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1.
Cell Rep ; 43(4): 114060, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38568809

ABSTRACT

Human cognitive abilities ranging from basic perceptions to complex social behaviors exhibit substantial variation in individual differences. These cognitive functions can be categorized into a two-order hierarchy based on the levels of cognitive processes. Second-order cognition including metacognition and mentalizing monitors and regulates first-order cognitive processes. These two-order hierarchical cognitive functions exhibit distinct abilities. However, it remains unclear whether individual differences in these cognitive abilities have distinct origins. We employ the classical twin paradigm to compare the genetic and environmental contributions to the two-order cognitive abilities in the same tasks from the same population. The results reveal that individual differences in first-order cognitive abilities were primarily influenced by genetic factors. Conversely, the second-order cognitive abilities have a stronger influence from shared environmental factors. These findings suggest that the abilities of metacognition and mentalizing in adults are profoundly shaped by their environmental experiences and less determined by their biological nature.


Subject(s)
Cognition , Humans , Cognition/physiology , Adult , Male , Female , Environment , Young Adult , Gene-Environment Interaction , Individuality
2.
Ann Hematol ; 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38148344

ABSTRACT

The E2A-PBX1 gene fusion is a common translocation in B-cell acute lymphoblastic leukaemia. Patients harbouring the E2A-PBX1 fusion gene typically exhibit an intermediate prognosis. Furthermore, minimal residual disease has unsatisfactory prognostic value in E2A-PBX1 B-cell acute lymphoblastic leukaemia. However, the mechanism of E2A-PBX1 in the occurrence and progression of B-cell acute lymphoblastic leukaemia is not well understood. Here, we mainly review the roles of E2A and PBX1 in the differentiation and development of B lymphocytes, the mechanism of E2A-PBX1 gene fusion in B-cell acute lymphoblastic leukaemia, and the potential therapeutic approaches.

3.
J Neurosci ; 43(49): 8442-8455, 2023 12 06.
Article in English | MEDLINE | ID: mdl-37848283

ABSTRACT

Mentalizing is a core faculty of human social behaviors that involves inferring the cognitive states of others. This process necessitates adopting an allocentric perspective and suppressing one's egocentric perspective, referred to as self-other distinction (SOD). Meanwhile, individuals may project their own cognitive states onto others in prosocial behaviors, a process known as self-other mergence (SOM). It remains unclear how the two opposing processes coexist during mentalizing. We here combined functional magnetic resonance imaging (fMRI) and repetitive transcranial magnetic stimulation (rTMS) techniques with intranasal oxytocin (OTint) as a probe to examine the SOM effect in healthy male human participants, during which they attributed the cognitive states of decision confidence to an anonymous partner. Our results showed that OTint facilitated SOM via the left temporoparietal junction (lTPJ), but did not affect neural representations of internal information about others' confidence in the dorsomedial prefrontal cortex, which might be dedicated to SOD, although the two brain regions, importantly, have been suggested to be involved in mentalizing. Further, the SOM effect induced by OTint was fully mediated by the lTPJ activities and became weakened when the lTPJ activities were suppressed by rTMS. These findings suggest that the lTPJ might play a vital role in mediating SOM during mentalizing.SIGNIFICANCE STATEMENT Every human mind is unique. It is critical to distinguish the minds of others from the self. On the contrary, we often project the current mental states of the self onto others; that is to say, self-other mergence (SOM). The neural mechanism underlying SOM remains unclear. We here used intranasal oxytocin (OTint) as a probe to leverage SOM, which is typically suppressed during mentalizing. We revealed that OTint specifically modulated the left temporoparietal junction (lTPJ) neural activities to fully mediate the SOM effect, while suppressing the lTPJ neural activities by transcranial magnetic stimulations causally attenuated the SOM effect. Our results demonstrate that the lTPJ might mediate SOM during social interactions.


Subject(s)
Mentalization , Theory of Mind , Humans , Male , Oxytocin , Transcranial Magnetic Stimulation/methods , Brain , Prefrontal Cortex/physiology , Brain Mapping , Magnetic Resonance Imaging , Theory of Mind/physiology
4.
Front Endocrinol (Lausanne) ; 14: 1191830, 2023.
Article in English | MEDLINE | ID: mdl-37564987

