Human intelligence-based metaverse for co-learning of students and smart machines.

This paper proposes a Human Intelligence (HI)-based Computational Intelligence (CI) and Artificial Intelligence (AI) Fuzzy Markup Language (CI&AI-FML) Metaverse as an educational environment for co-learning of students and machines. The HI-based CI&AI-FML Metaverse is based on the spirit of the Heart Sutra that equips the environment with teaching principles and cognitive intelligence of ancient words of wisdom. There are four stages of the Metaverse: preparation and collection of learning data, data preprocessing, data analysis, and data evaluation. During the data preparation stage, the domain experts construct a learning dictionary with fuzzy concept sets describing different terms and concepts related to the course domains. Then, the students and teachers use the developed CI&AI-FML learning tools to interact with machines and learn together. Once the teachers prepare relevant material, students provide their inputs/texts representing their levels of understanding of the learned concepts. A Natural Language Processing (NLP) tool, Chinese Knowledge Information Processing (CKIP), is used to process data/text generated by students. A focus is put on speech tagging, word sense disambiguation, and named entity recognition. Following that, the quantitative and qualitative data analysis is performed. Finally, the students' learning progress, measured using progress metrics, is evaluated and analyzed. The experimental results reveal that the proposed HI-based CI&AI-FML Metaverse can foster students' motivation to learn and improve their performance. It has been shown in the case of young students studying Software Engineering and learning English.

Assessment of Brown and Beige Adipose Tissue Activation in Mice Using PET/CT Imaging.

In response to cold induction, brown adipose tissues (BAT) and emerged brown-like adipocytes (beige adipocytes) in subcutaneous white adipose tissues (WAT browning/beiging) are activated. Thermogenesis is increased during glucose and fatty acid uptake and metabolism in adult humans and mice. This activation of BAT or WAT beiging to generate heat helps to counteract diet-induced obesity. This protocol applies the glucose analog radiotracer 18F-fluorodeoxyglucose (FDG), coupled with positron emission tomography and computed tomography (PET/CT) scanning to evaluate cold-induced thermogenesis in the active BAT (interscapular region) and browned/beiged WAT (subcutaneous adipose region) in mice. The PET/CT scanning technique not only can quantify cold-induced glucose uptake in well-known BAT and beige-fat depots but also helps to visualize the anatomical location of novel uncharacterized mouse BAT and beige fat where cold-induced glucose uptake is high. Histological analysis is further employed to validate signals of delineated anatomical regions in PET/CT images as bona fide mouse BAT or beiged WAT fat depots.

Thioacetamide-Induced Norepinephrine Production by Hepatocytes is Associated with Hepatic Stellate Cell Activation and Liver Fibrosis.

BACKGROUND: Collagen production by activated hepatic stellate cells (HSCs) to encapsulate injury is part of the natural wound-healing response in injured liver. However, persistent activation of HSCs can lead to pathological fibrogenesis. Such persistent HSC activation could be mediated by norepinephrine (NE), a reaction product of dopamine beta-hydroxylase (DBH). OBJECTIVE: To investigate the potential paracrine role of NE in hepatotoxin thioacetamide (TAA)-induced liver fibrosis. METHODS: In TAA-treated mice, fibrotic liver tissue showed significant increases in the mRNA expression of DBH up to 14-fold and collagen up to 7-fold. Immunohistochemical staining showed increased DBH protein expression in fibrotic liver tissue. Parenchymal hepatocyte cell line HepG2 expressed DBH and secreted NE, and the conditioned medium of HepG2 cells promoted collagenesis in nonparenchymal HSC cell line LX-2. TAA treatment increased DBH expression by 170% in HepG2 cells, as well as increased NE by 120% in the conditioned medium of HepG2 cells. The conditioned medium of TAA-treated HepG2 cells was used to culture LX-2 cells, and was found to increase collagen expression by 80% in LX-2 cells. Collagen expression was reduced by pre-treating HepG2 cells with siRNA targeting DBH or by adding NE antagonists to the conditioned medium. RESULTS: Finally, TAA-induced oxidative stress in HepG2 cells was associated with induction of DBH expression. Collectively, our results suggest a potential role for DBH/NE-mediated crosstalk between hepatocytes and HSCs in fibrogenesis. CONCLUSION: From a therapeutic standpoint, antagonism of DBH/NE induction in hepatocytes might be a useful strategy to suppress pathological fibrogenesis.

