Exploring the mechanism and experimental validation of Fuzi Lizhong Tang in treating gastric cancer based on network pharmacology and molecular docking.

OBJECTIVE: This study aimed to explore the mechanism of Fuzi Lizhong Tang (FZLZT) in treating gastric cancer using network pharmacology and molecular docking, and to validate the results through in vitro experiments. MATERIALS AND METHODS: Active ingredients and target genes of FZLZT were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, while disease targets of gastric cancer were collected from GeneCards, OMIM, and DrugBank databases. The "herb-active ingredient-target gene" network was constructed using Cytoscape software, and core active ingredients were obtained through topological analysis. Protein-protein interaction analysis was performed using the STRING database, and core targets were obtained through topological analysis. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis were performed using the DAVID database. Molecular docking was conducted using AutoDock Vina software to verify the interaction between core ingredients and core targets. Cholecystokinin octapeptide (CCK-8) assay was used to determine the proliferation inhibition effect of FZLZT on AGS, BGC823, HGC-27, MGC-803, and SGC-7901 gastric cancer cell lines, and ANNEXIN V-FITC/PI double staining combined with flow cytometry was used to measure the cell apoptosis rate. RESULTS: Network pharmacology analysis revealed 117 active ingredients and 261 target genes of FZLZT, and 211 overlapping targets with gastric cancer. Ten core active ingredients were identified through topological analysis, including quercetin, 7-methoxy-2-methyl isoflavone, kaempferol, luteolin, naringenin, isorhamnetin, quercetagetin, glycyrrhizic acid A, ß-sitosterol, and medioresinol. GO and KEGG enrichment analysis showed that the mechanism of FZLZT in treating gastric cancer mainly involves cancer, inflammation, metabolism, and blood rheology-related pathways, and may act through 7 core targets (CDKN1A, MYC, MAPK1, MAPK14, RB1, RELA, and STAT3). Molecular docking results further confirmed the prediction of network pharmacology. In vitro experiments showed that FZLZT inhibited the proliferation of all five gastric cancer cell lines, with the strongest effect on SGC-7901 cells, and induced apoptosis in SGC-7901 cells. CONCLUSIONS: FZLZT has a multi-component, multi-target, and multi-pathway characteristic in treating gastric cancer. Its active ingredients may regulate the expression of proteins such as CDKN1A, MYC, MAPK1, MAPK14, RB1, RELA, and STAT3 to activate cancer-related signaling pathways to achieve its therapeutic effect.

[The relationship between classroom environment and myopia].

Objective: Based on a cohort and intervention study of the Eastern Chinese Student Surveillance, Cohort and Intervention Study (ES-SCI), this research aims to explore the correlation between monitor of the school environment and longitudinal data on myopia and provide evidence for the government myopia intervention strategy. Methods: This survey adopts the stratified cluster sampling method with the school as the unit. Students from grade 1 to grade 3 were selected according to the whole class to monitor the school environment in the classroom. Students will use the full-automatic computer optometer (TOPCON RM800) to conduct optometry from 2019 to 2021 under the condition of mydriasis to perform refractive eye examinations. Meantime eye axis length monitoring was also conducted. Cox proportional risk regression model was used to explore the relationship between school environmental monitoring and the occurrence and development of students' myopia. Results: From 2019 to 2021, 2 670 students from 77 classrooms participated in the observation study. The students' diopter after right/left eye mydriasis decreased in varying degrees (P<0.001), and the axial length of the right/left eye increased in various degrees (P<0.001). The weighted qualified rate of per capita area of primary school classrooms increased from 18.0% in 2019 to 26.0% in 2021, the weighted average illuminance pass rate of blackboard surface increased from 23.8% in 2019 to 26.4% in 2021, and the weighted average illuminance pass rate of classroom table decreased from 86.7% in 2019 to 77.5% in 2021. The trend chi-square test was significant (P<0.05). Cox proportional risk regression showed that after correcting for the grade, gender, parental myopia, diet, sleep, near work (sitting posture, working time, electronic mobile equipment, eye exercises), and outdoor activities, the per capita area of 1.36- m2 was the protective factor of eye axis length (HR=0.778, 95%CI: 0.659-0.918, P=0.003); The average reflection ratio of blackboard 0.15-0.19 was the protective factor of eye axis length (HR=0.685, 95%CI: 0.592-0.793, P<0.001); The average illumination of the blackboard 150-, 300-, 500- lx was the protective factor of the eye axis length (HR=0.456, 95%CI: 0.534-0.761, P<0.001; HR=0.794, 95%CI: 0.705-0.895, P<0.001; HR=0.690, 95%CI: 0.619-0.768, P<0.001). The blackboard evenness 0.40-0.59 was the risk factor of eye axis length (HR=1.528, 95%CI: 1.018-2.293, P=0.041), and the blackboard evenness 0.80- was the protection factor of eye axis length (HR=0.542, 95%CI: 0.404-0.726, P<0.001). The evenness of the desktop 0.40-0.59 was the protective factor of eye axis length (HR=0.820, 95%CI: 0.698-0.965, P=0.017). The average illuminance of 150-, 300-, 500- lx was the protective factor of a diopter (HR=0.638, 95%CI: 0.534-0.761, P<0.001; HR=0.911, 95%CI: 0.848-0.978, P=0.011; HR=0.750, 95%CI: 0.702-0.801, P<0.001). The average illumination of desktop 500- lx was a protective factor of a diopter (HR=0.855, 95%CI: 0.763-0.958, P=0.007). Conclusion: School environmental monitoring indicators, such as meeting per capita area standards, passing blackboard, and desk top-related indicators, all play protective effects on myopia development in students.

[Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure].

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.

[Immune cells role and their new potential therapeutic targets in the pathogenesis of alcoholic liver disease].

The key factors driving the pathogenesis of alcoholic liver disease are still not fully understood. At present, it is believed that the direct toxic effects of ethanol and its intermediate metabolite acetaldehyde can cause oxidative stress, mitochondrial damage, adipogenesis, malnutrition, intestinal endotoxin leakage, etc., thereby participating in the occurrence and progression of alcoholic liver disease. Among the many pathogenic factors that have been revealed, the immunological mechanism plays an important role. Therefore, the role of immune cells and inflammatory mediators has attracted much attention. This article reviews and summarizes the new progress of specific immune cell mechanisms involved in innate and adaptive immune response during the formation and development of alcoholic liver disease, and proposes potential therapeutic targets and clinical trials of related new drugs, which may improve the re-recognition of molecular mechanism and treatment expectation in clinical practice.

Performance of the BL03U beamline at SSRF.

The vacuum ultraviolet beamline BL03U with a photon energy range from 7 eV upwards has been constructed at the 3.5 GeV Shanghai Synchrotron Radiation Facility. Equipped with an APPLE-Knot undulator, this beamline is dedicated to angle-resolved photoemission spectroscopy. An energy-resolving power of higher than 4.6 × 104 has been achieved in the photon energy range 21.6-48 eV, which is almost the same as the theoretical estimation.

Research Progress?on?Age?Determination?of?Venous?Thrombosis in Forensic Medicine.

ABSTRACT: Pulmonary thromboembolism （PTE）, which is caused by detachment of venous thrombosis, is a common cause of sudden death in forensic practice. In the cases which die of PTE after trauma or die of PTE during non-thrombosis disease hospitalization, forensic pathologists are required to analyze the time sequence between trauma or medical practice and venous thrombosis, and then analyze their causal relationship. This review summarizes the history of thrombus age estimation and recent advances in forensic medicine, and then gives a brief outlook for future research to provide reference for forensic identification of PTE and guide follow-up studies.

Profiling of miRNAs in neonatal cloned bovines with collapsed lungs and respiratory distress.

Neonatal respiratory distress is a major mortality factor in cloned animals; however, the pathogenesis of this disease has rarely been investigated. Previous studies have shown that miRNAs regulate critical genes related to lung development, cell differentiation, surfactant synthesis, secretion and lung disease. This study aimed to examine differentially expressed miRNAs in collapsed lungs of cloned bovine neonates and normal lungs in order to identify key pathways and functions that might be related to the pathogenesis of neonatal respiratory distress. In this study, miRNA transcriptomes of collapsed lungs of neonatal cloned bovines and normal lungs were analysed by next-generation sequencing and the results were validated using quantitative real-time PCR (qRT-PCR). A total of 177 differentially expressed miRNAs were identified in the two groups (fold change > 2, RPM ≥ 5), some of which were associated with type II cell differentiation, for example, mmu-miR-29a-5p_L-2R+1, hsa-miR-200c-5p_L-1R+1 and mmu-miR-18a-3p_R+1. The differentially expressed miRNAs were predicted to 6,031 target genes. By Gene Ontology (GO) and Kyoto Encyclopeida of Genes and Genomes (KEGG) DATA base, 133 significant GO terms (p < .05) and 13 significant KEGG pathways (p < .05) were obtained. Many of them were associated with lung development and surfactant homoeostasis, such as lipid biosynthetic processes, protein transport, endocytosis, lysosome, endosome, Golgi apparatus and membrane. Our results of miRNAs express profiles may partially explain the respiratory distress and lung collapse in neonatal bovine clones and could provide novel insights into roles of miRNAs in regulation of lung collapse and neonatal respiratory distress in cloned farm animals.

