Hepatitis C virus hypervariable region 1 antibodies interrupt E2-SR-B1 interaction to suppress viral infection.

Whether hypervariable region 1 (HVR1)-targeting antibodies elicited during natural hepatitis C virus (HCV) infection contribute to virus clearance and what is the mechanism underlying remain unclear. Here, we demonstrated that treatment of HCV-infected hepatoma Huh7.5 cells with the IgGs purified from 2 of 28 (7.1%) chronic hepatitis C (CHC) patients efficiently controlled the infection, for which genotype 1b HVR1 (1bHVR1)-binding antibody was critical. Moreover, we found that 1bHVR1 peptide was superior to 2aHVR1 in rabbit immunization to elicit antibodies neutralizing genotypes 1a, 2a, 3a, and 4a. The neutralization effect of 1bHVR1 IgG could be augmented by HH-1, an antibody constructed from CHC memory B cells but without binding to HVR1 peptide. Mechanistic studies showed that 1bHVR1 antisera and IgGs disrupted the interaction of E2-SR-B1 receptor. This study highlights the neutralizing activity of HVR1 antibody elicited by CHC patients and generated by HVR1-immunization against the established infections of multiple HCV genotypes.

Insight into phase structure-dependent soot oxidation activity of K/MnO2 catalyst.

In the present study, two nanosized MnO2 with ß and δ phase structures and potassium loaded MnO2 catalysts with varied K loading amounts (denoted as K/MnO2) were prepared. Temperature programmed oxidation and isothermal reactions in loose contact modes were employed to examine the soot oxidation activity of the as-prepared catalysts. Characterization results show that as compared with ß-MnO2, δ-MnO2 has larger surface area and higher content of hydroxyl groups. Upon K loading, abundant hydroxyl groups in δ-MnO2 effectively sequestrate K cation to form bound K species and free K species are available only at K loading above 3.0 wt.%. In contrast, the majority of K species present as free state in ß-MnO2 even at a K loading of 1.0 wt.% due to its very low hydroxyl group content. The O2 temperature-programmed desorption (O2-TPD) demonstrates that the catalysts with free K species exhibit strong ability in activating gaseous O2, whereas the catalysts only having bound K display minor O2 activation capability. As a result, despite of slightly lower activity of ß-MnO2 than δ-MnO2, the K/ß-MnO2 catalysts exhibit substantially higher activities than K/δ-MnO2 catalysts with identical K loadings. The finding in this study clearly demonstrates that for MnO2 based catalysts, the enhancement of catalytic activity for soot oxidation is highly K loading amount dependent and the dependency is strongly associated with the phase structure of MnO2.

Influence of science education on mental health of adolescents based on virtual reality.

This work is developed to explore the form of mental health education, strengthen scientific educational ideas, and improve the effect of psychological therapy. Virtual reality (VR) technology is innovatively applied in adolescent mental health treatment and education. Based on this, the mental health treatment and system design based on virtual reality technology are discussed, and the feasibility of applying VR technology to adolescent mental health education is explored. Second, the research concept of adolescent mental health is discussed. Based on the VR platform setup, questionnaire survey is implemented to analyze the factors influencing the mental health of primary and secondary school students in Xi'an, Shaanxi Province (the permission of the adolescent guardian is obtained during the interview), and five factors are obtained. Based on this, the adolescent mental health treatment system based on VR is designed, and the effectiveness of the system is tested and evaluated. The results show that the integrated delay of the VR equipment used is 29 ms, which can effectively provide service. There are significant differences in mental health status among adolescents of different genders, different ages, only children and non-only children, parents' accompaniment during growing up, and urban and rural adolescents. Finally, after 3 months of psychological treatment, the mental health score of the experimental group of teenagers is 50-55 points. However, the mental health scores of the control group remain at 56-65 points, indicating that the mental health treatment system designed in this work can effectively help the adolescents to improve their mental health, thus proving the effectiveness of the system. To sum up, this work provides scientific reference for adolescent mental health education in schools. Psychological treatment system can help teenagers improve their psychological problems and promote the development of mental health education.

