The perception of silence.

Auditory perception is traditionally conceived as the perception of sounds-a friend's voice, a clap of thunder, a minor chord. However, daily life also seems to present us with experiences characterized by the absence of sound-a moment of silence, a gap between thunderclaps, the hush after a musical performance. In these cases, do we positively hear silence? Or do we just fail to hear, and merely judge or infer that it is silent? This longstanding question remains controversial in both the philosophy and science of perception, with prominent theories holding that sounds are the only objects of auditory experience and thus that our encounter with silence is cognitive, not perceptual. However, this debate has largely remained theoretical, without a key empirical test. Here, we introduce an empirical approach to this theoretical dispute, presenting experimental evidence that silence can be genuinely perceived (not just cognitively inferred). We ask whether silences can "substitute" for sounds in event-based auditory illusions-empirical signatures of auditory event representation in which auditory events distort perceived duration. Seven experiments introduce three "silence illusions"-the one-silence-is-more illusion, silence-based warping, and the oddball-silence illusion-each adapted from a prominent perceptual illusion previously thought to arise only from sounds. Subjects were immersed in ambient noise interrupted by silences structurally identical to the sounds in the original illusions. In all cases, silences elicited temporal distortions perfectly analogous to the illusions produced by sounds. Our results suggest that silence is truly heard, not merely inferred, introducing a general approach for studying the perception of absence.

Mutation status of the KMT2 family associated with immune checkpoint inhibitors (ICIs) therapy and implicating diverse tumor microenvironments.

Mounting evidence suggests a strong association between tumor immunity and epigenetic regulation. The histone-lysine N-methyltransferase 2 (KMT2) family plays a crucial role in the methylation of histone H3 at lysine 4. By influencing chromatin structure and DNA accessibility, this modification serves as a key regulator of tumor progression and immune tolerance across various tumors. These findings highlight the potential significance of the KMT2 family in determining response to immune checkpoint inhibitor (ICI) therapy, which warrants further exploration. In this study, we integrated four ICI-treated cohorts (n = 2069) across 10 cancer types and The Cancer Genome Atlas pan-cancer cohort and conducted a comprehensive clinical and bioinformatic analysis. Our study indicated that patients with KMT2 family gene mutations benefited more from ICI therapy in terms of overall survival (P < 0.001, hazard ratio [HR] = 0.733 [95% confidence interval (CI): 0.632-0.850]), progression-free survival (P = 0.002, HR = 0.669 [95% CI: 0.518-0.864]), durable clinical benefit (P < 0.001, 54.1% vs. 32.6%), and objective response rate (P < 0.001, 40.6% vs. 22.0%). Through a comprehensive analysis of the tumor microenvironment across different KMT2 mutation statuses, we observed that tumors harboring the KMT2 mutation exhibited enhanced immunogenicity, increased infiltration of immune cells, and higher levels of immune cell cytotoxicity, suggesting a propensity towards a "hot tumor" phenotype. Therefore, our study indicates a potential association between KMT2 mutations and a more favorable response to ICI therapy and implicates different tumor microenvironments associated with ICI therapy response.

Machine Learning-Assisted Optimization of Mixed Carbon Source Compositions for High-Performance Denitrification.

Appropriate mixed carbon sources have great potential to enhance denitrification efficiency and reduce operational costs in municipal wastewater treatment plants (WWTPs). However, traditional methods struggle to efficiently select the optimal mixture due to the variety of compositions. Herein, we developed a machine learning-assisted high-throughput method enabling WWTPs to rapidly identify and optimize mixed carbon sources. Taking a local WWTP as an example, a mixed carbon source denitrification data set was established via a high-throughput method and employed to train a machine learning model. The composition of carbon sources and the types of inoculated sludge served as input variables. The XGBoost algorithm was employed to predict the total nitrogen removal rate and microbial growth, thereby aiding in the assessment of the denitrification potential. The predicted carbon sources exhibited an enhanced denitrification potential over single carbon sources in both kinetic experiments and long-term reactor operations. Model feature analysis shows that the cumulative effect and interaction among individual carbon sources in a mixture significantly enhance the overall denitrification potential. Metagenomic analysis reveals that the mixed carbon sources increased the diversity and complexity of denitrifying bacterial ecological networks in WWTPs. This work offers an efficient method for WWTPs to optimize mixed carbon source compositions and provides new insights into the mechanism behind enhanced denitrification under a supply of multiple carbon sources.