[Reliability and validity of the Chinese version on Alcohol Use Disorders Identification Test].

Objective: To assess the reliability and validity of the Chinese version on Alcohol Use Disorders Identification Test (AUDIT) among medical students in China and to provide correct way of application on the recommended scales. Methods: An E-questionnaire was developed and sent to medical students in five different colleges. Students were all active volunteers to accept the testings. Cronbach's α and split-half reliability were calculated to evaluate the reliability of AUDIT while content, contract, discriminant and convergent validity were performed to measure the validity of the scales. Results: The overall Cronbach's α of AUDIT was 0.782 and the split-half reliability was 0.711. Data showed that the domain Cronbach's α and split-half reliability were 0.796 and 0.794 for hazardous alcohol use, 0.561 and 0.623 for dependence symptoms, and 0.647 and 0.640 for harmful alcohol use. Results also showed that the content validity index on the levels of items I-CVI) were from 0.83 to 1.00, the content validity index of scale level (S-CVI/UA) was 0.90, content validity index of average scale level (S-CVI/Ave) was 0.99 and the content validity ratios (CVR) were from 0.80 to 1.00. The simplified version of AUDIT supported a presupposed three-factor structure which could explain 61.175% of the total variance revealed through exploratory factor analysis. AUDIT semed to have good convergent and discriminant validity, with the success rate of calibration experiment as 100%. Conclusion: AUDIT showed good reliability and validity among medical students in China thus worth for promotion on its use.

Adiponectin partially rescues high glucose/high fat-induced impairment of mitochondrial biogenesis and function in a PGC-1α dependent manner.

OBJECTIVE: Plasma adiponectin (APN) levels are decreased in diabetic patients. Dysfunctional mitochondrial biogenesis is involved in type 2 diabetes (T2DM) pathogenesis, by unclear mechanisms. The present study determined (1) whether myocardial mitochondrial biogenesis was impaired in cardiomyocytes exposed to a high glucose/high fat (HGHF) medium (a T2DM in vitro model), (2) the effects of APN administration upon mitochondrial biogenesis in cardiomyocytes affected by HGHF incubation, and 3) the involved underlying mechanisms. MATERIALS AND METHODS: Neonatal rat ventricular myocytes (NRVMs) were isolated and incubated in HGHF medium. Mitochondrial function was assessed by ATP content, and fluorescent microscopic analysis of myocardial apoptosis was determined by TUNEL staining and caspase-3 activity. RESULTS: HGHF treatment reduced mitochondrial biogenesis, altered mitochondrial structure, and induced mitochondrial dysfunction in NRVMs. Administration of APN partially rescued these effects. However, siRNA-mediated knockdown of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) significantly blocked the beneficial effects of APN in mitochondria and cardiomyocytes subjected to hypoxia/reoxygenation injury. CONCLUSIONS: In the current study, we have provided the direct in vitro evidence that APN partially rescues HGHF-induced impairment of mitochondrial biogenesis and function via PGC-1α-mediated signaling.

RESEARCH ARTICLE Molecular cloning and expression analysis of a matrix Gla protein gene in the spinyhead croaker, Collichthys lucidus.

The matrix Gla (gamma-carboxyglutamic acid-rich) protein (MGP), a vitamin K-dependent and Gla-containing protein, is a calcification inhibitor that mainly functions in tissue calcification and mineralization. In this study, we obtained the complete cDNA sequence of MGP from the spinyhead croaker (Collichthys lucidus), which we named Cl-MGP. Cl-MGP was 923 bp long with a 384-bp open reading fragment that encoded 127 amino acids. The predicted MGP protein sequence contained a 19-residue hydrophobic signal peptide, suggesting that it possesses secretory characteristics. The Gla domain and the invariant unit ErraEtCedyspC, which has been identified in all known vitamin K-dependent vertebrate proteins, were highly conserved in Cl-MGP, suggesting that it uses the same mechanism to function as the known proteins. An alignment analysis revealed that Cl-MGP had the highest identity with Larimichthys crocea (93%), which had lost five amino acid residues in the C-terminal. A quantitative real-time polymerase chain reaction revealed that Cl-MGP expression was highest in the gill, followed by the cholecyst and spleen, with almost no expression in the blood, muscle, or testes. The high Cl-MGP expression in the gill is similar to that observed in other fish species, but the relatively high expression found in the cholecyst and spleen is not seen in all species. Future studies should investigate the tissue distributions of both mRNA and proteins in different species, in order to understand the function and evolution of MGP in different species.

