The Nuclear Matrix Protein SAFB Cooperates with Major Satellite RNAs to Stabilize Heterochromatin Architecture Partially through Phase Separation.

Interphase chromatin is hierarchically organized into higher-order architectures that are essential for gene functions, yet the biomolecules that regulate these 3D architectures remain poorly understood. Here, we show that scaffold attachment factor B (SAFB), a nuclear matrix (NM)-associated protein with RNA-binding functions, modulates chromatin condensation and stabilizes heterochromatin foci in mouse cells. SAFB interacts via its R/G-rich region with heterochromatin-associated repeat transcripts such as major satellite RNAs, which promote the phase separation driven by SAFB. Depletion of SAFB leads to changes in 3D genome organization, including an increase in interchromosomal interactions adjacent to pericentromeric heterochromatin and a decrease in genomic compartmentalization, which could result from the decondensation of pericentromeric heterochromatin. Collectively, we reveal the integrated roles of NM-associated proteins and repeat RNAs in the 3D organization of heterochromatin, which may shed light on the molecular mechanisms of nuclear architecture organization.

MATR3-antisense LINE1 RNA meshwork scaffolds higher-order chromatin organization.

Long interspersed nuclear elements (LINEs) play essential roles in shaping chromatin states, while the factors that cooperate with LINEs and their roles in higher-order chromatin organization remain poorly understood. Here, we show that MATR3, a nuclear matrix protein, interplays with antisense LINE1 (AS L1) RNAs to form a meshwork via phase separation, providing a dynamic platform for chromatin spatial organization. MATR3 and AS L1 RNAs affect the nuclear localization of each other. After MATR3 depletion, the chromatin, particularly H3K27me3-modified chromatin, redistributes in the cell nuclei. Topologically associating domains (TADs) that highly transcribe MATR3-associated AS L1 RNAs show decreased intra-TAD interactions in both AML12 and ES cells. MATR3 depletion increases the accessibility of H3K27me3 domains adjacent to MATR3-associated AS L1, without affecting H3K27me3 modifications. Furthermore, amyotrophic lateral sclerosis (ALS)-associated MATR3 mutants alter biophysical features of the MATR3-AS L1 RNA meshwork and cause an abnormal H3K27me3 staining. Collectively, we reveal a role of the meshwork formed by MATR3 and AS L1 RNAs in gathering chromatin in the nucleus.

High-frequency repetitive transcranial magnetic stimulation promotes ipsilesional functional hyperemia and motor recovery in mice with ischemic stroke.

Neurovascular decoupling plays a significant role in dysfunction following an ischemic stroke. This study aimed to explore the effect of low- and high-frequency repetitive transcranial magnetic stimulation on neurovascular remodeling after ischemic stroke. To achieve this goal, we compared functional hyperemia, cerebral blood flow regulatory factors, and neurochemical transmitters in the peri-infract cortex 21 days after a photothrombotic stroke. Our findings revealed that low- and high-frequency repetitive transcranial magnetic stimulation increased the real-time cerebral blood flow in healthy mice and improved neurobehavioral outcomes after stroke. Furthermore, high-frequency (5-Hz) repetitive transcranial magnetic stimulation revealed stronger functional hyperemia recovery and increased the levels of post-synaptic density 95, neuronal nitric oxide synthase, phosphorylated-endothelial nitric oxide synthase, and vascular endothelial growth factor in the peri-infract cortex compared with low-frequency (1-Hz) repetitive transcranial magnetic stimulation. The magnetic resonance spectroscopy data showed that low- and high-frequency repetitive transcranial magnetic stimulation reduced neuronal injury and maintained excitation/inhibition balance. However, 5-Hz repetitive transcranial magnetic stimulation showed more significant regulation of excitatory and inhibitory neurotransmitters after stroke than 1-Hz repetitive transcranial magnetic stimulation. These results indicated that high-frequency repetitive transcranial magnetic stimulation could more effectively promote neurovascular remodeling after stroke, and specific repetitive transcranial magnetic stimulation frequencies might be used to selectively regulate the neurovascular unit.