Characteristics of Thermosensitive and Targeted F127-Triethoxysilane/Gold Nanorod Combined with Photothermal Therapy in Tumor Model Mice.

Even with all the recent technological improvements, cancer remains to be the disease with the highest impact on global health. Due to obviously disadvantages or limitations on traditional therapy, researchers are engaged to search for safely and effective methods in cancers' therapy. Photothermal therapy (PTT) has been employed in treating cancers and several of other diseases. In this study, novel thermosensitive and targeting nanoparticle, C225-silane-F127/gold nanorod (C-SFGR) combined with PTT was investigated in EGFR-overexpressing xenografts mice model. For better light to heat transformation exposed with 808 nm near-infrared (NIR) laser, the diameter of thermosensitive C-SFGR was designed at about 120 nm. To address the biocompatibility, the viability of A549 cell line was greater than 80% under high concentrations of C-SFGR (1,000 µg/mL), indicating its low cytotoxicity. After intravenous injection of C-SFGR and combined with NIR treatment for 2 min in A549 bearing mice, tumors were almost completely shriveled after 2 weeks. For developing as theranostic agent, C-SFGR was then labeled with 67Ga, with radiochemical purity over 98%. These present results suggest that C-SFGR could be also applied as a SPECT-imaging agent and as an effective antitumor agent.

Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice.

Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing "healthy obese" by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [18F] fluorodeoxyglucose-PET/CT (18F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic Ucp1, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic Ucp1, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.

Genetic analysis and plasmid-mediated blaCMY-2 in Salmonella and Shigella and the Ceftriaxone Susceptibility regulated by the ISEcp-1 tnpA-blaCMY-2-blc-sugE.

BACKGROUND: Nontyphoid Salmonella and Shigella can cause gastroenteritis in humans. Ceftriaxone (CRO) has been used to treat their infection, however, development of CRO resistance are often associated with plasmid-mediated blaCMY. Here, we investigated the presence of plasmid-mediated ISEcp-1 tnpA-blaCMY-2-blc-sugE and the role of these genes in regulation of CRO susceptibility in different hosts. METHODS: 194 strains of Salmonella serovars and Shigella were tested for CRO susceptibility. Non-susceptibility strains were examined for plasmid-mediated ISEcp-1 tnpA-blaCMY-2-blc-sugE by PCR amplification, Southern blot, and DNA sequencing. The plasmid profiles were determined by HindIII-digested restriction fragment length polymorphism (RFLP). Four recombinant plasmids with different genes from ISEcp-1 tnpA-blaCMY-2-blc-sugE were constructed and then were transferred into Escherichia coli and different Salmonella serovars to evaluate the CRO susceptibility. RESULTS: Among 20 CRO-nonsusceptible isolates of Salmonella Choleraesuis (5), S. Typhimurium (4), S. Mons (1), S. Stanley (2) and Shigella sonnei (8) with plasmid-mediated blaCMY-2, 19 isolates carried the ISEcp-1 tnpA-blaCMY-2-blc-sugE and only one isolate with tnpA-blaCMY-2. Transformation of these plasmids into E. coli pir116 produced multidrug resistance. Furthermore, PCR-RFLP analysis determined 5 different plasmid profiles and identical RFLP pattern between S. Typhimurium and S. sonnei. Transformation of the recombinant plasmids into E. coli and different Salmonella serovars resulted in phenotypes ranging from susceptible to resistant (especially inducible resistance) to CRO that were dependent on the genes, and host. CONCLUSION: The CRO susceptibility associated with the ISEcp-1 tnpA-blaCMY-2-blc-sugE element is regulated positively by ISEcp-1 tnpA and SugE and negatively regulated by Blc and unknown species-dependent host factor(s).

Integrated response of growth, antioxidant defense and isotopic composition to microplastics in juvenile guppy (Poecilia reticulata).

