A connectome-wide association study of altered functional connectivity in schizophrenia based on resting-state fMRI.

BACKGROUND: Aberrant resting-state functional connectivity is a neuropathological feature of schizophrenia (SCZ). Prior investigations into functional connectivity abnormalities have primarily employed seed-based connectivity analysis, necessitating predefined seed locations. To address this limitation, a data-driven multivariate method known as connectome-wide association study (CWAS) has been proposed for exploring whole-brain functional connectivity. METHODS: We conducted a CWAS analysis involving 46 patients with SCZ and 40 age- and sex-matched healthy controls. Multivariate distance matrix regression (MDMR) was utilized to identify key nodes in the brain. Subsequently, we conducted a follow-up seed-based connectivity analysis to elucidate specific connectivity patterns between regions of interest (ROIs). Additionally, we explored the spatial correlation between changes in functional connectivity and underlying molecular architectures by examining correlations between neurotransmitter/transporter distribution densities and functional connectivity. RESULTS: MDMR revealed the right medial frontal gyrus and the left calcarine sulcus as two key nodes. Follow-up analysis unveiled hypoconnectivity between the right medial frontal superior gyrus and the right fusiform gyrus, as well as hypoconnectivity between the left calcarine sulcus and the right lingual gyrus in SCZ. Notably, a significant association between functional connectivity strength and positive symptom severity was identified. Furthermore, altered functional connectivity patterns suggested potential dysfunctions in the dopamine, serotonin, and gamma-aminobutyric acid systems. CONCLUSIONS: This study elucidated reduced functional connectivity both within and between the medial frontal regions and the occipital cortex in patients with SCZ. Moreover, it indicated potential alterations in molecular architecture, thereby expanding current knowledge regarding neurobiological changes associated with SCZ.

Aberrant positive affect dynamics in individuals with subthreshold depression: Evidence from laboratory and real-world assessments / Dinámica aberrante del afecto positivo en individuos con depresión subumbral: evidencia de evaluaciones de laboratorio y del mundo real

Background/Objective: Reduced positive affect (PA) is a core feature of major depressive disorder (MDD). However, the precursor of MDD, subthreshold depression (StD), has received less attention in this regard. Therefore, we examined PA dynamics in StD, integrating laboratory-based and ecological momentary assessment (EMA) approaches. Method: Participants were college students recruited from Chinese universities (31 with StD, and 39 healthy controls (HC)). Positive mood was induced in the laboratory by an eight-minute comedy clip used to assess PA reactivity and maintenance. To extend findings to the real world and explore mechanisms of PA maintenance, 53 participants with StD and 64 HC reported their emotional states 14 times daily for one week via EMA. Multilevel models were used to test for predictors of PA inertia. Results: In the laboratory, participants with StD achieved the same PA reactivity as HC when facing positive stimuli, yet the curve-fitting revealed difficulties for the StD group in maintaining PA over time. Such reduced capacity was further observed in real-world settings, manifesting in significantly greater PA inertia. Conclusions: High PA inertia in daily life may reflect resistance to mood change in StD, explaining anhedonia and difficulties with emotional maintenance, and highlighting the need for early identification.(AU)

Effect of synthesis temperature on the structural morphology of a metal-organic framework and the capacitor performance of derived cobalt-nickel layered double hydroxides.

Three-dimensional interconnected nickel-cobalt layered double hydroxides (NiCo-LDHs) were prepared on nickel foam by ion exchange using a cobalt-based metal-organic framework (Co-MOF) as a template at different temperatures. The effects of the Co-MOF preparation temperature on the growth, mass, morphology, and electrochemical properties of the Co-MOF and derived NiCo-LDH samples were studied. The synthesis temperature from 30 to 50 °C gradually increased the mass of the active material and the thickness of the Co-MOF sheets grown on the nickel foam. The higher the temperature is, the larger the proportion of Co3+. ß-Cobalt hydroxide (ß-Co(OH)2) sheets were generated above 60 °C. The morphology and mass loading pattern of the derived flocculent layer clusters of NiCo-LDH were inherited from metal-organic frameworks (MOFs). The areal capacitance of NiCo-LDH shows an inverted U-shaped curve trend with increasing temperature. The electrode material synthesized at 50 °C had a tremendous specific capacitance of 7631 mF·cm-2 at a current density of 2 mA·cm-2. The asymmetric supercapacitor assembled with the sample and active carbon (AC) achieved an energy density of 55.0 Wh·kg-1 at a power density of 800.0 W·kg-1, demonstrating the great potential of the NiCo-LDH material for energy storage. This work presents a new strategy for designing and fabricating advanced green supercapacitor materials with large power and energy densities.

