Dynamic trans-acting factor colocalization in human cells.

Different trans-acting factors (TFs) collaborate and act in concert at distinct loci to perform accurate regulation of their target genes. To date, the cobinding of TF pairs has been investigated in a limited context both in terms of the number of factors within a cell type and across cell types and the extent of combinatorial colocalizations. Here, we use an approach to analyze TF colocalization within a cell type and across multiple cell lines at an unprecedented level. We extend this approach with large-scale mass spectrometry analysis of immunoprecipitations of 50 TFs. Our combined approach reveals large numbers of interesting TF-TF associations. We observe extensive change in TF colocalizations both within a cell type exposed to different conditions and across multiple cell types. We show distinct functional annotations and properties of different TF cobinding patterns and provide insights into the complex regulatory landscape of the cell.

Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation.

Sphingosine 1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. The sphingosine phosphate receptor 1 (S1P1) agonist FTY-720 (Gilenya) arrests immune trafficking and prevents multiple sclerosis (MS) relapses. However, alternative mechanisms of S1P-S1P1 signaling have been reported. Phosphoproteomic analysis of MS brain lesions revealed S1P1 phosphorylation on S351, a residue crucial for receptor internalization. Mutant mice harboring an S1pr1 gene encoding phosphorylation-deficient receptors (S1P1(S5A)) developed severe experimental autoimmune encephalomyelitis (EAE) due to autoimmunity mediated by interleukin 17 (IL-17)-producing helper T cells (TH17 cells) in the peripheral immune and nervous system. S1P1 directly activated the Jak-STAT3 signal-transduction pathway via IL-6. Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These mechanisms may be pathogenic in MS.

PPP1r18 promotes tumor progression in esophageal squamous cell carcinoma by regulating the calcineurin-mediated ERK pathway.

Esophageal cancer is one of the most common malignant tumors, and the 5-year overall survival rate is only 20%. Esophageal squamous cell carcinoma (ESCC) is the primary histological type of esophageal carcinoma in China. Protein phosphatase 1 regulatory subunit 18 (PPP1r18) is one of the actin-regulatory proteins and is able to bind to protein phosphatase 1 catalytic subunit alpha (PPP1CA). Yet, little is known about the role of PPP1r18 in ESCC. This study aimed to elucidate the biological functions of PPP1r18 in the ESCC progression. Clinical samples first confirmed that PPP1r18 expression was upregulated in ESCC, and PPP1r18 was correlated with tumor invasion depth, lymph node metastasis, distant metastasis and reduced overall survival. We then observed that PPP1r18 overexpression enhanced cell proliferation in vitro and in vivo. Mechanistically, PPP1r18 regulated tumor progression of ESCC through activating the calcineurin-mediated ERK pathway, rather than binding to PPP1CA. Collectively, our results suggest that PPP1r18 promotes ESCC progression by regulating the calcineurin-mediated ERK pathway. PPP1r18 might be a potential target for the diagnosis and treatment of ESCC.

Expression of SOX4 Significantly Predicts the Risk of Lymph Node Metastasis for Patients With Early-Stage Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma stands as a notably aggressive malignancy within the digestive system. In cases of early esophageal cancer without lymph node metastasis, endoscopic surgical resection offers a viable alternative, often resulting in improved patient quality of life. However, the paucity of methods to preoperatively ascertain lymph node involvement complicates surgical planning. SOX4 gene was previously found to be highly associated with invasive metastasis in our work through single-cell RNA sequencing on 5 paired tumor/peritumor tissues. This research included the collection of 124 tissue samples from 106 patients (106 tumor and 18 lymph node specimens). Samples were methodically arranged into a tissue microarray and treated with immunohistochemical staining. Statistical analysis was conducted to assess the relationship between them. In the univariate analysis, 3 factors were identified as statistically significant in relation to lymph node metastasis: T category (P = .014), vascular invasion (P < .001), and SOX4 intensity (P = .001). Additionally, when evaluating SOX4 intensity alongside other clinical indicators, SOX4 was shown to independently influence lymph node metastasis. Further, the multivariate analysis revealed that vascular invasion (P < .001) and SOX4 intensity (P = .003) were significantly associated with lymph node metastasis, exhibiting hazard ratios of 10.174 and 7.142, respectively. The results of our study indicate that both SOX4 expression and vascular invasion serve as predictors of lymph node metastasis in patients diagnosed with category T1 esophageal squamous cell carcinoma, underscoring the potential utility of SOX4 in prognostic evaluations.

