Involvement of nucleus accumbens SERCA2b in methamphetamine-induced conditioned place preference.

Methamphetamine (METH) is a highly addictive psycho-stimulant that induces addictive behaviour by stimulating increased dopamine release in the nucleus accumbens (NAc). The sarco/endoplasmic reticulum calcium ion transport ATPases (SERCA or ATP2A) is a calcium ion (Ca2+) pump in the endoplasmic reticulum (ER) membrane. SERCA2b is a SERCA subtype mainly distributed in the central nervous system. This study used conditioned place preference (CPP), a translational drug reward model, to observe the effects of SERCA and SERCA2b on METH-CPP in mice. Result suggested that the activity of SERCA was significantly decreased in NAc after METH-CPP. Intraperitoneal SERCA agonist CDN1163 injection or bilateral CDN1163 microinjection in the NAc inhibited METH-CPP formation. SERCA2b overexpression by the Adeno-associated virus can reduce the DA release of NAc and inhibit METH-CPP formation. Although microinjection of SERCA inhibitor thapsigargin in the bilateral NAc did not significantly aggravate METH-CPP, interference with SERCA2b expression in NAc by adeno-associated virus increased DA release and promoted METH-CPP formation. METH reduced the SERCA ability to transport Ca2+ into the ER in SHSY5Y cells in vitro, which was reversed by CDN1163. This study revealed that METH dysregulates intracellular calcium balance by downregulating SERCA2b function, increasing DA release in NAc and inducing METH-CPP formation. Drugs that target SERCA2b may have the potential to treat METH addiction.

Predictive role of impulsivity, anxiety, and depression in the efficacy of intermittent theta burst transcranial magnetic stimulation modalities for treating methamphetamine use disorder: A randomized clinical trial.

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.

Effects of Online Game and Short Video Behavior on Academic Delay of Gratification - Mediating Effects of Anxiety, Depression and Retrospective Memory.

Objective: Learner dependence on short videos has many pitfalls for learning outcomes, but the negative effects of excessive short video use have been little discussed in the learning psychology literature. Therefore, this study investigated the effects of excessive short video use on anxiety, depression, prospective memory, and academically delayed gratification (ADOG) in relation to online gaming-related behaviours, and explored the possible mechanisms by which excessive online gaming and short video use may lead to decreased ADOG, to expand our understanding of excessive short video use. Methods: Based on the whole class random sampling method, a questionnaire survey was conducted among college students in Northern Anhui, China from May 7 to July 27, 2022. The questionnaires included the Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire Scale (PHQ-9), Prospective and Retrospective Memory (PRM) Questionnaire, and ADOG Scale. Results: A total of 1016 participants completed the survey. The study found that of all the internet behaviors, 20.8% of the college students mainly played online games, 43.9% mainly played short videos, and 35.3% conducted other online behaviors. When compared with other internet behaviors, online gaming and short video behaviors can cause more serious anxiety/depression and worse PRM and ADOG scores. As time spent playing online games and short videos increased, anxiety and depression became worse, and the scores for PRM and ADOG also declined. Anxiety, depression, and PRM mediate the relationship between time spent on online gaming/short videos and ADOG. Conclusion: Excessive short videos behaviour may produce the same psychological problems and learning problems as online gaming disorder. Excessive short video and online gaming behaviors may affect ADOG performance through anxiety, depression, and prospective memory. These findings could be used as a basis for future studies on the improvement of ADOG.

p-Nrf2/HO-1 Pathway Involved in Methamphetamine-induced Executive Dysfunction through Endoplasmic Reticulum Stress and Apoptosis in the Dorsal Striatum.

Methamphetamine (METH) abuse is known to cause executive dysfunction. However, the molecular mechanism underlying METH induced executive dysfunction remains unclear. Go/NoGo experiment was performed in mice to evaluate METH-induced executive dysfunction. Immunoblot analysis of Nuclear factor-E2-related factor 2 (Nrf2), phosphorylated Nrf2 (p-Nrf2), heme-oxygenase-1 (HO-1), Glucose Regulated Protein 78(GRP78), C/EBP homologous protein (CHOP), Bcl-2, Bax and Caspase3 was performed to evaluate the levels of oxidative stress, endoplasmic reticulum (ER) stress and apoptosis in the dorsal striatum (Dstr). Malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activity was conducted to evaluate the level of oxidative stress. TUNEL staining was conducted to detect apoptotic neurons. The animal Go/NoGo testing confirmed that METH abuse impaired the inhibitory control ability of executive function. Meanwhile, METH down-regulated the expression of p-Nrf2, HO-1 and GSH-Px and activated ER stress and apoptosis in the Dstr. Microinjection of Tert-butylhydroxyquinone (TBHQ), an Nrf2 agonist, into the Dstr increased the expression of p-Nrf2, HO-1, and GSH-Px, ameliorated ER stress, apoptosis and executive dysfunction caused by METH. Our results indicated that the p-Nrf2/HO-1 pathway was potentially involved in mediating methamphetamine-induced executive dysfunction by inducing endoplasmic reticulum stress and apoptosis in the dorsal striatum.