Age-related positive emotional reactivity decline associated with the anterior insula based resting-state functional connectivity.

Recent studies have suggested that emotional reactivity changes with age, but the neural basis is still unclear. The insula may be critical for the emotional reactivity. The current study examined how ageing affects emotional reactivity using the emotional reactivity task data from a human sample (Cambridge Center for Age and Neuroscience, N = 243, age 18-88 years). The resting-state magnetic resonance measurements from the same sample were used to investigate the potential mechanisms of the insula. In the initial analysis, we conducted partial correlation assessments to examine the associations between emotional reactivity and age, as well as between the gray matter volume (GMV) of the insula and age. Our results revealed that emotional reactivity, especially positive emotional reactivity, decreased with age and that the GMV of the insula was negatively correlated with age. Subsequently, the bilateral insula was divided into six subregions to calculate the whole brain resting-state functional connectivity (rsFC). The mediating effect of the rsFC on age and emotional reactivity was then calculated. The results showed that the rsFC of the left anterior insula (AI) with the right hippocampus, and the rsFCs of the right AI with the striatum and the thalamus were mediated the relationship between positive emotional reactivity and age. Our findings suggest that attenuating emotional reactivity with age may be a strategic adaptation fostering emotional stability and diminishing emotional vulnerability. Meanwhile, the findings implicate a key role for the AI in the changes in positive emotional reactivity with age.

Aberrant positive affect dynamics in individuals with subthreshold depression: Evidence from laboratory and real-world assessments.

Background/Objective: Reduced positive affect (PA) is a core feature of major depressive disorder (MDD). However, the precursor of MDD, subthreshold depression (StD), has received less attention in this regard. Therefore, we examined PA dynamics in StD, integrating laboratory-based and ecological momentary assessment (EMA) approaches. Method: Participants were college students recruited from Chinese universities (31 with StD, and 39 healthy controls (HC)). Positive mood was induced in the laboratory by an eight-minute comedy clip used to assess PA reactivity and maintenance. To extend findings to the real world and explore mechanisms of PA maintenance, 53 participants with StD and 64 HC reported their emotional states 14 times daily for one week via EMA. Multilevel models were used to test for predictors of PA inertia. Results: In the laboratory, participants with StD achieved the same PA reactivity as HC when facing positive stimuli, yet the curve-fitting revealed difficulties for the StD group in maintaining PA over time. Such reduced capacity was further observed in real-world settings, manifesting in significantly greater PA inertia. Conclusions: High PA inertia in daily life may reflect resistance to mood change in StD, explaining anhedonia and difficulties with emotional maintenance, and highlighting the need for early identification.

Global-brain functional connectivity related with trait anxiety and its association with neurotransmitters and gene expression profiles.

BACKGROUND: Numerous studies have explored the neural correlates of trait anxiety, a predisposing factor for several stress-related disorders. However, the findings from previous studies are inconsistent, which might be due to the limited regions of interest (ROI). A recent approach, named global-brain functional connectivity (GBC), has been demonstrated to address the shortcomings of ROI-based analysis. Furthermore, research on the transcriptome-connectome association has provided an approach to link the microlevel transcriptome profile with the macroscale brain network. In this paper, we aim to explore the neurobiology of trait anxiety with an imaging transcriptomic approach using GBC, biological neurotransmitters, and transcriptome profiles. METHODS: Using a sample of resting-state fMRI data, we investigated trait anxiety-related alteration in GBC. We further used behavioral analysis, spatial correlation analysis, and postmortem gene expression to separately assess the cognitive functions, neurotransmitters, and transcriptional profiles related to alteration in GBC in individuals with trait anxiety. RESULTS: GBC values in the ventromedial prefrontal cortex and the precuneus were negatively correlated with levels of trait anxiety. This alteration was correlated with behavioral terms including social cognition, emotion, and memory. A strong association was revealed between trait anxiety-related alteration in GBC and neurotransmitters, including dopaminergic, serotonergic, GABAergic, and glutamatergic systems in the ventromedial prefrontal cortex and the precuneus. The transcriptional profiles explained the functional connectivity, with correlated genes enriched in transmembrane signaling. LIMITATIONS: Several limitations should be taken into account in this research. For example, future research should consider using some different approaches based on dynamic or task-based functional connectivity analysis, include more neurotransmitter receptors, additional gene expression data from different samples or more genes related to other stress-related disorders. Meanwhile, it is of great significance to include a larger sample size of individuals with a diagnosis of major depression disorder or other disorders for analysis and comparison and apply stricter multiple-comparison correction and threshold settings in future research. CONCLUSIONS: Our research employed multimodal data to investigate GBC in the context of trait anxiety and to establish its associations with neurotransmitters and transcriptome profiles. This approach may improve understanding of the neural mechanism, together with the biological and molecular genetic foundations of GBC in trait anxiety.