Bone density and fracture risk factors in ankylosing spondylitis: a meta-analysis.

We included 39 studies in our meta-analysis, finding that patients with ankylosing spondylitis (AS) exhibit decreased bone mineral density (BMD) and an elevated risk of fractures. Additionally, we analyzed the risk factors associated with fractures in these patients. INTRODUCTION: AS is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints, with reduced BMD, osteoporosis, and fractures being common complications. This study aims to systematically consolidate and conduct a meta-analysis of existing research to comprehensively understand decreased bone mineral density, osteoporosis, and fracture risks at various anatomical sites in AS patients. The objective is to provide reliable information for the management of AS patients and to inform clinical decision making. METHODS: We conducted a thorough search in various databases including Embase, PubMed, Cochrane Library, and Web of Science. These studies focused on the risk of and risk factors for decreased BMD, osteopenia, osteoporosis, and fractures at different sites among AS patients such as the lumbar spine and femoral neck. The quality of eligible studies was evaluated. Sensitivity analysis was performed to assess the reliability of our analysis results and understand the effects of individual studies on the heterogeneity across studies. RESULTS: A total of 39 studies were included. Our meta-analysis results revealed significant differences between AS patients and healthy controls. AS patients had significantly lower BMDs at the femoral neck, hip, lumbar vertebra 2 (L2), lumbar vertebra 3 (L3), and lumbar vertebra 4 (L4), but higher BMDs at 1/3 distal radius and ultra distal radius. Risk factors for fractures among AS patients included old age, long course of disease, and low BMD at the lumbar spine. In contrast, factors such as erythrocyte sedimentation rate (ESR), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, gender, and body mass index (BMI) were not risk factors for fractures in AS patients. CONCLUSION: Our study highlights that BMD at the femoral neck is more effective for evaluating AS patients compared with the BMD at the lumbar spine. Additionally, the risk of osteoporosis and fractures in AS patients is higher in younger patients and those at the early stage of this disease.

Fbxo45 facilitates the malignant progression of breast cancer by targeting Bim for ubiquitination and degradation.

BACKGROUND: Breast cancer is one of the common malignancies in women. Evidence has demonstrated that FBXO45 plays a pivotal role in oncogenesis and progression. However, the role of FBXO45 in breast tumorigenesis remains elusive. Exploration of the regulatory mechanisms of FBXO45 in breast cancer development is pivotal for potential therapeutic interventions in patients with breast cancer. METHODS: Hence, we used numerous approaches to explore the functions of FBXO45 and its underlaying mechanisms in breast cancer pathogenesis, including CCK-8 assay, EdU assay, colony formation analysis, apoptosis assay, RT-PCR, Western blotting, immunoprecipitation, ubiquitination assay, and cycloheximide chase assay. RESULTS: We found that downregulation of FBXO45 inhibited cell proliferation, while upregulation of FBXO45 elevated cell proliferation in breast cancer. Silencing of FBXO45 induced cell apoptosis, whereas overexpression of FBXO45 inhibited cell apoptosis in breast cancer. Moreover, FBXO45 interacted with BIM and regulated its ubiquitination and degradation. Furthermore, knockdown of FBXO45 inhibited cell proliferation via regulation of BIM pathway. Notably, overexpression of FBXO45 facilitated tumor growth in mice. Strikingly, FBXO45 expression was associated with poor survival of breast cancer patients. CONCLUSION: Our study could provide the rational for targeting FBXO45 to obtain benefit for breast cancer patients. Altogether, modulating FBXO45/Bim axis could be a promising strategy for breast cancer therapy.