Molecular cloning and gene expression analysis of cystatin C-like proteins in spinyhead croaker Collichthys lucidus.

Cystatins are natural tight-binding reversible inhibitors of cysteine proteases. In this study, a cDNA library was constructed from Collichthys lucidus using the SMART technique. A complete cDNA sequence with high identity to the conserved sequence of the cystatin C gene was cloned from the library using EST analysis and rapid amplification of cDNA ends (RACE), then subjected to further investigation. The full-length cDNA of cystatin C from C. lucidus (Clcys) was 699 bp long, including a 5'-terminal untranslated region (5'-UTR) of 52 bp, a 3'-UTR of 290 bp, and an open-reading frame of 357 bp. The gene encoded a polypeptide of 118 amino acids, constituting a predicted molecular weight of 12.875 kDa and a theoretical isoelectric point of 8.81. The amino acid sequence of Clcys possessed typical features of type II cystatins and had the highest identity with cystatin C of Pseudosciaena crocea (89%); therefore, it clustered with the cystatin C group in the UPGMA phylogenetic tree. Quantitative real-time reverse transcription analysis revealed that the highest expression was found in the kidney, followed by the liver, heart, and testis, with the lowest expression in muscle. Interestingly, Clcys had relatively low identity with cystatin C genes from other fish and mammals, and its expression pattern did not possess features of a housekeeping gene. Based on these findings, we suspect that the classification of cystatins in fish is somewhat confusing, and the identification of more cystatin gene sequences is needed before a definite conclusion can be drawn.

Characterization, molecular cloning, and expression analysis of Ecsit in the spinyhead croaker, Collichthys lucidus.

Evolutionarily conserved signaling intermediate in Toll pathways (Ecsit) is reported to play an essential role in innate immunity, embryogenesis, and assembly or stability of the mitochondrial complex I. In this study, the full-length cDNA of Ecsit was cloned from the spinyhead croaker Collichthys lucidus based on the expressed sequence tags from our cDNA library constructed using the SMART technique. The cDNA was 1669 bp long, including a 5'-terminal untranslated region (UTR) of 121 bp, a 3'-terminal UTR of 183 bp, and an open reading frame of 1365 bp encoding a 454-amino acid polypeptide. The estimated molecular weight of C. lucidus Ecsit (ClEcsit) was 52.50 kDa with an isoelectric point of 6.14, and contained a typical Ecsit domain that is conserved in other Ecsits. Multiple alignment of ClEcsit with other selected Ecsits suggested that some amino acid residues were highly conserved. Phylogenetic analysis indicated that ClEcsit was more similar to its identities in Sciaenidae and grouped with Ecsits from other Perciformes. Quantitative real-time reverse transcription PCR analysis revealed broad expression of ClEcsit and the transcript was strongly expressed in the gill and weakly expressed in other tissues.

Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials.

Dyslipidemia is one of the most common adverse effects in schizophrenia patients treated with antipsychotics. However, there are no established effective treatments. In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities. In total, 201 schizophrenia patients with dyslipidemia after being treated with an antipsychotic were assigned to take 1000 mg day-1 metformin (n=103) or placebo (n=98) for 24 weeks, with evaluation at baseline, week 12 and week 24. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) levels. After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P<0.0001); and 25.3% of patients in the metformin group had LDL-C ≥3.37 mmol l-1, which is significantly <64.8% in the placebo group (P<0.001) at week 24. Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol. The treatment effects on weight and insulin resistance appeared at week 12 and further improved at week 24, but the effects on improving dyslipidemia only significantly occurred at the end of week 24. We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia.

Feasibility of radical gastrectomy for elderly patients with gastric cancer.

