Establishment of a transgene-free iPS cell line (SDCHi007-A) from a young patient bearing a ATP1A2 mutation and suffering from Epilepsy.

Epilepsy is a chronic neurological disease. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient diagnosed as epilepsy caused by ATP1A2 gene mutation. Induced pluripotent stem cells (iPSCs) were developed using non-integrating episomal vectors containing OCT4, SOX2, KLF4, BCL-XL and C-MYC. The established iPSC line (SDCHi007-A) displayed pluripotent cell morphology, high expression levels of pluripotency markers, differentiation potential in vitro, normal karyotype, and remaining the original ATP1A2 gene mutation.

A nomogram for risk stratification of central cervical lymph node metastasis in patients with papillary thyroid carcinoma.

Background: Whether to perform prophylactic central lymph node dissection for cN0 papillary thyroid carcinoma (PTC) patients is still controversial. This retrospective study aimed to develop and validate a nomogram based on ultrasound and dual-energy computed tomography (DECT) for the risk stratification of central lymph node metastasis (CLNM) in patients with PTC. Methods: A total of 525 patients from 2017 to 2019 [Tianjin First Central Hospital (Hospital A)] were retrospectively analyzed to form the training cohort and to conduct internal validation. Another group of 204 patients in 2020 (Hospital A) formed the temporal validation cohort. A total of 107 patients in 2020 [Binzhou Medical University Hospital (Hospital B)] formed the geographic validation cohort, which was a retrospective cohort study. The area under the curve (AUC), calibration curve, and decision curve were used to evaluate the performance of the nomogram. The locally weighted regression curve was used for risk stratification. Results: Diameter, taller-than-wide, calcification, capsular invasion, and iodine concentration in the arterial and venous phases were independent risk predictors of CLNM. The AUC of the nomogram was 0.922 (95% confidence interval: 0.895-0.943) in the training cohort. Two external validation cohorts demonstrated the good performance of the nomogram in predicting CLNM, with AUCs of 0.912 and 0.861. The significantly improved net reclassification index and integrated discriminatory improvement index indicated that DECT was a powerful supplement to ultrasound for predicting CLNM. The risk stratification system divided all patients into low-risk (0-50 points), intermediate-risk (51-100 points), and high-risk groups (>100 points). Conclusions: The nomogram and risk stratification system estimated the utility of CLNM to guide individualized treatment of patients with PTC.

Dislocation loop and irradiation-induced synergistic-competitive mechanism in Cu-rich precipitates: a phase-field study.

Both irradiation and dislocations have been proposed as routes to rationally manipulate spatial distribution and micromorphology of precipitate. An interesting effect emerges in Fe-10at.%Cu-3at.%Mn-1.5at.%Ni-1.5at.%Al alloy due to the synergistic-competitive roles of dislocation loop and irradiation. Base on cascade mixing, vacancy-interstitial atoms and dislocation stress field model, we examine nucleation and growth dynamics of Cu-rich precipitates, where both dislocation loop and irradiation act in conjunction. Analytical treatments identify regimes, where the distribution of elements and point defects due to irradiation and dislocations are specific to the Cu-rich precipitates. Simulation results reveal that density, size and distribution of Cu-rich precipitates are a manifestation of the competing effects of the dislocation loop and the irradiation rate. More specifically, the dislocation loop preferentially assists the formation of precipitates and new dislocations at lower irradiation rates. Only the irradiation induces the formation of Cu-rich precipitates with the irradiation rate continues to increase. Equipped with molecular dynamics, where reproduces major interaction features of the solutes with point defects under displacement cascade, can verify multi-component morphologies of Cu-rich precipitates. This modeling framework provides an avenue to explore the role of dislocation loop and irradiation on the microstructural evolution of Cu-rich precipitates.

PADI4 negatively regulates RIG-I-mediated antiviral response through deacetylation of IFN-ß promoter via HDAC1.