LUCC-induced dust aerosol change increase surface and reduce atmospheric direct radiative forcing in Northern China.

Land use and land cover change (LUCC) can alter surface properties, such as albedo, roughness, and vegetation coverage, directly affecting dust emissions and aerosol concentrations, leading to variations in direct radiative forcing (DRF) of dust aerosols and consequently impacting the climate. This study utilized the Weather Research and Forecasting model with Chemistry (WRF-Chem) to quantify the impact of LUCC in northern China from 2000 to 2020 on dust aerosol DRF. Results indicated that LUCC's influence on shortwave radiative forcing of dust was significantly greater than its influence on longwave radiative forcing and exhibited obvious seasonal variations. Overall, LUCC can cause net direct radiative forcing to increase by 5.3 W m-2 at the surface and decrease by 7.8 W m-2 in the atmosphere. Different types of LUCC transformation showed distinct impacts on dust aerosol DRF, with the conversion from sparse vegetation to barren land had the most significant effect on net radiative intensity, resulting in a decrease of 8.1 W m-2 at the surface, an increase of 12.2 W m-2 in the atmosphere, and an increase of 4.1 W m-2 at the top of the atmosphere. Conversely, the conversion from barren land to sparse vegetation led to surface cooling and atmospheric warming. These findings are of great significance for enhancing our knowledge of the effects of LUCC on the radiative balance of dust aerosols.

Analysis of driving factors for potential toxic metals in major urban soils of China: a geodetetor-based quantitative study.

Potential toxic metal (PTM) is hazardous to human health, but the mechanism of spatial heterogeneity of PTM at a macro-scale remains unclear. This study conducts a meta-analysis on the data of PTM concentrations in the soil of 164 major cities in China from 2006 to 2021. It utilizes spatial analysis methods and geodetector to investigate the spatial distribution characteristics of PTMs. The geographic information systems (GIS) and geodetector were used to investigate the spatial distribution characteristics of PTMs, assess the influence of natural factors (NFs) and anthropogenic factors (AFs) on the spatial heterogeneity of PTMs in urban soils, and identified the potential pollution areas of PTMs. The results indicated that the pollution levels of PTMs in urban soils varied significantly across China, with higher pollution levels in the south than in the north. Cd and Hg were the most severely contaminated elements. The geodetector analysis showed that temperature and precipitation in NFs and land use type in AFs were considered as the main influencing factors, and that both AF and NF together led to the PTM variation. All these factors showed a mutually enhancing pattern which has important implications for urban soil management. PTM high-risk areas were identified to provide early warning of pollution risk under the condition of climate change.

Biobased Biodegradable Copolyesters from 2,5-Thiophenedicarboxylic Acid: Effect of Aliphatic Diols on Barrier Properties and Degradation.

The demand for sustainable development has led to increasing attention in biobased polyesters due to their adjustable thermal and mechanical properties and biodegradability. In this study, we used a novel bioderived aromatic diacid, 2,5-thiophenedicarboxylic acid (TDCA) to synthesize a list of novel aromatic-aliphatic poly(alkylene adipate-co-thiophenedicarboxylate) (PAATh) copolyesters through a facile melt polycondensation method. PAAThs are random copolyesters with weight-average molecular weights of 58400 to 84200 g·mol-1 and intrinsic viscosities of 0.80 to 1.27 dL·g-1. All PAAThs exhibit sufficiently high thermal stability as well as the highest tensile strength of 6.2 MPa and the best gas barrier performances against CO2 and O2, 4.3- and 3.3-fold better than those of poly(butylene adipate-co-terephthalate) (PBAT). The biodegradability of PAAThs was fully evaluated through a degradation experiment and various experimental parameters, including residue weights, surface morphology, and molecular compositions. The state-of-the-art molecular dynamics (MD) simulations were applied to elucidate the different enzymatic degradation behaviors of PAAThs due to the effect of diols with different chain structures. The sterically hindered carbonyl carbon of the PHATh-enzyme complex was more susceptible to nucleophilic attack and exhibited a higher tendency to enter a prereaction state. This study has introduced a group of novel biobased copolyesters with their structure-property relationships investigated thoroughly, and the effect of diol components on the enzymatic degradation was revealed by computational analysis. These findings may lay the foundation for the development of promising substitutes for commercial biodegradable polyesters and shed light on their complicated degradation mechanisms.