BACKGROUND: The aim of this study was to evaluate the short-term safety and long-term benefits of radical gastrectomy for gastric cancer in elderly patients. METHODS: A total of 729 patients undergoing gastrectomy for adenocarcinoma between December 2008 and December 2011 were enrolled in this retrospective study. Patients were divided into three groups: young group (<65 years), young-old group (65-79 years) and old-old group (≥80 years). RESULTS: Lower albumin levels, higher ASA grades, comorbidities, tumors located in the upper third of the stomach and advanced TNM stages were more common in the young-old and old-old age groups. Overall complications increased significantly with advancing age (15.4%, 24.9%, 48.7%, respectively); respiratory complications largely contributed to the dramatic increase. Severe complications were similar between the young and young-old groups (3.9%, 3.7%), but were significantly increased in the old-old group (12.8%). In multivariate analysis, old-old age, multiple comorbidities and no epidural use were strong predictors for overall complications. Both overall survival and disease-specific survival (DSS) rates declined with advancing age. Multivariate analysis showed that old-old age and TNM stage ≥ II were major independent risk factors for the DSS rate. When adjusted for confounding factors, young-old age was not a risk factor. The median survival time for the old-old patients with stage III tumors was 12.9 months. CONCLUSIONS: It is relatively safe and beneficial for young-old patients to undergo radical gastrectomy as the young patients. However, the decision to perform radical gastrectomy for old-old patients with TNM stage III tumors should be made carefully.

Characterization of hemocyanin from the mud crab Scylla paramamosain and its expression analysis in different tissues, at various stages, and under Vibrio parahaemolyticus infection.

Hemocyanin is an important respiratory protein in many arthropod and mollusk species. Here, four cDNAs (SpHc1, SpHc2, SpHc3, and SpHc4), encoding distinct hemocyanin subunits from Scylla paramamosain were cloned using EST analyses and the rapid amplification of cDNA ends. The four full-length cDNA fragments (SpHc1-4) were 2281, 2002, 2184, and 2069 bp, respectively, and they encoded four putative proteins (570-676 amino acids) with a molecular mass of ~65.0-76.8 kDa. Quantitative real-time PCR analyses revealed that the four genes were mainly expressed in the hepatopancreas, testis, and hemocytes. SpHc mRNA expression during continuous developmental stages in zoeal phases (Z1, Z2, Z3, Z4, and Z5), megalopa, and juvenile crab I stages were also detected. The expression levels of SpHc3 and SpHc4 were higher than that of SpHc1 and SpHc2 during the first six stages, and they sharply declined during the juvenile stage. After infection with Vibrio parahaemolyticus, the temporal expression of both the four SpHc mRNAs in the megalopa stage rapidly declined during the first 3 h, followed by upregulation and peak expression at 12 h after the challenge. The expression levels of the four SpHc subunits were upregulated at 48 h after the challenge, and were then gradually downregulated. These findings suggest that hemocyanin may potentially be involved in the crab immune response, and that the role of the four subunits may differ in different tissues and during various developmental stages.

Characterization and expression analysis of the prophenoloxidase activating factor from the mud crab Scylla paramamosain.

Prophenoloxidase activating factors (PPAFs) are a group of clip domain serine proteinases that can convert prophenoloxidase (pro-PO) to the active form of phenoloxidase (PO), causing melanization of pathogens. Here, two full-length PPAF cDNAs from Scylla paramamosain (SpPPAF1 and SpPPAF2) were cloned and characterized. The full-length SpPPAF1 cDNA was 1677 bp in length, including a 5'-untranslated region (UTR) of 52 bp, an open reading frame (ORF) of 1131 bp coding for a polypeptide of 376 amino acids, and a 3'-UTR of 494 bp. The full-length SpPPAF2 cDNA was 1808 bp in length, including a 5'-UTR of 88 bp, an ORF of 1125 bp coding for a polypeptide of 374 amino acids, and a 3'-UTR of 595 bp. The estimated molecular weight of SpPPAF1 and SpPPAF2 was 38.43 and 38.56 kDa with an isoelectric point of 7.54 and 7.14, respectively. Both SpPPAF1 and SpPPAF2 proteins consisted of a signal peptide, a characteristic structure of clip domain, and a carboxyl-terminal trypsin-like serine protease domain. Expression analysis by qRT-PCR showed that SpPPAF1 mRNA was mainly expressed in the gill, testis, and hemocytes, and SpPPAF2 mRNA was mainly expressed in hemocytes. In addition, SpPPAF1 and SpPPAF2 mRNA was expressed in a time-dependent manner after Vibrio parahaemolyticus challenge. The results showed that expression of both SpPPAF1 and SpPPAF2 was related to the bacterial challenge but the expression patterns differed. These findings suggest that SpPPAF is a serine proteinase and may be involved in the pro-PO activation pathway of the crab innate immune system.