Cloud-Based English Multimedia for Universities Test Questions Modeling and Applications.

This study constructs a cloud computing-based college English multimedia test question modeling and application through an in-depth study of cloud computing and college English multimedia test questions. The emergence of cloud computing technology undoubtedly provides a new and ideal method to solve test data and paper management problems. This study analyzes the advantages of the Hadoop computing platform and MapReduce computing model and builds a distributed computing platform based on Hadoop using universities' existing hardware and software resources. The study analyzes the advantages of the Hadoop computing platform and the MapReduce computing model. The UML model of the system is given, the system is implemented, the system is tested functionally, and the results of the analysis are given. Multimedia is the critical link to realizing the optimization of English test questions. The proper use of multimedia test questions will undoubtedly become an inevitable trend in the development of English test questions in the future, which requires every worker on the education front to continuously analyze and study the problems arising from multimedia teaching, summarize the experience of multimedia teaching, and explore new methods of multimedia teaching, so that multimedia teaching can better promote the optimization of English test questions in colleges and universities and better serve the education teaching.

Multimedia Fusion Privacy Protection Algorithm Based on IoT Data Security under Network Regulations.

This study provides an in-depth analysis and research on multimedia fusion privacy protection algorithms based on IoT data security in a network regulation environment. Aiming at the problem of collusion and conspiracy to deceive users in the process of outsourced computing and outsourced verification, a safe, reliable, and collusion-resistant scheme based on blockchain is studied for IoT outsourced data computing and public verification, with the help of distributed storage methods, where smart devices encrypt the collected data and upload them to the DHT for storage along with the results of this data given by the cloud server. After testing, the constructed model has a privacy-preserving budget value of 0.6 and the smallest information leakage ratio of multimedia fusion data based on IoT data security when the decision tree depth is 6. After using this model under this condition, the maximum value of the information leakage ratio of multimedia fusion data based on IoT data security is reduced from 0.0865 to 0.003, and the data security is significantly improved. In the consensus verification process, to reduce the consensus time and ensure the operating efficiency of the system, a consensus node selection algorithm is proposed, thereby reducing the time complexity of the consensus. Based on the smart grid application scenario, the security and performance of the proposed model are analyzed. This study proves the correctness of this scheme by using BAN logic and proves the security of this scheme under the stochastic prediction machine model. Finally, this study compares the security aspects and performance aspects of the scheme with some existing similar schemes and shows that the scheme is feasible under IoT.

Design of Knowledge Graph Retrieval System for Legal and Regulatory Framework of Multilevel Latent Semantic Indexing.

Latent semantic analysis (LSA) is a natural language statistical model, which is considered as a method to acquire, generalize, and represent knowledge. Compared with other retrieval models based on concept dictionaries or concept networks, the retrieval model based on LSA has the advantages of strong computability and less human participation. LSA establishes a latent semantic space through truncated singular value decomposition. Words and documents in the latent semantic space are projected onto the dimension representing the latent concept, and then the semantic relationship between words can be extracted to present the semantic structure in natural language. This paper designs the system architecture of the public prosecutorial knowledge graph. Combining the graph data storage technology and the characteristics of the public domain ontology, a knowledge graph storage method is designed. By building a prototype system, the functions of knowledge management, knowledge query, and knowledge push are realized. A named entity recognition method based on bidirectional long-short-term memory (bi-LSTM) combined with conditional random field (CRF) is proposed. Bi-LSTM-CRF performs named entity recognition based on character-level features. CRF can use the transition matrix to further obtain the relationship between each position label, so that bi-LSTM-CRF not only retains the context information but also considers the influence between the current position and the previous position. The experimental results show that the LSTM-entity-context method proposed in this paper improves the representation ability of text semantics compared with other algorithms. However, this method only introduces relevant entity information to supplement the semantic representation of the text. The order in the case is often ignored, especially when it comes to the time series of the case characteristics, and the "order problem" may eventually affect the final prediction result. The knowledge graph of legal documents of theft cases based on ontology can be updated and maintained in real time. The knowledge graph can conceptualize, share, and perpetuate knowledge related to procuratorial organs and can also reasonably utilize and mine many useful experiences and knowledge to assist in decision-making.