UPLC-MS/MS Method for Simultaneous Determination of Valnemulin and Its Metabolites in Crucian Carp: In Vivo Metabolism and Tissue Distribution Analyses.

Valnemulin (VML) is a semi-synthetic pleuromutilin derivative widely used to treat animal bacterial diseases. However, no study has comprehensively evaluated VML metabolism in aquatic animals, including crucian carp. This study aimed to investigate VML metabolism in crucian carp. VML metabolites in crucian carp were quantified via intraperitoneal injection and analyzed via ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Three VML metabolites were detected in crucian carp via ultra-performance liquid chromatography-tandem quadrupole and time-of-flight mass spectrometry (UPLC-Q-TOF/MS) structural analysis. The enrichment and metabolism rules of the metabolites were summarized based on tissue distribution and concentration changes of the three metabolites. The metabolites were mainly found in the liver at 0.1 h after VML injection. The levels of the metabolites were abundant in the bile from 4 h to 12 h and in the skin after 72 h. The levels of the metabolites in the bile first increased, then decreased. The metabolism in the liver was completed at 72 h. The metabolites were detected in the skin following a 72 h period, which increased with time.

Vegetation drought risk assessment based on the multi-weight methods in Northwest China.

Vegetation makes an outstanding contribution to the stability of ecosystems and to a certain extent reflects the state of the terrestrial ecosystem. Drought conditions greatly affect the growth and development process of vegetation due to its remarkable stochasticity and complexity. Due to the complex coupling mechanism between vegetation and drought, the research on vegetation drought risk is still limited. In this work, we focus on Northwest China and use the improved vegetation health index (VHI) and other multi-source data. We selected indicator factors based on both hazard and vulnerability, and adopt three weight determination methods, namely entropy method, critic method, and coefficient of variation method, to construct the corresponding index model, and also to establish a vegetation drought risk assessment model to quantitatively evaluate the drought risk of vegetation in northwest China. Results show that the percentage of each drought category remarkably changed during the period encompassing 1981-2020, and the vegetation drought shows deterioration in more areas of northwest China. The vegetation drought risks derived from the three weight determination methods were generally consistent, but differed for a particular vegetation type. The overall spatial distribution pattern of vegetation drought risk in Northwest China is higher in the west and lower in the east, and the vegetation in southern Qinghai and northwestern Xinjiang presents higher drought risk. This study may be used as a tool to provide quantitative basis for vegetation protection and vegetation drought management.

Staging Liver Fibrosis: Comparison of Native T1 Mapping, T2 Mapping, and T1ρ: An Experimental Study in Rats With Bile Duct Ligation and Carbon Tetrachloride at 11.7 T MRI.