Low-field Switching Four-state Nonvolatile Memory Based on Multiferroic Tunnel Junctions.

Multiferroic tunneling junction based four-state non-volatile memories are very promising for future memory industry since this kind of memories hold the advantages of not only the higher density by scaling down memory cell but also the function of magnetically written and electrically reading. In this work, we demonstrate a success of this four-state memory in a material system of NiFe/BaTiO3/La0.7Sr0.3MnO3 with improved memory characteristics such as lower switching field and larger tunneling magnetoresistance (TMR). Ferroelectric switching induced resistive change memory with OFF/ON ratio of 16 and 0.3% TMR effect have been achieved in this multiferroic tunneling structure.

HOW EXPRESSIONS OF CLAUDIN-1 AND MMP-2 IN RETINOBLASTOMA CORRELATE WITH HISTOLOGICAL DIFFERENTIATION AND OPTIC NERVE INVASION.

Retinoblastoma is a commonly seen and dangerous intraocular malignant tumor in infants. Studies have found that Claudin-1 and MMP-2, whose expressions may be connected, play roles in tissues of retinoblastoma. In this study we analyze and discuss changes of Claudin-1 and MMP-2 expressions, and the correlation between the expressions and retinoblastoma histological differentiation and optic nerve invasion. MaxVisionTM was applied to detect expressions of Claudin-1 and MMP-2 in 45 samples of retinoblastoma and 15 paraffin-embedded samples of normal retina. The correlation between Claudin-1 expression and MMP-2 expression was analyzed based on chi-squared test and Spearman’s correlation test. Positive expressions of Claudin-1 in retinoblastoma were fewer than those in retina; higher positive expressions were found in differentiated tissues than in undifferentiated tissues; while compared to expressions in invasive optic nerves, Claudin-1 expressed more positively in optic nerves without invasion. As for MMP-2, its expressions were higher in retinoblastoma than in normal retina; undifferentiated tissues had higher positive expressions than differentiated tissues, which were not statistically significant; higher positive expressions were detected in invasive optic nerves. Thus, it could be concluded that the correlation between Claudin-1 expression and MMP-2 expression in retinoblastoma was negative. Expressions of Claudin-1 were positively related to histological differentiation and optic nerve invasion of retinoblastoma; while MMp-2 expression had negative correlation with histological differentiation and optic nerve invasion of retinoblastoma. Claudin-1 and MMP-2 played a negative role in the optic nerve invasion and tumor development of retinoblastoma.

Molecular characterization of thioredoxin-1 and thioredoxin reductase activity in mud crab Scylla paramamosain.

The thioredoxin (Trx) system consists of thioredoxin reductase (TrxR), Trx, and nicotinamide adenine dinucleotide phosphate (NADPH). TrxR is an NADPH-dependent oxidoreductase. Trx is a ubiquitous small protein with a redox-active disulfide bridge that plays important regulatory roles in some vital metabolic reactions. In this study, a cDNA sequence (SpTrx1) showing high identity to the first Trx gene was isolated from a hepatopancreas cDNA library of the mud crab Scylla paramamosain. The full-length cDNA of SpTrx1 consisted of 672 bp and contained a complete open reading frame of 318 bp encoding a polypeptide of 105 amino acids. Quantitative real-time polymerase chain reaction analysis revealed that SpTrx1 expression was ubiquitous in various organs of S. paramamosain, including the gill, muscle, heart, hemolymph, testis, and hepatopancreas. SpTrx1 expression was upregulated significantly after Vibrio parahaemolyticus challenge: it obviously rose at 48 h and reached the highest level at 72 h. Furthermore, TrxR activity was detected in the gill, heart, muscle, hemolymph, and hepatopancreas. The relative TrxR activity in different tissues after V. parahaemolyticus injection had the same tendency in each tissue (P < 0.01) as SpTrx1 expression. The TrxR activity increased 2 h after injection, peaked at 8 h, slowly decreased from 12 to 24 h, and returned to normal levels at 48 h. The consistency of the expression between the Trx transcript and TrxR activity demonstrated that Trx was closely related to TrxR in the Trx system in S. paramamosain, suggesting that it may participate in the immune system of mud crabs.