The robust reciprocal relationship between loneliness and depressive symptoms among the general population: Evidence from a quantitative analysis of 37 studies.

BACKGROUND: Loneliness has long been associated with depressive symptoms, but there is no evidence on the question of "which comes first". To help us to answer this question, this study conducted a meta-analysis using a cross-lagged formula to examine the reciprocal relations between loneliness and depressive symptoms, as well as potential moderators. METHODS: The meta-analytic dataset consisted of 37 studies with sample sizes ranging from 52 to 5991. Effect sizes (including autoregressive effects and lagged coefficients) were included. We computed weighted mean effect sizes for the correlation effect and cross-lagged effect between loneliness and depressive symptoms. We also performed a meta-regression to investigate potential moderators. RESULTS: The results showed that loneliness and depressive symptoms reciprocally predicted each other over time with similar effect sizes. There was no moderation of our overall effect size in either direction by time interval between measurements, the proportion of female participants, mean age of the sample, or type of measurement. LIMITATIONS: Caution should be taken in drawing final conclusions about the relative strength of reciprocal effects between loneliness and depressive symptoms due to the potential influence of varied research focus in the included studies, which could affect the effect size. CONCLUSIONS: These findings advance the study of the relationship between loneliness and depressive symptoms by providing evidence that the link between them is symmetrically reciprocal and robust, which may help clinicians to develop effective intervention methods.

A Novel Approach for Dry Cutting Inconel 718 in a More Sustainable and Low-Cost Way by Actively and Purposely Utilizing the Built-Up Layer.

Due to its physical and mechanical properties, Inconel 718 remains a difficult-to-cut material and there is an urgent need to develop a more sustainable and low-cost way to machine it. A novel approach for dry cutting Inconel 718 by actively and purposely utilizing the built-up layer (BUL), which can be called the self-protective tool (SPT) method, is proposed and investigated in detail in this paper. Various cutting experiments were carried out using the age-treated Inconel 718 and uncoated cemented carbide tools. The formation condition of the BUL, its formation mechanism, its stability, and its protective effect were examined by measuring the tools after cutting using a scanning electron microscope (SEM) and laser confocal microscopy (LCM). The influences of BUL on the cutting process were investigated using cutting force analysis and surface roughness analysis. The results confirmed that the stability of the BUL is very high, and the BUL can not only significantly protect the tool from wear but also reduce friction at the tool-chip interface and maintain surface roughness. It also revealed that the height of the BUL can play a very important role in its protective effect. Comparative experiments verified the effectiveness and generalizability of the proposed SPT method.

Intercultural sensitivity as a mediator in the relationship between implicit intercultural identification and emotional disturbance-An exploratory study of international high school students.