BACKGROUND: T1, T2, and T1ρ might be potential biomarkers for assessing liver fibrosis. However, few studies reported the value of them in different animal models. PURPOSE: To investigate and compare the performances of T1, T2, and T1ρ for noninvasively staging liver fibrosis in bile duct ligation (BDL) or carbon tetrachloride (CCl4 ) model. STUDY TYPE: Prospective animal model. SUBJECTS: Liver fibrosis was induced by BDL or injection of CCl4 in 120 rats. FIELD STRENGTH/SEQUENCE: 11.7 T, T1 mapping with 10 repetition times, T2 mapping with 32 echo times, and T1ρ with 10 spin-lock times. ASSESSMENT: T1, T2, and T1ρ were measured and correlated with liver fibrosis stages, as well as the degree of inflammation, steatosis, iron deposition, and the expression of cytokeratin 19. The discriminative performance of T1, T2, and T1ρ for staging liver fibrosis was compared. STATISTICAL TESTS: One-way analysis of variance (ANOVA), Spearman's correlation analysis, factorial design ANOVA, and receiver operating characteristic curves (P < 0.05 was considered statistically significant). RESULTS: T1, T2, and T1ρ (BDL: rho = 0.73, 0.85, 0.68; CCl4 : rho = 0.80, 0.29, 0.61) were significantly correlated with liver fibrosis stages, while there was no significant difference in T2 among stage F0-F4 in the CCl4 model (P = 0.204). The area under the curves (AUCs) range of T1, T2, and T1ρ for predicting ≥F1, ≥F2, ≥F3, and F4 were 0.76-0.95, 0.89-0.98, and 0.80-0.94 in the CCl4 model. For the CCl4 model, the AUCs range of T1, T2, and T1ρ for predicting ≥F1, ≥F2, ≥F3, and F4 were 0.83-0.95, 0.61-0.74, and 0.73-0.89, respectively. T2 had significantly higher AUC in the BDL model than CCl4 model for diagnosing liver fibrosis. DATA CONCLUSION: The most sensitive and accurate method for staging liver fibrosis appeared to be T1 in our animal models followed by T1ρ. T2 may not be suitable for evaluating liver fibrosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

The nuclear matrix protein HNRNPU maintains 3D genome architecture globally in mouse hepatocytes.

Eukaryotic chromosomes are folded into higher-order conformations to coordinate genome functions. In addition to long-range chromatin loops, recent chromosome conformation capture (3C)-based studies have indicated higher levels of chromatin structures including compartments and topologically associating domains (TADs), which may serve as units of genome organization and functions. However, the molecular machinery underlying these hierarchically three-dimensional (3D) chromatin architectures remains poorly understood. Via high-throughput assays, including in situ Hi-C, DamID, ChIP-seq, and RNA-seq, we investigated roles of the Heterogeneous Nuclear Ribonucleoprotein U (HNRNPU), a nuclear matrix (NM)-associated protein, in 3D genome organization. Upon the depletion of HNRNPU in mouse hepatocytes, the coverage of lamina-associated domains (LADs) in the genome increases from 53.1% to 68.6%, and a global condensation of chromatin was observed. Furthermore, disruption of HNRNPU leads to compartment switching on 7.5% of the genome, decreases TAD boundary strengths at borders between A (active) and B (inactive) compartments, and reduces chromatin loop intensities. Long-range chromatin interactions between and within compartments or TADs are also significantly remodeled upon HNRNPU depletion. Intriguingly, HNRNPU mainly associates with active chromatin, and 80% of HNRNPU peaks coincide with the binding of CTCF or RAD21. Collectively, we demonstrated that HNRNPU functions as a major factor maintaining 3D chromatin architecture, suggesting important roles of NM-associated proteins in genome organization.

Pronounced Increases in Future Soil Erosion and Sediment Deposition as Influenced by Freeze-Thaw Cycles in the Upper Mississippi River Basin.

Soil erosion and sediment deposition are relevant to multiple important ecosystem services essential for natural and human systems. The present study aims to project future soil erosion and sediment deposition in the Upper Mississippi River Basin (UMRB) using climate projections by five Global Circulation Models (GCMs) under the Representative Concentrations Pathway (RCP) 8.5 scenario. To understand the importance of freeze-thaw cycles (FTCs) for soil erosion and sediment deposition estimation with climate change, this study compared two Soil and Water Assessment Tool (SWAT) models with different representations of the FTCs, with the standard SWAT using a simple regression method and SWAT-FT employing a physically based method. Modeling results show that future climate change can pronouncedly intensify soil erosion and increase sediment deposition, and the impacts are sensitive to how FTCs are represented in the model. The standard SWAT projected an increase in soil erosion by nearly 40% by the end of the 21st century, which is much lower than the projected over 65% increase in soil erosion by SWAT-FT. For sediment deposition, the projected percent changes by the standard SWAT and SWAT-FT also deviate from each other (i.e., about 70% by the standard SWAT vs about 120% by SWAT-FT). Overall, these results demonstrate the important roles of FTCs in projecting future soil erosion and sediment deposition and underline the need to consider the effects of conservation practices on FTCs to realistically assess the effectiveness of those measures.