Role of hepatitis B core-related antigen in predicting the occurrence and recurrence of hepatocellular carcinoma in patients with chronic hepatitis B: A systemic review and meta-analysis.

BACKGROUND AND AIM: The purpose of the current study was to investigate the predictive value of hepatitis B core-related antigen (HBcrAg) on the occurrence and recurrence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). METHODS: We searched PubMed, Embase, Scopus, and Web of Science from database inception to April 6, 2023. Pooled hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was calculated for the occurrence and recurrence of HCC. RESULTS: Of the 464 articles considered, 18 articles recruiting 10 320 patients were included. The pooled results showed that high serum HBcrAg level was an independent risk factor for the occurrence of HCC in CHB patients (adjusted HR = 3.12, 95% CI: 2.40-4.06, P < 0.001, I2 = 43.2%, P = 0.043; OR = 5.65, 95% CI: 3.44-5.82, P < 0.001, I2 = 0.00%, P = 0.42). Further subgroup analysis demonstrated that the predictive ability of HBcrAg for the occurrence of HCC is not influenced by the hepatitis B e antigen (HBeAg) status or the use of nucleoside/nucleotide analogs (NAs). In addition, our meta-analysis also suggests that HBcrAg is a predictor of HCC recurrence (adjusted HR = 1.71, 95% CI: 1.26-2.32, P < 0.001, I2 = 7.89%, P = 0.031). CONCLUSIONS: For patients with CHB, serum HBcrAg may be a potential predictive factor for the occurrence of HCC, regardless of HBeAg status or NA treatment. It may also serve as a novel prognostic biomarker for the recurrence of HCC. More studies are needed to confirm our conclusions.

Analysis of cuproptosis-related lncRNA signature for predicting prognosis and tumor immune microenvironment in pancreatic cancer.

Pancreatic cancer (PC) is a highly malignant digestive tract tumor, with a dismal 5-year survival rate. Recently, cuproptosis was found to be copper-dependent cell death. This work aims to establish a cuproptosis-related lncRNA signature which could predict the prognosis of PC patients and help clinical decision-making. Firstly, cuproptosis-related lncRNAs were identified in the TCGA-PAAD database. Next, a cuproptosis-related lncRNA signature based on five lncRNAs was established. Besides, the ICGC cohort and our samples from 30 PC patients served as external validation groups to verify the predictive power of the risk signature. Then, the expression of CASC8 was verified in PC samples, scRNA-seq dataset CRA001160, and PC cell lines. The correlation between CASC8 and cuproptosis-related genes was validated by Real-Time PCR. Additionally, the roles of CASC8 in PC progression and immune microenvironment characterization were explored by loss-of-function assay. As showed in the results, the prognosis of patients with higher risk scores was prominently worse than that with lower risk scores. Real-Time PCR and single cell analysis suggested that CASC8 was highly expressed in pancreatic cancer and related to cuproptosis. Additionally, gene inhibition of CASC8 impacted the proliferation, apoptosis and migration of PC cells. Furthermore, CASC8 was demonstrated to impact the expression of CD274 and several chemokines, and serve as a key indicator in tumor immune microenvironment characterization. In conclusion, the cuproptosis-related lncRNA signature could provide valuable indications for the prognosis of PC patients, and CASC8 was a candidate biomarker for not only predicting the progression of PC patients but also their antitumor immune responses.