Background: Intercultural adaptation is always associated with emotional disturbances. Intercultural communication competence, as an important competence of intercultural adaptation, involves implicit intercultural identification and intercultural sensitivity. Competence in these areas promotes the process of intercultural adaptation. Little is known about the relationship between intercultural communication competence and emotional disturbances in new students attending international high schools. The intercultural adaptation process of this population requires attention because of the increasing number of high school students attending international schools, and the fact that most of these teenagers are immersed in intercultural contexts for the first time. Objective: This study aimed to investigate the prevalence of emotional disturbance in new students in an international high school and confirm the relationship among implicit intercultural identification, intercultural sensitivity, and emotional disturbances. Methods: Study 1 was an investigation of the prevalence of emotional disturbance in 105 students in their 1st year at an international high school using the Self-rating Depression Scale and Self-rating Anxiety Scale. Of these students, 34 were invited to participate in Study 2 to further explore the relationship between intercultural sensitivity, implicit intercultural identification, and emotional disturbances using the Intercultural Sensitivity Scale and Single Category Implicit Association procedure. Results: Study 1 indicated that 15.24% of students were affected by apparent depression and 10.48% had anxiety symptoms. Study 2 revealed that emotional disturbances significantly correlated with intercultural sensitivity (p < 0.01) and implicit intercultural identification (p < 0.01). The openness factor from intercultural sensitivity mediated the relationship between implicit intercultural identification and depression (ratio of indirect effect = 41.04%, p < 0.05) and anxiety symptoms (ratio of indirect effect = 34.65%, p < 0.05). Conclusion: The study revealed that a significant proportion of students in the 1st year of international high school are affected by emotional difficulties. However, intercultural communication competence is a protective factor. Enhancing the international communication competence of senior students in international high schools is important to mitigate mental health challenges.

The prevalence and risk of developing major depression among individuals with subthreshold depression in the general population.

BACKGROUND: Subthreshold depression could be a significant precursor to and a risk factor for major depression. However, reliable estimates of the prevalence and its contribution to developing major depression under different terminologies depicting subthreshold depression have to be established. METHODS: By searching PubMed and Web of Science using predefined inclusion criteria, we included 1 129 969 individuals from 113 studies conducted. The prevalence estimates were calculated using the random effect model. The incidence risk ratio (IRR) was estimated by measuring the ratio of individuals with subthreshold depression who developed major depression compared to that of non-depressed individuals from 19 studies (88, 882 individuals). RESULTS: No significant difference in the prevalence among the different terminologies depicting subthreshold depression (Q = 1.96, p = 0.5801) was found. By pooling the prevalence estimates of subthreshold depression in 113 studies, we obtained a summary prevalence of 11.02% [95% confidence interval (CI) 9.78-12.33%]. The youth group had the highest prevalence (14.17%, 95% CI 8.82-20.55%), followed by the elderly group (12.95%, 95% CI 11.41-14.58%) and the adult group (8.92%, 95% CI 7.51-10.45%). Further analysis of 19 studies' incidence rates showed individuals with subthreshold depression had an increased risk of developing major depression (IRR = 2.95, 95% CI 2.33-3.73), and the term minor depression showed the highest IRR compared with other terms (IRR = 3.97, 95% CI 3.17-4.96). CONCLUSIONS: Depression could be a spectrum disorder, with subthreshold depression being a significant precursor to and a risk factor for major depression. Proactive management of subthreshold depression could be effective for managing the increasing prevalence of major depression.

Distinct neural activation patterns of age in subcomponents of inhibitory control: A fMRI meta-analysis.

Inhibitory control (IC) is a fundamental cognitive function showing age-related change across the healthy lifespan. Since different cognitive resources are needed in the two subcomponents of IC (cognitive inhibition and response inhibition), regions of the brain are differentially activated. In this study, we aimed to determine whether there is a distinct age-related activation pattern in these two subcomponents. A total of 278 fMRI articles were included in the current analysis. Multilevel kernel density analysis was used to provide data on brain activation under each subcomponent of IC. Contrast analyses were conducted to capture the distinct activated brain regions for the two subcomponents, whereas meta-regression analyses were performed to identify brain regions with distinct age-related activation patterns in the two subcomponents of IC. The results showed that the right inferior frontal gyrus and the bilateral insula were activated during the two IC subcomponents. Contrast analyses revealed stronger activation in the superior parietal lobule during cognitive inhibition, whereas stronger activation during response inhibition was observed primarily in the right inferior frontal gyrus, bilateral insula, and angular gyrus. Furthermore, regression analyses showed that activation of the left anterior cingulate cortex, left inferior frontal gyrus, bilateral insula, and left superior parietal lobule increased and decreased with age during cognitive inhibition and response inhibition, respectively. The results showed distinct activation patterns of aging for the two subcomponents of IC, which may be related to the differential cognitive resources recruited. These findings may help to enhance knowledge of age-related changes in the activation patterns of IC.