The production of type I interferon (IFN) is precisely modulated by host to protect against viral infection efficiently without obvious immune disorders. Elucidating the tight control towards type I IFN production would be helpful to get insight into natural immunity and inflammatory diseases. As yet, however, the mechanisms that regulate IFN-ß production, especially the epigenetic regulatory mechanisms, remain poorly explored. This study elucidated the potential function of Peptidylarginine deiminases (PADIs)-mediated citrullination in innate immunity. We identified PADI4, a PADIs family member that can act as an epigenetic coactivator, could repress IFN-ß production upon RNA virus infection. Detailed experiments showed that PADI4 deficiency increased IFN-ß production and promoted antiviral immune activities against RNA viruses. Mechanistically, the increased PADI4 following viral infection translocated to nucleus and recruited HDAC1 upon binding to Ifnb1 promoter, which then led to the deacetylation of histone H3 and histone H4 for repressing Ifnb1 transcription. Taken together, we identify a novel non-classical role for PADI4 in the regulation of IFN-ß production, suggesting its potential as treatment target in inflammatory or autoimmune diseases.

Epstein-Barr virus immediate-early protein Zta mediates the proliferation and migration of HER2-overexpressing cancer cells.

Epstein-Barr virus immediate-early protein Zta plays an active role in altering cellular gene expression, which may be fundamentally linked to the viral life cycle, cell cycle, cell growth, and differentiation. HER2 is associated with a wide variety of human cancers, and its knockdown significantly reverses the malignant features of HER2-positive cancers. The aim of this study was to investigate the potential role of Zta in regulating HER2 expression and phenotype changes of MDA-MB-453 cells. Our results indicate that ectopic expression of Zta resulted in downregulation of the HER2 protein in cancer cells (MDA-MB-453, SKBR-3, BT474, and SKOV-3). The Zta protein significantly decreased HER2 mRNA and protein expression in MDA-MB-453 cells in a dose-dependent manner. Mechanistically, Zta recognized and targeted the promoter of HER2 gene, reducing the transcriptional activity of the HER2 gene. Zta induced G0/G1 arrest of MDA-MB-453 cells, inhibiting their proliferation and migration activity. These data suggest that Zta may act as a transforming suppressor of the HER2 gene.

Synthesis and nitroxyl (HNO) donating properties of benzoxadiazole-based Piloty's acids.

Developing functional nitroxyl (HNO) donors play a significant role in the further exploration of endogenous HNO in biochemistry and pharmacology. In this work, two novel Piloty's acids (SBD-D1 and SBD-D2) were proposed by incorporating benzoxadiazole-based fluorophores, in order to achieve the dual-function of releasing both HNO and a fluorophore in situ. Under physiological conditions, both SBD-D1 and SBD-D2 efficiently donated HNO (t1/2 = 10.96 and 8.18 min, respectively). The stoichiometric generation of HNO was determined by both Vitamin B12 and phosphine compound trap. Interestingly, due to the different substitution groups on the aromatic ring, SBD-D1 with the chlorine showed no fluorescence emission, but SBD-D2 was strongly fluorescent due to the presence of the dimethylamine group. Specifically, the fluorescent signal would decrease during the release process of HNO. Moreover, theoretical calculations were performed to understand the emission difference. A strong radiation derived from benzoxadiazole with dimethylamine group due to the large transition dipole moment (∼4.3 Debye), while the presence of intramolecular charge transfer process in the donor with chlorine group caused a small transition dipole moment (<0.1 Debye). Finally, these studies would contribute to the future design and application of novel functional HNO donors for the exploration of HNO biochemistry and pharmacology.

Efficacy and safety of early chest tube removal after selective pulmonary resection with high-output drainage: A systematic review and meta-analysis.

BACKGROUND: There is controversy over the drainage threshold for removal of chest tubes in the absence of significant air leakage after selective pulmonary resection. METHODS: A comprehensive search of online databases (PubMed, Web of Science, Embase, Cochrane Library, Scopus, Ovid, Elsevier, Ebsco, and Wiley) and clinical trial registries (WHO-ICTRP and ClinicalTrials.gov) was performed to investigate the efficacy and safety of early chest tube removal with high-output drainage. Primary outcome (postoperative hospital day) and secondary outcomes (30-day complications, rate of thoracentesis, and chest tube placement) were extracted and synthesized. Subgroup analysis, meta-regression, and sensitivity analysis were used to explore the potential heterogeneity. Study quality was assessed with the Newcastle-Ottawa Scale, and evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment by the online GRADEpro Guideline Development Tool. RESULTS: Six cohort studies with a total of 1262 patients were included in the final analysis. The postoperative hospital stay in the high-output group was significantly shorter than in the conventional treatment group (weighted mean difference: -1.34 [-2.34 to -0.34] day, P = .009). While there was no significant difference between 2 groups in 30-day complications (relative ratio [RR]: 0.92 [0.77-1.11], P = .38), the rate of thoracentesis (RR: 1.93 [0.63-5.88], P = .25) and the rate of chest tube placement (RR: 1.00 [0.37-2.70], P = .99). According to the sensitivity analysis, the relative impacts of the 2 groups had already stabilized. Subgroup analysis revealed that postoperative hospital stay was modified by Newcastle-Ottawa Scale score. The online GRADEpro Guideline Development Tool presented very low quality of evidence for the available data. CONCLUSIONS: This meta-analysis revealed that it is feasible and safe to remove a chest tube with high-output drainage after pulmonary resection for selected patients.