Liquid Chromatography-Mass Spectrometry Analysis of Frataxin Proteoforms in Whole Blood as Biomarkers of the Genetic Disease Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is caused primarily by expanded GAA repeats in intron 1 of both alleles of the FXN gene, which causes transcriptional silencing and reduced expression of frataxin mRNA and protein. FRDA is characterized by slowly progressive ataxia and cardiomyopathy. Symptoms generally appear during adolescence, and patients slowly progress to wheelchair dependency usually in the late teens or early twenties with death on average in the 4th decade. There are two known mature proteoforms of frataxin. Mitochondrial frataxin (frataxin-M) is a 130-amino acid protein with a molecular weight of 14,268 Da, and there is an alternatively spliced N-terminally acetylated 135-amino acid form (frataxin-E) with a molecular weight of 14,953 Da found in erythrocytes. There is reduced expression of frataxin in the heart and brain, but frataxin is not secreted into the systemic circulation, so it cannot be analyzed in serum or plasma. Blood is a readily accessible biofluid that contains numerous different cell types that express frataxin. We have found that pig blood can serve as an excellent surrogate matrix to validate an assay for frataxin proteoforms because pig frataxin is lost during the immunoprecipitation step used to isolate human frataxin. Frataxin-M is expressed in blood cells that contain mitochondria, whereas extra-mitochondrial frataxin-E is found in erythrocytes. This means that the analysis of frataxin in whole blood provides information on the concentration of both proteoforms without having to isolate the individual cell types. In the current study, we observed that the distributions of frataxin levels for a sample of 25 healthy controls and 50 FRDA patients were completely separated from each other, suggesting 100% specificity and 100% sensitivity for distinguishing healthy controls from FRDA cases, a very unusual finding for a biomarker assay. Additionally, frataxin levels were significantly correlated with the GAA repeat length and age of onset with higher correlations for extra-mitochondrial frataxin-E than those for mitochondrial frataxin-M. These findings auger well for using frataxin levels measured by the validated stable isotope dilution ultrahigh-performance liquid chromatography-multiple reaction monitoring/mass spectrometry assay to monitor therapeutic interventions and the natural history of FRDA. Our study also illustrates the utility of using whole blood for protein disease biomarker discovery and validation.

Comparison of safety and short-term outcomes between endoscopic and laparoscopic resections of gastric gastrointestinal stromal tumors with a diameter of 2-5 cm.

BACKGROUND AND AIM: Developments of endoscopic techniques brought the possibility of endoscopic resection for gastrointestinal stromal tumors (GISTs) of larger sizes. We aim to compare safety and short-term outcomes between endoscopic and laparoscopic resections of gastric GISTs with a diameter of 2-5 cm. METHODS: This is a single-center, retrospective cohort study. The clinical data, perioperative conditions, and the adverse events of patients who underwent endoscopic or laparoscopic resection for gastric GIST of 2-5 cm in Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were retrospectively reviewed. RESULTS: A total of 346 patients were reviewed; 12 patients who failed to accomplish the planned procedure were excluded; 182 underwent laparoscopic resection; and 152 underwent endoscopic resection. Significant differences exist in the tumor size between the laparoscopic group (3.43 ± 0.86 cm) and the endoscopic group (2.78 ± 0.73 cm) (P < 0.01). Compared with laparoscopic resection, endoscopic resection was associated with faster recovery (P < 0.01), shorter hospital stays (P < 0.01), and lower cost (P < 0.01). The incidence of Clavien-Dindo grade II-V adverse events in the endoscopic group (3/152) was significantly lower than that in the laparoscopic group (12/182) (P = 0.04). After a propensity score matching analysis, the endoscopic group showed similar incidences of complications with the laparoscopic group, while the advantages over laparoscopic resection in postoperative hospital stay, time to first oral intake, and hospitalization expenses remained significant (P < 0.01). CONCLUSIONS: Endoscopic resection is a safe and cost-effective method for 2-5 cm of gastric GISTs compared with laparoscopic resection.

Examining the Effects of Gender Transfer in Virtual Reality on Implicit Gender Bias.

OBJECTIVE: To investigate the effect of gender transfer in virtual reality on implicit gender bias. BACKGROUND: Gender bias is a type of discrimination based on gender, which can lead to increased self-doubt and decreased self-esteem. Sexual harassment is a hostile form of gender bias that can cause anxiety, depression, and significant mental health issues. Virtual reality (VR) has been employed to help make people become aware of their biases and change their attitudes regarding gender, race, and age. METHODS: Forty participants were embodied in avatars of different genders and experienced sexual harassment scenarios in VR. A gender Implicit Association Test (IAT) was administered before and after the experience. RESULTS: There was a statistically significant main effect of participant gender (F (1,36) = 10.67, p = .002, partial η2 = .23) on ΔIAT, where males and females reported a decrease (M = -.12, SD = .24) and an increase (M = .10, SD = .25) in IAT scores, respectively. A statistically significant two-way interaction between gender transfer and participant gender was revealed (F (1,36) = 6.32, p = .02, partial η2 = .15). There was a significant simple effect of gender transfer for male participants (F (1,36) = 8.70, p = .006, partial η2 = .19). CONCLUSIONS: Implicit gender bias can be modified, at least temporarily, through embodiment in VR. Gender transfer through embodiment while encountering different sexual harassment scenarios helped reduce implicit gender bias. There was a tendency for individuals to increase bias for the gender of the avatar in which they embodied. APPLICATIONS: The current research provided promising evidence that a virtual environment system may be used as a potential training tool to improve implicit gender bias.