Charting the neural circuits disruption in inhibitory control and its subcomponents across psychiatric disorders: A neuroimaging meta-analysis.

BACKGROUND: Inhibitory control, comprising cognitive inhibition and response inhibition, showed consistent deficits among several major psychiatric disorders. We aim to identify the trans-diagnostic convergence of neuroimaging abnormalities underlying inhibitory control across psychiatric disorders. METHODS: Inhibitory control tasks neuroimaging, including functional magnetic resonance imaging, single-photon emission computed tomography, and positron emission tomography articles published in PubMed and Web of Science before April 2020 comparing healthy controls with patients with several psychiatric disorders were searched. RESULTS: 146 experiments on 2653 patients with different disorders and 2764 control participants were included. Coordinates of case-control differences coded by diagnosis and inhibitory control components were analyzed using activation likelihood estimation. A robust trans-diagnostic pattern of aberrant brain activation in the bilateral cingulate gyri extending to medial frontal gyri, right insula, bilateral lentiform nuclei, right inferior frontal gyrus, right precuneus extending to inferior parietal lobule, and right supplementary motor area were detected. Frontostriatal pathways are the commonly disrupted neural circuits in the inhibitory control across psychiatric disorders. Furthermore, Patients showed aberrant activation in the dorsal frontal inhibitory system in cognitive inhibition, while in the frontostriatal system in response inhibition across disorders. CONCLUSION: Consistent with the Research Domain Criteria initiative, current findings show that psychiatric disorders may be productively formulated as a phenotype of trans-diagnostic neurocircuit disruption. Our results provide new insights for future research into mental disorders with inhibition-related dysfunctions.

Psychometric Properties of the Chinese Version of the Brief State Rumination Inventory.

State rumination, unlike trait rumination which is described as a persistent and stable response style, is usually triggered by a specific stressful event and causes negative emotions within a short period of time. The measurement methods of trait rumination, such as the ruminative response scale (RRS), are therefore not fully applicable to state rumination. Recently, researchers have developed the brief state rumination inventory (BSRI) to characterize state rumination, addressing the gap in the field of accurate measurement of state rumination. To develop such an effective tool in the Chinese context, we developed a Chinese version of the BSRI and tested its psychometric properties. Two studies were conducted to address the research goal. In Study 1, we recruited 512 subjects, each of whom completed the Chinese version of the BSRI, RRS, emotional regulation questionnaire (ERQ), depression-anxiety-stress scale (DASS), and positive and negative affect scale (PANAS). Results showed that the scores of the BSRI were positively correlated with all other scale scores (ps < 0.001), and the correlation with the RRS was the highest, indicating that the BSRI showed good convergent validity. Additionally, the Cronbach's alpha coefficient for the Chinese version of the BSRI was 0.93. Study 2 aimed to examine the ecological validity of the Chinese version of the BSRI. We recruited another 54 subjects who were randomly divided into two groups, with 27 in the rumination induction group and 27 in the distraction group, and recorded the BSRI scores of the two groups before and after a specific experiment. We found there was a significant increase in BSRI scores after rumination induction (t = 3.91, p < 0.001), while there was no significant difference in the concrete distraction group before and after the experiment (t = 0.70, p = 0.48). In sum, the Chinese version of the BSRI showed good reliability and validity for assessing state rumination in the general Chinese population.

The inter-relationships of the neural basis of rumination and inhibitory control: neuroimaging-based meta-analyses.