Determination of local chromatin interactions using a combined CRISPR and peroxidase APEX2 system.

The architecture and function of chromatin are largely regulated by local interacting molecules, such as transcription factors and noncoding RNAs. However, our understanding of these regulatory molecules at a given locus is limited because of technical difficulties. Here, we describe the use of Clustered Regularly Interspaced Short Palindromic Repeats and an engineered ascorbate peroxidase 2 (APEX2) system to investigate local chromatin interactions (CAPLOCUS). We showed that with specific small-guide RNA targets, CAPLOCUS could efficiently identify both repetitive genomic regions and single-copy genomic locus with high resolution. Genome-wide sequencing revealed known and potential long-range chromatin interactions for a specific single-copy locus. CAPLOCUS also identified telomere-associated RNAs. CAPLOCUS, followed by mass spectrometry, identified both known and novel telomere-associated proteins in their native states. Thus, CAPLOCUS may be a useful approach for studying local interacting molecules at any given chromosomal location.

Self-adapting extraction of cropland phenological transitions of rotation agroecosystems using dynamically fused NDVI images.

Remote sensing can be used to monitor cropland phenological characteristics; however, tradeoffs between the spatial and temporal resolutions of cloudless satellite images limit the accuracy of their retrieval. In this study, an improved enhanced spatial and temporal adaptive reflectance fusion model (ESTARFM) was applied to human-dominated Xiong'an New Area to develop a self-adapting algorithm automating the extraction of main phenological transition points (greenup, maturity, senescence, and dormancy). The analyses of cropland phenological characteristics were performed utilizing the Softmax classification method. By examining three different phases of fusion images, it was found that the improved ESTARFM was more accurate than the original ESTARFM (correlation coefficient > 0.76; relative root mean square error < 0.25; structural similarity index > 0.79). The reconstructed normalized difference vegetation indexes were consistent with that acquired by the Moderate Resolution Imaging Spectroradiometer (average discrepancy: 0.1136, median absolute deviation: 0.0110). The greenup, maturity, senescence, and dormancy points were monitored in 5-day resolution and 50-day length on a 30-m grid scale, and their average day of year (DOY) were 67, 119, 127, and 166 for wheat; 173, 224, 232, and 283 for single-season corn; and 189, 227, 232, and 285 for rotation corn, respectively. The corresponding median absolute deviations were 2, 3, 2, and 2 days for wheat; 2, 5, 3, and 4 days for single-season corn; and 2, 5, 2, and 2 days for rotation corn, respectively, while all coefficients of variation did not exceed 6%. The proposed self-adapting approach can be used for identifying the planting modes at grid level in rotation agroecosystems and cropland phenological dynamics on a global or regional scale.

High-field mr diffusion-weighted image denoising using a joint denoising convolutional neural network.