Microplastics (MPs) pollution becomes a research hotspot and many studies focus on threats of MPs, but few have integrated multi-level indicators to assess response to MPs of organisms. Here we exposed guppy (Poecilia reticulata) to MPs (polystyrene; 32-40 µm diameter) with two concentrations (100 and 1000 µg/L) for 28 days. We found that higher accumulation of MPs appeared in guppy gill than that in gut. MPs had no obvious effect on guppy growth but significantly inhibited the condition factor. Oxidative stress presented in guppy viscera with activated antioxidants. The decline of Na+/K+-ATP activity in guppy indicated that MPs might interfere with the osmotic balance of gills. MPs reduced body molar ratio of C:N and δ13C value, but no apparent impact on δ15N. It implied that MPs probably altered elemental transition. Eventually, through integrated biomarkers response index (IBR) of guppy, we found that catalase activity was the highest index in response to MPs, and the response of growth performance to MPs was lower than that of oxidative stress and element alteration. Risks of MPs aggravated in a concentration-dependent manner. These findings suggested that multi-level IBR approach should be adopted to quantify effects of MPs on aquatic organisms, especially on fish.

Hexavalent lactoside labeled with [18F]AlF for PET imaging of asialoglycoprotein receptor.

Several methods have been developed to label compounds with 18F. However, in general these are laborious and require a multistep synthesis. A method based on the chelation of 18F-aluminum fluoride ([18F]AlF) by 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) was developed recently. The present work was aimed to radiolabel hexavalent lactoside (NOTA-HL) by [18F]AlF method for PET imaging of asialoglycoprotein receptor (ASGPR). METHODS: hexavalent lactoside was conjugated with the NOTA chelate and labeled with 18F in a one-pot method. The labeling procedure was investigated with different amounts of NOTA-HL and aluminum concentration. Radiochemical yield and radiochemical purity were determined by radio-TLC and radio-HPLC respectively. In vitro stability study of [18F]AlF-HL were carried out. PET/CT imaging of normal mice injected with [18F]AlF-NOTA-HL was performed. RESULTS: The Radiochemical yield of [18F]AlF-NOTA-HL was higher with more precursor and optimal Al+ concentration. The radiochemical purity of labeled product was >95% after purified by Sep-Pak cartridge to remove unbound [18F]AlF. The radiolabeling, including purification, was performed in 30 min [18F]AlF-NOTA-HL exhibited good in vitro stability. PET studies in normal mice revealed high specific accumulation of activity in the liver. CONCLUSION: NOTA-HL could be labeled rapidly and efficiently with aqueous 18F using AlF method. [18F]AlF-NOTA-HL would provide another efficient approach for PET imaging of ASGPR.

Biophysical and chemical stability of surfactant/budesonide and the pulmonary distribution following intra-tracheal administration.

Intra-tracheal instillation of budesonide using surfactant as a vehicle significantly decreased the incidence of bronchopulmonary dysplasia or death in preterm infants. The formularity of surfactant supplemented with budesonide and biophysical and chemical stability of the suspension has not been well reported. The aims are to investigate the biophysical and chemical stability of two surfactant preparations, Survanta and Curosurf, supplemented with budesonide. Biophysical property of the surface tension of Survanta and Survanta/budesonide suspension and of Curosurf and Curosurf/budesonide suspension was conducted by a pulsating bubble surfactometer and by a drop shape tensiometer. Chemical stability of Survanta/budesonide and of Curosurf/budesonide suspensions was tested by high-performance liquid chromatography analysis (HPLC). Pulmonary distribution of Survanta/18F-budesonide suspension was examined by a Nano/PET digital scan in rats. The Marangoni effect of Survanta, Curosurf, and budesonide was tested by digital high speed photography. For Survanta supplemented with budesonide, with a concentration ratio of ≥50, the surface tension-lowering activity was minimally affected. Similarly, the surface tension-lowering activity of Curosurf was not significantly affected by addition of budesonide, if the concentration ratio was ≥160. With these concentration ratios of both suspensions, HPLC analysis revealed no new compounds identified. Curosurf as compared to Survanta exhibited a significantly higher Marangoni effect. We conclude that with current dosage recommended for Survanta and Curosurf, both surfactant/budesonide suspensions are biophysically and chemically stable. Both surfactants can act as an effective vehicle for budesonide delivery.

Green Tea Polyphenol Epigallocatechin-3-Gallate Promotes Reendothelialization in Carotid Artery of Diabetic Rabbits by Reactivating Akt/eNOS Pathway.