Rumination, as a clinical manifestation and pathogenic factor of depression, has long been the focus of psychological research regarding its causes and ameliorating approaches. Behavioral studies have shown that rumination is related to inhibitory control deficits, which provides ideas for reducing it. However, the neural relationship between them has not been clearly discussed. In this study, we first used multi-level kernel density analysis to conduct two meta-analyses of published functional magnetic resonance imaging studies: one was rumination comprising 17 studies with 180 foci, and the other was inhibitory control comprising 205 studies with 3791 foci. Conjunction analysis was then performed to explore the common brain regions and further decode them through Neurosynth to confirm the cognitive specificity. Results showed that rumination was mainly related to the default mode network (DMN), while inhibitory control was associated with the frontoparietal network (FPN). In addition, the common activation areas were mainly concentrated in the bilateral precuneus, right superior frontal gyrus, bilateral median cingulate, paracingulate gyri, and the left triangular part of inferior frontal gyrus (IFG). Decoding results also revealed they were involved in inhibition, memory retrieval, and self-related processes. Our findings support that rumination is associated with inhibitory control and can be explained neurologically by an antagonistic relationship between the DMN and FPN. In sum, inhibitory control may be related to rumination via inhibiting task-unrelated attention and controlling self-related processing. This research will help us understand and predict rumination from the perspective of inhibitory control and reduce rumination through behavioral training of inhibitory control or the application of neuromodulation techniques to common activation regions.

Morphologic Analysis of Congenital Heart Disease With Anomalous Tracheobronchial Arborization.

BACKGROUND: This study investigated the morphologic characteristics of congenital heart disease (CHD) combined with anomalous tracheobronchial arborization (ATBA) to provide new considerations for surgically treating congenital tracheal stenosis. METHODS: A retrospective review of surgical experience with ATBA was conducted of 147 patients. The proportion of patients with ATBA combined with tracheal stenosis was determined. Four ATBA types were identified: type A, tracheal bronchus (n = 58); type B, bronchial trifurcation (n = 46); type C, bridging bronchus (n = 38); and type D, tracheal bronchus combined with bronchial trifurcation (n = 5). The rate of tracheoplasty for each type was determined. We measured the carina/pseudocarina angle and assessed the distribution of CHD, especially pulmonary artery sling. RESULTS: The tracheal diameter of 14 patients (24.1%) with type A and 5 patients (10.9%) with type B was normal. There were 128 patients with tracheal stenosis and complete tracheal rings; of them, 113 patients received tracheoplasty. The tracheoplasty rate was higher for type C than type A (100% vs 62.1%, P < .001). The carina/pseudocarina angle was significantly reduced postoperatively (P < .001). The repair in 78 patients (60.9%) was combined with a pulmonary artery sling. A pulmonary azygos lobe was found in 10 patients (6.8%) and was resected. CONCLUSIONS: ATBA is common in patients with congenital tracheal stenosis and may be associated with abnormal embryonic development. The new classification of ATBA has clinical significance in treating patients with congenital tracheal stenosis. The poor tracheal development cannot be explained merely with vascular compression. Tracheoplasty is currently the optimal option for every type.

Risk factors for low cardiac output syndrome in children with congenital heart disease undergoing cardiac surgery: a retrospective cohort study.

BACKGROUND: Low cardiac output syndrome (LCOS) is an important complication of cardiac surgery. It is associated with increased morbidity and mortality. The incidence of LCOS after surgery is high in patients with congenital heart disease (CHD). Therefore, determining the risk factors of LCOS has clinical significance for the management of CHD. This study aimed to analyze the risk factors of LCOS. METHODS: We conducted a retrospective analysis of children with CHD who underwent cardiac surgery at Shanghai Children's Medical Center between January 1, 2014, and December 31, 2017. Demographic characteristics and baseline data were extracted from the health data resource center of the hospital, which integrates clinical routine data including medical records, diagnoses, orders, surgeries, laboratory tests, imaging, nursing, and other subsystems. Logistic regressions were performed to analyze the risk factors of LCOS. RESULTS: Overall, 8660 infants with CHD were included, and 864 (9.98%) had LCOS after surgery. The multivariate regression analysis identified that age (OR 0.992, 95% CI: 0.988-0.997, p = 0.001), tricuspid regurgitation (1.192, 1.072-1.326, p = 0.001), Risk Adjustment in Congenital Heart Surgery-1 risk grade (1.166, 1.011-1.345, p = 0.035), aortic shunt (left-to-right: 1.37, 1.005-1.867, p = 0.046; bi-directional: 1.716, 1.138-2.587, p = 0.01), atrial shunt (left-to-right: 1.407, 1.097-1.805, p = 0.007; right-to-left: 3.168, 1.944-5.163, p < 0.001; bi-directional: 1.87, 1.389-2.519, p < 0.001), ventricular level shunt (left-to-right: 0.676, 0.486-0.94, p = 0.02; bi-directional: 2.09, 1.611-2.712, p < 0.001), residual shunt (3.489, 1.502-8.105, p = 0.004), left ventricular outflow tract obstruction (3.934, 1.673-9.254, p = 0.002), right ventricular outflow tract obstruction (3.638, 1.225-10.798, p = 0.02), circulating temperature (mild hypothermia: 1.526, 95% CI: 1.205-1.934, p < 0.001; middle and low temperature: 1.738, 1.236-2.443, p = 0.001), duration of cardiopulmonary bypass (1.009, 1.006-1.012, p < 0.001), myocardial preservation using histidine-tryptophan-ketoglutarate (1.677, 1.298-2.167, p < 0.001), and mitral insufficiency (1.714, 1.239-2.37, p < 0.001) were independent risk predictors of LCOS. CONCLUSIONS: The incidence of postoperative LCOS in CHD children remains high. Circulation temperature, myocardial preservation using histidine-tryptophan-ketoglutarate, and usage of residual shunt after surgery were independent risk predictors for LCOS.

