at the single electrode level was confirmed by the current data rather than the theta. Interestingly, the alteration of low-beta power over the single electrode of the midline (p < 0.05, d > 0.71) was difference between groups. Short-term mindfulness improves practitioners' mental health, and the potentially electrophysiological biomarkers of mindfulness on neuron oscillations were alpha activity over frontal sites and low-beta activity over midline sites.

Tim3scFv-Transforming Lactobacillus Inhibits Transplanted Tumor of Renal-Cell Carcinoma.

INTRODUCTION: T-cell immunoglobulin-3 (Tim-3) antibody drugs can treat malignant renal tumors but are expensive. To overcome this limitation, Lactococcus lactis host bacteria were used to express Tim-3 single-chain antibodies. METHODS: The pLAN-CTB-Tim3scFv plasmid was constructed using molecular cloning technology and transformed into Lactococcus lactis. Expression and immune activity of proteins in the transformed bacteria were analyzed using Western blotting and enzyme-linked immunosorbent assay in vitro. A mouse subcutaneously transplanted tumor model of renal adenocarcinoma was constructed. The promoting effect of transformed bacteria on mouse spleen lymphocyte activation and their inhibitory effect on transplanted tumors were analyzed. RESULTS: Transformed L. lactis NZ-CTB-Tim3scFv and NZ-Tim3scFv were successfully constructed. CTB-Tim3scFv secreted by NZ-CTB-Tim3scFv showed immunological activity. Compared with the NZ-Tim3scFv and NZ-Vector groups, the subgroups of splenic lymphocytes in the NZ-CTB-Tim3scFv group had a higher proportion of CD3+CD4+, CD3+CD8a+, and CD3+CD69+ cells. Ki67 and CD31 expression in the NZ-CTB-Tim3scFv group was significantly reduced. Tumor volume in the NZ-CTB-Tim3scFv group increased the least. DISCUSSION/CONCLUSION: Secretion of CTB-Tim3scFv promoted the proliferation and activation of spleen lymphocytes and inhibited growth, cell proliferation, and angiogenesis of tumors. The proposed method is low cost and convenient with potential to become a new immunotherapy approach for renal-cell carcinoma.

Prenatal Morphine Exposure Differentially Alters Addictive and Emotional Behavior in Adolescent and Adult Rats in a Sex-Specific Manner.

The effects of prenatal opioid exposure in adult animals has been widely studied, but little is known about the effects of prenatal opioid on adolescents. Most of the risk behaviors associated with drug abuse are initiated during adolescence. The developmental state of the adolescent brain makes it vulnerable to initiate drug use and susceptible to drug-induced brain changes. In this study, pregnant rats were subcutaneously injected with an increasing dose of morphine (5 mg/kg, 7 mg/kg, 10 mg/kg) for 9 days since the gestation day 11. The effects of prenatal morphine (PNM) on learning and memory, anxiety- and depressive- like behavior, morphine induced conditioned place preference (CPP) as well as locomotor sensitization were tested in both adolescent and adult rats. The results showed that: (1) PNM decreased anxiety-like behavior in both adolescent and adult female rats, but not males; (2) PNM decreased depressive-like behavior in adolescent but increased depressive -like behavior in adult females; (3) PNM increased low dose morphine induced locomotor sensitization in females; (4) PNM decreased tyrosine hydroxylase (TH) expression in the prefrontal cortex but decreased dopamine D1 receptor expression in the nucleus-accumbens (NAc) in female rats. These results suggested that PNM altered the emotional and addictive behavior mainly in female rats, with female rats being less anxiety and depressive during adolescence, but more depressive in adult, and more sensitive to low dose morphine induced locomotor activity sensitization, which might be mediated in part by the differential expression of the TH, dopamine D1 receptors in the female brain.

Pseudogene HSPB1P1 contributes to renal cell carcinoma proliferation and metastasis by targeting miR-296-5p to regulate HMGA1 expression.