MALAT1/ mir-1-3p mediated BRF2 expression promotes HCC progression via inhibiting the LKB1/AMPK signaling pathway.

BACKGROUND: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to play a vital role in the occurrence and development of various tumors. However, the underlying mechanism of MALAT1 in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. METHODS: The expression levels of MALAT1 in HCC tissues and different cell lines were detected by qRT-PCR. Antisense oligonucleotides (ASO)-MALAT1 transfected cells were used to explore the biological effects of MALAT1 in HCC cells by cell counting kit 8 (CCK-8), colony formation, transwell, wound healing, and flow cytometry analysis. Western blotting was performed to measure AMPK and apoptosis-related protein levels. Dual-luciferase reporter assay was performed to verify the relationship between MALAT1 and its specific targets. RESULTS: We found that MALAT1 was upregulated in HCC, and MALAT1 knockdown in HCC cells inhibited cell proliferation, migration, and invasion and inhibited apoptosis in vitro. Further studies demonstrated that MALAT1 positively regulated the expression of transcription factor II B­related factor 2 (BRF2), which was associated with tumor recurrence, large tumor size, and poor prognosis in HCC. Mechanistically, MALAT1 was found to act as a competitive endogenous RNA to sponge has-miR-1-3p, which upregulated BRF2 expression. Knockdown of BRF2 inhibited the progression of HCC by activating the LKB1/AMPK signaling pathway. Overexpression of BRF2 reversed the inhibitory effect of MALAT1 knockdown on HCC cell viability. Moreover, ASO targeting MALAT1 inhibited the growth of xenograft tumors. CONCLUSIONS: Our results demonstrate a novel MALAT1/miR-1-3p/BRF2/LKB1/AMPK regulatory axis in HCC, which may provide new molecular therapeutic targets for HCC in the future.

Survey of NF1 inactivation by surrogate immunohistochemistry in ovarian carcinomas.

OBJECTIVE: Inhibition of the MAPK pathway by MEK inhibitors (MEKi) is currently a therapeutic standard in several cancer types, including ovarian low-grade serous carcinoma (LGSC). A common MAPK pathway alteration in tubo-ovarian high-grade serous carcinoma (HGSC) is the genomic inactivation of neurofibromin 1 (NF1). The primary objectives of our study were to survey the prevalence of NF1 inactivation in the principal ovarian carcinoma histotype as well as to evaluate its associations with clinico-pathological parameters and key biomarkers including BRCA1/2 status in HGSC. METHODS: A recently commercialized NF1 antibody (clone NFC) was orthogonally validated on an automated immunohistochemistry (IHC) platform and IHC was performed on tissue microarrays containing 2140 ovarian carcinoma cases. Expression was interpreted as loss/inactivated (complete or subclonal) versus normal/retained. RESULTS: Loss of NF1 expression was detected in 250/1429 (17.4%) HGSC including 11% with subclonal loss. Survival of NF1-inactivated HGSC patients was intermediate between favorable BRCA1/2 mutated HGSC and unfavorable CCNE1 high-level amplified HGSC. NF1 inactivation was mutually exclusive with CCNE1 high-level amplifications, co-occurred with RB1 loss and occurred at similar frequencies in BRCA1/2 mutated versus wild-type HGSC. NF1 loss was found in 21/286 (7.3%) endometrioid carcinomas with a favorable prognostic association (p = 0.048), and in 4/64 (5.9%) LGSC, mutually exclusive with other driver events. CONCLUSIONS: NF1 inactivation occurs in a significant subset of BRCA1/2 wild-type HGSC and a subset of LGSC. While the functional effects of NF1 inactivation need to be further characterized, this signifies a potential therapeutic opportunity to explore targeting NF1 inactivation in these tumors.

Survival after minimally invasive radical hysterectomy without using uterine manipulator for early-stage cervical cancer: A systematic review and meta-analysis.