BACKGROUND: Low signal-to-noise ratio (SNR) has been a major limiting factor for the application of higher-resolution diffusion-weighted imaging (DWI). Most of the conventional denoising models suffer from the drawbacks of shallow feature extraction and hand-crafted parameter tuning. Although multiple studies have shown the promising applications of image denoising using convolutional neural networks (CNNs), none of them have considered denoising multiple b-value DWIs using a multichannel CNN model. PURPOSE: To present a joint denoising CNN (JD-CNN) model to improve the SNR of multiple b-value DWI. STUDY TYPE: Retrospective technical development. POPULATION: Twenty healthy rats and two rats with clinically confirmed focal cortical dysplasia were included to evaluate the performance of the proposed method. FIELD STRENGTH/SEQUENCE: 11.7T MRI, a multiple b-values DWI sequence. ASSESSMENT: The total variation (TV) and BM3D denoising methods were also performed on the same dataset for comparison. Peak SNR (PSNR) and normalized mean square error (NMSE) were calculated for the assessment of image qualities. STATISTICAL TESTS: A paired Student's t-test was conducted to compare the diffusion parameter measurements between different approaches. P < 0.01 was considered statistically significant. RESULTS: Simulation results showed substantial improvement of image quality after JD-CNN denoising (PSNR of original image: 23.15 ± 1.77; PSNR of denoised image: 42.94 ± 2.12). The proposed method outperforms the state-of-the-art methods on high b-value DWIs in terms of PSNR (TV: 33.51 ± 0.83, BM3D: 35.12 ± 0.94, JD-CNN: 46.52 ± 0.98). In addition, the NMSE of the estimated apparent diffusion coefficient (ADC) reduces from 0.72 ± 0.13 to 0.45 ± 0.06 (P < 0.01) with the application of the JD-CNN model. DATA CONCLUSION: The proposed method is able to remove noise with a wide range of noise levels in multiple b-value DWI and improve the diffusion parameter estimation. This shows potential clinical promise. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1937-1947.

A comprehensively quantitative method of evaluating the impact of drought on crop yield using daily multi-scale SPEI and crop growth process model.

The quantitative evaluation of the impact of drought on crop yield is one of the most important aspects in agricultural water resource management. To assess the impact of drought on wheat yield, the Environmental Policy Integrated Climate (EPIC) crop growth model and daily Standardized Precipitation Evapotranspiration Index (SPEI), which is based on daily meteorological data, are adopted in the Huang Huai Hai Plain. The winter wheat crop yields are estimated at 28 stations, after calibrating the cultivar coefficients based on the experimental site data, and SPEI data was taken 11 times across the growth season from 1981 to 2010. The relationship between estimated yield and multi-scale SPEI were analyzed. The optimum time scale SPEI to monitor drought during the crop growth period was determined. The reference yield was determined by averaging the yields from numerous non-drought years. From this data, we propose a comprehensive quantitative method which can be used to predict the impact of drought on wheat yields by combining the daily multi-scale SPEI and crop growth process model. This method was tested in the Huang Huai Hai Plain. The results suggested that estimation of calibrated EPIC was a good predictor of crop yield in the Huang Huai Hai Plain, with lower RMSE (15.4 %) between estimated yield and observed yield at six agrometeorological stations. The soil moisture at planting time was affected by the precipitation and evapotranspiration during the previous 90 days (about 3 months) in the Huang Huai Hai Plain. SPEIG90 was adopted as the optimum time scale SPEI to identify the drought and non-drought years, and identified a drought year in 2000. The water deficit in the year 2000 was significant, and the rate of crop yield reduction did not completely correspond with the volume of water deficit. Our proposed comprehensive method which quantitatively evaluates the impact of drought on crop yield is reliable. The results of this study further our understanding why the adoption of counter measures against drought is important and direct farmers to choose drought-resistant crops.

Perceived reputation of others modulates empathic neural responses.

Empathy enables us to understand and share the emotional and affective states of another person and plays a key role in social behaviors. The current study investigated whether and how empathic neural responses to pain were modulated by the perceived reputation of others. Action histories reflecting individuals' past cooperation or betrayal actions in the repeated prisoner's dilemma game were introduced as an index of reputation. We assessed brain activity with functional magnetic resonance imaging while the participants observed individuals with a good or bad reputation receiving or not receiving pain. The results indicated that the participants exhibited reduced empathic responses in AI and dACC to the individual who had a bad reputation relative to the one who had a good reputation, suggesting that their empathy for pain was modulated by the perceived reputation of others.

