Wanting-liking dissociation and altered dopaminergic functioning: Similarities between internet gaming disorder and tobacco use disorder.

Background: Although internet gaming disorder (IGD) has been included in the DSM-5 for approximately 10 years, debate remains regarding its existence and classification. Methods: The current research incorporated three approaches. First, implicit association tests were used to examine for potential dissociation between wanting and liking in IGD. Second, brain features in wanting and liking circuits were tested and compared with tobacco use disorder (TUD) when performing a cue-craving task to explore the neural features of wanting and liking. Third, dopaminergic systems were investigated in IGD and TUD using neuromelanin-sensitive MRI. Results: The implicit association test results supported a wanting-liking dissociation in IGD participants. Functional MRI data suggested neural correlates underlying wanting-liking dissociation in IGD and TUD participants, with positive correlations suggesting greater dissociation with increasing addiction severity. Neuromelanin results suggest dopaminergic differences in IGD and TUD relative to healthy control participants. Conclusions: A wanting-liking dissociation in IGD participants suggests gaming motivations in IGD relating to incentive sensitization rather than hedonic responses. The neuromelanin-sensitive MRI results suggest dopaminergic involvement in IGD and TUD. The findings suggest similar brain-behaviour mechanisms for IGD and TUD based on an incentive-sensitization model for addiction, having implications for potential therapeutic strategies and policy-based interventions.

Generation of an induced pluripotent stem cell line (SDASi001-A) from a Schimke immune-osseous dysplasia patient with SMARCAL1 mutations.

A human induced pluripotent stem cell (iPSC) line (SDASi001-A) was generated from patient with Schimke immune-osseous dysplasia (SIOD), carrying heterozygous mutations in SMARCAL1 gene. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating delivery of OCT4, SOX2, KFL4, BCL-XL and c-MYC. The iPSC line expresses pluripotency markers, displays a normal karyotype, and has the ability to differentiate into cells of three germ layers in vitro. This iPSC line represents a valuable cell model for SIOD in humans.

Connectome-based predictive modelling of smoking severity in smokers.

The functional connectivity within and between networks could provide a framework to characterize the neurobiological mechanism of nicotine addiction. This study examined the brain regions that were functionally connected in response to smoking cues and established the brain-behaviour relationships in smokers. Sixty-seven male smokers were enrolled and scanned while performing the cue-reactivity and Stroop task. A whole-brain analysis approach, connectome-based predictive modelling (CPM), was conducted on the data from the cue-reactivity task to identify the networks that could predict the smoking severity with the Shen atlas as templates. Then, the brain-behaviour relationships were verified in a different brain state (Stroop task). CPM identified the smoking severity-related network, as indicated by a significant correlation between predicted and actual smoking severity scores (r = 0.31, p = 0.02). Identified networks mainly involved the canonical networks implicated in the reward process (motor/sensory network and salience network) and executive control (frontoparietal network). Network strength in the Stroop task marginally significantly predicted smoking severity scores (r = 0.23, p = 0.06), partially replicating the brain-behaviour relationship. The CPM results identified the whole-brain neural network related to smoking severity, which was cross-validated by the AAL and Shen atlas. These findings contribute to more profound insights into neural substrates underlying the smoking severity.

Similarities and differences between internet gaming disorder and tobacco use disorder: A large-scale network study.

Studies have shown that internet gaming disorder (IGD) has the potential to be a type of addiction; however, direct comparisons (similarities and differences) between IGD and traditional addictions remain scarce, especially at the neuroimaging level. Resting-state functional magnetic resonance imaging (fMRI) data were collected from 92 individuals with IGD, 96 individuals with tobacco use disorders (TUDs) and 107 individuals who served as healthy controls (HCs). Independent component analysis (ICA) was performed to explore the similarities and differences among these three groups; Granger causality analysis (GCA) was further performed based on the ICA results to determine potential neural features underlying the differences and similarities among the groups. The ICA results indicated significant differences in the subcortical network and cerebellar network. GCA results found that significant differences in bilateral caudate among three groups, and the efferents of dorsal frontostriatal circuit showed significant differences in insula among three groups, whereas efferents of ventral frontostriatal circuit showed significant differences in the medial prefrontal cortex (mPFC). Two kinds of addiction showed differences in thalamus and frontostriatal circuits, and similar changes found in cerebellum and mPFC regions. It suggested that addiction disorders have psychopathology features, and the craving and reward dysfunctions may be the key reasons. Although both substance addiction and behaviour addiction showed craving dysfunction in cerebellum, however, the key reward dysfunction of substance addiction was found in subcortical regions, whereas behaviour addiction located in cortical regions.

Social Isolation Is Associated With Rapid Kidney Function Decline and the Development of Chronic Kidney Diseases in Middle-Aged and Elderly Adults: Findings From the China Health and Retirement Longitudinal Study (CHARLS).

