Copelandblanchard2623

Substance use disorder (SUD) is a chronic neuropsychiatric condition characterized by long-lasting alterations in the neural circuitry regulating reward and motivation. Substantial work has focused on characterizing the molecular substrates that underlie these persistent changes in neural function and behavior. However, this work has overwhelmingly focused on male subjects, despite mounting clinical and preclinical evidence that females demonstrate dissimilar progression to SUD and responsivity to stimulant drugs of abuse, such as cocaine. Here, we show that sex is a critical biological variable that defines drug-induced plasticity in the nucleus accumbens (NAc). Using quantitative mass spectrometry, we assessed the protein expression patterns induced by cocaine self-administration and demonstrated unique molecular profiles between males and females. We show that 1. Cocaine self-administration induces non-overlapping protein expression patterns in significantly regulated proteins in males and females and 2. Critically, cocaine-induced protein regulation differentially interacts with sex to eliminate basal sexual dimorphisms in the proteome. Finally, eliminating these baseline differences in the proteome is concomitant with the elimination of sex differences in behavior for non-drug rewards. Together, these data suggest that cocaine administration is capable of rewriting basal proteomic function and reward-associated behaviors.Radiating amorphous In-Ga-Zn-O (a-IGZO) thin-film transistors (TFTs) with deep ultraviolet light (λ = 175 nm) is found to induce rigid negative threshold-voltage shift, as well as a subthreshold hump and an increase in subthreshold-voltage slope. These changes are attributed to the photo creation and ionization of oxygen vacancy states (VO), which are confined mainly to the top surface of the a-IGZO film (backchannel). Photoionization of these states generates free electrons and the transition from the neutral to the ionized VO is accompanied by lattice relaxation, which raises the energy of the ionized VO. This and the possibility of atomic exchange with weakly bonded hydrogen leads to metastability of the ionized VO, consistent with the rigid threshold-voltage shift and increase in subthreshold-voltage slope. The hump is thus a manifestation of the highly conductive backchannel and its formation can be suppressed by reduction of the a-IGZO film thickness or application of a back bias after radiation. These results support photo creation and ionization of VO as the main cause of light instability in a-IGZO TFTs and provide some insights on how to minimize the effect.It remains uncertain how best to set positive end-expiratory pressure (PEEP) for mechanically ventilated patients with the acute respiratory distress syndrome (ARDS). Among patients on low tidal volume ventilation (LTVV), we investigated if further adherence to the low PEEP/FIO2 (inspired oxygen fraction) table would be associated with better survival compared to nonadherence. Patients with ARDS, admitted directly from the Emergency Department to our 20-bed Medical Intensive Care Unit (ICU) from August 2016 to July 2017, were retrospectively studied. To determine adherence to the low PEEP/FIO2 table, PEEP and FIO2 12 h after ICU admission were used, to reflect ventilator adjustments by ICU clinicians after initial stabilization. Logistic regression was used to analyze hospital mortality as an outcome with adherence to the low PEEP/FIO2 as the key independent variable, adjusted for age, APACHE II score, initial P/F ratio and initial systolic blood pressure. 138 patients with ARDS were analysed. Overall adherence to the low PEEP/FIO2 table was 75.4%. Among patients on LTVV, nonadherence to the low PEEP/FIO2 table was associated with increased mortality compared to adherence (adjusted odds ratio 4.10, 95% confidence interval 1.68-9.99, P = 0.002). Patient characteristics at baseline were not associated with adherence to the low PEEP/FIO2 table.Cathepsin A (CTSA) is a lysosomal protease that regulates galactoside metabolism. The previous study has shown CTSA is abnormally expressed in various types of cancer. However, rarely the previous study has addressed the role of CTSA in hepatocellular carcinoma (HCC) and its prognostic value. To study the clinical value and potential function of CTSA in HCC, datasets from the Cancer Genome Atlas (TCGA) database and a 136 HCC patient cohort were analyzed. CTSA expression was found to be significantly higher in HCC patients compared with normal liver tissues, which was supported by immunohistochemistry (IHC) validation. selleck kinase inhibitor Both gene ontology (GO) and The Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated that CTSA co-expressed genes were involved in ATP hydrolysis coupled proton transport, carbohydrate metabolic process, lysosome organization, oxidative phosphorylation, other glycan degradation, etc. Survival analysis showed a significant reduction both in overall survival (OS) and recurrence-free survival (RFS) of patients with high CTSA expression from both the TCGA HCC cohort and 136 patients with the HCC cohort. Furthermore, CTSA overexpression has diagnostic value in distinguishing between HCC and normal liver tissue [Area under curve (AUC) = 0.864]. Moreover, Gene set enrichment analysis (GSEA) showed that CTSA expression correlated with the oxidative phosphorylation, proteasome, and lysosome, etc. in HCC tissues. These findings demonstrate that CTSA may as a potential diagnostic and prognostic biomarker in HCC.The voltage-dependent potassium channel Kv1.3 plays essential roles in the immune system, participating in leukocyte activation, proliferation and apoptosis. The regulatory subunit KCNE4 acts as an ancillary peptide of Kv1.3, modulates K+ currents and controls channel abundance at the cell surface. KCNE4-dependent regulation of the oligomeric complex fine-tunes the physiological role of Kv1.3. Thus, KCNE4 is crucial for Ca2+-dependent Kv1.3-related leukocyte functions. To better understand the role of KCNE4 in the regulation of the immune system, we