ABSTRACT

Objective: To determine the preventive effect of melatonin on delirium in the intensive care units. Methods: We conducted a systematic search of the PubMed, Cochrane Library, Science, Embase, and CNKI databases, with retrieval dates ranging from the databases' inception to September 2022. Controlled trials on melatonin and placebo for preventing delirium in the intensive care units were included. The meta-analysis was performed using Review Manager software (version 5.3) and Stata software (version 14.0). Results: Six studies involving 2374 patients were included in the meta-analysis. The results of the meta-analysis showed that melatonin did not reduce the incidence of delirium in ICU patients (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.46 to 1.12; p = 0.14). There was a strong hetero-geneity between the selected studies (I2 = 74%). Subgroup analysis results showed that melatonin reduced the incidence of delirium in cardiovascular care unit (CCU) patients (OR: 0.52; 95% CI: 0.37 to 0.73; p=0.0001), but did not in general intensive care unit (GICU) patients (OR: 1.14; 95% CI: 0.86 to 1.50; p=0.35). In terms of the secondary outcomes, there were no significant differences in all-cause mortality (OR: 0.85; 95% CI: 0.66 to 1.09; p=0.20), length of ICU stay (mean difference [MD]: 0.33; 95% CI: -0.53 to 1.18; p=0.45), or length of hospital stay (MD: 0.51; 95% CI: -1.17 to 2.19; p=0.55). Conclusion: Melatonin reduced the incidence of delirium in CCU patients, but did not significantly reduce the incidence of delirium in GICU patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022367665.


Subject(s)
Delirium , Melatonin , Humans , Melatonin/therapeutic use , Delirium/epidemiology , Delirium/prevention & control , Delirium/drug therapy , Randomized Controlled Trials as Topic , Intensive Care Units , Length of Stay
5.
J Oncol ; 2022: 4974027, 2022.
Article in English | MEDLINE | ID: mdl-36420359

ABSTRACT

Objective: The aim of the study is to analyze the impact of intra-abdominal pressure (IAP) on perioperative outcomes in robotic-assisted radical prostatectomy (RARP). Methods: We searched the PubMed, Cochrane Library, Science, Embase, and CNKI databases systematically, and the retrieval date was from the inception of the databases to April 2022. Randomized controlled trials on high intraabdominal pressure (HIAP) and low intraabdominal pressure (LIAP) in RARP were included. The meta-analysis was performed using Review Manager software (version 5.3). Results: Six studies involving 2,271 patients were included in the meta-analysis. Compared with patients who experienced HIAP, those who experienced LIAP had a lower incidence of postoperative ileus (POI) (risk ratio (RR): 0.42; 95% confidence interval (CI): 0.24 to 0.72; p = 0.002). However, there were no significant differences in hematoma (RR 2.22; 95% CI, 0.61 to 8.15; p = 0.23), positive margin rate (RR, 1.06; 95% CI, 0.84 to 1.32; p = 0.64), urinary retention (RR, 0.99; 95% CI, 0.51 to 1.94; p = 0.98), operative time (mean difference (MD), -0.36; 95% CI, -12.24 to 6.12; p = 0.51), or intraoperative blood loss (MD, -21.80; 95% CI, -55.28 to 11.68; p = 0.20) among patients undergoing LIAP and HIAP. Conclusion: Our study of published trials indicates that using LIAP during RARP may reduce the incidence of POI, and there were no differences in terms of hematoma, positive margin rate, urinary retention, operative time, or intraoperative blood loss.

6.
PLoS Biol ; 20(5): e3001301, 2022 05.
Article in English | MEDLINE | ID: mdl-35559898

ABSTRACT

Metacognition and mentalizing are both associated with meta-level mental state representations. Conventionally, metacognition refers to monitoring one's own cognitive processes, while mentalizing refers to monitoring others' cognitive processes. However, this self-other dichotomy is insufficient to delineate the 2 high-level mental processes. We here used functional magnetic resonance imaging (fMRI) to systematically investigate the neural representations of different levels of decision uncertainty in monitoring different targets (the current self, the past self [PS], and others) performing a perceptual decision-making task. Our results reveal diverse formats of internal mental state representations of decision uncertainty in mentalizing, separate from the associations with external cue information. External cue information was commonly represented in the right inferior parietal lobe (IPL) across the mentalizing tasks. However, the internal mental states of decision uncertainty attributed to others were uniquely represented in the dorsomedial prefrontal cortex (dmPFC), rather than the temporoparietal junction (TPJ) that also represented the object-level mental states of decision inaccuracy attributed to others. Further, the object-level and meta-level mental states of decision uncertainty, when attributed to the PS, were represented in the precuneus and the lateral frontopolar cortex (lFPC), respectively. In contrast, the dorsal anterior cingulate cortex (dACC) represented currently experienced decision uncertainty in metacognition, and also uncertainty about the estimated decision uncertainty (estimate uncertainty), but not the estimated decision uncertainty per se in mentalizing. Hence, our findings identify neural signatures to clearly delineate metacognition and mentalizing and further imply distinct neural computations on internal mental states of decision uncertainty during metacognition and mentalizing.