AXL upregulates c­Myc expression through AKT and ERK signaling pathways in breast cancers.

Breast cancer (BC) is common worldwide. c-Myc and AXL are both overexpressed in BC, promoting its progression. The present study aimed to investigate the role of AXL in c-Myc expression in BC. Overexpression of AXL increased c-Myc expression while knockdown of AXL decreased c-Myc expression as determined by western blot analysis. Pharmaceutical inhibition of AXL also suppressed c-Myc expression. AKT and ERK inhibitor LY294002 and U0126 suppressed c-Myc expression, respectively. AXL overexpression which activates AKT and ERK signaling, upregulates c-Myc expression, while kinase-dead AXL which cannot activate AKT and ERK signaling, does not upregulate c-Myc expression, emphasizing the important role of these two signaling pathways in c-Myc upregulation. Finally, expression data of BC tissues from The Cancer Proteome Atlas displayed an association between AXL and c-Myc. Taken together, the present study revealed that AXL upregulates c-Myc expression through AKT and ERK signaling pathways in BC.

Roles of PADI4 in the expression of cytokines involved in inflammation and adhesion in differentiated NB4 cells treated with ATRA.

Differentiation syndrome (DS) is a common complication in patients with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA). However, the target of ATRA during DS in patients with APL remains to be elucidated. Therefore, the current study aimed to investigate the role of peptidylarginine deiminase 4 (PADI4) in the differentiation of ATRA-induced NB4 APL cells. The results showed that PADI4 was significantly upregulated in peripheral blood samples derived from patients with APL DS compared with patients with APL only. In addition, whether ATRA could enhance the expression levels of PADI4 in NB4 cells in vitro was subsequently investigated. The results also showed that PADI4 overexpression promoted the differentiation of NB4 cells treated with ATRA, which was reversed after PADI4 silencing. To uncover the potential mechanisms underlying the above process, PADI4 overexpression induced the secretion of inflammation-related cytokines, such as TNF-α, IL-1ß, IL-8, C-C motif chemokine (CCL)2, CCL4, CCR1 and intercellular adhesion molecule-1 in ATRA-treated NB4 cells. However, PADI4 knockdown in the same cells had the opposite effect. The above findings indicated that PADI4 could be involved in the differentiation of ATRA-induced NB4 cells and upregulation of cytokines.

Heterogeneous catalysis mediated by light, electricity and enzyme via machine learning: Paradigms, applications and prospects.

Energy crisis and environmental pollution have become the bottleneck of human sustainable development. Therefore, there is an urgent need to develop new catalysts for energy production and environmental remediation. Due to the high cost caused by blind screening and limited valuable computing resources, the traditional experimental methods and theoretical calculations are difficult to meet with the requirements. In the past decades, computer science has made great progress, especially in the field of machine learning (ML). As a new research paradigm, ML greatly accelerates the theoretical calculation methods represented by first principal calculation and molecular dynamics, and establish the physical picture of heterogeneous catalytic processes for energy and environment. This review firstly summarized the general research paradigms of ML in the discovery of catalysts. Then, the latest progresses of ML in light-, electricity- and enzyme-mediated heterogeneous catalysis were reviewed from the perspective of catalytic performance, operating conditions and reaction mechanism. The general guidelines of ML for heterogeneous catalysis were proposed. Finally, the existing problems and future development trend of ML in heterogeneous catalysis mediated by light, electricity and enzyme were summarized. We highly expect that this review will facilitate the interaction between ML and heterogeneous catalysis, and illuminate the development prospect of heterogeneous catalysis.

Metagenomic analysis reveals the response of microbial community in river sediment to accidental antimony contamination.