High-performance all-inorganic CsPbBr3 quantum dots with a low-threshold amplified spontaneous emission.

All-inorganic halide perovskite CsPbX3(X = Br/Cl/I)quantum dots have gained a considerable attention in the optoelectronic fields. However, the high cost and poor stability of the prepared CsPbX3 quantum dots (QDs) are inevitable challenges for their future practical applications. And the high-performance CsPbX3 QDs are always needed. Herein, a facile and low-cost synthesis scheme was adopted to prepare the CsPbBr3 QDs modified by lead bromide (PbBr2) and tetraoctylammonium bromide (TOAB) ligands at room temperature in open air. The prepared CsPbBr3 QDs exhibited a high photoluminescence quantum yield (PLQY) of 96.6% and a low amplified spontaneous emission (ASE) threshold of 12.6 µJ/cm2. Stable ASE intensity with little degradation was also realized from the CsPbBr3 QDs doped with PMMA. Furthermore, the enhanced ASE properties of the CsPbBr3 QDs-doped PMMA based on distributed feedback (DFB) substrate was achieved with a lower threshold of 3.6 µJ/cm2, which is 28.6% of that of the (PbBr2 + TOAB)-treated CsPbBr3 QDs without PMMA. This work exhibits a promising potential in the on-chip light source.

Association between glomerular C4d deposition, proteinuria, and disease severity in children with IgA nephropathy.

BACKGROUND: C4d may be used as a marker to evaluate the condition and prognosis of adults with IgA nephropathy, but there have been few studies of children with IgA nephropathy. METHODS: C4d immunohistochemical staining was performed on samples from children with IgA nephropathy with C1q-negative immunofluorescence. The clinical and pathological treatment and prognostic characteristics of children in the C4d-positive and -negative groups were compared. RESULTS: A total of sixty-five children with IgA nephropathy were included in the study and were followed up for an average of 37 months. C4d was mainly deposited along the capillary loops. The urinary protein-to-creatinine ratio (UPCR) in the C4d-positive group was significantly higher than that in the C4d-negative group (3.97 vs. 0.81, P < 0.001), and the average integrated optical density value of each child was positively correlated with the UPCR (r = 0.441, P < 0.001). There was a significant difference in the proportions of children with mesangial hypercellularity (M1) (68.97% vs. 44.44%, P = 0.048) and segmental glomerulosclerosis (S1) (65.52% vs. 33.33%, P = 0.010) between the C4d-positive group and the C4d-negative group. The proportion of children who received immunosuppressants in the C4d-positive group was higher than that in the C4d-negative group (86.21% vs. 36.11%, P < 0.001). There was no significant difference in the proportion of children developing kidney failure between the two groups. CONCLUSION: C4d was found to be associated with proteinuria, segmental lesions, and immunosuppressant treatment. Activation of the lectin pathway may reflect the severity of clinical and pathological manifestations of IgA nephropathy in children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sex, executive function, and prospective memory regulate the chain-mediation pathway of alcohol use and impulsivity.

Objective: Evidence from previous studies indicates that impulsive behaviors are closely linked to alcohol use and misuse and that female drinkers are more impulsive than male drinkers. However, studies investigating the psychological mechanisms of alcohol use and impulsivity based on sex differences are relatively limited. Methods: This cross-sectional study comprised 713 residents from 16 cities in Anhui Province, China. Each subject was evaluated for self-reporting measures using several questionnaires, including the general information questionnaire, the Alcohol Use Disorders Identification Test (AUDIT), the Prospective and Retrospective Memory Questionnaire (PRM), the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A), and the Barratt Impulsiveness Scale-11 (BIS-11). Results: Executive function and prospective memory may serve as intermediary links between alcohol use and impulsivity. Although the female alcohol usage level was significantly lower than that of males, the female drinkers had more severe executive dysfunction, prospective memory impairment, and impulsivity than male drinkers. Sex moderated the relationship between alcohol use and impulsivity. Furthermore, the indirect effect of executive function, and prospective memory between AUDIT and BIS was more significant in males than in females. Conclusion: Alcohol consumption may be associated with impulsivity formation through executive dysfunction and PM impairment, implying that impulsivity in those with AUD or at risk for AUD might be treated by improving EF and PM. Alcohol use may cause more severe executive dysfunction, PM impairment, and impulsive behavior in females than in males, and impulsive behavior in women with AUD was more likely to be due to the direct effects of alcohol consumption, while impulsive behavior in men with AUD was more likely to be due to the indirect effects of executive dysfunction and PM impairment. These findings provide both clinical and theoretical foundations for addressing issues related to alcohol use.