Small ubiquitin-related modifier 2/3 interacts with p65 and stabilizes it in the cytoplasm in HBV-associated hepatocellular carcinoma.

BACKGROUND: SUMOylation, an important post-translational modification, associates with the development of hepatocellular carcinoma (HCC). p65, one of the most important subunits of NF-κB, is a key regulator in the development of HCC and has been reported to be SUMOylated by exogenous small ubiquitin-related modifier 3 (SUMO3) in HEK 293T cells. However, the relationship between p65 and SUMO2/3 in HCC remains unknown. This study was to investigate the interaction between p65 and SUMO2/3 and explore the potential roles involved in HCC. METHODS: The expressions of p65 and SUMO2/3 in the liver tissues were detected by using immunohistochemistry. We performed double-labeled immunofluorescence and co-immunoprecipitation assay to verify the interaction between p65 and SUMO2/3. The extraction of nuclear and cytoplasmic proteins was performed, and the subcellular localization of p65 was detected. The proliferation and migration of hepatoma cells were observed using MTT, colony formation, and transwell assays. RESULTS: We found a strong SUMO2/3-positive immunoreactivity in the cytoplasm in the non-tumor tissues of HCC. However, SUMO2/3 level was down regulated in the tumor tissues as compared with the adjacent non-tumor tissues. In accordance with this finding, p65 was up regulated in the adjacent non-tumor tissues and almost localized in the cytoplasm. There was a close correlation between SUMO2/3 and p65 expressions in the liver tissues (R = 0.800, p = 0.006). The interaction between p65 and SUMO2/3 was verified by co-immunoprecipitation and double-labeled immunofluorescent assays. TNF-α (10 ng/ml) treatment for 30 min not only up regulated the cytoplasmic conjugated SUMO2/3, but also enhanced SUMO2/3-p65 interaction. Furthermore, we found that SUMO2/3 up regulated the cytoplasmic p65 protein level in a dose-dependent manner, but not affected its mRNA level. The increase of p65 protein by SUMO2/3 was abolished by MG132 treatment, a reversible inhibitor of proteasome. Meanwhile, TNF-α-induced increase of SUMO2/3-conjugated p65 was along with the reduction of the ubiquitin-conjugated p65. The further study showed that SUMO2/3 over-expression decreased the proliferative ability of hepatoma cells, but did not affect the migration. CONCLUSION: SUMO2/3-p65 interaction may be a novel mechanism involved in the transformation from chronic hepatitis B to HCC via stabilizing cytoplasmic p65, which might shed light on understanding the tumorigenesis and development.

The neural basis of implicit learning of task-irrelevant Chinese tonal sequence.

The present study sought to investigate the neural basis of implicit learning of task-irrelevant perceptual sequence. A novel SRT task, the serial syllable identification task (SSI task), was used in which the participants were asked to recognize which one of two Chinese syllables was presented. The tones of the syllables were irrelevant to the task but followed an underlying structured sequence. Participants were scanned while they performed the SSI task. Results showed that, at the behavioral level, faster RTs for the sequential material indicated that task-irrelevant sequence knowledge could be learned. In the subsequent prediction test of knowledge of the tonal cues using subjective measures, we found that the knowledge was obtained unconsciously. At the neural level, the left caudate, bilateral hippocampus and bilateral superior parietal lobule were engaged during the sequence condition relative to the random condition. Further analyses revealed that greater learning-related activation (relative to random) in the right caudate nucleus, bilateral hippocampus and left superior parietal lobule were found during the second half of the training phase compared with the first half. When people reported that they were guessing, the magnitude of the right hippocampus and left superior parietal lobule activations was positively related to the accuracy of prediction test, which was significantly better than chance. Together, the present results indicated that the caudate, hippocampus and superior parietal lobule played critical roles in the implicit perceptual sequence learning even when the perceptual features were task irrelevant.