Background: Epigallocatechin gallate (EGCG) is the most abundant catechin in green tea and has proven benefits on endothelial cells in diabetes. However, it remains unclear whether EGCG could improve function of late endothelial progenitor cells (L-EPCs) in diabetes. Methods: Thirty-six rabbits were randomized into six groups. Thirty diabetic rabbits were induced by a single dose of alloxan (100 mg/kg injection intraperitoneally). All of them were given intragastrically EGCG (50 mg/kg/day) or saline for 7 days after carotid injury. In autotransfusion experiment, L-EPCs were cultured with pre-treated EGCG (40 µM for 72 h) and then were injected into the site of injured vascular. Proliferation and migration of EGCG pre-treated L-EPCs in high glucose condition were assessed by EDU incorporation assay and modified Boyden chamber assay, respectively. The mRNA and protein expression of Akt-eNOS pathway were detected by real-time PCR and western blot. Results: Reendothelialization rate in injured carotid artery of diabetic rabbits was augmented in the EGCG group (50 mg/kg/d for 7 days) compared with the non-EGCG group (74.2 ± 4.6% vs. 25.6 ± 5.9%, P < 0.001). EGCG pre-treated L-EPCs autologous transfusion also accelerated the diabetic rabbits' carotid reendothelialization compared with the diabetic sham-operated group (65.6 ± 8.5% vs. 32.9 ± 5.0%, P = 0.011). In vitro studies showed, 40 µM EGCG treatment for 72 h recovered L-EPCs' proliferation and migration, as well as restored the phosphorylation level of Akt and eNOS blocked by high glucose condition. Conclusion: EGCG accelerated reendothelialization in diabetic rabbits after carotid injury in part by reactivating the Akt/eNOS pathway, which might contribute to recovering proliferation and migration of L-EPCs impaired by high glucose.

Use of 111In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with Thioacetamide-Induced Hepatic Fibrosis.

Many biochemical tests detecting the presence of liver disease are not liver-specific and may be abnormal in nonhepatic conditions. The asialoglycoprotein receptor (ASGPR) is a hepatocyte-specific receptor for Gal/GalNAc-terminated glycopeptide or glycoprotein. The number of these receptors decreases in patients with chronic liver diseases. Here, we aimed to evaluate the use of 111In-hexavalent lactoside, a known ASGPR imaging biomarker, as a more sensitive probe to detect small changes in liver reserve in animal models of chronic liver injury. Thioacetamide (TAA) treatment via intraperitoneal injection every 2 days in BALB/c mice continued for 1, 2, 3, or 4 months. The liver fibrosis stages were determined by Sirius Red staining and were based on the METAVIR classification method. Serum transaminase enzymes (alanine transaminase (ALT) and aspartate transaminase (AST)), alkaline phosphatase, albumin, and bilirubin were measured using a FUJI FDC3500 i/s analyzer. The ASGPR staining was performed by immunohistocytochemical stain. The percentages of fibrosis and ASGPR were calculated using ImageJ software after collagen staining and anti-ASGPR staining, respectively. A nanoSPECT/CT was used for molecular imaging and liver uptake measurement. We observed fibrosis grades of F0-F1 in mice treated with TAA for 1 month, F2 in mice treated for 2 months, F3-F4 in mice treated for 3 months, and F4 in mice treated for 4 months. The levels of ALT and albumin were not significantly different in the TAA groups from those in the controls. Although the average levels of AST, alkaline phosphatase, and bilirubin in the TAA groups were different from those in the control group, there was little difference between TAA groups. More sensitive distinctions among TAA groups were detected in 111In-hexavalent lactoside uptake of ASGPR, ASGPR staining, and fibrosis % than when using the conventional AST, ALT, albumin, alkaline phosphatase, and bilirubin tests. The absorption and distribution of 111In-hexavalent lactoside were lower in the chronic hepatitis models than the normal controls. The liver reserves measured by 111In-hexavalent lactoside uptake were 71.7 ± 7.5% and 50.9 ± 5.6% after 1 and 2 months, respectively, of TAA treatment. As an ASGPR biomarker, 111In-hexavalent lactoside has higher sensitivity than traditional liver function tests and collagen stain to provide more objective data for evaluating compensated cirrhosis or changes in liver damage. ASGPR staining can reflect the regenerated hepatocytes, but the need for a biopsy limits its use. 111In-hexavalent lactoside measurement is comparable with ASGPR staining, which suggests that 111In-hexavalent lactoside measurement will be more useful as a practical, noninvasive test of chronic liver injury.