Subject(s)
Mentalization , Metacognition , Brain Mapping , Gyrus Cinguli , Magnetic Resonance Imaging , Uncertainty
7.
Chemosphere ; 300: 134409, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35390413

ABSTRACT

Arsenic and antimony are widely distributed toxic metalloids in aquatic environments. However, their partitioning behaviors in the sediment profile remain not well understood. Here, partitioning behaviors, diffusive fluxes, as well as the ecological risks of As and Sb in the sediment-porewater profile system in the tributaries of the Three Gorges Reservoir (TGR) were investigated. As and Sb showed markedly different spatial variations in the longitudinal profiles of both porewater and sediment samples. Specifically, the concentration of As showed an accumulation trend with depth, while that of Sb showed a relatively complicated trend. Further, As showed lower sediment-porewater partitioning coefficient (Kd) values, suggesting that it had a relatively lower sediment affinity and a higher mobility than Sb. Its residual fraction (30%-60%) was also lower than that of Sb. This phenomenon could be attributed to the chemical fractions of the trace metals and the pH value of the sediments. Furthermore, the Kd values corresponding to As were influenced by both the residual fraction (r = 0.338, p < 0.05) and the exchangeable fraction (r = -0.643, p < 0.01), while those corresponding to Sb were only influenced by pH. Additionally, even though these two trace metals showed low ecological and mobility risks, the diffusive fluxes at the sediment-water interface suggested that the sediment acted as a source of As and a sink for Sb relative to the overlying water. This study indicated that As and Sb had different partitioning behaviors and release risks in the sediment-porewater profile system, enhanced the understanding the transport and fate of As and Sb in the aquatic environment.


Subject(s)
Arsenic , Trace Elements , Water Pollutants, Chemical , Antimony/analysis , Arsenic/analysis , China , Environmental Monitoring , Geologic Sediments , Rivers , Water , Water Pollutants, Chemical/analysis
8.
Sci Total Environ ; 828: 154268, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35247407

ABSTRACT

Urban rivers are potential sinks for microplastic (MP) contamination in the environment. However, the footprint of MPs in urban rivers is not well understood because it is influenced by natural and anthropogenic factors. This study focused on the occurrence, pollution risk, and potential sources of MPs in surface water and sediments before and after thawing in Shahe River, Beijing. The size distribution, morphological characteristics and polymer types of MPs were analyzed using a micro-Raman spectroscopy. The results showed that the average abundance of MP obviously increased after river thawing, from 1772 ± 1668 items·m-3 to 3877 ± 2517 items·m-3 in surface water and 4776 ± 4817 items·kg-1 to 14,004 ± 5371 items·kg-1 in sediments. The MP polymer types were more diverse after thawing. The main MP type in surface water changed from polyethylene terephthalate (PET) to polypropylene (PP). Moreover, PP was the most common type in sediments. Small-sized MPs (SMPs, 10-300 µm) were dominant in Shahe River, with the proportion increasing from 48.5% to 83.3% in surface water and from 84.3% to 94.4% in sediments after thawing. Although the MP pollution risk increased after thawing, it was still low in the Shahe River. Unfortunately, changes in polymer types caused by thawing and the emergence of toxic polymers increased the ecological risk in the urban river. These results revealed the information of MP contamination before and after thawing, and highlighted the barrier influence of river icing on the migration of MPs. Overall, the results presented a new perspective on the environmental behavior of microplastics in urban rivers, suggesting that the occurrence and dominance of SMPs and the emergence of toxic polymers in urban environmental media require close attention in the future.


Subject(s)
Microplastics , Water Pollutants, Chemical , Beijing , China , Environmental Monitoring , Plastics , Polypropylenes , Rivers , Water , Water Pollutants, Chemical/analysis
9.
Water Res ; 211: 118018, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35021122

ABSTRACT

The Three Gorges Dam (TGD) is the world's largest hydropower project. It could potentially influence the footprint and transport of microplastics (MPs) in Yangtze River, which is the largest riverine input of oceanic MPs worldwide. In addition to analyzing the MP particles of all size categories and polymer groups, we also evaluated the stability, pollution risk and source identification of MPs after the catastrophic flood of 2020 in the Three Gorges Reservoir (TGR) and downstream of the TGD. We found that the MP abundance (6214 ± 5394 particles/m3) in the TGR water increased by a 57.9% growth after this catastrophic flood. Interestingly, we observed the small-sized MPs (SMPs; < 300 µm) were dominant in the TGR (accounting for ∼65.4% of the total MP particles). After flooding, the main morphological types were fragment and fiber, while the major polymer was polyethylene (PE). Although the MP level was at a low pollution risk, 13.6% of the sampling sites in the TGR water faced potential ecological risks driven by SMPs. In particular, there was no significant difference in the abundances, morphological types, and polymer composition of MPs between upstream and downstream of the TGD (p > 0.05), indicating flooding control operation could weaken the barrier effect of the dam on MPs. Further, based on the conditional fragmentation model, the PE fragments in SMPs of the TGR remained at a stable state. MPs in the TGR mainly originated from anthropogenic activities (wastewater, containers, and agriculture films), with atmospheric deposition as a potential transport pathway for polymers. Our study demonstrates that dam operation during the flood period can influence the MP organization in TGR, providing new insights of the global land-sea transportation of MPs in the Yangtze River.