BACKGROUND: Minimally invasive radical hysterectomy has been reported to increase the risk of cancer relapse and death compared with open surgery in women with early-stage cervical cancer. The use of a uterine manipulator is considered one of the risk factors. OBJECTIVES: To investigate whether women with early-stage cervical cancer treated with minimally invasive radical hysterectomy without using uterine manipulator have oncological outcomes similar to those of open surgery. SEARCH STRATEGY: Searches were performed in MEDLINE, Embase and CENTRAL from their inception until 31 March 2022. SELECTION CRITERIA: Inclusion criteria were: (1) randomised controlled trials or observational cohort studies published in English, (2) studies comparing minimally invasive radical hysterectomy without using a uterine manipulator with open radical hysterectomy in women with early-stage cervical cancer, and (3) studies comparing survival outcomes. DATA COLLECTION AND ANALYSIS: Two authors independently conducted data extraction and assessed study quality. We calculated the hazard ratios (HR) and the 95% confidence intervals (CI) using the inverse variance approach for survival outcome. MAIN RESULTS: Six observational studies with 2150 women were included. The minimally invasive surgery group had a significantly higher risk of cancer relapse compared with open surgery group (HR 1.55, 95% CI 1.15-2.10). CONCLUSIONS: Minimally invasive radical hysterectomy without using a uterine manipulator resulted in an inferior recurrence-free survival compared with open radical hysterectomy in the treatment of women with early-stage cervical cancer.

ADAMTS12 promotes migration and epithelial-mesenchymal transition and predicts poor prognosis for pancreatic cancer.

BACKGROUND: ADAMTS (a disintegrin and metalloproteinase with thrombospondin-like motifs) family, a group of extracellular multifunctional enzymes, has been proven to play a pivotal role in the tumor. In pancreatic cancer, the role and mechanism of this family remain unclear. The present study aimed to figure out the hub gene of ADAMTSs and explore the exact roles in the prognosis and biological functions in pancreatic ductal adenocarcinoma (PDAC). METHODS: We used several databases to analyze the ADAMTS family and then screen out the hub genes. The expression of ADAMTS12 in 106 pairs of PDAC tumors and adjacent normal tissues was examined by immunohistochemistry, and its correlations with clinical parameters were further analyzed. The impacts of ADAMTS12 on the migration of PDAC cells were predicted by gene set enrichment analysis and confirmed by transwell assays. The potential impacts of ADAMTS12 on the epithelial-mesenchymal transition (EMT) were identified by database analysis and experimental proof of real-time quantitative polymerase chain reaction (qPCR) and Western blotting. RESULTS: Our study found that ADAMTS12 was a crucial gene in PDAC, and it was highly expressed in tumor tissues when compared to that in the adjacent tissues. ADATMS12 had predictive value of a poor prognosis for PDAC. The elevation of ADAMTS12 was parallel to the progression of PDAC. Inhibition of ADAMTS12 suppressed the migration of PDAC cells and interfered with the process of EMT. CONCLUSIONS: ADAMTS12 is a crucial member of ADAMTSs in PDAC and a predictor of poor prognosis. Additionally, based on its impacts on migration and metastasis in PDAC and the relationship with EMT, ADAMTS12 plays a role of an oncogene in PDAC and may be a promising target for treatment.

ROS-NLRP3 signaling pathway induces sterile inflammation after thulium laser resection of the prostate.