Clinical guidelines of UTIs in children: quality appraisal with AGREE II and recommendations analysis.

OBJECTIVE: To explore the current Chinese and English guidelines of urinary tract infection (UTI) in children and provide a summary of the recommendations of the guidelines. METHODS: An electronic search was conducted on databases, including Pubmed, SinoMed, Wangfang Data, CHKD,VIP, NICE, WHO, GIN and Medliveto retrieve data of the clinical practice guidelines on UTI from the establishment of the database to June 2020. Four assessors assessed the quality of guidelines using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and evaluated the specific recommendations in guidelines. RESULTS: (1) Nine guidelines including two from the USA (AAP and A guideline for the inpatient care of children with pyelonephritis) and the remaining from EAU/ESPU, SINEPE, KHA-CARI, CPS, ISPN, NICE and CMA-CSP were explored. (2) The AGREE II evaluation demonstrated higher scores of UTI guidelines in terms of 'scope and purpose' (72.99%±11.19%) and 'clarity of presentation' (75.62%±7.75%), whereas the average scores were lower in the aspect of 'stakeholder involvement' (35.49%±14.41%), 'rigour of development' (37.05%±10.05%), 'applicability' (37.75%±11.98%) and 'editorial independence' (43.06%±48.14%). The average scores of the guidelines were as follows: SINePe (72.57%), CMA-CSP (62.96%), EAU/ESPU (59.61%), AAP (56.86%), NICE (47.54%), CPS (40.93%), KHA-CARI (38.86%), ISPN (38.63%) and A guideline for the inpatient care of children with pyelonephritis (34.72%). (3) All the selected guidelines basically reached a consensus on urine sample retention methods in older children, the antibiotic treatment course and renal and bladder ultrasonography application but lacked a conclusion on the determination of urine culture results, the choice of voiding cystourethrography and Tc-99mdimercaptosuccinicacid, and antibiotic prophylaxis. CONCLUSION: There remains a need to improve the quality of guidelinesfor UTI in clinical practice. Existing controversies on the current guidelines of UTI in some recommendations warrant further exploration to provide more evidence on formulating more unified and practical guidelines in the future. ETHICS AND DISSEMINATION: No ethical approval is required for this research, as it did not include patients or patient data.

Generation of a human iPSC line from a Bardet-Biedl syndrome patient compound heterozygous for the BBS7 variants c.849 + 1G > C/c.754G > A.

Bardet-Biedl syndrome (BBS) is primarily a multisystem nonmotile ciliopathy. In this study, we describe the successful establishment and characterization of an iPSC line from a patient diagnosed with BBS who was compound heterozygous for the BBS7 variants c.849 + 1G > C (splicing) and c.754G > A (p.D252N).

Neuroprotective effect of asymmetric dimethylarginine against 1-methyl-4-phenylpyridinium ion-induced damage in PC12 cells.

1. Asymmetric dimethylarginine (ADMA) is a well-known endogenous nitric oxide synthase (NOS) inhibitor. Although it has been shown to be a novel risk marker in cardiovascular medicine and chronic kidney disease, we speculated that in some states associated with excess of nitric oxide (NO), such as 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neuronal injury, ADMA might be protective by limiting the toxic effect of high concentrations of NO. 2. The aim of the present study is to explore the protection of ADMA against MPP(+)-induced apoptosis and the molecular mechanisms underlying in PC12 cells. 3. We found that exogenous application of ADMA obviously protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by reducing the loss of mitochondrial membrane potential, but also by attenuating an increase in intracellular reactive oxygen species. Moreover, ADMA attenuated MPP(+)-induced excessive activation of nitric oxide synthase and overproduction of NO. 4. The results of the present study suggest that the protection caused by ADMA is related to preserving mitochondrial membrane potential and attenuating the MPP(+)-induced intracellular reactive oxygen species generation through inhibiting nitric oxide synthase activity and limiting NO generation.