Effects of NanoAg-ACP Microparticles as Bioactive Fillers on the Mechanical and Remineralization Properties of Dental Resin Cement.

PURPOSE: To investigate the potential of adding silver-nanoparticle-containing amorphous calcium phosphate microparticles as bioactive fillers into commercially available nonbioactive dental resin cement. MATERIALS AND METHODS: Experimental cement was formulated by adding 7.5% silver-nanoparticle-containing amorphous calcium phosphate microparticles to Multilink Automix resin cement (Ivoclar Vivadent). The experimental cement was evaluated for shear bond strength (N = 11 per group) and demineralization/remineralization (N = 16 per group), with BioCem® Universal BioActive cement (NuSmile) as the positive control and Multilink Automix cement as the negative control. One-way analysis of variance and post hoc tests were used to assess the significance of differences among or between the groups RESULTS: The addition of silver-nanoparticle-containing amorphous calcium phosphate microparticles at the level of 7.5% by weight into Multilink Automix did not have a statistically significant effect on the shear bond strength (p > 0.05), but statistically significantly increased the depth of remineralization on both dentin and enamel (p = 0.01 and p < 0.001, respectively) when compared to Multilink Automix alone. The experimental cement prepared in the present study was comparable to BioCem® on the depths of remineralization on both dentin and enamel (p = 0.59 and p = 0.99, respectively). CONCLUSION: When incorporated into nonbioactive commercial dental resin cements as bioactive fillers at the level of 7.5% by weight, silver-nanoparticle-containing amorphous calcium phosphate microparticles could provide remineralization potential without affecting the shear bond strength.

Widely tunable surface plasmon resonance and uniquely superior SERS performance of Au nanotube network films.

Three-dimensional Au network films with flexibility and transferability were fabricated based on sputtering deposition onto electrospun nanofibers as a template. The films are constructed using long Au nanotubes that are cross-linked with each other and that have dense nanoparticles on the tube wall surface. The surface plasmon resonance (SPR) peaks for the films are tunable in a wide range, from visible light to the near-infrared region, by tuning the inner diameter and/or wall thickness of the nanotubes. Such structured film exhibits significant surface-enhanced Raman scattering (SERS) activity with good signal uniformity and stability, and possesses great potential in thein situdetection of trace organic pollutants on a solid surface by simple transferring. This study provides a Au film with a unique structure and widely tunable SPR forin situSERS sensing and other needs.

Antidepressant-like effect of Ganoderma lucidum spore polysaccharide-peptide mediated by upregulation of prefrontal cortex brain-derived neurotrophic factor.

A 28-kDa polysaccharide-peptide (PGL) with antidepressant-like activities was isolated from spores of the mushroom Ganoderma lucidum. It was unadsorbed on DEAE-cellulose. Its internal amino acid sequences manifested pronounced similarity with proteins from the mushrooms Lentinula edodes and Agaricus bisporus. The monosaccharides present in 28-kDa PGL comprised predominantly of glucose (over 90%) and much fewer galactose, mannose residues, and other residues. PGL manifested antidepressant-like activities as follows. It enhanced viability and DNA content in corticosterone-injured PC12 cells(a cell line derived from a pheochromocytoma of the rat adrenal medulla with an embryonic origin from the neural crest containing a mixture of neuroblastic cells and eosinophilic cells) and reduced LDH release. A single acute PGL treatment shortened the duration of immobility of mice in both tail suspension and forced swimming tests. PGL treatment enhanced sucrose preference and shortened the duration of immobility in mice exposed to chronic unpredictable mild stress (CUMS). Chronic PGL treatment reversed the decline in mouse brain serotonin and norepinephrine levels but did not affect dopamine levels. PGL decreased serum corticosterone levels and increased BDNF mRNA and protein levels and increased synapsin I and PSD95 levels in the prefrontal cortex. This effect was completely blocked by pretreatment with the BDNF antagonist K252a, indicating that PGL increased synaptic proteins in a BDNF-dependent manner.Key points• An antidepressive polysaccharide-peptide PGL was isolated from G. lucidum spores.• PGL protected PC12 nerve cells from the toxicity of corticosterone.• PGL upregulated BDNF expression and influenced key factors in the prefrontal cortex.