manipulated its expression in various leukocyte cell lines. Jurkat T lymphocytes exhibit low KCNE4 levels, whereas CY15 dendritic cells, a model of professional antigen-presenting cells, robustly express KCNE4. When the cellular KCNE4 abundance was increased in T cells, the interaction between KCNE4 and Kv1.3 affected important T cell physiological features, such as channel rearrangement in the immunological synapse, cell growth, apoptosis and activation, as indicated by decreased IL-2 production. Conversely, ablation of KCNE4 in dendritic cells augmented proliferation. Furthermore, the LPS-dependent activation of CY15 cells, which induced Kv1.3 but not KCNE4, increased the Kv1.3-KCNE4 ratio and increased the expression of free Kv1.3 without KCNE4 interaction. Our results demonstrate that KCNE4 is a pivotal regulator of the Kv1.3 channelosome, which fine-tunes immune system physiology by modulating Kv1.3-associated leukocyte functions.Previous studies regarding the zinc status in attention-deficit/hyperactivity disorder (ADHD) yielded inconsistent results. Thus, the present meta-analysis was aimed to estimate the association between hair and serum/plasma zinc levels and ADHD. Online databases of Medline, EMBASE, and Scopus were searched up to October 2020 with no limitation in time and language. Weighted mean differences (WMDs) of hair and serum/plasma zinc levels were calculated using a random-effects model. Overall, 22 articles with 1280 subjects with ADHD and 1200 controls were included. The pooled effect size indicated that serum/plasma zinc levels in subjects with ADHD were not statistically different than their controls (WMD = - 1.26 µmol/L; 95% CI - 3.72, 1.20). Interestingly, the exclusion of one study from the analysis showed that people with ADHD significantly have lower circulating levels of zinc compared to their controls (WMD - 2.49 µmol/L; 95% CI - 4.29, - 0.69). Also, the pooled effect size indicated that hair zinc levels in cases with ADHD were not statistically different than their controls (WMD = - 24.19 μg/g; 95% CI - 61.80, 13.42). Present meta-analysis raises the possibility that subjects with ADHD are prone to have declined levels of zinc levels. Based on current findings, screening the zinc levels in subjects with ADHD could be reasonable. Further well-designed studies are needed to clarify the role of zinc in the etiology of ADHD.While there has been significant progress in the development of rapid COVID-19 diagnostics, as the pandemic unfolds, new challenges have emerged, including whether these technologies can reliably detect the more infectious variants of concern and be viably deployed in non-clinical settings as "self-tests". Multidisciplinary evaluation of the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW, a widely used rapid antigen test, included limit of detection, variant detection, test performance across different age-groups, and usability with self/caregiver-administration. While BinaxNOW detected the highly infectious variants, B.1.1.7 (Alpha) first identified in the UK, B.1.351 (Beta) first identified in South Africa, P.1 (Gamma) first identified in Brazil, B.1.617.2 (Delta) first identified in India and B.1.2, a non-VOC, test sensitivity decreased with decreasing viral loads. Moreover, BinaxNOW sensitivity trended lower when devices were performed by patients/caregivers themselves compared to trained clinical staff, despite universally high usability assessments following self/caregiver-administration among different age groups. Overall, these data indicate that while BinaxNOW accurately detects the new viral variants, as rapid COVID-19 tests enter the home, their already lower sensitivities compared to RT-PCR may decrease even more due to user error.Electrostatic samplers have been increasingly studied for sampling of viral and bacterial aerosols, and bioaerosol samplers are required to provide concentrated liquid samples with high physical collection and biological recovery, which would be critical for rapid detection. Here, the effects of sampling media and protocols on the physical collection and biological recovery of two airborne bacteria (Pseudomonas fluorescens and Micrococcus luteus) under electrostatic field were investigated using a personal electrostatic particle concentrator (EPC). Deionized (DI) water with/without sodium dodecyl sulfate (SDS) and phosphate buffered saline were tested as sampling media. A polystyrene container was mounted onto the collection electrode of the EPC for stable storage and vortexing after capture. Many bacterial cells were found to be deposited on the bottom surface of the container submerged in the media via electrophoresis, and among the tested sampling protocols, wet sampling with a container and subsequent vortexing offered the most bacteria in the collection suspension. Experiments with several sampling media showed that 0.001-0.01% SDS-DI water demonstrated the highest recovery rate in the EPC. These findings would be valuable in the field of sampling and subsequent rapid detection of bioaerosols.This study aims to evaluate the predictive value of the prognostic nutritional index (PNI) and albumin-bilirubin grade (ALBI) for the postoperative prognosis of hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) patients undergoing radical hepatectomy (RH). Besides, we seek to identify novel prognosis indicators for HBV-HCC patients. Between April 2009 and March 2015, this work enrolled 868 patients diagnosed with HBV-HCC and undergoing RH in the Liver Surgery Department, West China Hospital, Sichuan University (WCHSU). The basic information, laboratory examination indicators, pathological reports, and follow-up data of patients were included. SPSS 22.0 statistical software was used for statistical data analyses. Platelet (PLT), alpha-fetoprotein (AFP), maximum diameter (max-D), number of tumors (Number), degree of differentiation (DD), Microvascular invasion situation (MVI), satellite focus situation (SF), PNI, and ALBI were the independent risk factors for both overall survival (OS) and disease-free survival (DFS) of HBV-HCC patients undergoing RH.