Implementation of a System for Assessing the Quality of Spoken English Pronunciation Based on Cognitive Heuristic Computing.

This paper analyzes and investigates the quality assessment of spoken English pronunciation using a cognitive heuristic computing approach and designs a corresponding spoken pronunciation quality assessment system for practical training. Using the general Goodness of Pronunciation assessment algorithm as a benchmark, the shortcomings of the traditional Goodness of Pronunciation method are explored through statistical experiments, and the validity of the overall posterior probability output from the speech model for pronunciation quality assessment is verified. For the analysis of rhythm, there is no common algorithm framework, but in this paper, the F0 similarity algorithm based on dynamic time regularization and the stop similarity algorithm based on forced alignment is proposed for the two main factors of rhythm, intonation, and pause, respectively. After framing, the Hamming window processing is used to make the signal smoother, reduce the side lobe size after fast Fourier transform processing, and solve the problem of spectrum leakage. Compared with the ordinary rectangular window function, the Hamming window can obtain a higher quality spectrum. And combined with CTC for speech recognition modeling, the recognition rates are comparable in the case of using BLSTM and bidirectional threshold cyclic unit BGRU as the hidden layer unit, respectively, and the training time is 23% less than BLSTM using BGRU; in addition, the BGRU-CTC model is improved by using a 2-BGRU-CTC model with 256 hidden layer nodes, so that the error rate of phoneme recognition is reduced to 33%. The effectiveness of the algorithm framework is also verified through experiments, which further proves the effectiveness of our proposed phoneme segment feature and rhyme similarity algorithm.

Pattern Recognition of Holographic Image Library Based on Deep Learning.

The final loss function in the deep learning neural network is composed of other functions in the network. Due to the existence of a large number of non-linear functions such as activation functions in the network, the entire deep learning model presents the nature of a nonconvex function. As optimizing the nonconvex model is more difficult, the solution of the nonconvex function can only represent the local but not the global. The BP algorithm is an algorithm for updating parameters and is mainly applied to deep neural networks. In this article, we will study the volume holographic image library technology, design the basic optical storage path, realize single-point multistorage in the medium, and multiplex technology with simple structure to increase the information storage capacity of volume holography. We have studied a method to read out the holographic image library with the same diffraction efficiency. The test part of the system is to test the entire facial image pattern recognition system. The reliability and stability of the system have been tested for performance and function. Successful testing is the key to the quality and availability of the system. Therefore, this article first analyzes the rules of deep learning, combines the characteristics of image segmentation algorithms and pattern recognition models, designs the overall flow chart of the pattern recognition system, and then conducts a comprehensive inspection of the test mode to ensure that all important connections in the system pass through high-quality testing is guaranteed. Then in the systematic research of this paper, based on the composite threshold segmentation method of histogram polynomial fitting and the deep learning method of the U-NET model, the actual terahertz image is cut, and the two methods are organically combined to form terahertz. The coaxial hologram reconstructs the image for segmentation and finally completes the test of the system. After evaluation, the performance of the system can meet the needs of practical applications.

ZNF671 Inhibits the Proliferation and Metastasis of NSCLC via the Wnt/ß-Catenin Pathway.