HTLV screening of blood donors using chemiluminescence immunoassay in three major provincial blood centers of China.

BACKGROUND: Human T-cell lymphotropic virus (HTLV) remains a major safety concern for blood supplies. Despite many HTLV positive cases being reported in southeastern China, the detection of HTLV has not been prioritized in routine blood screening. Additionally, data on the prevalence of HTLV infection among blood donors is also limited. The objective of this study was to investigate the prevalence of HTLV among blood donors in three Chinese provinces through their representative blood centers, to evaluate the feasibility of chemiluminescence immunoassay (CLIA) for blood screening. METHODS: From November 2018 to March 2019, blood plasma samples were collected from Hebei, Changsha, and Shenzhen blood centers and were screened for the HTLV-1/2 antibody using a CLIA and enzyme-linked immunosorbent assay (ELISA). This was followed by confirmatory tests using INNO-LIA HTLV I/II. RESULTS: A total of 59,929 blood donations were collected and screened for HTLV-1/2. The reactive rate of CLIA and ELISA among donations in the Shenzhen blood center (0.0943%, 27/28,621) was higher than Hebei (0.0248%, 4/16,144), and Changsha (0.0198%, 3/15,164) (p < 0.05). After confirmation, 3 samples were confirmed as indeterminate for HTLV antibodies, and only one sample from the Shenzhen blood center was confirmed as HTLV-1. The overall prevalence of HTLV-1/2 was 1.67 per 100,000 (1/59,929). The HTLV-infected blood came from a 32-year-old first-time female donor with a high school degree, who belonged to the SHE ethnic minority and was born in the Fujian province. CONCLUSIONS: In summary, the overall prevalence of HTLV-1/2 among blood donors in the three blood centers in China remains relatively low. However, blood donations with positive or indeterminate results for HTLV antibodies reminded us of the importance of HTLV screening among blood donors in China.

Revealing the detailed structure in flow-induced crystallization of semicrystalline polymers.

We systematically investigate the detailed structure in the flow-induced crystallization of a lightly cross-linked high-density polyethylene as a model semicrystalline polymer sample by combining the small-angle X-ray scattering (SAXS) and the spherical harmonic expansion (SHE) method. The SHE divides the two-dimensional SAXS pattern into several components according to the deformation geometry, and allows extraction of the most relevant information. Employing the first two anisotropic components in the expansion and a comprehensive model, we determine the crystalline morphological parameters, such as the long period, the lamellar diameter and thickness, and their polydispersities. In particular, we find that the lamellar diameter exhibits bimodal distributions at high strains. Lamellae with similar diameters tend to gather rather than to randomly distribute with others, suggesting the existence of heterogeneity in the semicrystalline structure. Moreover, we observe the strong polydispersities of the lamellar structure at low strains. The structural heterogeneity and polydispersities could be related to the inhomogeneities in crystal growth and nucleation processes.

Thromboelastography Detects Possible Coagulation Disturbance in Pediatric Patients with Portal Cavernoma.

BACKGROUND: Thromboelastography (TEG) allows a dynamic assessment of clot formation and dissolution that might be useful for assessing the relative contribution of the coagulation components to overall clot formation and dissolution, but it has not been fully defined in patients with portal cavernoma (PC). METHODS: We retrospectively recruited consecutive patients with PC between July 2006 and June 2016 who had no abdominal malignancy or liver cirrhosis. Blood samples were drawn on admission and were subjected to coagulation parameter assessment, including conventional coagulation tests, measurement of the circulating levels of procoagulant and anticoagulant factors, and TEG assessment. RESULTS: Compared with controls, patients with PC showed significant reductions in the serum levels of procoagulant factors and anticoagulants factors, whereas factor VIII was slightly elevated. TEG showed clot formation (α-angle), and the maximal clot strength (MA) was higher in patients with PC than in controls, indicating a hypercoagulable state. Thrombocytopenia decreased both clot formation (α-angle) and the maximal clot strength (MA) but was still significantly higher than the control. Furthermore, patients with PC had a higher level of D-dimer and LY30 than did controls, indicating the in vivo activation of coagulation and fibrinolysis. CONCLUSION: TEG analysis showed that patients with PC were in a hypercoagulable state that could be partially masked by thrombocytopenia secondary to splenomegaly and hypersplenism in these patients, which indicates that our current prophylaxis and therapy regimen could be improved.