The sterile inflammation (SI) of the urinary tract is a common problem requiring serious consideration after prostatectomy. This study mainly focuses on the role of the reactive oxygen species-NLR family, pyrin domain-containing 3 (ROS-NLRP3) signaling pathway in SI after thulium laser resection of the prostate (TmLRP). Urinary cytokines were determined in patients who received TmLRP, and heat shock protein 70 (HSP70) was detected in the resected tissues. The involvement of ROS signaling in HSP70-induced inflammation was explored in THP-1 cells with or without N-acetyl- l-cysteine (NAC) pretreatment. The function of NLRP3 and Caspase-1 was determined by Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction. These phenomena and mechanisms were verified by the beagle models that received TmLRP. Clinical urine samples after TmLRP showed high expression of inflammatory factors and peaked 3-5 days after surgery. The high expression of HSP70 in the resected tissues was observed. After HSP70 stimulation, the expression of ROS, NLRP3, Caspase-1, and interleukin-18 (IL-18) increased significantly and could be reduced by ROS inhibitor NAC. The expression of IL-1ß and IL-18 could be inhibited by NLRP3 or Caspase-1 inhibitors. In beagle models that received TmLRP, HSP70, NLRP3, Caspase-1, IL-1ß, and IL-18 were highly expressed in the wound tissue or urine, and could also be reduced by NAC pretreatment. Activation of the ROS-NLRP3 signaling pathway induces SI in the wound after prostatectomy. Inhibition of this pathway may be effective for clinical prevention and treatment of SI and related complications after prostatectomy.

Bimetallic Cage-Based Metal-Organic Frameworks for Electrochemical Hydrogen Evolution Reaction with Enhanced Activity.

A cage-based metal-organic framework (Ni-NKU-101) with biphenyl-3,3',5,5'-tetracarboxylic acid was synthesized via solvothermal method. Ni-NKU-101 contains two types of cages based on trinuclear and octa-nuclear nickel-clusters that are connected with each other by the 4-connected ligands, to form a 3D framework with a new topology. A mixed-metal strategy was used to synthesize isostructural bimetallic MOFs of Mx Ni1-x -NKU-101 (M=Mn, Co, Cu, Zn). The electrocatalytic studies showed that the hydrogen evolution reaction (HER) activity of Cux Ni1-x -NKU-101 is much higher than that of other Mx Ni1-x -NKU-101 catalysts in acidic aqueous solution, owing to the synergistic effect of the bimetallic centers. The optimized Cu0.19 Ni0.81 -NKU-101 has an overpotential of 324 mV at 10 mA cm-2 and a Tafel slope of 131 mV dec-1 . The mechanism of HER activity over these bimetallic MOF-based electrocatalysts are discussed in detail.

Initial CT-based radiomics nomogram for predicting in-hospital mortality in patients with traumatic brain injury: a multicenter development and validation study.

OBJECTIVE: To develop and validate a radiomic prediction model using initial noncontrast computed tomography (CT) at admission to predict in-hospital mortality in patients with traumatic brain injury (TBI). METHODS: A total of 379 TBI patients from three cohorts were categorized into training, internal validation, and external validation sets. After filtering the unstable features with the minimum redundancy maximum relevance approach, the CT-based radiomics signature was selected by using the least absolute shrinkage and selection operator (LASSO) approach. A personalized predictive nomogram incorporating the radiomic signature and clinical features was developed using a multivariate logistic model to predict in-hospital mortality in patients with TBI. The calibration, discrimination, and clinical usefulness of the radiomics signature and nomogram were evaluated. RESULTS: The radiomic signature consisting of 12 features had areas under the curve (AUCs) of 0.734, 0.716, and 0.706 in the prediction of in-hospital mortality in the internal and two external validation cohorts. The personalized predictive nomogram integrating the radiomic and clinical features demonstrated significant calibration and discrimination with AUCs of 0.843, 0.811, and 0.834 in the internal and two external validation cohorts. Based on decision curve analysis (DCA), both the radiomic features and nomogram were found to be clinically significant and useful. CONCLUSION: This predictive nomogram incorporating the CT-based radiomic signature and clinical features had maximum accuracy and played an optimized role in the early prediction of in-hospital mortality. The results of this study provide vital insights for the early warning of death in TBI patients.

Family socioeconomic status and mental health in Chinese adolescents: the multiple mediating role of social relationships.