Development of single vial kits for preparation of 68 Ga-labelled hexavalent lactoside for PET imaging of asialoglycoprotein receptor.

The aim of this study was to formulate and evaluate the freeze-dried kit of NOTA-hexavalent lactoside (NOTA-HL) for the preparation of 68 Ga-labeled glycoligand for PET imaging of the asialoglycoprotein receptor (ASGPR). 68 GaCl3 was obtained from a commercial 68 Ge/68 Ga generator. Single-vial kits of HL were formulated. Optimization of radiolabeling with 68 Ga, various evaluations of NOTA-HL kits, and in vitro stability study of 68 Ga-HL were carried out. PET/CT imaging of normal mice injected with 68 Ga-NOTA-HL was performed. NOTA-HL kit was successfully formulated. High radiochemical yields (>95%) were obtained by 68 Ga radiolabeling. The NOTA-HL kits were stable for at least 12 months, and 68 Ga-NOTA-HL exhibited good in vitro stability. PET studies in normal mice revealed high specific accumulation of activity in the liver. The NOTA-HL kit was developed for fast 68 Ga labeling. 68 Ga-NOTA-HL showed high specific uptake in liver. The availability of ready-to-use NOTA-HL kits combined with 68 Ge/68 Ga generators would provide an efficient approach for PET imaging of ASGPR.

Regorafenib inhibits tumor progression through suppression of ERK/NF-κB activation in hepatocellular carcinoma bearing mice.

Regorafenib has been demonstrated in our previous study to trigger apoptosis through suppression of extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) activation in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro However, the effect of regorafenib on NF-κB-modulated tumor progression in HCC in vivo is ambiguous. The aim of the present study is to investigate the effect of regorafenib on NF-κB-modulated tumor progression in HCC bearing mouse model. pGL4.50 luciferase reporter vector transfected SK-Hep1 (SK-Hep1/luc2) and Hep3B 2.1-7 tumor bearing mice were established and used for the present study. Mice were treated with vehicle or regorafenib (20 mg/kg/day by gavage) for 14 days. Effects of regorafenib on tumor growth and protein expression together with toxicity of regorafenib were evaluated with digital caliper and bioluminescence imaging (BLI), ex vivo Western blotting immunohistochemistry (IHC) staining, and measurement of body weight and pathological examination of liver tissue, respectively, in SK-Hep1/luc2 and Hep3B 2.1-7 tumor bearing mice. The results indicated regorafenib significantly reduced tumor growth and expression of phosphorylated ERK, NF-κB p65 (Ser536), phosphorylated AKT, and tumor progression-associated proteins. In addition, we found regorafenib induced both extrinsic and intrinsic apoptotic pathways. Body weight and liver morphology were not affected by regorafenib treatment. Our findings present the mechanism of tumor progression inhibition by regorafenib is linked to suppression of ERK/NF-κB signaling in SK-Hep1/luc2 and Hep3B 2.1-7 tumor bearing mice.

Analysis of baseline hepatitis B virus DNA levels in chronic hepatitis B patients with non-hematological malignancies prior to the initiation of cancer chemotherapy.

Reactivation of hepatitis B virus (HBV) infection is common (~20-50%) during cancer chemotherapy. Baseline HBV replication status is an important risk factor for HBV reactivation. To date, data on the baseline HBV DNA level for chronic hepatitis B (CHB) patients prior to chemotherapy, particularly for non-hematological malignancies, are limited. A total of 105 consecutive CHB patients with solid tumors who received prophylactic antiviral therapy prior to chemotherapy from November, 2011 to December, 2014, were enrolled in this study. The patients' tumors included: Breast cancer (37.1%), lung cancer (18.1%), colon cancer (17.1%), head and neck cancer (10.5%), other gastrointestinal tract malignancies (8.6%), gynecological cancer (4.8%) and others (3.8%). The mean age of the enrolled patients was 55.2±1.1 years, 48 of the patients were male, 3 were hepatitis B e antigen-positive, and 26.7% had abnormal alanine aminotransferase (ALT) levels at baseline. The median HBV DNA level measured by quantitative polymerase chain reaction assay prior to chemotherapy was 3.30 log10 IU/ml and 49.5% of the enrolled patients had a baseline HBV DNA level >2,000 IU/ml. A wide range of HBV distribution was found: <20 IU/ml (15.2%), 20≤DNA<2,000 IU/ml (35.3%), 2,000≤DNA<20,000 IU/ml (26.6%), 20,000≤DNA<106 IU/ml (17.2%) and <106 IU/ml (5.7%). Age and baseline ALT level were not strongly associated with virological activity. The mean HBV DNA and the percentage of patients with HBV DNA >2,000 IU/ml were comparable between different cancer groups. Quantitative HBsAg level was a major determinant of baseline HBV DNA, and a significant correlation was noted between log10 hepatitis B surface antigen and log10 HBV DNA levels (γ=0.641, P<0.001). Our study demonstrated a wide distribution of baseline HBV DNA level among CHB patients diagnosed with non-hematological malignancies. Of note, approximately half of the patients (i.e., those with HBV DNA >2,000 IU/ml) had a higher risk of HBV reactivation if no appropriate antiviral prophylaxis was undertaken.