With the aid of next-generation sequencing technology, pseudogenes have been widely recognized as functional regulators in the development and progression of certain diseases, especially cancer. Our present study aimed to investigate the functions and molecular mechanisms of HSPB1-associated protein 1 pseudogene 1 (HSPB1P1) in renal cell carcinoma (RCC). HSPB1P1 expression at the mRNA levels was determined by quantitative real-time polymerase chain reaction, and its clinical significance was assessed. Cell viability was detected by Cell Counting Kit-8 assay. Cell migration and invasion were detected by transwell assays. The location of HSPB1P1 in RCC cells was detected by subcellular distribution analysis. The direct relationship between HSPB1P1 and miR-296-5p/HMGA1 axis was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Our results identify the elevated expression of HSPB1P1 in RCC tissues and cell lines, which predicted advanced progression and poor prognosis in patients with RCC. Knockdown of HSPB1P1 suppressed cell proliferation, migration, and invasion, and reversed epithelial-mesenchymal transition process in RCC. HSPB1P1 was mostly enriched in the cytoplasm and functioned as a miRNA sponge for miR-296-5p and then regulated high-mobility group A1 expression. In conclusion, our study indicated that HSPB1P1 contributed to RCC progression by targeting the miR-296-5p/HMGA1 axis, and should be considered as a promising biomarker and therapeutic target for clinical applications.

Circular RNA hsa_circ_001895 serves as a sponge of microRNA-296-5p to promote clear cell renal cell carcinoma progression by regulating SOX12.

There is an urgent need to find novel potential therapeutic targets for the diagnosis and treatment of clear cell renal cell carcinoma (ccRCC) due to its highly invasive ability as a common urological malignant tumor. Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression. We first used qRT-PCR analysis to find dysregulated circRNAs in ccRCC. A novel circRNA, hsa_circ_001895, was upregulated in ccRCC specimens and associated with metastatic properties of ccRCC. However, the tumorigenic mechanism of hsa_circ_001895 on ccRCC is yet to be found. We first indicated that hsa_circ_001895 predicted a poor prognosis in ccRCC patients. Additionally, overexpression of hsa_circ_001895 not only promoted cell proliferation, invasion and migration of ccRCC, but also inhibited cell apoptosis, whereas hsa_circ_001895 knockdown reversed the effect on ccRCC progression. In vivo s.c. xenotransplanted tumor model also showed that silencing hsa_circ_001895 could suppress in vivo ccRCC growth. Mechanistically, hsa_circ_001895 directly binds with microRNA (miR)-296-5p and inhibits its expression. Moreover, sex determining region Y (SRY)-box 12 (SOX12) was identified as a target of miR-296-5p, the expression of which was suppressed by miR-296-5p. Notably, the inhibitory effect of hsa_circ_001895 on ccRCC progression was reversed by miR-296-5p inhibitor. In general, our findings indicated that hsa_circ_001895 may sponge miR-296-5p and promote SOX12 expression, which is the underlying mechanism of hsa_circ_001895-induced ccRCC progression.

Risk-adapted treatment reduced chemotherapy exposure for clinical stage I pediatric testicular cancer.