BACKGROUND: The purpose of this study is to explore whether social relationships of family and school contexts mediate the influence of socioeconomic status (SES) on Chinese adolescents' mental health. METHODS: A school-based study was conducted among a sample aged 13-18 in East China (n = 6902). We used scales for measuring social relationships and self-rated mental health. Family SES was computed from subjective socioeconomic status, education and occupation of parents.The mediation model was tested by using Path Analysis in IBM SPSS-Amos. RESULTS: The results showed that SES can significantly influence adolescent mental health through parent-child relationship, student-teacher relationship and student-student relationship. The total effect, direct effect and total indirect effect were -0.209 (95% CI = -0.299, -0.136), -0.090 (95% CI = -0.174, -0.007), -0.119 (95% CI = -0.187, -0.078) for boys, and -0.337 (95% CI = -0.478, -0.230), -0.132 (95% CI = -0.283, 0.010), -0.205 (95% CI = -0.351, -0.085) for girls. CONCLUSION: The link between SES and adolescent mental health can be explained by social relationships. Focusing on the parent-child, student-student and student-teacher relationship interventions may contribute to improving the mental health of Chinese adolescents, especially in low socioeconomic groups, as well as female students.

Analysis on pregnancy outcomes and risk factors of cervical polypectomy during the first and second trimester pregnancy.

AIM: To evaluate the risk factors of miscarriage in patients attempted cervical polypectomy during the first and second trimester pregnancy. METHODS: Pregnant women with singleton infants who underwent cervical polypectomy during the first and second trimester between January 2013 and May 2019 were investigated. The study retrospectively reviewed the clinical features and pregnancy outcomes after cervical polypectomy. A multivariable regression was performed to predict the risk factors of miscarriage. RESULTS: A total of 307 pregnant females were eventually included in our study. Twenty-seven patients (8.8%, 27/307) had a miscarriage before 28 weeks, 37 patients (12.1%, 37/307) had a preterm delivery. After univariate analysis, we found that the presence of decidual polyps and vaginal bleeding after polypectomy were the risk factors for miscarriage. Moreover, the incidence of miscarriage was significantly higher in the patients with decidual polyps than in those with endocervical polyps (14.9% vs. 5.6%, p = 0.010). CONCLUSIONS: The most suitable hemostasis method should be taken in the cervical polypectomy during pregnancy. The risk of miscarriage associated with polypectomy during pregnancy is higher in females with decidual polyps. If decidual polyps are highly suspected and they do not cause excessive vaginal bleeding and can be ruled out the possibility of malignancy, conservative treatment may lead to a better outcome.

Interfacial Superconductivity Achieved in Parent AEFe2As2 (AE = Ca, Sr, Ba) by a Simple and Realistic Annealing Route.

Materials with interfaces often exhibit extraordinary phenomena exemplified by rich physics, such as high-temperature superconductivity and enhanced electronic correlations. However, demonstrations of confined interfaces to date have involved intensive effort and fortuity, and no simple path is consistently available. Here, we report the achievement of interfacial superconductivity in the nonsuperconducting parent compounds AEFe2As2, where AE = Ca, Sr, or Ba, by simple subsequent annealing of the as-grown samples in an atmosphere of As, P, or Sb. Our results indicate that the superconductivity originates from electron transfer at the interface of the hybrid van der Waals heterostructures, consistent with the two-dimensional superconducting transition observed. The observations suggest a common origin of interfaces for the nonbulk superconductivity previously reported in the AEFe2As2 compound family and provide insight for the further exploration of interfacial superconductivity.

Joint Resource Allocation for Multiuser Opportunistic Beamforming Systems with OFDM-NOMA.