Subject(s)
Microplastics , Water Pollutants, Chemical , China , Environmental Monitoring , Floods , Plastics , Water , Water Pollutants, Chemical/analysis
10.
J Neurosci ; 42(7): 1275-1291, 2022 02 16.
Article in English | MEDLINE | ID: mdl-34907025

ABSTRACT

The dorsal anterior cingulate cortex (dACC) plays a critical role in cognitive control over different domains of tasks. The dACC activities uniformly represent task-generic intensities of control signals across different tasks. However, it remains unclear whether the dACC activities could also encode task identities of control signals across different tasks. If so, how the two types of control information are coherently organized in the dACC? Decision uncertainty is an internally-generated control signal by retrospective monitoring, namely, metacognition, even with no external feedback. We here investigated neural representations of decision uncertainty accompanying three decision-making tasks in the domains of perception, rule-based inference, and memory using trial-by-trial univariate and multivariate analyses on functional magnetic resonance imaging (fMRI) data acquired on human male and female healthy subjects. Our results demonstrated that the dACC represented decision uncertainty commonly across the three decision-making tasks. Further, the multivariate fMRI analyses revealed a mosaic form of neural representations of decision uncertainty across tasks in the dACC. The identity and intensity information was separately represented in two dissociable components, the high-dimensional pattern and the scalar magnitude, of the dACC multivoxel fMRI activities. Lastly, a follow-up behavioral experiment confirmed that this mosaic form of neural representations of parallelly existing decision uncertainty across different tasks should lead to mutual interferences more on the intensity, but less on the identity of control signals. Thus, our findings suggest that the dACC with the mosaic form of neural representations could provide task-generic and task-specific metacognitive control signals to guide appropriate control on different decision-making tasks.SIGNIFICANCE STATEMENT Metacognition is a form of cognitive control using internally generated decision uncertainty to guide behavior adjustment with no needs of external feedback. Decision uncertainty as a generalizable control signal is commonly encoded in the human dorsal anterior cingulate cortex (dACC) accompanying different decision-making tasks. It remains unknown whether or not the task-specific control information is represented in the dACC. We here revealed that multivoxel functional magnetic resonance imaging (fMRI) activities associated with decision uncertainty in the dACC concurrently represented the identity and intensity information. The mixtures of neural representations of decision uncertainty across different tasks should cause specific interferences on each other. Hence, the neural representations of control signals in the human dACC should be task-generic and task-specific.


Subject(s)
Decision Making/physiology , Gyrus Cinguli/physiology , Metacognition/physiology , Adult , Female , Humans , Magnetic Resonance Imaging , Male
11.
Front Psychol ; 12: 759987, 2021.
Article in English | MEDLINE | ID: mdl-34744938

ABSTRACT

The COVID-19 pandemic and its related public health restrictions are having an increasingly serious impact on mental health, and measures need to be taken to curb this trend. The positive relationship between physical exercise and mental health has been well-established, but during the COVID-19 pandemic, with various restrictions, the space and facilities for physical exercise are limited. This article explores the relationship between physical exercise and mental health during the COVID-19 pandemic based on the latest research findings published in 2019-2021. We offer a novel model that consists of three central arguments. First, physical exercises during COVID-19, especially supervised exercises, are conducive to enhancing happiness and improving mental health. Second, physical exercise reduces people's anxiety, sadness and depression during the COVID-19 pandemic. Third, the maintenance and improvement of mental health are related to the intensity and frequency of physical exercise. Intensive and frequent physical exercise are conducive to maintaining mental health. Finally, this article proposes important directions for future research.