Factors for predicting reversion from mild cognitive impairment to normal cognition: A meta-analysis.

OBJECTIVE: Subjects with mild cognitive impairment (MCI) may revert to normal cognition (NC), but predictive factors are under study. We therefore sought to identify factors which could help in predicting reversion from MCI to NC. METHODS: Relevant studies were retrieved from PubMed, EMBASE, Cochrane Library, MEDLINE, Web of Science, EBSCO, and OVID. According to the inclusion and exclusion criteria, high-quality assessments of relevant literatures were conducted, followed by data extraction and meta-analysis with Stata 12.0 software. RESULTS: A total of 17 studies with 6829 participants were included in the meta-analysis. The overall reversion rate is 27.57%. Positive predictive factors were found in younger age (SMD = -0.345, 95% CI, -0.501 to -0.189), higher education level (SMD = 0.337, 95% CI, 0.117-0.558), no APOE ε4 allele (OR = 0.728, 95% CI, 0.575-0.922), no hypertension (OR = 0.826, 95% CI, 0.692-0.987), no stroke (OR = 0.696, 95% CI, 0.507-0.953), and higher Mini-Mental State Examination (MMSE) score (SMD = 0.707, 95% CI, 0.461-0.953). CONCLUSION: Individuals who are at young age, have higher education level and MMSE score, and have no APOEe4 allele, no hypertension, and no stroke had a high probability to revert from MCI to NC.

Variation and genetic control of protein abundance in humans.

Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations, our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest. Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project. We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.

Application of the cerebral edema monitor on cardiopulmonary bypass in infants.

A diagnostic accuracy study was adopted to evaluate the ability of Cerebral edema monitor by comparing the index test results with those of the reference standard. The serum levels of astrocyte S100 protein and neuron-specific enolase (NSE) were determined. Changes in the cerebral electrical impedance coefficient (CEIC) was detected with the BORN-BE monitor. The left- and right-sided CEIC values, serum levels of S100, and serum NSE in the CPB group significantly increased from the beginning to the end of the operation (P < .05). Furthermore, left and right-sided CEIC values, serum levels of S100, and serum NSE in the CPB-B group were significantly higher than those of the CPB-A group (P < .05). Detection rates of cerebral edema in the CPB-B group at the 24 h post-operative time point were significantly higher than those in the CPB-A group (P < .05). The degree of brain damage is positively correlated with the CPB and aortic cross-clamping. CEIC is a sensitive index reflecting brain damage during CPB in infants.

Antibacterial properties of silver-loaded gelatin sponges prepared with silver diamine fluoride.

PURPOSE: To evaluate the antibacterial efficiency of silver-loaded gelatin sponges prepared from gelatin and silver diamine fluoride, Ag(NH3)2F. METHODS: A series of novel silver-loaded gelatin sponges were prepared from gelatin and silver diamine fluoride. They were characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electronic microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX). The antibacterial activities against one oral bacteria model S. mutans were evaluated using the agar disk diffusion method and biofilm-grown bacteria assay. For the purpose of comparison, a second series of silver-loaded sponges were prepared using silver nitrate (AgNO3) as the silver source. RESULTS: FT-IR, SEM and EDX results confirmed the successful preparation of silver-loaded gelatin sponges from both silver diamine fluoride and silver nitrate. Agar disk diffusion assays revealed that the antibacterial activity of silver-loaded sponges was strongly correlated with the silver content, and also depending on the silver source used in the preparation of sponges. Sustained inhibition of S. mutans in agar plates was observed for silver-loaded gelatin sponges containing about 5 wt% Ag or more. Biofilm assays showed different viabilities when treated with different formulations, with the viability of 11.4±3.1% for the sponges containing 5.30±1.18 wt% Ag prepared from silver diamine fluoride, and the viability of 15.4±3.1% for the sponges containing 29.13±10.34 wt% Ag prepared from silver nitrate. CLINICAL SIGNIFICANCE: The silver loading contents had a significant effect on the antibacterial activities of silver-loaded gelatin sponges prepared with silver diamine fluoride. In addition, silver diamine fluoride was a superior silver source to prepare antibacterial silver-loaded gelatin sponges when compared with silver nitrate.

Architecture of the human regulatory network derived from ENCODE data.

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.