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While 15 to 20% of cancers are associated with microbial infection, the relationship between oral microorganisms and oral squamous cell carcinoma (OSCC) remains unclear. The location of bacteria in a tumor is closely related to its carcinogenic mechanism. The aim of this study was to analyse bacterial diversity in clinical OSCC tissue samples and tumor distant normal tissues, locate target bacteria, and search for proteins that may interact with target bacteria.The 16S rDNA method was used to analyse bacterial diversity in clinical OSCC tissue samples and tumor distant normal tissues. Correlations between Fusobacterium abundance and clinicopathological characteristics were analysed using the χ2 test. The position of target bacteria was analysed by fluorescence in situ hybridization (FISH), and the expression of CK, CD31, CD45, CD68, cyclin D1, β-catenin, E-cadherin, NF-κB, and HIF-1α was analysed by immunohistochemistry (IHC) in OSCC tumor tissues and tumor distant normal tissues.The 16S rDNA results showed that the detected amount of Fusobacterium in OSCC tumor tissues was significantly larger than that in tumor distant normal tissues. High expression of Fusobacterium was significantly correlated with the lifestyle-related oral risk habits, including smoking (p=0.036) and alcohol consumption (p=0.022), but did not correlate with patient sex, age, tumor laterality, tumor size, grade or TNM stage. Fusobacterium nucleatum was enriched in tumor stroma, where CD31+ blood vessels and inflammatory cells (including CD45+ leukocytes and CD68+ macrophages) were densely distributed. Cyclin D1 was mainly expressed in the nucleus of tumor cells. β-catenin was expressed in the tumor cell membrane and was positively expressed in tumor interstitial vascular endothelial cells. E-cadherin was mainly expressed in tumor cell membranes. NF-κB was positively expressed in the cytoplasm of tumor cells, tumor interstitial cells and myo-fibrocytes. HIF-1α was mainly expressed in the cytoplasm of tumor interstitial cells. HIF-1α was highly expressed where Fusobacterium nucleatum was densely distributed.According to our study, the detected amount of Fusobacterium in OSCC tumor tissues was significantly larger than that in tumor distant normal tissues, and Fusobacterium nucleatum might aggravate inflammation and hypoxia by interacting with NF-κB and HIF-1α in OSCC.

Increased endogenous hydrogen sulfide (H2S) level by cystathionine β-synthase (CBS) has been shown to closely relate tumorigenesis. H2S promotes angiogenesis, stimulates bioenergy metabolism and inhibits selective phosphatases. However, the role of CBS and H2S in chronic myeloid leukemia (CML) remains elusive. In this study, we found that CBS and H2S levels were increased in the bone marrow mononuclear cells of pediatric CML patients, as well as in the CML-derived K562 cells and CBS expression levels were correlated with different disease phases. Inhibition of CBS reduced the proliferation of the CML primary bone marrow mononuclear cells and induced growth inhibition, apoptosis, cell cycle arrest, and migration suppression in K562 cells and tumor xenografts. The knockdown of CBS expression by shRNA and inhibiting CBS activity by AOAA decreased the endogenous H2S levels, promoted mitochondrial-related apoptosis and inhibited the NF-κB-mediated gene expression. Our study suggests that inhibition of CBS induces cell apoptosis, as well as limits cell proliferation and migration, a potential target for the treatment of chronic myeloid leukemia.

Diabetic retinopathy (DR) is one of the most common causes of blindness globally. Proliferative DR (PDR), an advanced stage of DR, is characterized by the formation of fibrotic membranes at the vitreoretinal interface. The proliferation, migration, and secretion of extracellular matrix molecules in retinal pigment epithelial (RPE) cells contribute to the formation of fibrotic membranes in PDR. Gremlin has been reported to be upregulated in response to elevated glucose levels in the retina of diabetic rat and bovine pericytes. However, the role of gremlin in PDR remains unclear. In the present study, the vitreous concentrations of gremlin were significantly higher in the PDR (67.79±33.96) group than in the control (45.31±12.31) group, and high glucose levels induced the expression of gremlin in RPE cells. The elevated expression of extracellular matrix molecules, such as fibronectin and collagen IV, was significantly reduced by gremlin siRNA in human RPE cells under high-glucose conditions. Thus, gremlin may play a vital role in the development of PDR.