BACKGROUND: Different from adult clinical stage I (CS1) testicular cancer, surveillance has been recommended for CS1 pediatric testicular cancer. However, among high-risk children, more than 50% suffer a relapse and progression during surveillance, and adjuvant chemotherapy needs to be administered. Risk-adapted treatment might reduce chemotherapy exposure among these children. METHODS: A decision model was designed and calculated using TreeAge Pro 2011 software. Clinical utilities such as the relapse rates of different groups during surveillance or after chemotherapy were collected from the literature. A survey of urologists was conducted to evaluate the toxicity of first-line and second-line chemotherapy. Using the decision analysis model, chemotherapy exposure of the risk-adapted treatment and surveillance strategies were compared based on this series of clinical utilities. One-way and two-way tests were applied to check the feasibility. RESULTS: In the base case decision analysis of CS1 pediatric testicular cancer, risk-adapted treatment resulted in a lower exposure to chemotherapy than surveillance (average: 0.7965 cycles verse 1.3419 cycles). The sensitivity analysis demonstrated that when the relapse rate after primary chemotherapy was ≤ 0.10 and the relapse rate of the high-risk group was ≥ 0.40, risk-adapted treatment would result in a lower exposure to chemotherapy, without any association with the proportion of low-risk patients, the relapse rate of the low-risk group, the relapse rate after salvage chemotherapy or the toxicity utility of second-line chemotherapy compared to first-line chemotherapy. CONCLUSIONS: Based on the decision analysis, risk-adapted treatment might decrease chemotherapy exposure for these high-risk patients, and an evaluation after orchiectomy was critical to this process. Additional clinical studies are needed to validate this statement.

Intravenous misplacement of nephrostomy tube following percutaneous nephrolithotomy: Three new cases and review of seven cases in the literature.

PURPOSE: We investigated the characteristics and management of patients with intravenous misplacement of a nephrostomy tube. MATERIALS AND METHODS: Between July 2007 and July 2013, 4148 patients with urolithiasis underwent percutaneous nephrolithotomy (PCNL) in our hospital. Intravenous misplacement of a nephrostomy tube occurred in two of these patients. Another patient with intravenous misplacement of a nephrostomy tube, who underwent PCNL in another hospital, was transferred to our hospital. The data of the three patients were retrospectively analyzed. RESULTS: The incidence of intravenous misplacement of a nephrostomy tube following PCNL was 0.5% (2/4148) at our hospital. A solitary kidney was present in one of the three patients. The tip of tube was located into the inferior vena cava (IVC) in two patients and into the renal vein in one patient. All three patients were successfully managed with strict bed rest, intravenous antibiotics and one-step (one patient) or two-step (two patients) tube withdrawal under close monitoring. None of the patients underwent antithrombotic therapy. The original operations were performed successfully under close observation in two patients and changed to another operation in one patient. All patients were discharged uneventfully. CONCLUSIONS: The incidence of intravenous misplacement of a nephrostomy tube following PCNL is 0.5% at our hospital. Intravenous nephrostomy tube misplacement is an uncommon complication of PCNL. A solitary kidney may render patients susceptible to this complication. Most patients may be managed conservatively with strict bed rest, intravenous antibiotics and one-step or two-step tube withdrawal under close monitoring.

Effects of brief mindfulness training on smoking cue-reactivity in tobacco use disorder: Study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of Tobacco Use Disorder (TUD) represents a significant and pressing global public health concern, with far-reaching and deleterious consequences for individuals, communities, and healthcare systems. The craving caused by smoking cue is an important trigger for relapse, fundamentally hindering the cessation of cigarette smoking. Mindfulness interventions focusing on cue-reactivity was effective for the treatment of related dependence. Brief mindfulness training (BMT) meets the short-term needs for intervention but the effects still need to be examined. The objective of the present study is to investigate the impact of BMT intervention on smoking cue-reactivity among Chinese college students with TUD, to uncover the dynamic models of brain function involved in this process. METHOD: A randomized control trial (RCT) based on electroencephalography (EEG) was designed. We aim to recruit 90 participants and randomly assign to the BMT and control group (CON) with 1:1 ratio. A brief mindfulness training will be administered to experimental group. After the intervention, data collection will be conducted in the follow-up stage with 5 timepoints of assessments. EEG data will be recorded during the smoking cue-reactivity task and 'STOP' brief mindfulness task. The primary outcomes include subjective reports of smoking craving, changes in EEG indicators, and mindfulness measures. The secondary outcomes will be daily smoking behaviours, affect and impulsivity, as well as indicators reflecting correlation between mindfulness and smoking cue-reactivity. To evaluate the impact of mindfulness training, a series of linear mixed-effects models will be employed. Specifically, within-group effects will be examined by analysing the longitudinal data. Additionally, the effect size for all statistical measurements will be reported, offering a comprehensive view of the observed effects. DISCUSSION: The current study aims to assess the impact of brief mindfulness-based intervention on smoking cue-reactivity in TUD. It also expected to enhance our understanding of the underlying processes involved in brain function and explore potential EEG biomarkers at multiple time points. TRIAL REGISTRATION: Trial registration number: ChiCTR2300069363, registered on 14 March 2023. Protocol Version 1.0., 10 April 2023.