BACKGROUND: Lung cancer is the most common cancer in the world and is the main cause of cancer-related death. Revealing the potential mechanism of malignant characteristics of lung cancer is urgent for treating this disease effectively. Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. The role of ZNF671 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of this study was to investigate the function and mechanism of ZNF671 in NSCLC. METHODS: ZNF671 expression in NSCLC cells and tissues were detected by Real-Time PCR, Western blot and TCGA databases. Then, we evaluated the prognostic value of ZNF671 expression in NSCLC using the Kaplan-Meier plotter (KM plotter) and TCGA databases. Moreover, the function of ZNF671 in the proliferation and metastasis of lung cancer was investigated by MTT assay, colony formation assay, in vivo experiment, EdU assay, wound healing assay, transwell assay, and 3D culture assay. Luciferase reporter and subcellular fractionation assays were performed to determine the underlying mechanism of ZNF671-mediated proliferation and metastasis of NSCLC. RESULTS: ZNF671 expression was significantly reduced in both NSCLC cell lines and clinical specimens compared to that in normal controls. The survival analysis results indicated that the downregulation of ZNF671 significantly correlates with poor prognosis and predicts a shorter overall survival and post-progression survival among NSCLC patients. Ectopic overexpression of ZNF671 dramatically restrains, whereas silencing ZNF671 enhanced, cell proliferation and metastasis of NSCLC. Mechanically, gene set enrichment analysis (GSEA) showed that the expression of ZNF671 was significantly correlated with Wnt/ß-catenin signaling. Simultaneously, our results confirm that the overexpression of ZNF671 inhibits cell cycle progression and metastasis by weakening the Wnt/ß-catenin pathway, and then downregulating the expression of downstream target genes CyclinD1 and MMP9. CONCLUSION: This study found that the overexpression of ZNF671 restrains the proliferation and metastasis of lung cancer through inhibiting Wnt/ß-catenin signaling pathway. Furthermore, our current results provide important insights into ZNF671 as an excellent predictive biomarker for NSCLC, thus providing a novel perspective for the treatment of NSCLC.

Successful management of germanium poisoning-induced multiple organ dysfunctions by combined blood purification therapy.

Background: Blood purification therapy has not been applied in the detoxification of germanium compounds. This report described a case of germanium poisoning with renal failure, liver dysfunction, and acute pancreatitis which was successfully treated by continuous venovenous hemodiafiltration (CVVHDF) combined with plasmapheresis.Case report: A 58-year-old male was admitted to a local hospital due to polydipsia, polyuria, and weight loss for 2 months. The patient was definitely diagnosed with germanium poisoning and was treated with blood purification therapy, CVVHDF combined with plasmapheresis. The blood and urinary germanium concentrations decreased rapidly during the first week after the combined blood purification therapy. The blood germanium concentration gradually reduced to within the normal range within the next three weeks and fluctuated at a normal level. However, the urinary germanium concentration exceeded the normal level after three months, indicating an accumulation of germanium in the organs and tissues. The patient's clinical symptoms ameliorated and the functions of kidney, liver and pancreatitis gradually recovered.Conclusion: Combined CVVHDF with plasmapheresis is an effective treatment for germanium poisoning and the associated multiple organ dysfunctions.

Complete dehalogenation of bromochloroacetic acid by liquid phase catalytic hydrogenation over Pd/CeO2 catalysts.