Opportunistic beamforming (OBF) is an effective technique to improve the spectrum efficiencies (SEs) of multiple-input-multiple-output (MIMO) systems, which can obtain multiuser diversity gains with both low computation complexity and feedback information. To serve multiple users simultaneously, many multiple-access schemes have been researched in OBF. However, for most of the multiple-access schemes, the SEs are not satisfactory. To further improve the SE, this paper proposes a downlink multiuser OBF system, where both orthogonal frequency division multiplexing (OFDM) and non-orthogonal multiple-access (NOMA) methods are applied. The closed-form expressions of the equivalent channels and SE are derived in frequency selective fading channels. Then, an optimization problem is formulated to maximize the SE, although the optimization problem is non-convex and hard to solve. To obtain the solution, we divide the optimization problem into two suboptimal issues, and then a joint iterative algorithm is applied. In the proposed optimization scheme, the subcarrier mapping ϑ, user pairing knc and allocated power Pknc are determined to maximize spectrum efficiency (SE) and reduce bit error ratio (BER). According to numerical results, the proposed method achieves approximately 5 dB gain on both SE and BER, compared to the existing beamforming methods with low feedback information. Moreover, the SE of the proposed method is approximately 2 (bps/Hz) higher than sparse code multiple-access (SCMA), when the number of waiting users and the ratio of transmit power to noise variance are respectively 10 and 20 dB. It is indicated that the proposed scheme can achieve high and low BER with the limited feedback and computation complexity, regardless of the transmit power and the number of waiting users.

Overlapping attentional networks yield divergent behavioral predictions across tasks: Neuromarkers for diffuse and focused attention?

Attention is a critical cognitive function, allowing humans to select, enhance, and sustain focus on information of behavioral relevance. Attention contains dissociable neural and psychological components. Nevertheless, some brain networks support multiple attentional functions. In this study, we used the visual attentional blink (VAB) as a test of the functional generalizability of the brain's attentional networks. In a VAB task, attention devoted to a target often causes a subsequent item to be missed. Although frequently attributed to limitations in attentional capacity or selection, VAB deficits attenuate when participants are distracted or deploy attention diffusely. The VAB is also behaviorally and theoretically dissociable from other attention tasks. Here we used Connectome-based Predictive Models (CPMs), which associate individual differences in task performance with functional connectivity patterns, to test their ability to predict performance for multiple attentional tasks. We constructed visual attentional blink (VAB) CPMs, and then used them and a sustained attention network model (saCPM; Rosenberg et al., 2016a) to predict performance. The latter model had been previously shown to successfully predict performance across tasks involving selective attention, inhibitory control, and even reading recall. Participants (n â€‹= â€‹73; 24 males) underwent fMRI while performing the VAB task and while resting. Outside the scanner, they completed other cognitive tasks over several days. A vabCPM constructed from VAB task data (behavior and fMRI) successfully predicted VAB performance. Strikingly, the network edges that predicted better VAB performance (positive edges) predicted worse performance for selective and sustained attention tasks, and vice versa. Predictions from applying the saCPM to the data mirrored these results, with the network's negative edges predicting better VAB performance. The vabCPM's positive edges partially yet significantly overlapped with the saCPM's negative edges, and vice versa. Many positive edges from the vabCPM involved the default mode network, whereas many negative edges involved the salience/ventral attention network. We conclude that the vabCPM and saCPM networks reflect general attentional functions that influence performance on many tasks. The networks may indicate an individual's propensity to deploy attention in a more diffuse or a more focused manner.

QKI-6 inhibits bladder cancer malignant behaviours through down-regulating E2F3 and NF-κB signalling.