12.
FASEB J ; 34(11): 14710-14724, 2020 11.
Article in English | MEDLINE | ID: mdl-32918765

ABSTRACT

Sprouting angiogenesis is a highly coordinately process controlled by vascular endothelial growth factor receptor (VEGFR)-Notch signaling. Here we investigated whether Tripartite motif-containing 28 (TRIM28), which is an epigenetic modifier implicated in gene transcription and cell differentiation, is essential to mediate sprouting angiogenesis. We observed that knockdown of TRIM28 ortholog in zebrafish resulted in developmental vascular defect with disorganized and reduced vasculatures. Consistently, TRIM28 knockdown inhibited angiogenic sprouting of cultured endothelial cells (ECs), which exhibited increased mRNA levels of VEGFR1, Delta-like (DLL) 3, and Notch2 but reduced levels of VEGFR2, DLL1, DLL4, Notch1, Notch3, and Notch4.The regulative effects of TRIM28 on these angiogenic factors were partially mediated by hypoxia-inducible factor 1 α (HIF-1α) and recombination signal-binding protein for immunoglobulin kappa J region (RBPJκ). In vitro DNA-binding assay showed that TRIM28 knockdown increased the association of RBPJκ with DNA sequences containing HIF-1α-binding sites. Moreover, the phosphorylation of TRIM28 was controlled by VEGF and Notch1 through a mechanism involving RBPJκ-dual-specificity phosphatase (DUSP)-p38 MAPK, indicating a negative feedback mechanism. These findings established TRIM28 as a crucial regulator of VEGFR-Notch signaling circuit through HIF-1α and RBPJκ in EC sprouting angiogenesis.


Subject(s)
Neovascularization, Physiologic , Signal Transduction , Tripartite Motif-Containing Protein 28/metabolism , Animals , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Hypoxia-Inducible Factor 1/metabolism , Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Male , Rats , Rats, Sprague-Dawley , Receptors, Notch/genetics , Receptors, Notch/metabolism , Receptors, Vascular Endothelial Growth Factor/genetics , Receptors, Vascular Endothelial Growth Factor/metabolism , Tripartite Motif-Containing Protein 28/genetics , Zebrafish , Zebrafish Proteins/genetics , Zebrafish Proteins/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
13.
FASEB J ; 34(5): 6271-6283, 2020 05.
Article in English | MEDLINE | ID: mdl-32162409

ABSTRACT

Vascular smooth muscle cells (VSMCs) in the normal arterial media continually express contractile phenotypic markers which are reduced dramatically in response to injury. Tripartite motif-containing proteins are a family of scaffold proteins shown to regulate gene silencing, cell growth, and differentiation. We here investigated the biological role of tripartite motif-containing 28 (TRIM28) and tripartite motif-containing 27 (TRIM27) in VSMCs. We observed that siRNA-mediated knockdown of TRIM28 and TRIM27 inhibited platelet-derived growth factor (PDGF)-induced migration in human VSMCs. Both TRIM28 and TRIM27 can regulate serum response element activity and were required for maintaining the contractile gene expression in human VSMCs. At the same time, TRIM28 and TRIM27 knockdown reduced the expression of PDGF receptor-ß (PDGFRß) and the phosphorylation of its downstream signaling components. Immunoprecipitation showed that TRIM28 formed complexes with TRIM27 through its N-terminal RING-B boxes-Coiled-Coil domain. Furthermore, TRIM28 and TRIM27 were shown to be upregulated and mediate the VSMC contractile marker gene and PDGFRß expression in differentiating human bone marrow mesenchymal stem cells. In conclusion, we identified that TRIM28 and TRIM27 cooperatively maintain the endogenous expression of PDGFRß and contractile phenotype of human VSMCs.


Subject(s)
DNA-Binding Proteins/metabolism , Gene Expression Regulation , Mesenchymal Stem Cells/cytology , Muscle Contraction , Muscle, Smooth, Vascular/physiology , Nuclear Proteins/metabolism , Receptor, Platelet-Derived Growth Factor beta/metabolism , Tripartite Motif-Containing Protein 28/metabolism , Cell Differentiation , Cell Movement , Cell Proliferation , Cells, Cultured , DNA-Binding Proteins/genetics , Humans , Mesenchymal Stem Cells/metabolism , Muscle, Smooth, Vascular/cytology , Nuclear Proteins/genetics , Phenotype , Receptor, Platelet-Derived Growth Factor beta/genetics , Serum Response Element , Signal Transduction , Tripartite Motif-Containing Protein 28/genetics
14.
Hum Brain Mapp ; 41(6): 1445-1458, 2020 04 15.
Article in English | MEDLINE | ID: mdl-31789478

ABSTRACT

The metacognitive deficit in awareness of one's own mental states is a core feature of schizophrenia (SZ). The previous studies suggested that the metacognitive deficit associates with clinical symptoms. However, the neural mechanisms underlying the relationship remain largely unknown. We here investigated the neural activities associated with the metacognitive deficit and the neural signatures associated with clinical symptoms in 38 patients with SZ using functional magnetic resonance imaging with a perceptual decision-making task accompanied with metacognition, in comparison to 38 age, gender, and education matched healthy control subjects. The metacognitive deficit in patients with SZ was associated with reduced regional activity in both the frontoparietal control network (FPCN) and the default mode network. Critically, the anticorrelational balance between the two disrupted networks was substantially altered during metacognition, and the extent of alteration positively scaled with negative symptoms. Conversely, decoupling between the two networks was impaired when metacognitive monitoring was not required, and the strength of excessive neural activity positively scaled with positive symptoms. Thus, disruptions of the FPCN and the default mode network underlie the metacognitive deficit, and alternations of network balance between the two networks correlate with clinical symptoms in SZ. These findings implicate that rebalancing these networks holds important clinical potential in developing more efficacious therapeutic treatments.