Bromochloroacetic acid is classified as one of the typical disinfection byproducts (DBPs). In this work, supported palladium catalysts on different supports (CeO2, Al2O3, SiO2 and activated carbon (AC)) (labelled as Pd/support) were synthesized via the deposition-precipitation method (D-P method) and their activities for the complete dehalogenation of bromochloroacetic acid by liquid phase catalytic hydrogenation were evaluated. Comprehensive characterizations of the catalysts were conducted by powder X-ray diffraction (XRD), transmission electron microscopy (TEM), point of zero charge (PZC), X-ray photoelectron spectroscopy (XPS) and CO chemisorption. Results indicated that the PZCs of the supports varied with each other. The stronger Pd-support interaction and higher Pd dispersion of Pd/CeO2 and Pd/Al2O3 than those of Pd/AC and Pd/SiO2 were confirmed by X-ray photoelectron spectroscopy and CO chemisorption. Pd/CeO2 had a higher ratio of positively charged Pd to metallic Pd (Pdn+/Pd0) than Pd/Al2O3 and Pd/AC due to a stronger metal-support interaction. Accordingly, a negligible bromochloroacetic acid conversion was observed on Pd/SiO2, whereas bromochloroacetic acid was found to be readily decomposed on Pd/CeO2, Pd/Al2O3 and Pd/AC. However, the dechlorination reaction could not further proceed on Pd/Al2O3 and Pd/AC catalysts after the bromine functionality was removed from bromochloroacetic acid. A complete dehalogenation of bromochloroacetic acid occurred only on Pd/CeO2. Furthermore, the dechlorination rate constants of monochloroacetic acid and bromochloroacetic acid over Pd(1.40)/CeO2 were 0.018 and 0.031 min-1 respectively, confirming an induced synergistic effect due to the existence of bromine atoms. It was worth noting that a stepwise-concerted pathway was verified during the liquid phase catalytic hydrodehalogenation of bromochloroacetic acid.

Hepatitis B virus core protein dimer­dimer interface is critical for viral replication.

Hepatitis B virus (HBV) core protein (HBc) serves pivotal roles in the viral life cycle, particularly serving as the basic unit for capsid assembly, and is closely associated with HBV genome replication and progeny virion production. Previous studies have demonstrated that HBc has at least two functional interfaces; two HBc monomers form a homodimer via an intradimer interface, and then 90 or 120 homodimers form an icosahedral capsid via a dimer­dimer interface. In the present study, the role of the HBc dimer­dimer interface in HBV replication was investigated. A panel of residues located at the dimer­dimer interface were identified based on the crystal structure of HBc. Native gel electrophoresis and western blotting revealed that, despite mutations in the dimer­dimer interface, HBc formed a capsid­like structure, whereas mutations at amino acid residues 23­39 completely disrupted capsid assembly. Using denaturing gel electrophoresis, Southern and Northern blotting, and quantitative polymerase chain reaction, it was demonstrated that none of the mutations in the dimer­dimer interface supported pregenomic RNA encapsidation or DNA replication. In addition, these mutants interacted with the wild-type (WT) HBc monomer and inhibited WT genome replication and virion production in a dose­dependent manner. However, the quantity of covalently closed circular DNA in the nucleus was not affected. The present study highlighted the importance of the HBc dimer­dimer interface for normal capsid function and demonstrated that the HBc dimer­dimer interface may be a novel antiviral target.

Human hepatocytes express absent in melanoma 2 and respond to hepatitis B virus with interleukin-18 expression.

Absent in melanoma 2 (AIM2) is a recently recognized cytoplasmic receptor which could sense cytoplasmic double-stranded DNA (dsDNA). After AIM2 detects the presence of parasitic nucleic acids (dsDNA) derived from invasive bacteria or viral genomes (for example, vaccinia virus and cytomegalovirus) within infected cells, AIM2 inflammasome could be formed. The formed AIM2 inflammasome could induce innate immune response and increase expressions of IL-1ß and IL-18. Hepatitis B virus (HBV) is a hepatotropic, non-cytopathic double-stranded DNA virus. The immune response to viral antigens or virus is thought to be responsible for both liver damage and viral clearance in patients with HBV infection. However, there are no reports about whether AIM2 inflammasome exists in hepatocytes. In the present study, we investigated the presence and activity of AIM2 inflammasome in human hepatocytes. We found that AIM2 was expressed in cytoplasm of hepatocytes, and IL-18 expression was increased after AIM2 sensed HBV in hepatocytes in vitro. These results showed that AIM2 inflammasome was active in hepatocytes. We also found that hepatic AIM2 expression of chronic hepatitis B (CHB) patients was higher than that of controls. Hepatic AIM2 expression levels were positively correlated to the severity of liver inflammation. IL-18 is already considered to be associated with hepatic injury during HBV infection. In conclusion, we, therefore, believe that AIM2 inflammasome in hepatocytes might play an important role in the development and maintenance of HBV-related hepatitis.