Alendronate prevents angiotensin II-induced collagen I production through geranylgeranylation-dependent RhoA/Rho kinase activation in cardiac fibroblasts.

Collagen I is the main component of extracellular matrix in cardiac fibrosis. Our previous studies have reported inhibition of farnesylpyrophosphate synthase prevents angiotensin II-induced cardiac fibrosis, while the exact molecular mechanism was still unclear. This paper was designed to investigate the effect of alendronate, a farnesylpyrophosphate synthase inhibitor, on regulating angiotensin II-induced collagen I expression in cultured cardiac fibroblasts and to explore the underlying mechanism. By measuring the mRNA and protein levels of collagen I, we found that alendronate prevented angiotensin II-induced collagen I production in a dose-dependent manner. The inhibitory effect on collagen I expression was reversed by geranylgeraniol, and mimicked by inhibitors of RhoA/Rho kinase pathway including C3 exoenzyme and GGTI-286. Thus we suggested geranylgeranylation-dependent RhoA/Rho kinase activation was involved in alendronate-mediated anti-collagen I synthetic effect. Furthermore, we accessed the activation status of RhoA in alendronate-, geranylgeraniol- and GGTI-286-treated cardiac fibroblasts and gave an indirect evidence for RhoA activation via geranylgeranylation. Then we came to the conclusion that in cardiac fibroblasts, alendronate could protect against angiotensin II-induced collagen I synthesis through inhibition of geranylgeranylation and inactivation of RhoA/Rho kinase signaling. Targeting geranylgeranylation and RhoA/Rho kinase signaling will hopefully serve as therapeutic strategies to reduce fibrosis in heart remodeling.

The specificity and accuracy of (111)In-hexavalent lactoside in estimating liver reserve and its threshold value for mortality in mice.

BACKGROUND & AIMS: The asialoglycoprotein receptor on hepatocyte membranes recognizes the galactose residues of glycoproteins. We investigated the specificity, accuracy and threshold value of asialoglycoprotein receptor imaging for estimating liver reserve via scintigraphy using (111)In-hexavalent lactoside in mouse models. METHODS: (111)In-hexavalent lactoside scintigraphy for asialoglycoprotein receptor imaging was performed on groups of normal mice, orthotopic SK-HEP-1-bearing mice, subcutaneous HepG2-bearing mice, mice with 20-80% partial hepatectomy and mice with acute hepatitis induced by acetaminophen. Liver reserve was measured by relative liver uptake and compared with normal mice. Asialoglycoprotein receptor blockade was performed via an in vivo asialofetuin competitive binding assay. RESULTS: A total of 73.64±7.11% of the injection dose accumulated in the normal liver tissue region, and radioactivity was barely detected in the hepatoma region. When asialoglycoprotein receptor was blocked using asialofetuin, less than 0.41±0.04% of the injection dose was detected as background in the liver. Asialoglycoprotein receptor imaging data revealed a linear correlation between (111)In-hexavalent lactoside binding and residual liver mass (R(2)=0.8548) in 20-80% of partially hepatectomized mice, demonstrating the accuracy of (111)In-hexavalent lactoside imaging for measuring the functional liver mass. Asialoglycoprotein receptor imaging data in mice with liver failure induced using 600mg/kg acetaminophen revealed 19-45% liver reserve relative to normal mice and a fatal threshold value of 25% liver reserve. CONCLUSION: The (111)In-hexavalent lactoside imaging method appears to be a good, specific, visual and quantitative predictor of functional liver reserve. The diagnostic threshold for survival was at 25% liver reserve in mice.