The mining of deposits containing metals like antimony (Sb) causes serious environmental issues that threaten human health and ecological systems. However, information on the effect of Sb on freshwater sediment microorganisms and the mechanism of microbial Sb resistance is still very limited. This was the first attempt to explore microbial communities in river sediments impacted by accidental Sb spill. Metagenomic analysis revealed the high relative abundance of Proteobacteria and Actinobacteria in all the studied river sediments, showing their advantage in resistance to Sb pollution. Under Sb stress, microbial functions related to DNA repair and ion transport were enhanced. Increase in heavy metal resistance genes (HMRGs), particularly Sb transport-related arsB gene, was observed at Sb spill-impacted sites. HMRGs were significantly correlated with ARGs and MGEs, and the abundant MGEs at Sb spill-impacted sites might contribute to the increase in HMRGs and ARGs via horizontal gene transfer. Deinococcus, Sphingopyxis and Paracoccus were identified as potential tolerant genera under Sb pressure and might be related to the transmission of HMRGs and ARGs. This study can add new insights towards the effect of accidental metal spill on sediment microbial community.

[Effect of PADI4 on the Expression of Inflammatory Cytokines During NB4 Cells Differentiation].

OBJECTIVE: To investigate the expression of peptidylarginine deiminase 4 (PADI4) during the process of differentiation into granulocyte of NB4 cells induced by all-trans-retinoic acid (ATRA) and whether PADI4 is involved in the inflammatory cytokines expression. METHODS: Granulocyte differentiation model of NB4 cells induced by ATRA was established. The cell morphology changes were observed by Wright-Giemsa staining. The expression of cell differentiation marker CD11b was analyzed by flow cytometry. The mRNA and protein expression of PADI4 was detected by RT-PCR and Western blot, respectively. The expression of tumor necrosis factor (TNF) α and interleukin (IL) 1ß was analyzed by ELISA, and also examined with the knockdown of PADI4 expression by siRNA. RESULTS: After NB4 cells induced by ATRA, the cytoplasm increased and the ratio of nuclear to cytoplasmic was reduced. Nuclear dented, and rod-shaped nucleus, lobulated phenomenon increased (P<0.05). Flow cytometry analysis results showed that the cell surface molecule CD11b expression increased (P<0.01). RT-PCR and Western blot showed the expression of PADI4 increased at both transcriptional and translational levels during the process of the differentiation. ELISA showed TNF-α and IL-1ß secretion increased in differentiated macrophages, while they could be inhibited by PADI4-specific siRNA. CONCLUSION: During the differentiation into granulocyte of NB4 cells induced by ATRA, PADI4 expression increased. Furthermore, PADI4 appeared to play a critical role in inflammatory cytokines secretion.

Effects of matrix modification and bacteria amendment on the treatment efficiency of municipal tailwater pollutants by modified vertical flow constructed wetland.

Although vertical flow constructed wetland (VFCW) has great potentials for degradation of water contaminants, traditional VFCW has limited removal efficiencies for pollutants. This study constructed three sets of modified VFCW systems, including VFCW-A with matrix-modification using mixture of biochar and activated carbon, VFCW-B with microbial amendment using denitrifying bacteria, and VFCW-C with combined treatments of both. Their removal efficiencies for various pollutants in synthetic municipal tailwater were investigated. Results showed that the removal efficiencies for NH4-N, NO3-N, total nitrogen (TN), total phosphorus (TP), and chemical oxygen demand (COD) by VFCW-C were higher than VFCW-B throughout the experimental period, indicating that matrix-modification could improve the VFCW performance. The higher removal efficiencies for TN, TP, and COD by VFCW-C than VFCW-A also suggested the effectiveness of microbial amendment in VFCW. However, the improved removal for NO3-N by VFCW-C over VFCW-A became less obvious at later operation stage due to insufficient carbon source. All three VFCWs achieved their best removal efficiency when carbon source was supplemented at CH3COO-/TN ratio of 0.5. Our study suggested that the combined treatment of matrix-modification using biochar/activated carbon mixture and microbial amendment using denitrifying bacteria could effectively enhance the treatment efficiency of VFCW systems for tailwater pollutants from sewage plant.

Long-term impact of accidental pollution on the distribution and risks of metals and metalloids in the sediment of the Longjiang River, China.