CYP2J3 gene delivery up-regulated adiponectin expression via reduced endoplasmic reticulum stress in adipocytes.

Ample evidences demonstrate that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play crucial and diverse roles in cardiovascular homeostasis. We and others have identified that EETs exert a beneficial role on insulin resistance and diabetes. This study investigated the effects of CYP2J3 epoxygenase gene delivery on adiponectin expression in rats treated with high-fat (HF) diet. CYP2J3 gene delivery in vivo increased EET generation, enhanced adiponectin expression and secretion and accompanied by activation of adiponectin downstream signaling, and decreased insulin resistance as determined by plasma insulin levels, insulin resistance index and glucose tolerance test, as well as phosphorylation of protein kinase B in both liver and muscle. Furthermore, CYP2J3 overexpression prevented HF diet-induced endoplasmic reticulum (ER) stress in adipose tissue of rats. Also, CYP2J3 gene transfection and exogenous administration of EETs inhibited thapsigargin-induced ER stress with increased adiponectin expression and secretion in differentiated 3T3-L1 adipocytes. Thus, CYP2J3 gene delivery up-regulated adiponectin expression and excretion in adipose tissue of rats treated with HF diet through inhibition of ER stress, which can decrease adiponectin expression. These results further highlight the beneficial roles of the CYP epoxygenase 2J3 and its metabolites EETs on adiponectin expression and secretion.

Gene delivery of cytochrome p450 epoxygenase ameliorates monocrotaline-induced pulmonary artery hypertension in rats.

Pulmonary arterial hypertension (PAH) is a life-threatening disease that leads to progressive pulmonary hypertension, right heart failure, and death. Endothelial dysfunction and inflammation were implicated in the pathogenesis of PAH. Epoxyeicosatrienoic acids (EETs), products of the cytochrome P450 epoxygenase metabolism of arachidonic acid, are potent vasodilators that possess anti-inflammatory and other protective properties in endothelial cells. We investigated whether gene delivery with the human cytochrome P450 epoxygenase 2J2 (CYP2J2) ameliorates monocrotaline (MCT)-induced pulmonary hypertension in rats. Significant pulmonary hypertension developed 3 weeks after the administration of MCT, but gene therapy with CYP2J2 significantly attenuated the development of pulmonary hypertension and pulmonary vascular remodeling, without causing changes in systemic arterial pressure or heart rate. These effects were associated with increased pulmonary endothelial NO synthase (eNOS) expression and its activity, inhibition of inflammation in the lungs, and transforming growth factor (TGF)-ß/type II bone morphogenetic protein receptor (BMPRII)-drosophila mothers against decapentaplegic proteins (Smads) signaling. Collectively, these data suggest that gene therapy with CYP2J2 may have potential as a novel therapeutic approach to this progressive and oftentimes lethal disorder.

Effects and mechanism of irbesartan on tubulointerstitial fibrosis in 5/6 nephrectomized rats.

Tubulointerstitial fibrosis (TIF) is a common pathological feature of end-stage kidney disease. Previous studies showed that upregulation of TGFbeta1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction. This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFbeta1 in the rodent model of chronic renal failure involving 5/6 nephrectomy. The results showed that irbesartan significantly attenuated the rise in blood pressure and tubulointerstitial injury observed in this model. Masson staining of the renal tissue revealed that there appeared severe renal tubule atrophy and fibrosis in operation group, but the lesion was attenuated mostly in irbesartan-treated group. Immunohistochemistry showed that irbesartan treatment apparently decreased the protein expression of TGFbeta1 which was up-regulated in operation groups. Western blot showed that irbesartan treatment down-regulated the expression of TGFbeta1, phosphorylated smad2 (p-smad2), AT1R and phosphorylated p38 (p-p38) MAPK, but significantly up-regulated the protein expression of smad6 as compared with operation group. These findings suggest that irbesartan attenuates hypertension and reduces the development of TIF in rats with 5/6 renal mass reduction via changes in the expression of these proteins at least including smad6, TGF-beta1, p-smad2, AT1 and p-p38 MAPK.

Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice.

OBJECTIVE: Accumulating evidence suggests that cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play crucial and diverse roles in cardiovascular homeostasis. The anti-inflammatory, antihypertensive, and pro-proliferative effects of EETs suggest a possible beneficial role for EETs on insulin resistance and diabetes. RESEARCH DESIGN AND METHODS: This study investigated the effects of CYP2J3 epoxygenase gene therapy on insulin resistance and blood pressure in diabetic db/db mice and in a model of fructose-induced hypertension and insulin resistance in rats. RESULTS: CYP2J3 gene delivery in vivo increased EET generation, reduced blood pressure, and reversed insulin resistance as determined by plasma glucose levels, homeostasis model assessment insulin resistance index, and glucose tolerance test. Furthermore, CYP2J3 treatment prevented fructose-induced decreases in insulin receptor signaling and phosphorylation of AMP-activated protein kinases (AMPKs) in liver, muscle, heart, kidney, and aorta. Thus, overexpression of CYP2J3 protected against diabetes and insulin resistance in peripheral tissues through activation of insulin receptor and AMPK pathways. CONCLUSIONS: These results highlight the beneficial roles of the CYP epoxygenase-EET system in diabetes and insulin resistance.

Effects and Mechanism of Irbesartan on Tubulointerstitial fibrosis in 5/6 Nephrectomized Rats / 华中科技大学学报（医学）（英德文版）

Tubulointerstitial fibrosis(TIF)is a common pathological feature of end-stage kidney disease.Previous studies showed that upregulation of TGFβ1 notably contributed to the chronic renal injury and irbesartan halted the development of TIF in rats with 5/6 renal mass reduction.This study was to investigate the effects of irbesartan on chronic TIF and the mechanism involved TGFβ1 in the rodent model of chronic renal failure involving 5/6 nephrectomy.The results showed that irbesartan significantly attenuated the rise in blood pressure and tubulointerstitial injury observed in this model.Masson staining of the renal tissue revealed that there appeared severe renal tubule atrophy and fibrosis in operation group,but the lesion was attenuated mostly in irbesartan-treated group.Immunohistochemistry showed that irbesartan treatment apparently decreased the protein expression of TGFβ1 which was up-regulated in operation groups.Western blot showed that irbesartan treatment down-regulated the expression of TGFβ1,phosphorylated smad2(p-smad2),AT1R and phosphorylated p38(p-p38)MAPK,but significantly up-regulated the protein expression of smad6 as compared with operation group.These findings suggest that irbesartan attenuates hypertension and reduces the development of TIF in rats with 5/6 renal mass reduction via changes in the expression of these proteins at least including smad6,TGF-β1,p-smad2,AT1 and p-p38 MAPK.

Identification and characterization of a functional Candida albicans homolog of the Saccharomyces cerevisiae TCO89 gene.

As one of the components of target of rapamycin complex 1 (TORC1), ScTco89p is involved in rapamycin sensitivity and cellular integrity in Saccharomyces cerevisiae. Here we provide evidence showing that deletion of ScTCO89 causes yeast cells to be hypersensitive to salt stress in a high osmolarity glycerol pathway-independent fashion. In addition, we have identified and characterized a functional Candida albicans homolog (CaTCO89) of ScTCO89, which encodes a protein of 708 amino acids that shows overall 15% identity with ScTco89p at the amino acid level. However, CaTCO89 could complement the functions of ScTCO89 in rapamycin sensitivity, salt tolerance, and cellular integrity. Candida albicans cells disrupted for CaTCO89 are also sensitive to rapamycin and lithium salt, but not susceptible to challenges to cellular integrity.