Continuous high-frequency repetitive transcranial magnetic stimulation at extremely low intensity affects exploratory behavior and spatial cognition in mice.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been shown to be effective for cognitive intervention. However, whether HF-rTMS with extremely low intensity could influence cognitive functions is still under investigation. The present study systematically investigated the effects of continuous 40 Hz and 10 Hz rTMS on cognition in young adult mice at extremely low intensity (10 mT and 1 mT) for 11 days (30 min/day). Cognitive functions were assessed using diverse behavioral tasks, including the open field, Y-maze, and Barnes maze paradigms. We found that 40 Hz rTMS significantly impaired exploratory behavior and spatial memory in both 10 mT and 1 mT conditions. In addition, 40 Hz rTMS induced remarkably different effects on exploratory behavior between 10 mT and 1mT, compared to 10 Hz stimulation. Our results indicate that extremely low intensity rTMS can significantly alter cognitive performance depending on intensity and frequency, shedding light on the understanding of the mechanism of rTMS effects.

Role of GABAB receptors in cognition and EEG activity in aged APP and PS1 transgenic mice.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Recent evidence suggests that gamma-aminobutyric acid B (GABAB) receptor-mediated inhibition is a major contributor to AD pathobiology, and GABAB receptors have been hypothesized to be a potential target for AD treatment. The aim of this study is to determine how GABAB regulation alters cognitive function and brain activity in an AD mouse model. Early, middle and late stage (8-23 months) amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice were used for the study. The GABAB agonist baclofen (1 and 2.5 mg/kg, i. p.) and the antagonist phaclofen (0.5 mg/kg, i. p.) were used. Primarily, we found that GABAB activation was able to improve spatial and/or working memory performance in early and late stage AD animals. In addition, GABAB activation and inhibition could regulate global and local EEG oscillations in AD animals, with activation mainly regulating low-frequency activity (delta-theta bands) and inhibition mainly regulating mid- and high-frequency activity (alpha-gamma bands), although the regulated magnitude at some frequencies was reduced in AD. The cognitive improvements in AD animals may be explained by the reduced EEG activity in the theta frequency band (2-4 Hz). This study provides evidence for a potential therapeutic effect of baclofen in the elderly AD brain and for GABAB receptor-mediated inhibition as a potential therapeutic target for AD.

Cue-reactivity targeted smoking cessation intervention in individuals with tobacco use disorder: a scoping review.

Objectives: Cue-reactivity is a critical step leading to the emergence of addictive psychology and the triggering of addictive behaviors within the framework of addiction theory and is considered a significant risk factor for addiction-related behaviors. However, the effect of cue-reactivity targeted smoking cessation intervention and the cue-reactivity paradigms used in the randomized controlled trials varies, which introduces more heterogeneity and makes a side-by-side comparison of cessation responses difficult. Therefore, the scoping review aims to integrate existing research and identify evidence gaps. Methods: We searched databases in English (PubMed and Embase) and Chinese (CNKI and Wanfang) using terms synonymous with 'cue' and 'tobacco use disorder (TUD)' to April 2023, and via hand-searching and reference screening of included studies. Studies were included if they were randomized controlled trials taking cue-reactivity as an indicator for tobacco use disorder (TUD) defined by different kinds of criteria. Results: Data were extracted on each study's country, population, methods, timeframes, outcomes, cue-reactivity paradigms, and so on. Of the 2,944 literature were retrieved, 201 studies met the criteria and were selected for full-text screening. Finally, 67 pieces of literature were selected for inclusion and data extraction. The results mainly revealed that non-invasive brain stimulation and exercise therapy showed a trend of greater possibility in reducing subjective craving compared to the remaining therapies, despite variations in the number of research studies conducted in each category. And cue-reactivity paradigms vary in materials and mainly fall into two main categories: behaviorally induced craving paradigm or visually induced craving paradigm. Conclusion: The current studies are still inadequate in terms of comparability due to their heterogeneity, cue-reactivity can be conducted in the future by constructing a standard library of smoking cue materials. Causal analysis is suggested in order to adequately screen for causes of addiction persistence, and further explore the specific objective cue-reactivity-related indicators of TUD.