Subject(s)
Cognition Disorders/drug therapy , Cognition Disorders/physiopathology , Default Mode Network/diagnostic imaging , Default Mode Network/physiopathology , Frontal Lobe/diagnostic imaging , Frontal Lobe/physiopathology , Metacognition , Nerve Net/diagnostic imaging , Nerve Net/physiopathology , Parietal Lobe/diagnostic imaging , Parietal Lobe/physiopathology , Schizophrenia/physiopathology , Schizophrenic Psychology , Adult , Brain Mapping , Cognition , Cognition Disorders/psychology , Decision Making , Female , Humans , Magnetic Resonance Imaging , Male , Psychomotor Performance , Young Adult
15.
Cell Commun Signal ; 17(1): 77, 2019 07 17.
Article in English | MEDLINE | ID: mdl-31315616

ABSTRACT

BACKGROUND: Lipogenesis is required for the optimal growth of many types of cancer cells, it is shown to control the biosynthesis of the lipid bilayer membrane during rapid proliferation and metastasis, provides cancer cells with signaling lipid molecules to support cancer development and make cancer cells more resistant to oxidative stress-induced cell death. Though multiple lipogenic enzymes have been identified to mediate this metabolic change, how the expression of these lipogenic enzymes are transcriptionally regulated remains unclear. METHODS: Gain- and loss-of-function experiments were conducted to assess the role of transcriptional repressor, nuclear receptor sub-family 6, group A, member 1 (NR6A1) in HepG2 cells. RT-qPCR method was performed to investigate target gene of NR6A1. Western blot was employed to determine the mechanisms by which NR6A1 regulates lipid accumulation in HepG2 cells. RESULTS: We provide evidence that NR6A1 is a novel regulator of lipid metabolism in HepG2 cells. NR6A1 knockdown can increase lipid accumulation as well as insulin-induced proliferation and migration of HepG2 cells. The lipogenic effect correlated well with the expression of lipogenic genes, including fatty acid synthase (FAS), diglyceride acyltransferase-2 (DGAT2), malic enzyme 1 (ME1), microsomal triglyceride transfer protein (MTTP) and phosphoenolpyruvate carboxykinase (PEPCK). NR6A1 knockdown also increased the expression of carnitine palmitoyltransferase 1A (CPT1a), the rate-limiting enzyme in fatty acid oxidation. Furthermore, NR6A1 knockdown induced lipid accumulation through mammalian target of rapamycin complex 1 (mTORC1), but not mTORC2. Moreover, siRNA-mediated knockdown of NR6A1 increased expression of insulin receptor (INSR) and potentitated insulin-induced phosphorylation of mTOR and AKT partly via miR-205-5p in HepG2 cells. CONCLUSIONS: These findings provide important new insights into the role of NR6A1 in the lipogenesis in HepG2 cells. .


Subject(s)
Lipid Metabolism , Mechanistic Target of Rapamycin Complex 1/metabolism , Nuclear Receptor Subfamily 6, Group A, Member 1/metabolism , Animals , Cell Movement , Cell Proliferation , Gene Expression Regulation , Gene Silencing , HEK293 Cells , Hep G2 Cells , Humans , Insulin/metabolism , Lipogenesis , MicroRNAs/genetics , Nuclear Receptor Subfamily 6, Group A, Member 1/deficiency , Nuclear Receptor Subfamily 6, Group A, Member 1/genetics , Receptor, Insulin/genetics , Signal Transduction
16.
Sci Total Environ ; 646: 1546-1553, 2019 Jan 01.
Article in English | MEDLINE | ID: mdl-30235639