Background: There is limited evidence on the relationship between social isolation and renal outcomes. To address this gap, this study estimated the prospective relationship of social isolation with rapid kidney function decline and the development of chronic kidney disease (CKD) in middle-aged and elderly Chinese with normal kidney function. Methods: We analyzed data from 3,031 participants aged ≥ 45 years with baseline estimated glomerular filtration rates (eGFR) ≥ 60 ml/min/1.73 m2. All data were obtained from the 2011 and 2015 waves of the Chinese Longitudinal Study of Health and Retirement (CHARLS). eGFR was estimated based on a combination of serum creatinine and cystatin C. The primary outcome was rapid decline in renal function, as defined by an eGFR decrease of > 5 ml/min/1.73 m2 per year, while the secondary outcome was the development of CKD, as defined by an eGFR decrease to a level < 60 ml/min/1.73 m2. Results: During the follow-up of 4 years, 258 (8.5%) participants experienced a rapid decline in renal function, while 87 (2.9%) developed CKD. In the fully adjusted model, high social isolation was significantly related to an increased risk of experiencing a rapid decline in renal function (OR 1.805, 95% CI 1.310-2.487) and CKD onset (OR 1.842, 95% CI 1.084-3.129). Among the five components of social isolation, being unmarried, not participating in social activities, and living alone independently predicted declined renal function. Conclusions: Social isolation is significantly associated with the risk of rapid eGFR decline and CKD onset in middle-aged and older adults with normal kidney function in China.

Association Between Muscle Strength and Cystatin C-Based Estimated Glomerular Filtration Rate Among Middle-Aged and Elderly Population: Findings Based on the China Health and Retirement Longitudinal Study (CHARLS), 2015.

BACKGROUND: Patients with chronic kidney disease (CKD) are prone to muscle strength degeneration. However, the relationship between mild-to-moderate renal insufficiency and low muscle strength remains unclear. As cystatin C is not subject to muscular conditions and is a sensitive serum marker in preclinical renal disease, we aimed to investigate the association between estimated glomerular filtration rate (eGFR) based on cystatin C and muscle strength in the Chinese population. METHODS: This was a cross-sectional study enrolling 12,398 Chinese participants aged above 45 years (5762 men and 6636 women) from the 2015 China Health and Retirement Longitudinal Study. Handgrip strength (HGS) was used to assess muscle strength. Locally weighted scatterplot smoothing (LOWESS) curves were employed to visualize the relationships between eGFR and HGS. Multivariable logistic regression was conducted to analyze the correlation between kidney function and low muscle strength. RESULTS: Significant differences in HGS by CKD stage were observed in both sexes after adjusting for age and body mass index. LOWESS curves demonstrated concomitant decreases in HGS and kidney function at eGFR levels below 120 mL/min/1.73 m2 in both sexes. According to multivariate logistic regression, participants with CKD stages 2 (odds ratio [OR]: 1.256, 95% confidence interval [CI]: 1.120-1.409), 3 (OR: 2.725, 95% CI: 2.2585-3.288), and 4-5 (OR: 3.069, 95% CI 1.747-5.392) had higher risk of low muscle strength than those who were normal or had CKD stage 1 after adjusting for demographic and clinical variables. CONCLUSION: Our study illustrated that CKD stage was independently associated with low muscle strength in Chinese middle-aged and elderly populations.

High Expression of TRIM15 Is Associated with Tumor Invasion and Predicts Poor Prognosis in Patients with Gastric Cancer.

BACKGROUND: Gastric cancer is the third leading cause of cancer-related mortality worldwide. Most tripartite motif (TRIM) family proteins are known as E3 ubiquitin ligases and considerable previous research has revealed the involvement of TRIM proteins in carcinogenesis. TRIM15 is a protein from the TRIM family and the aim of this study is to investigate the role of TRIM15 in gastric cancer. METHODS: We conducted immunohistochemical staining to examine TRIM15 expression using samples from Zhongshan Hospital of Fudan University. We also conducted transwell assay as well as western blot by using gastric cancer cells. RESULTS: The expression of TRIM15 in gastric cancer tissues was higher than normal tissues. Present data demonstrated that high TRIM15 staining intensity had a positive relation to tumor invasion depth (P = 0.007), lymph node metastasis (P = 0.013), distant metastasis (P = 0.031), the tumor-node-metastasis (TNM) staging system (P = 0.002) and shorter overall survival (OS) in gastric cancer patients (P < 0.001). It was also worthwhile mentioning that TRIM15 was an adverse prognostic variable for OS. To gain more insight, we incorporated TRIM15 expression into the tumor-node-metastasis (TNM) staging system and thus established a nomogram. Data derived from the nomogram suggested that fitting TRIM15 expression into the prognostic model exhibited better efficiency for predicting OS in gastric cancer patients. Furthermore, TRIM15 promoted migration, invasion and epithelial-mesenchymal transition of gastric cancer cells. CONCLUSIONS: Together, TRIM15 expression was found as a specific and independent adverse predictor in gastric cancer patients and the nomogram may contribute to better clinical management.