CircRNA_001895 promotes sunitinib resistance of renal cell carcinoma through regulation of apoptosis and DNA damage repair.

Sunitinib, an inhibitor of receptor tyrosine kinase, possesses anti-tumor activity in renal cell carcinoma (RCC) through its anti-angiogenic effects. However, patients with advanced RCC are resistant to sunitinib. Dysregulated circRNAs has been shown to be associated with drug resistance in various tumors. However, little is known about the effect of circRNA_001895 on sunitinib resistance of RCC. First, the expression of circRNA_001895 was found to be higher in sunitinib-resistant RCC tissues than chemosensitive tumor tissues. Half maximal inhibitory concentration of sunitinib-resistant RCC cells (786-O/R and ACHN/R) was higher than sunitinib-sensitive 786-O and ACHN cells. CircRNA_001895 was also upregulated in 786-O/R and ACHN/R cells. Second, data from colony formation and flow cytometry analysis showed that knockdown of circRNA_001895 suppressed cell proliferation and promoted cell apoptosis in 786-O/R and ACHN/R cells. Moreover, the protein expression of phosphorylated histone H2AX (γH2AX) was enhanced, while phosphorylated DNA-dependent protein kinase (p-DNA-PK) and Rad51 were reduced in 786-/R and ACHN/R by knockdown of circRNA_001895. Lastly, knockdown of circRNA_001895 conferred sensitivity of in vivo tumor growth to sunitinib. In conclusion, circRNA_001895 was implicated in the sunitinib resistance in RCC through regulation of apoptosis and DNA damage repair, suggesting that circRNA_001895 might be a potential therapeutic target for advanced RCC.

Social support and prosocial behavior in Chinese college students during the COVID-19 outbreak: a moderated mediation model of positive affect and parental care.

Purpose: Prosocial behavior (PSB) plays a critical role in everyday society, especially during the pandemic of COVID-19. Understanding the underlying mechanism will provide insight and advance its implementation. According to the theory of PSB, social interaction, family and individual characters all contribute to its development. The current study aimed to investigate the influencing factor of PSB among Chinese college students during COVID-19 outbreak. This is an attempt to understand the mechanism of PSB and to provide a reference for the formulation of policies aimed at promoting healthy collaborative relationships for college students. Method: The online questionnaire was administered to 664 college students from 29 provinces of China via Credamo platform. There were 332 medical students and 332 non-medical students aged between 18 and 25 included for final study. The mediating role of positive emotion/affect (PA) and the moderating role of parental care in the association between social support and PSB during the pandemic of COVID-19 was explored by using Social Support Rate Scale (SSRS), Prosocial Tendencies Measurement Scale (PTM), The Positive and Negative Affect (PANAS), as well as Parental Bonding Instrument (PBI). The process macro model of SPSS was adopted for mediating and moderating analysis. Results: The results showed that social support positively predicted PSB among Chinese college students, even after adding PA as a mediation variable. PA during COVID-19 mediated the association between social support and PSB. PSB also revealed as a predictor of PA by regression analysis. Moreover, the moderating effect of parental care in the relationship between PA and PSB was detected. Conclusion: PA under stress acts as a mediator between social support and PSB. This mediating effect was moderated by PC in childhood. In addition, PSB was observed to predict PA reversely. The promoting factors and path between the variables of PSB are complex and need to be explored extensively. The underlying factors and process should be further investigated for the development of intervention plans.