In January 2012, a serious accident polluted the Longjiang River with high concentrations of cadmium (Cd) and other concomitant metals and metalloids in the water. After emergency treatment (i.e., the addition of coagulants), these metals and metalloids were transferred from the water into the sediment through precipitation of the flocculent materials produced. In this study, the long-term distribution of six metals and metalloids in the sediment of the Longjiang River was investigated and their ecological risks were assessed. Approximately 1 year after the accident (i.e., late 2012), the average Cd content in the sediment of the affected sites decreased to 25.6 ± 19.5 mg/kg, which was 8 times higher than that of 3.16 ± 3.18 mg/kg in the upstream reference sites. In 2016 and 2017, the average Cd content in the sediment of the affected sites further decreased to 4.91 ± 2.23 and 6.27 ± 4.27 mg/kg, respectively. Compared with late 2012, the amounts of Zn, Pb, and Cu obviously decreased in 2016 and 2017, whereas there were no obvious differences in the As and Hg amounts during 3 years considered. Among metals and metalloids, the average contribution of Cd to the potential ecological risk index (RI) was 90%, 69%, and 70% in the affected areas in 2012, 2016, and 2017, respectively, suggesting that Cd was the most important factor affecting the ecological risk of metals in the Longjiang River. It should be noted that the average contribution of Hg to RI in the affected areas increased from 8% in 2012 to 25% and 23% in 2016 and 2017, respectively. The sequence of contribution of six elements was Cd > Hg > As>Pb > Cu ≈ Zn. A high ecological risk of metals and metalloids was found in the sediments of two reservoirs, probably owing to the barrier effect of the dam. This study will be useful for the environmental management of rivers affected by accidental pollution of metals and metalloids.

Effects of F-, Cl-, Br-, NO3-, and SO42- on the colloidal stability of Fe3O4 nanoparticles in the aqueous phase.

The effect of ions on the colloidal behavior of magnetic nanoparticles (MNPs) is an important factor for determining the dispersibility of MNPs. Compared with the effects of cations and organic matter, the effect of anions on MNPs has rarely been studied. Hence, in this study, the effect of anions on the aggregation of Fe3O4 MNPs in the aqueous phase was investigated using F-, Cl-, Br-, NO3-, and SO42-. The results indicated that the effect of anions on the colloidal behavior of the MNPs varied widely depending on their valence state, concentration, hydration ability, solution pH, and the magnetic force between the MNPs. Specifically, at pH 5.0, the anions were mainly adsorbed on the particle surface by electrostatic attraction, decreasing the electrostatic repulsion between the MNPs and causing an aggregation of the particles in the order of SO42- > F- > Br- > Cl- ≈ NO3-. At pH 9.0, anions strengthened the suspension of the MNPs at low ionic strength (IS) (≤5); however, with increasing IS, an aggregation of the MNPs in the following order was formed: NO3- > Cl- > Br- ≥ F- > SO42-. This was a result of the combined effects of the IS of solution, hydrability, and polarizability of the anions. Furthermore, the Derjaguin-Landau-Vervey-Overbeek (DLVO) theory can explain the colloidal behavior of MNPs in the presence of magnetic forces, but it fails to differentiate the MNP behaviors between monovalent anions because the effects of ionic hydrability and polarizability are not considered. Distinctively, the secondary minimum between the MNPs particles were induced via magnetic attraction and played a critical role in adjusting the colloidal stability of the MNPs. Overall, these results indicate that specific ionic effects and magnetic attraction are important for interpreting the colloidal stability of MNPs in aqueous conditions.

Investigation of a simple coded-aperture based multi-narrow beam x-ray luminescence computed tomography system.

The purpose of this paper is to introduce and study a multi-narrow beam X-ray Luminescence Computed Tomography (XLCT) system based on a simple coded aperture. The proposed XLCT system is studied through simulations of x rays and diffuse light propagation and the implementation of the multi-narrow beam XLCT reconstruction algorithm. The relationship between the reconstructed quality of the XLCT image and the pass-element distribution of the coded aperture mask is investigated. The coded aperture that produces the best image quality metrics for the numerical phantom is selected for the XLCT system. The effects of detection positions and the number of projection angles are also investigated for considering the scanning efficiency and system structural complexity. The results demonstrate that the proposed multi-narrow beam XLCT system is competent in resolving targets with high complexity when comparing with the coded aperture compressed sensing XLCT system based on a complicated mask. It can also offer an enhancement in scanning efficiency in comparison with the conventional multi-narrow beam XLCT system.

IL13Rα1 protects against rheumatoid arthritis by combating the apoptotic resistance of fibroblast-like synoviocytes.