Background Wieacker‐Wolff syndrome (WWS) is a congenital X‐linked neuromuscular disorder, which was firstly reported in 1985. Zinc finger C4H2‐type containing (ZC4H2) gene has been found to be associated with the disease pathogenesis. However, the underlying mechanism remains elusive. Methods Whole‐exome sequencing was performed to identify the mutations. Expression plasmids were constructed and cell culture and immune‐biochemical assays were used to examine the effects of the mutation. Results We reported a female patient with classical symptoms of WWS and discovered a novel nonsense heterozygous mutation (p.R67X; c.199C>T) in ZC4H2 gene in the patient but not in her parents. The mutation resulted in a 66 amino‐acid truncated ZC4H2 protein. The mutation is located in the key helix domain and it altered the subcellular locations of the mutant ZC4H2 protein. X‐chromosome inactivation (XCI) pattern analysis revealed that the XCI ratio of the proband was 22:78. Conclusion Female heterozygous carriers with nonsense mutation with a truncated ZC4H2 protein could lead to the pathogenesis of Wieacker‐Wolff syndrome and our study provides a potential new target for the disease treatment., A novel nonsense heterozygous mutation (p.R67X; c.199C>T) in ZC4H2 (Zinc Finger C4H2‐Type Containing) gene was discovered in a patient with Wieacker‐Wolff syndrome. The mutation resulted in a 66 amino‐acid truncated ZC4H2 protein. The results demonstrated that female heterozygous carriers with nonsense mutation with a truncated ZC4H2 protein could lead to the pathogenesis of Wieacker‐Wolff syndrome and our study provides a potential new target for the disease treatment.

Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. In this study, we investigated the effects of EGCG on insulin resistance and insulin clearance in non-alcoholic fatty liver disease (NAFLD) mice.Mice were fed on a high-fat diet for 24 weeks. During the last 4 weeks, the mice were injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip). Glucose tolerance, insulin tolerance and insulin clearance were assessed. After the mice were euthanized, blood samples and tissue specimens were collected. Glucose-stimulated insulin secretion was examined in isolated pancreatic islets. The progression of NAFLD was evaluated histologically and by measuring lipid contents. Insulin-degrading enzyme (IDE) protein expression and enzyme activity were detected using Western blot and immunocapture activity assays, respectively.The high-fat diet significantly increased the body weight and induced grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning) accompanied by severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in the model mice. Administration of EGCG dose-dependently ameliorated the hepatic morphology and function, reduced the body weight, and alleviated hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in NAFLD mice. Furthermore, EGCG dose-dependently enhanced insulin clearance and upregulated IDE protein expression and enzyme activity in the liver of NAFLD mice.EGCG dose-dependently improves insulin resistance in NAFLD mice not only by reducing body weight but also through enhancing the insulin clearance by hepatic IDE. The results suggest that IDE be a potential drug target for the treatment of NAFLD.

The pathology of the fibrotic proliferative vitreoretinopathy (PVR) membrane represents an excessive wound healing response characterised by cells’ proliferation, migration and secretion of extracellular matrix molecules (ECMs). Retinal pigment epithelial (RPE) cells are a major cellular component of the fibrotic membrane. Endothelin-1 (ET-1) has been reported to be involved in the development of PVR in vivo research. However, little is known about the role of ET-1 in RPE cells in vitro. In the present study, we investigated the role of ET-1 in the proliferation, migration and secretion of ECMs (such as type I collagen and fibronectin) in RPE cells in vitro. Our results illustrated that ET-1 promoted the proliferation, migration and secretion of ECMs through the protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) signaling pathways in RPE cells in vitro. These findings strongly suggested that ET-1 may play a vital role in the development of PVR.

Two membrane bioreactors (toxic MBR and blank MBR) were established and compared to treat high ammonia wastewater in the presence and absence of 2,4-dichlorophenol (2,4-DCP). After 130 days operation, both MBRs expressed NH4+-N removal efficiency (>95%) and 2,4-DCP removal efficiency was (96.47 ± 1.54) %. Specific oxygen uptake rate (SOUR) data showed that nitrifying bacteria receive more severe inhibition than heterotrophic bacteria. Trans-membrane pressure (TMP) data indicated that the presence of 2,4-DCP caused more serious membrane fouling. The protein/polysaccharide ratio increased to 1.1 and 6.3 in the loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) after 2,4-DCP addition. Excitation-emission matrix (EEM) showed that TB-EPS were mainly composed of aromatic and tryptophan PN-like substances, and LB-EPS of humic acid-like and fulvic acid-like substances. The microbial community analysis showed that the abundance of Proteobacteria, Firmicutes, and Nitrospirae under 2,4-DCP stress increased from 22.56%, 27.10%, and 1.27% to 38.89%, 28.25% and 3.59%, respectively.