Quaking homolog (QKI) is a member of the RNA-binding signal transduction and activator of proteins family. Previous studies showed that QKI possesses the tumour suppressor activity in human cancers by interacting with the 3'-untraslated region (3'-UTR) of various gene transcripts via the STAR domain. This study first assessed the association of QKI-6 expression with clinicopathological and survival data from bladder cancer patients and then investigated the underlying molecular mechanisms. Bladder cancer tissues (n = 223) were subjected to immunohistochemistry, and tumour cell lines and nude mice were used for different in vitro and in vivo assays following QKI-6 overexpression or knockdown. QKI-6 down-regulation was associated with advanced tumour TNM stages and poor patient overall survival. QKI-6 overexpression inhibited bladder cancer cell growth and invasion capacity, but induced tumour cell apoptosis and cell cycle arrest. Furthermore, ectopic expression of QKI-6 reduced tumour xenograft growth and expression of proliferation markers, Ki67 and PCNA. However, knockdown of QKI-6 expression had opposite effects in vitro and in vivo. QKI-6 inhibited expression of E2 transcription factor 3 (E2F3) by directly binding to the E2F3 3'-UTR, whereas E2F3 induced QKI-6 transcription by binding to the QKI-6 promoter in negative feedback mechanism. QKI-6 expression also suppressed activity and expression of nuclear factor-κB (NF-κB) signalling proteins in vitro, implying a novel multilevel regulatory network downstream of QKI-6. In conclusion, QKI-6 down-regulation contributes to bladder cancer development and progression.

Substrate-Triggered Formation of a Peroxo-Fe2(III/III) Intermediate during Fatty Acid Decarboxylation by UndA.

The iron-dependent oxidase UndA cleaves one C3-H bond and the C1-C2 bond of dodecanoic acid to produce 1-undecene and CO2. A published X-ray crystal structure showed that UndA has a heme-oxygenase-like fold, thus associating it with a structural superfamily that includes known and postulated non-heme diiron proteins, but revealed only a single iron ion in the active site. Mechanisms proposed for initiation of decarboxylation by cleavage of the C3-H bond using a monoiron cofactor to activate O2 necessarily invoked unusual or potentially unfeasible steps. Here we present spectroscopic, crystallographic, and biochemical evidence that the cofactor of Pseudomonas fluorescens Pf-5 UndA is actually a diiron cluster and show that binding of the substrate triggers rapid addition of O2 to the Fe2(II/II) cofactor to produce a transient peroxo-Fe2(III/III) intermediate. The observations of a diiron cofactor and substrate-triggered formation of a peroxo-Fe2(III/III) intermediate suggest a small set of possible mechanisms for O2, C3-H and C1-C2 activation by UndA; these routes obviate the problematic steps of the earlier hypotheses that invoked a single iron.

Heat injured stromal cells-derived exosomal EGFR enhances prostatic wound healing after thulium laser resection through EMT and NF-κB signaling.

BACKGROUND: This study investigated shallow heat injury to prostate stromal fibroblasts and epithelial cells and their interaction to regulate the wound healing and the underlying molecular events. METHODS: Prostate stromal fibroblasts and epithelial cells were cultured individually or cocultured and subjected to shallow heat injury for assessments of cell proliferation, migration, apoptosis, cell cycle distribution, and gene expression. The supernatant of heat-injured WPMY-1 cells was collected for exosome extraction and assessments. Furthermore, beagle dogs received thulium laser resection of the prostate (TmLRP) and randomly divided into Gefitinib, GW4869, and control treatment for the histological analysis, tissue re-epithelialization, and epidermal growth factor receptor (EGFR) expression on the prostatic wound surface. Immunofluorescence was to evaluate p63-positive basal progenitor cell trans-differentiation and macrophage polarization and ELISA was to detect cytokine levels in beagles' urine. RESULTS: Shallow heat injury caused these cells to enter a stressed state and enhanced their crosstalk. The prostate stromal fibroblasts produced and secreted more exosomal-EGFR and other cytokines and chemokines after shallow heat injury, resulting in increased proliferation and migration of prostate epithelial cells during wound healing. The wound healing of the canine prostatic urethra following the TmLRP procedure was slower in the Gefitinib and GW4869 treatment group than in the control group of animals. Immunofluorescence and ELISA showed that reduced EGFR expression interrupted macrophage polarization but increased the inflammatory response. CONCLUSIONS: Shallow heat injury was able to promote the interaction of prostate stromal cells with prostate epithelial cells to enhance wound healing. Stromal-derived exosomal-EGFR plays a crucial role in the balance of the macrophage polarization and prostatic wound healing.