E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells.

Upon recognition of dsRNA, toll-like receptor 3 (TLR3) recruits the adaptor protein TRIF to activate IRF3 and NF-κB signaling, initiating innate immune responses. The ubiquitination of TLR3 downstream signaling molecules and their roles in the innate response have been discovered; however, whether TLR3 itself is ubiquitinated and then functionally involved remains to be elucidated. By immunoprecipitating TLR3-binding proteins in macrophages, we identified ring finger protein 170 (RNF170) as a TLR3-binding E3 ligase. RNF170 mediated the K48-linked polyubiquitination of K766 in the TIR domain of TLR3 and promoted the degradation of TLR3 through the proteasome pathway. The genetic ablation of RNF170 selectively augmented TLR3-triggered innate immune responses both in vitro and in vivo. Our results reveal a novel role for RNF170 in selectively inhibiting TLR3-triggered innate immune responses by promoting TLR3 degradation.

Nuclear RNF2 inhibits interferon function by promoting K33-linked STAT1 disassociation from DNA.

Prolonged activation of interferon-STAT1 signaling is closely related to inflammatory autoimmune disorders, and therefore the identification of negative regulators of these pathways is important. Through high-content screening of 115 mouse RING-domain E3 ligases, we identified the E3 ubiquitin ligase RNF2 as a potent inhibitor of interferon-dependent antiviral responses. RNF2 deficiency substantially enhanced interferon-stimulated gene (ISG) expression and antiviral responses. Mechanistically, nuclear RNF2 directly bound to STAT1 after interferon stimulation and increased K33-linked polyubiquitination of the DNA-binding domain of STAT1 at position K379, in addition to promoting the disassociation of STAT1/STAT2 from DNA and consequently suppressing ISG transcription. Our study provides insight into the regulation of interferon-dependent responses via a previously unrecognized post-translational modification of STAT1 in the nucleus.

Downregulated expression of miR-142-3p in macrophages contributes to increased IL-6 levels in aged mice.

Macrophages are innate immune cells that are important contributors to age-related functional impairment of the immune system. During the cell aging process, microRNAs are differentially expressed and participate in the regulation of aging-related immune responses. However, the role of aging-associated changes in miRNA expression in macrophages remains unclear. Here, we found that miR-142-3p expression is downregulated 50% in peritoneal macrophages from aged mice compared with young mice and is not upregulated by cell treatment with lipopolysaccharide (LPS), CpG, or polyinosinic-polycytidylic acid. Serum levels of miR-142-3p are also lower in aged mice than in young mice by q-PCR. Luciferase reporter analysis showed that IL-6 is a target of miR-142-3p in macrophages. In addition, the histone deacetylase inhibitor trichostatin A increased miR-142-3p expression by more than 3-fold in LPS-treated macrophages from aged mice compared with young mice, which in turn suppressed LPS-stimulated IL-6 production, suggesting that inhibition of miR-142-3p by histone deacetylation may be involved in the lack of response to LPS stimulation in macrophages of aged mice. These findings suggest that downregulation of miR-142-3p in macrophages of aged mice might contribute to IL-6-associated aging disorders and that epigenetic modification might be involved in age-related inflammatory diseases.