Wnt/ß-catenin agonist BIO alleviates cisplatin-induced nephrotoxicity without compromising its efficacy of anti-proliferation in ovarian cancer.

AIMS: Cisplatin is an anticancer agent marred by nephrotoxicity. Limiting this adverse effect may allow the use of higher doses to improve its efficacy. The Wnt/ß-catenin signaling pathway plays a critical role in nephrogenesis and repair of renal diseases. BIO, a small molecule agonist of this pathway, exerted a protective effect in adriamycin nephropathy and promoted nephrogenesis. The aim of this study, therefore, was to investigate whether Wnt/ß-catenin agonist BIO could protect against cisplatin-induced nephrotoxicity in vivo and in vitro, as well as its possible mechanism. MAIN METHODS: Male mice and human renal proximal tubular cells (HK-2) were subjected to cisplatin to study reno-protective effect of BIO. Renal function, cell viability, tubular apoptosis, production of reactive oxygen species (ROS) and proliferative level were analyzed respectively. Additionally, xenograft model was induced to investigate if BIO would impair the antitumor effect of cisplatin. KEY FINDINGS: Cisplatin increased serum creatinine levels and promoted histological renal injury as well as oxidative stress levels. Besides, renal apoptotic level and the expression of pro-apoptotic proteins, Bax/bcl-2 and cleaved-caspase3 included, in the kidney were increased. All these features were decreased by BIO, which also activated Wnt/ß-catenin pathway in cisplatin-induced nephrotoxicity. Similarly, accompanied by the motivation of Wnt/ß-catenin pathway, BIO exerted a positively protective effect on HK-2 challenged cisplatin. Last, the chemotherapeutic effects of cisplatin in xenograft mice of ovary tumor models and in lung cancer cells weren't compromised by BIO. SIGNIFICANCE: Wnt/ß-catenin agonist BIO has the potential to prevent cisplatin nephrotoxicity without compromising its anti-proliferation efficacy.

RacGAP1 ameliorates acute kidney injury by promoting proliferation and suppressing apoptosis of renal tubular cells.

BACKGROUND: Acute kidney injury (AKI) remains correlated with high mortality. Novel therapeutic strategies are urgently needed for AKI patients. Rac GTPase-activating protein 1 (RacGAP1) regulates the activity of RhoGTPase and acts as a predictive biomarker in several types of malignant tumor but the role of RacGAP1 in AKI has not been revealed. METHODS: Animal models of AKI induced by renal ischemia-reperfusion (I/R) and cisplatin treatment were generated in C57BL/6 mice. Hypoxia/reoxygenation (H/R) and cisplatin treatment were practiced in human renal tubular epithelial (HK-2) and renal tubular duct epithelial cells of rat (NRK-52E) cells. The role of RacGAP1 in cell proliferation and apoptosis was estimated using western bolting, immunocytochemistry and flow cytometry. Verteporfin was used to activate the Hippo pathway to show whether the protective effects of RacGAP1 on cell growth and survival in renal tubular cells were dependent on the activation of YAP. RESULTS: The expression of RacGAP1 was significantly increased in mice kidneys after I/R or cisplatin treatment, combined with increased expression of RacGAP1 in H/R or cisplatin challenged cells. Overexpression of RacGAP1 protected HK2 and NRK-52E cells by promoting proliferation and decreasing apoptosis. We also disclosed that RacGAP1 exerted its function through activation of YAP. CONCLUSION: The present study provides evidence that RacGAP1 is involved in AKI. It promotes proliferation and limits apoptosis of tubular epithelial cells via stimulating activation and nuclear translocation of YAP. Consequently, RacGAP1 may be a novel therapeutic target for AKI.

Application of Self-Assembled Raman Spectrum-Enhanced Substrate in Detection of Dissolved Furfural in Insulating Oil.

Accurate detection of dissolved aging features in transformer oil is the key to judging the aging degree of oil-paper insulation. In this work, in order to realize in situ detection of furfural dissolved in transformer oil, silver nanoparticles were self-assembled on the surface of gold film with P-aminophenylthiophenol (PATP) as a coupling agent. Rhodamine-6G (R6G) was used as the probe molecule to test the enhancement effect. By optimizing the molecular concentration, molecular deposition time, and silver sol deposition time of PATP, the nanoparticles were made more uniform and compact, and an enhanced substrate with rich hot spots was obtained. The optimum substrate was developed, and surface-enhanced Raman spectroscopy (SERS) detection of trace furfural dissolved in transformer oil was realized. The results showed that the substrate prepared under the conditions of 0.1 mol/L PATP, 5 hours deposition in PATP and 12 hours immersion in silver sol, had the best reinforcement effect (that is, uniform and compact particle arrangement and no particle clusters). By use of this substrate, the minimum detectable concentration of furfural in transformer oil was about 1.06 mg/L, which provides a new method for fast and nondestructive detection of transformer aging diagnosis.