BACKGROUND: Endoplasmic reticulum (ER) stress is closely related with the pathological progression of rheumatoid arthritis (RA), and fibroblast-like synoviocytes (FLSs) are known as its resistance against ER stress-induced apoptosis. Studies on overcoming such resistance would provide a novel treatment strategy for RA in a clinical setting. METHODS: IL13Rα1 expression was assessed in the synovial tissue by RT-qPCR, immunohistology, and Western blot. Gain or loss of functional analysis was applied to evaluate the biological roles of IL13Rα1 in RA FLSs. Cell viability and apoptosis were assessed by MTS, Western blot, and flow cytometry. The therapeutic effects of IL13Rα1 on the severity of type II collagen-induced arthritis (CIA) in DBA-/1 mouse model were evaluated by scoring synovitis, hyperplasia, cartilage degradation, and bone destruction. RESULTS: IL13Rα1 expression was selectively downregulated when RA FLSs were stimulated by ER stress inducers. Functionally, IL13Rα1 overexpression could inhibit the viability, but induce the apoptosis of RA FLSs in the presence of ER stress inducers. Mechanistically, IL13Rα1 promotes cell apoptosis via transcriptionally activating trail expression. Besides, IL13Rα1 could interact and stabilize DR5 protein, thus forming a positive loop involving trail and DR5 to render RA FLSs more susceptible to apoptosis. Additionally, intraarticular injection of IL13Rα1 conferred therapeutic effects in CIA models and showed a limited degree of synovial proliferation and joint destruction. CONCLUSIONS: Together, our data establishes a regulatory role for IL13Rα1 to combat the apoptotic resistance of RA FLSs against ER stress. The inhibitory effects of IL13Rα1 on arthritis progression suggest the therapeutic potential in RA.

Significant Association between the T2 Values of Vertebral Cartilage Endplates and Pfirrmann Grading.

OBJECTIVE: The T2 value of lumbar cartilage endplates was measured using the T2 mapping imaging technique, aiming to explore the correlation between the T2 value and Pfirrmann grading of intervertebral discs. METHODS: A total of 130 patients with lumbar spine MR examination due to persistent low back pain were enrolled, including 71 men and 59 women (age: 21-63 years). Lumbar Modic changes and Schmorl nodules were recognized by conventional T1WI and T2WI images in 49 patients, and these patients were excluded from the study. A total of 81 patients were enrolled in this study, including 45 men (45.16 ± 12.20 years) and 36 women (43.33 ± 11.27 years). Pfirrmann (Pm) grading of each lumbar disc was performed based on conventional T2WI median sagittal images and the position of cartilage endplates (CEP) was determined by IDEAL-SPGR images. Meanwhile, the T2 mapping technique was used to obtain T2 values of cartilage endplates. The T2 values of CEP corresponding to different Pm grade discs were compared, and the correlation between the T2 value and the Pm grade of intervertebral discs was analyzed. RESULTS: The T2 values of cephalic and caudal CEP of L1-2 in Pm grades I-II, Pm grades III, and Pm grades IV-V were 61.96 ± 5.89 ms, 54.45 ± 3.29 ms, 42.47 ± 3.69 ms and 64.35 ± 5.93 ms, 55.28 ± 3.97 ms, 44.75 ± 2.12 ms, respectively. For cephalic and caudal CEP of L2-3 , the T2 values in Pm grades I-II, Pm grades III, and Pm grades IV-V were 62.96 ± 6.93 ms, 55.19 ± 4.02 ms, 48.67 ± 4.56 ms and 65.51 ± 6.49 ms, 57.16 ± 5.55 ms, 52.05 ± 4.20 ms, respectively. The T2 values of cephalic and caudal CEP from L3-4 to L5 -S1 in Pm grades I-II, Pm grades III, and Pm grades IV-V were (63.72 ± 5.76 ms, 53.96 ± 6.52 ms, 48.05 ± 5.00 ms), (65.46 ± 6.37 ms, 55.70 ± 7.50 ms, 48.10 ± 3.27 ms); (66.34 ± 7.68 ms, 56.76 ± 9.48 ms, 47.80 ± 4.33 ms), (64.44 ± 4.65 ms, 59.30 ± 8.80 ms, 47.30 ± 5.78 ms), (65.32 ± 5.11 ms, 55.33 ± 6.65 ms, 48.18 ± 5.37 ms), and (63.47 ± 4.92 ms, 50.32 ± 8.86 ms, 44.77 ± 4.69 ms), respectively. There were significant differences in T2 values of cartilage endplates between the Pm grades I-II, III, and IV-V of intervertebral discs (P = 0.000). T2 values corresponding to Pm I-II grades were higher than those in Pm III grade, while T2 values in Pm grades IV-V were lowest. The T2 value of the L4-5 , L5 -S1 segment endplates was highly correlated with the Pm grades (r = -0.711, -0.721, -0.796, -0.745; P = 0.000) and that of L1-2 , L2-3 endplates were moderately correlated (r = -0.542, -0.562, -0.637, -0.612; P = 0.000). CONCLUSION: The T2 values of cartilage endplates revealed varying degrees of degeneration of intervertebral discs, and more severe degeneration corresponded to lower T2 values. Measurement of changes in the T2 value through cartilage endplates can be useful for the diagnosis of early intervertebral disc degeneration and the prevention of disc degeneration.