Trends of the Global Burden of Disease Attributable to Cannabis Use Disorder in 204 Countries and Territories, 1990-2019: Results from the Disease Burden Study 2019.

Cannabis is the fourth psychoactive substance to be legalized which are of far-reaching significance to the world. We analyzed data from the 2019 Global Burden of Disease Study (GBD) to estimate the incidence and prevalence of cannabis use disorder (CUD) and calculated the disease burden of CUD in 204 countries and territories and 21 regions over the past three decades. We reported disease burden due to CUD in terms of disability-adjusted life years (DALYs), age-standardized rate (ASR), estimated annual percentage change (EAPC), and analyzed associations between the burden of CUD and sociodemographic index (SDI) quintiles. Globally, the number of incidence cases of CUD was estimated to be increasing by 32.3% from 1990 to 2019 and males are nearly double higher than that of female. DALYs increase 38.6% from 1990. Young people aged 20-24 years old with cannabis use disorder have the highest DALYs in 2019, followed by those younger than 20 years old. India, Canada, USA, Qatar, Kenya, and high SDI quintile areas showed a high burden of disease. Nearly 200 million individuals are cannabis users worldwide, and CUD is a notable condition of GBD. The global cultivation of cannabis, rooted in different cultures, diversified access to cannabis, legalization in controversy, the promotion of medical cannabis, and many other factors promote the global cannabis industry is constantly updated and upgraded. It deserves more discussion in the future in terms of pathophysiological mechanisms, socioeconomics, law, and policy improvement. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-022-00999-4.

[Genome-wide association study with memory measures as a quantitative trait locus for schizophrenia].

OBJECTIVE: To assess the association between gene polymorphisms and memory function through a genome-wide association study (GWAS) of schizophrenia and control group. Memory cognition was used as a quantitative trait (QT). METHODS: Ninty-eight subjects with chronic schizophrenia and 60 matched controls were genotyped with HumanHap660 Bead Array. The results were correlated with quantitative traits including memory and memory delay. RESULTS: Five candidate genes, including RASGRF2 (rs401758, P = 8.03×10(-5)), PLCG2 (rs7185362, P= 4.54×10(-5)), LMO1 (rs484161, P=9.80×10(-7), CSMD1 (rs2469383, P= 2.77×10(-6)) and PRKG1 (rs7898516, P=6.94×10(-5)) were associated with memory cognition deficits. CONCLUSION: Using memory cognition as a quantitative trait, this Genome- wide association study has identified 5 susceptibility loci. With their association with nervous system development, neuronal growth, axon guidance and plasticity, brain development, above loci may play a role in the development of memory dysfunction in schizophrenia.

Analysis of the Underlying Mechanism of the Jiu Wei Zhen Xin Formula for Treating Generalized Anxiety Disorder Based on Network Pharmacology of Traditional Chinese Medicine.

Currently, there are many effective pharmacological treatments for generalized anxiety disorder (GAD), formulated herbal granule is also an alternative way. Our research intends to construct a pharmacological network on genetic targets and pathways between Jiu Wei Zhen Xin Formula (JWZXF) and GAD. Through the TCMSP database, we collected the active ingredients of JWZXF and potential targets of the active ingredients. The GAD-related proteins collected from GeneCards database and DisGeNET database were combined. Component-target protein networks were constructed and visualized using Cytoscape 3.8.2 software to comprehensively clarify the relationships between ingredients, components, and targets. The intersection targets were imported into the STRING database, and the protein-protein interaction (PPI) network was constructed. We constructed and analyzed the visualized "drug-target-disease" network. Gene Ontology (GO) enrichment together with Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were conducted on the common target through R language. Forty-one effective components and 106 potential targets of JWZXF were found. There were top ten hub genes and multiple important signaling pathways involved in the treatment of GAD with the JWZXF. This study expounded the pharmacological actions and molecular mechanisms of the JWZXF in treating GAD from a holistic perspective. The potential pharmacological effects of the JWZXF are closely related to regulation because not only does it comprehensively analyze the possible mechanism of JWZXF treatment of GAD but it can also facilitate further in-depth research and provide a theoretical basis for the clinical expansion of its application.