Loss of signal in recurrent nerve neuromonitoring: causes and management.

During recurrent laryngeal nerve (RLN) neuromonitoring in thyroid surgery, laryngeal electromyography (EMG) amplitude may be correlated with the number of muscle fibers participating in the polarization and these might be correlated with the function of RLN. If RLN is severely injured during the operation, most nerve fibers do not transmit nerve impulse and substantial decrease of EMG amplitude or loss of signal (LOS) will occur. True LOS at the end of an operation often indicates a postoperative fixed vocal cord, and the surgeon should consider the optimal contralateral surgery timing in patients with planned bilateral thyroid operation to avoid the disaster of bilateral vocal cord palsy. However, LOS recovery and false LOS may occur and may lead to an unnecessary 2(nd) operation. Therefore, a reliable modality for intraoperative LOS evaluation and management would afford the surgeon real-time information that could help guide surgical procedure and planning. The updated causes, algorithm, and management of LOS during RLN neuromonitoring are reviewed and summarized.

[An experience applying the transtheoretical model to assist a highly educated case to quit smoking].

Although smokers who are highly educated understand the risks involved in smoking, they tend to be highly influenced by the opinions of others and thus subject to severe social pressures. This is a case report on the application of the transtheoretical model of behavioral change to a an individual with a PhD in biotechnology who had been smoking for 20 years. The effects of the developed smoking cessation intervention were investigated and data were collected through personal meetings, telephone interviews, and e-mail during a smoking cessation counseling program that lasted from October 18th, 2012, to April 15th, 2013. The results of the assessment indicated that the main problem encountered by the case when quitting was a lack of confidence in attempting to quit smoking after experiencing previous failed attempts. In this report, strategies related to the transtheoretical model were used and counseling was provided during the smoking cessation process. Individualized strategic methods were developed to be effective in highly educated people who smoke in order to achieve successfully cessation of smoking. This report serves as a reference for using the transtheoretical model of behavioral change in developing smoking cessation programs.

Broadband TE(01) mode fiber coupler based on dual-core photonic crystal fiber.

A broadband TE(01) mode fiber coupler based on dual-core photonic crystal fiber (PCF) is proposed by introducing gold nanowires and fluorine-doped (F-doped) layers in the core areas. With an appropriate choice of the parameters of the F-doped layers and air hole space, the wavelength bandwidth can be increased to beyond 500 nm with the coupler length below 0.1 m for the 3 dB fiber coupler.

Transcriptome profiling of pyrethroid resistant and susceptible mosquitoes in the malaria vector, Anopheles sinensis.

BACKGROUND: Anopheles sinensis is a major malaria vector in China and other Southeast Asian countries, and it is becoming increasingly resistant to the insecticides used for agriculture, net impregnation, and indoor residual spray. Very limited genomic information on this species is available, which has hindered the development of new tools for resistance surveillance and vector control. We used the 454 GS FLX system and generated expressed sequence tag (EST) databases of various life stages of An. sinensis, and we determined the transcriptional differences between deltamethrin resistant and susceptible mosquitoes. RESULTS: The 454 GS FLX transcriptome sequencing yielded a total of 624,559 reads (average length of 290 bp) with the pooled An. sinensis mosquitoes across various development stages. The de novo assembly generated 33,411 contigs with average length of 493 bp. A total of 8,057 ESTs were generated with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation. A total of 2,131 ESTs were differentially expressed between deltamethrin resistant and susceptible mosquitoes collected from the same field site in Jiangsu, China. Among these differentially expressed ESTs, a total of 294 pathways were mapped to the KEGG database, with the predominant ESTs belonging to metabolic pathways. Furthermore, a total of 2,408 microsatellites and 15,496 single nucleotide polymorphisms (SNPs) were identified. CONCLUSIONS: The annotated EST and transcriptome databases provide a valuable genomic resource for further genetic studies of this important malaria vector species. The differentially expressed ESTs associated with insecticide resistance identified in this study lay an important foundation for further functional analysis. The identified microsatellite and SNP markers will provide useful tools for future population genetic and comparative genomic analyses of malaria vectors.