The present study evaluated the performance of biological denitrification in an anoxic sequencing batch biofilm reactor (ASBBR) and its nitrous oxide (N2O) emission. After 90 days operation, the effluent chemical oxygen demand and total nitrogen removal efficiencies high of 94.8% and 95.0%, respectively. Both polysaccharides and protein contents were reduced in bound EPS (TB-EPS) and loosely bound EPS (LB-EPS) after biofilm formation. According to typical cycle, N2O release rate was related to the free nitrous acid (FNA) concentration with the maximum value of 3.88 μg/min and total conversion rate of 1.27%. Two components were identified from EEM-PARAFAC model in soluble microbial products (SMP). Protein-like substances for component 1 changed significantly in denitrification process, whereas humic-like and fulvic acid-like substances for component 2 remained relatively stable. High-throughput sequencing results showed that Lysobacter, Tolumonas and Thauera were the dominant genera, indicating the co-existence of autotrophic and heterotrophic denitrifiers in ASBBR.

Purpose In performing human MREIT imaging experiments, we addressed two technical issues of the chemical shift artifact and measurement noise. In this study, we present improved conductivity images of in vivo human lower extremity using the chemical shift artifact correction and multi-echo methods.

Deep brain stimulation (DBS) is widely used for the treatment of various neurological diseases such as Parkinson's disease and tremors. Owing to the inherent limitations of the imaging modalities, physicians have a difficulty in the diagnosis of the exact response to the brain tissues during stimulation. Recent magnetic resonance (MR)-based electrical impedance tomography (MREIT) enables estimation of the current density distribution from the measured magnetic flux density data. Applying MREIT to DBS, one can predict the current pathway and electric field distribution which could be useful information for proving the therapeutic effects of electrical stimulation.

To establish a animal model of hepatic steatosis induced by chronic viral hepatitis in C(57)BL/6 mice.C(57)BL/6 mice were randomly assigned to control group, high-fat diet group, mouse hepatitis virus strain A59 (MHV-A59) virus infection group, and high-fat diet plus virus infection group. At 13 weeks of the experiment, serum samples were collected to detect MHV antibodies and transaminase and lipid levels. The hepatic pathologies of the mice were examined with Oil red O staining of the frozen sections the and HE staining of paraffin-embedded sections.The mice in the two virus infection groups showed strong positivity of MHV antibodies in the serum. Compared with the control group, the mice in high-fat diet group and the two virus infection groups had significantly increased AST and ALT levels with also elevated TC and LDL-C levels. The two virus infection groups both exhibited obvious pathologies in the liver characteristic of chronic viral hepatitis with increased lipid accumulation in the hepatocytes.We have successfully established a mouse model of hepatic steatosis induced by chronic viral hepatitis, which provides the basis for further study of the disease mechanism.

We present our recent developments in tissue conductivity imaging of the human lower extremity using MREIT. In performing in vivo human knee and calf imaging experiments, we addressed two technical issues of the chemical shift artifact and measurement noise. Adopting a recently developed chemical shift artifact correction method for MREIT, we could improve the quality of conductivity images of the knee and calf. We found that the correction method is advantageous in terms of the signal-to-noise ratio (SNR) compared with a fat suppression method. Since the knee is more sensitive to injection currents, we limited the current amplitude in knee experiments to 3 mA to avoid painful sensation. Reduction of the current amplitude requests a similar reduction of the noise level in measured magnetic flux density signals since the signal is proportional to the current amplitude. We incorporated a lately developed multi-echo based MREIT pulse sequence to enhance MR signals and prolong the total current injection time, thereby reducing the noise level in measured magnetic flux density signals.

Magnetic resonance electrical impedance tomography (MREIT) is being developed to produce high-resolution cross-sectional conductivity images of an object. In MREIT, we scan the imaging object using an MRI scanner while injecting low-frequency current through surface electrodes. This produces change in the phase of precessing protons which is reflected in the MRI phase image. The conductivity imaging method in MREIT is thus based on static bioelectromagnetism and physics of MRI. In this paper, we describe a three-dimensional MREIT simulator (MREITSim) to numerically simulate the underlying physical phenomena in MREIT. We demonstrate the static bioelectromagnetism simulation and MREIT k-space data simulation as applications of this simulator. The simulator will be useful in developing new MREIT pulse sequences and conductivity image reconstruction algorithms.

MREIT has reached the stage of in vivo animal and human imaging experiments. To support its clinical significance, we should demonstrate that the conductivity image provides meaningful diagnostic information that is not available from other imaging modalities. To investigate any change of electrical conductivity due to brain diseases of ischemia and abscess, we scanned an animal with such a regional brain disease along with a separate prior scan of the same animal having no disease model. Conductivity images shown in this study indicate that time-course variation of conductivity contrast between normal and abnormal regions are distinguishable in a different way compared with conventional MR image techniques.