ABSTRACT

As the sole drinking water source for Beijing City, Cd has been previously assessed as the major contaminant in Miyun Reservoir (MYR) riparian soils. However, the potential release risk of Cd in such soils, and the labile-Cd release-resupply process from the soil solid phase to solution after water impoundment remain poorly understood. We established a geochemical baseline concentration (GBC) of Cd in MYR riparian soils, combined with the diffusive gradient in thin films (DGT) technique and DGT-induced fluxes in soil (DIFS) model, to reveal a dynamic release-resupply process and influencing factors of labile Cd in riparian soils. The results showed that Cd GBC in riparian soils was 0.12 mg/kg, which was higher than the Cd background value (BV) for Beijing. Using Cd GBC as BV to assess the Cd contaminant level, the geo-accumulation index showed that Cd in riparian soils was at the uncontaminated level. In addition, Cd in the soils belonged to the non-residual fraction using the Community Bureau of Reference method. Cd mobility coefficients (F1/CTotal-Cd) of soils at low elevation had relatively high values, implying that Cd may be released during the initial impoundment of the MYR. Moreover, correlation analysis was used to found the major influencing factors between DGT-labile Cd and several parameters. The results showed that the DGT-labile Cd was positively correlated to the reducible and oxidizable fraction, CDGT-Fe, and total organic carbon, illustrating that the release of Cd from soils was controlled by Fe oxides and organic matter. The resupply ability (R values) and DIFS model parameters revealed that Cd in MYR soils belonged to the partially sustained case, and the slow desorption rate suggested that the release risk of Cd was low in the MYR riparian soils.

17.
Ecotoxicol Environ Saf ; 164: 226-233, 2018 Nov 30.
Article in English | MEDLINE | ID: mdl-30118956

ABSTRACT

Source identification of trace metals in the water environment is important in understanding its environmental behavior and in the prevention and remediation of further pollution. Here, the regional geochemical baseline (RGB) and Pb isotopic ratios are combined to decipher the anthropogenic contribution rate, main anthropogenic source, and transport pathway of trace metals in sediments collected from the largest freshwater lake in northern China, Baiyangdian (BYD) Lake. The established RGB values of Cr, Ni, Cu, Zn, Cd, and Pb were 63.0, 27.8, 24.7, 46.1, 0.18, and 22.0 mg/kg, respectively, which were slightly different from the regional soil background values. Based on the RGB and actual concentrations of trace metals in the lake sediments, the calculated average anthropogenic contribution were lower than 20% except for Cd. Compared with the other trace metals, Cd was the element most impacted by anthropogenic input, which was mainly caused by the point source pollution in some sites. The risk assessment (geo-accumulation index and potential ecological risk) using the RGB as the regional background values showed that BYD sediments were uncontaminated by the trace metals, and at low ecological risk from the trace metals. The results of these two risk assessments further validated the assessment of the anthropogenic contribution by the RGB. In addition, Pb isotopic ratios result showed that coal combustion was the main potential source of anthropogenic Pb in the BYD sediments and atmospheric deposition was the main transport pathway. This study tried to combine the geochemical baseline and Pb isotopic composition to identify the anthropogenic input of trace metals in the sediments. It will provide a new insight into assessing the anthropogenic contributions, identifying the main anthropogenic sources, and transport pathways of trace metals in water environment.


Subject(s)
Geologic Sediments/chemistry , Lakes/chemistry , Lead/analysis , Metals, Heavy/analysis , Water Pollutants, Chemical/analysis , China , Environmental Monitoring , Risk Assessment
18.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 30(4): 355-359, 2018 Apr.
Article in Chinese | MEDLINE | ID: mdl-29663999

ABSTRACT

OBJECTIVE: To investigate high risk factors of intensive care unit-acquired weakness (ICUAW) in patients with sepsis. METHODS: A retrospective study was conducted. 164 patients with mechanical ventilation (MV) who were diagnosed sepsis and multiple organ dysfunction syndrome (MODS), admitted to intensive care unit (ICU) of the Second Affiliated Hospital of Kunming Medical University from January 1st, 2015 to September 30th, 2017 were enrolled. The general situation, the basic diseases (hypertension, diabetes), body mass index (BMI), protopathy diseases, the level of albumin before ICU admission, the MV time, whether to use glucocorticoid and continuous renal replacement therapy (CRRT) or not, nutrition supply (nutritional way, nutrition initiation time, amino acid/protein supply, nutritional status on ICU 3 days and 7 days), myoglobin, the length of ICU stay, the length of hospital stay, and acute physiology and chronic health evaluation II (APACHE II) score were collected. The high risk factors of ICUAW in patients with sepsis complicated with MODS were analyzed further using multi-factor Logistic regression analysis. Multiple linear regression analysis was used to analyze the myoglobin related factors in sepsis patients. RESULTS: The ICUAW incidence was 25.6% (42/164). The risk factors with differences in univariate analysis were included in the multivariate Logistic regression analysis, and it was shown that the level of albumin before ICU [odds ratio (OR) = 0.232, 95% confidence interval (95%CI) = 0.061-0.885, P = 0.032], the MV time (OR = 0.380,95%CI = 0.154-0.935, P = 0.035), nutrition initiation time (OR = 2.642, 95%CI = 1.100-6.346, P = 0.030), myoglobin (OR = 4.129, 95%CI = 1.681-10.142, P = 0.002) were the independent risk factors for ICUAW in sepsis patients with MODS. The linear regression showed that the level of myoglobin was positively correlated with APACHE II score (ß= 38.297, P = 0.000), negatively correlated with the length of hospital stay (ß= -7.071, P = 0.048), and it had nothing to do with the MV time and the length of ICU stay. CONCLUSIONS: Evaluation of muscle function should be a routine part of ICU examination. The levels of albumin, MV time, hemoglobin and nutritional start-up time were independent risk factors for ICUAW in sepsis patients with MODS. Myoglobin levels can be used as an indicator of severity.