Anodal and cathodal transcranial direct current stimulations of prefrontal cortex in a rodent model of Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of dementia in the elderly, with no effective treatment currently available. Transcranial direct current stimulation (tDCS), a non-drug and non-invasive therapy, has been testified efficient in cognitive enhancement. This study aims to examine the effects of tDCS on brain function in a mouse model of AD. The amyloid precursor protein (APP) and presenilin 1 (PS1) transgenic mice (7-8 months old) were subjected to 20-min anodal and cathodal tDCS (atDCS and ctDCS; 300 µA, 3.12 mA/cm2) for continuous five days. tDCS was applied on the left frontal skull of the animals, targeting on their prefrontal cortex (PFC). Behavioral performances were assessed by open-field, Y-maze, Barnes maze and T-maze paradigms; and their PFC electroencephalogram (EEG) activities were recorded under spontaneous state and during Y-maze performance. Behaviorally, atDCS and ctDCS improved spatial learning and/or memory in AD mice without affecting their general locomotion and anxiety-like behaviors, but the effects depended on the testing paradigms. Interestingly, the memory improvements were accompanied by decreased PFC EEG delta (2-4 Hz) and increased EEG gamma (20-100 Hz) activities when the animals needed memory retrieval during task performance. The decreased EEG delta activities could also be observed in animals under spontaneous state. Specifically, atDCS increased PFC EEG activity in the alpha band (8-12 Hz) for spontaneous state, whereas ctDCS increased that in alpha-beta band (8-20 Hz) for task-related state. In addition, some EEG changes after ctDCS could be found in other cortical regions except PFC. These data indicate that tDCS can reverse the situation of slower brain activity in AD mice, which may further lead to cognitive improvement. Our work highlights the potential clinical use of tDCS to restore neural network activity and improve cognition in AD.

Construction and Characterization of n6-Methyladenosine-Related lncRNA Prognostic Signature and Immune Cell Infiltration in Kidney Renal Clear Cell Carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) lacks effective prognostic biomarkers and the role and mechanism of N6-methyladenosine (m6A) modification of long noncoding RNAs (lncRNAs) in KIRC remain unclear. Methods: We extracted standard mRNA-sequencing and clinical data from the TCGA database. The prognostic risk model was obtained by Lasso regression and Cox regression. We randomly divided the samples into training and test sets, each taking half of the cases. Based on Lasso regression and Cox regression for training set, the prognostic risk signature was constructed; risk scores were calculated with the R package "glmnet." Based on the median value of the prognostic risk score, risk scores were calculated for each patient and we divided all KIRC samples into high-risk and low-risk groups. Then, high- and low-risk subtypes were established and their prognosis, clinical features, and immune infiltration microenvironment were evaluated in test set and the entire sampled data set. The reliability of the prognostic model was confirmed by receiver operating characteristic curve analysis. Results: We found 28 prognostic m6A-related lncRNAs and established a m6A-related lncRNAs prognostic signature. Risk score=AC015813.1∗(0.0086)+EMX2OS∗(-0.0101)+LINC00173∗(0.0309)+PWAR5∗(-0.0146)+SNHG1∗(0.0043). The signature showed a better predictive ability than other clinical indicators, including tumor node metastasis classification (TNM), histological, and pathological stages. In the high-risk group, M0 macrophages, CD8+ T cells, and regulatory T cells had significantly higher scores. Contrarily, in the low-risk group, activated dendritic cells, M1 macrophages, mast resting cells, and monocytes had significantly higher scores. In the high-risk group, LSECtin was overexpressed. In the low-risk group, PD-L1 was overexpressed. Moreover, high-risk patients may benefit more from AZ628. Conclusions: In conclusion, prognosis prediction of patients with KIRC and new insights for immunotherapy are provided by the m6A-related lncRNA prognostic signature.