The Epstein-Barr virus-encoded G protein-coupled receptor BILF1 upregulates ICAM-1 through a mechanism involving the NF-қB pathway.

Although the Epstein-Barr virus (EBV) infection is usually asymptomatic, a primary encounter with the virus can cause mononucleosis. EBV infection is also strongly associated with lymphoma and epithelial cancers. The structure and infection mechanism of EBV have been well studied, but the EBV-encoded G protein-coupled receptor, BILF1, is not fully understood. Here, it was found that the EBV BILF1 was expressed early in the viral lytic cycle and its ectopic expression strikingly upregulated the ICAM-1 expression in Raji cells. The positive effect of BILF1 on the ICAM-1 promoter was observed and the BILF1 deficiency attenuated ICAM-1 promoter activity. Moreover, NF-κB binding sites were important for the regulation of ICAM-1 promoter by BILF1. Furthermore, BILF1 reduced the constitutive level of the IқB-a protein and increased the amount of nuclear NF-қB in Raji cells. In conclusion, this study determined that BILF1 upregulated ICAM-1 in a mechanism involving NF-қB.

CircLARP4 Suppresses Cell Proliferation, Invasion and Glycolysis and Promotes Apoptosis in Non-Small Cell Lung Cancer by Targeting miR-135b.

BACKGROUND: CircLARP4 is reported to act as a tumor suppressor in some cancers. However, the detailed roles and molecular basis of circLARP4 in non-small cell lung cancer (NSCLC) tumorigenesis are still unclear. The aim of the study is to explore the potential roles and molecular basis of circLARP4 in NSCLC tumorigenesis. MATERIALS AND METHODS: qRT-PCR was taken to detect circLARP4 and miR-135b expressions. MTT assay, transwell invasion assay and flow cytometry analysis were applied to evaluate cell proliferation, invasion and apoptosis, respectively. Glycolysis was assessed by measuring hexokinase2 (HK2) expression, glucose consumption and lactate production. Association between circLARP4 and miR-135a was examined by luciferase reporter and RIP assays. The changes of the phosphatase and tension homolog (PTEN)/protein kinase B (AKT)/hypoxia-inducible factor-1α (HIF-1α) pathway were evaluated by Western blot. The nude mouse xenograft models were applied to verify the regulation of circLARP4 in vivo. RESULTS: CircLARP4 was decreased in NSCLC tissues and cells. CircLARP4 overexpression blocked cell proliferation and invasion, and facilitated apoptosis in NSCLC cells. Meanwhile, circLARP4 overexpression suppressed glycolysis in NSCLC cells, as evidenced by the reduced HK2, glucose consumption and lactate production levels. Further analyses proved a downregulation of miR-135b by circLARP4 in a ceRNA-dependent manner in NSCLC cells. CircLARP4-mediated tumor suppression on NSCLC progression was partially overturned by overexpressing miR-135b. Moreover, we confirmed that circLARP4 had antitumor effect on xenograft tumors and downregulated miR-135b. Furthermore, circLARP4 overexpression inhibited the PTEN/AKT/HIF-1α pathway in NSCLC cells and xenograft tumors by downregulating miR-135b. CONCLUSION: Our findings suggested that circLARP4 suppressed NSCLC progression by sponging miR-135b through inactivation of the PTEN/AKT/HIF-1α pathway, which broadens our understanding concerning the roles of circLARP4 in NSCLC tumorigenesis.