Subject(s)
Sepsis , APACHE , Hospital Mortality , Humans , Intensive Care Units , Length of Stay , Retrospective Studies , Risk Factors
19.
PLoS Biol ; 16(4): e2004037, 2018 04.
Article in English | MEDLINE | ID: mdl-29684004

ABSTRACT

Decision-making is usually accompanied by metacognition, through which a decision maker monitors uncertainty regarding a decision and may then consequently revise the decision. These metacognitive processes can occur prior to or in the absence of feedback. However, the neural mechanisms of metacognition remain controversial. One theory proposes an independent neural system for metacognition in the prefrontal cortex (PFC); the other, that metacognitive processes coincide and overlap with the systems used for the decision-making process per se. In this study, we devised a novel "decision-redecision" paradigm to investigate the neural metacognitive processes involved in redecision as compared to the initial decision-making process. The participants underwent a perceptual decision-making task and a rule-based decision-making task during functional magnetic resonance imaging (fMRI). We found that the anterior PFC, including the dorsal anterior cingulate cortex (dACC) and lateral frontopolar cortex (lFPC), were more extensively activated after the initial decision. The dACC activity in redecision positively scaled with decision uncertainty and correlated with individual metacognitive uncertainty monitoring abilities-commonly occurring in both tasks-indicating that the dACC was specifically involved in decision uncertainty monitoring. In contrast, the lFPC activity seen in redecision processing was scaled with decision uncertainty reduction and correlated with individual accuracy changes-positively in the rule-based decision-making task and negatively in the perceptual decision-making task. Our results show that the lFPC was specifically involved in metacognitive control of decision adjustment and was subject to different control demands of the tasks. Therefore, our findings support that a separate neural system in the PFC is essentially involved in metacognition and further, that functions of the PFC in metacognition are dissociable.


Subject(s)
Choice Behavior/physiology , Decision Making/physiology , Gyrus Cinguli/physiology , Metacognition/physiology , Nerve Net/physiology , Prefrontal Cortex/physiology , Adult , Brain Mapping , Feedback, Psychological , Female , Gyrus Cinguli/anatomy & histology , Gyrus Cinguli/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Nerve Net/anatomy & histology , Nerve Net/diagnostic imaging , Prefrontal Cortex/anatomy & histology , Prefrontal Cortex/diagnostic imaging , Psychological Tests , Uncertainty
20.
J Neural Eng ; 13(6): 066016, 2016 12.
Article in English | MEDLINE | ID: mdl-27788128

ABSTRACT

OBJECTIVE: When prefrontal-transcranial magnetic stimulation (p-TMS) performed, it may evoke hybrid artifact mixed with muscle activity and blink activity in EEG recordings. Reducing this kind of hybrid artifact challenges the traditional preprocessing methods. We aim to explore method for the p-TMS evoked hybrid artifact removal. APPROACH: We propose a novel method used as independent component analysis (ICA) post processing to reduce the p-TMS evoked hybrid artifact. Ensemble empirical mode decomposition (EEMD) was used to decompose signal into multi-components, then the components were separated with artifact reduced by blind source separation (BSS) method. Three standard BSS methods, ICA, independent vector analysis, and canonical correlation analysis (CCA) were tested. MAIN RESULTS: Synthetic results showed that EEMD-CCA outperformed others as ICA post processing step in hybrid artifacts reduction. Its superiority was clearer when signal to noise ratio (SNR) was lower. In application to real experiment, SNR can be significantly increased and the p-TMS evoked potential could be recovered from hybrid artifact contaminated signal. Our proposed method can effectively reduce the p-TMS evoked hybrid artifacts. SIGNIFICANCE: Our proposed method may facilitate future prefrontal TMS-EEG researches.


Subject(s)
Artifacts , Electroencephalography/methods , Electromyography/methods , Electrooculography/methods , Prefrontal Cortex/physiology , Transcranial Magnetic Stimulation/methods , Algorithms , Computer Simulation , Electroencephalography/statistics & numerical data , Electromyography/statistics & numerical data , Electrooculography/statistics & numerical data , Evoked Potentials/physiology , Female , Humans , Male , Principal Component Analysis , Reproducibility of Results , Signal Processing, Computer-Assisted , Signal-To-Noise Ratio , Young Adult
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