Enhanced Resting-State Functional Connectivity With Decreased Amplitude of Low-Frequency Fluctuations of the Salience Network in Mindfulness Novices.

Mindfulness and accordant interventions are often used as complementary treatments to psychological or psychosomatic problems. This has also been gradually integrated into daily lives for the promotion of psychological well-being in non-clinical populations. The experience of mindful acceptance in a non-judgmental way brought about the state, which was less interfered by a negative effect. Mindfulness practice often begins with focused attention (FA) meditation restricted to an inner experience. We postulate that the brain areas related to an interoceptive function would demonstrate an intrinsic functional change after mindfulness training for the mindful novices along with paying more attention to internal processes. To further explore the influence of mindfulness on the organization of the brain regions, both functional connectivity (FC) in the voxel and the region of interest (ROI) level were calculated. In the current study, 32 healthy volunteers, without any meditation experiences, were enrolled and randomly assigned to a mindfulness-based stress reduction group (MBSR) or control group (CON). Participants in the MBSR group completed 8 weeks of mindfulness-based stress reduction (MBSR) and rated their mindfulness skills before and after MBSR. All subjects were evaluated via resting-state functional MRI (rs-fMRI) in both baselines and after 8 weeks. They also completed a self-report measure of their state and trait anxiety as well as a positive and negative affect. Pre- and post-MBSR assessments revealed a decreased amplitude of low-frequency fluctuations (ALFF) in the right anterior cingulate gyrus (ACC.R), left anterior and posterior insula (aIC.L, pIC.L), as well as left superior medial frontal gyrus (SFGmed.L) in MBSR practitioners. Strengthened FC between right anterior cingulate cortex (ACC.R) and aIC.R was observed. The mean ALFF values of those regions were inversely and positively linked to newly acquired mindful abilities. Along with a decreased negative affect score, our results suggest that the brain regions related to attention and interoceptive function were involved at the beginning of mindfulness. This study provides new clues in elucidating the time of evaluating the brain mechanisms of mindfulness novices.

Assessment of white matter abnormalities in paranoid schizophrenia and bipolar mania patients.

White matter abnormalities have been repeatedly reported in both schizophrenia and bipolar disorder (BD) in diffusion tensor imaging (DTI) studies, but the empirical evidence about the diagnostic specificity of white matter abnormalities in these disorders is still limited. This study sought to investigate the alterations in fractional anisotropy (FA) in white matter throughout the entire brain of patients from Chengdu, China with paranoid schizophrenia and bipolar mania. For this purpose, DTI was used to assess white matter integrity in patients with paranoid schizophrenia (n=25) and psychotic bipolar mania (n=18) who had been treated with standard pharmacotherapy for fewer than 5 days at the time of study, as well as in normal controls (n=30). The differences in FA were measured by use of voxel-based analysis. The results show that reduced FA was found in the left posterior corona radiata (PCR) in patients with psychotic bipolar mania and paranoid schizophrenia compared to the controls. Patients with psychotic bipolar mania also showed a significant reduction in FA in right posterior corona radiata and in right anterior thalamic radiation (ATR). A direct comparison between the two patient groups found no significant differences in any regions, and none of the findings were associated with illness duration. Correlation analysis indicated that FA values showed a significant negative correlation with positive symptom scores on the Positive and Negative Syndrome Scale in the left frontal-parietal lobe in the paranoid schizophrenia. It was concluded that common abnormalities in the left PCR might imply an overlap in white matter pathology in the two disorders and might be related to shared risk factors for the two disorders.