Irradiation-induced localization of IL-12-expressing mesenchymal stem cells to enhance the curative effect in murine metastatic hepatoma

Irradiation in conjunction with gene therapy is considered for efficient cancer treatment. Mesenchymal stem cells (MSCs), due to their irradiation-promotable tumor tropism, are ideal delivery vehicles for gene therapy. In this study, we investigated whether treatment with radiation and interleukin (IL)-12-expressing MSCs (MSCs/IL-12) exerts improved antitumor effects on murine metastatic hepatoma. HCa-I and Hepa 1-6 cells were utilized to generate heterotopic murine hepatoma models. Tumor-bearing mice were treated with irradiation or MSCs/IL-12 alone, or a combination. Monocyte chemoattractant protein-1 (MCP-1/CCL2) expression was assessed in irradiated hepatoma tissues to confirm a chemotactic effect. Combination treatment strategies were established and their therapeutic efficacies were evaluated by monitoring tumor growth, metastasis and survival rate. IL-12 expression was assessed and the apoptotic activity and immunological alterations in the tumor microenvironment were examined. MCP-1/CCL2 expression and localization of MSCs/IL-12 increased in the irradiated murine hepatoma cells. The antitumor effects, including suppression of pulmonary metastasis and survival rate improvements, were increased by the combination treatment with irradiation and MSCs/IL-12. IL-12 expression was increased in tumor cells, causing proliferation of cluster of differentiation 8(+) T-lymphocytes and natural killer cells. The apoptotic activity increased, indicating that the cytotoxicity of immune cells was involved in the antitumor effect of the combined treatment. Treatment with irradiation and MSCs/IL-12 showed effectiveness in treating murine metastatic hepatoma. IL-12-induced proliferation of immune cells played an important role in apoptosis of tumor cells. Our results suggest that treatment with irradiation and MSCs/IL-12 may be a useful strategy for enhancing antitumor activity in metastatic hepatoma. What's new? Mesenchymal stem cells (MSCs) are promising gene-delivery vehicles, with the potential to improve antitumor effects when used in combination with existing therapies. In the present study, the combined use of interleukin (IL)-12-expressing MSCs (MSCs/IL-12) and radiation therapy increased antitumor activity in murine metastatic hepatoma, a model that is representative of human metastatic hepatocellular carcinoma (HCC), which affects nearly half of HCC patients. Treatment with MSCs/IL-12 resulted in increased IL-12 expression in tumor cells and immune cell proliferation. Immune cell cytotoxicity, evidenced by increased apoptotic activity, appeared to play a role in MSCs/IL-12 augmentation of antitumor effects.1178Ysciescopu

Immunogenetics in SARS: a case-control study.

Key Messages: 1. Human leukocyte antigen (HLA) genotypes from 102 SARS patients (susceptible) and 108 SARS contacts (resistant) were obtained. 2. Allelic frequencies of the Class I (HLA-A, -B, and -Cw) and Class II (HLA-DR and -DQ) genes from these genetically unrelated subjects were compared. 3. A significantly higher frequency of DRB4*01010101 was found in the SARS-susceptible than SARS-resistant group. In contrast, significantly higher frequencies of HLA-B*1502 and HLADRB3*030101 were found in the SARS-resistant than SARSsusceptible group. However, none of these associations was significant after Bonferroni correction. Further, analysis of 10/36 genetically related families did not reveal any HLA alleles associated with SARS susceptibility or resistance. 4. We could not confirm previous findings of an HLA association with susceptibility or resistance to SARS. The significance of these associations needs to be validated by further independent studies.published_or_final_versio

Carbon nanotube-reduced graphene oxide fiber with high torsional strength from rheological hierarchy control

High torsional strength fibers are of practical interest for applications such as artificial muscles, electric generators, and actuators. Herein, we maximize torsional strength by understanding, measuring, and overcoming rheological thresholds of nanocarbon (nanotube/graphene oxide) dopes. The formed fibers show enhanced structure across multiple length scales, modified hierarchy, and improved mechanical properties. In particular, the torsional properties were examined, with high shear strength (914 MPa) attributed to nanotubes but magnified by their structure, intercalating graphene sheets. This design approach has the potential to realize the hierarchical dimensional hybrids, and may also be useful to build the effective network structure of heterogeneous materials

Highly photoresponsive and wavelength-selective circularly-polarized-light detector based on metal-oxides hetero-chiral thin film

A highly efficient circularly-polarized-light detector with excellent wavelength selectivity is demonstrated with an elegant and simple microelectronics-compatible way. The circularly-polarized-light detector based on a proper combination of the geometry-controlled TiO2-SnO2 hetero-chiral thin film as an effective chiroptical filter and the Si active layer shows excellent chiroptical response with external quantum efficiency as high as 30% and high helicity selectivity of similar to 15.8% in an intended wavelength range. Furthermore, we demonstrated the ability of manipulating both bandwidth and responsivity of the detector simultaneously in whole visible wavelength range by a precise control over the geometry and materials constituting hetero-chiral thin film. The high efficiency, wavelength selectivity and compatibility with conventional microelectronics processes enabled by the proposed device can result in remarkable developments in highly integrated photonic platforms utilizing chiroptical responses.1166Ysciescopu

Machine Learning to Identify Genetic Salt-Losing Tubulopathies in Hypokalemic Patients

Introduction: Clinically distinguishing patients with the inherited salt-losing tubulopathies (SLTs), Gitelman or Bartter syndrome (GS or BS) from other causes of hypokalemia (LK) patients is difficult, and genotyping is costly. We decided to identify clinical characteristics that differentiate SLTs from LK. Methods: A total of 66 hypokalemic patients with possible SLTs were recruited to a prospective observational cohort study at the University College London Renal Tubular Clinic, London. All patients were genotyped for pathogenic variants in genes which cause SLTs; 39 patients had pathogenic variants in genes causing SLTs. We obtained similar data sets from cohorts in Taipei and Kobe, as follows: the combined data set comprised 419 patients; 291 had genetically confirmed SLT. London and Taipei data sets were combined to train machine learning (ML) algorithms, which were then tested on the Kobe data set. Results: Single biochemical variables (e.g., plasma renin) were significantly, but inconsistently, different between SLTs and LK in all cohorts. A decision table algorithm using serum bicarbonate and urinary sodium excretion (FENa) achieved a classification accuracy of 74%. This was superior to all the single biochemical variables identified previously. Conclusion: ML algorithms can differentiate true SLT in the context of a specialist clinic with some accuracy. However, based on routine biochemistry, the accuracy is insufficient to make genotyping redundant

IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis

IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)(2) subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist-knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)(2) on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)(2) model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)(2) inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4(+)CD25(+)Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor-related organ receptor gamma t and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)(2) suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling.1156Ysciescopu

Kawasaki disease in Hong Kong, 1994 to 2000

OBJECTIVE. To describe the epidemiology, clinical characteristics, and management of Kawasaki disease in children in Hong Kong. DESIGN. Retrospective survey of medical records from July 1994 to June 1997, and prospective data collection from July 1997 to June 2000. SETTING. Hospitals with a paediatric unit in Hong Kong. PATIENTS. Patients diagnosed with Kawasaki disease between July 1994 and June 2000 in public hospitals in Hong Kong. MAIN OUTCOME MEASURES. Incidence of Kawasaki disease and coronary artery aneurysm rates. RESULTS. A total of 696 cases of Kawasaki disease were reported. There were 435 (62.5%) boys and 261 (37.5%) girls giving a male to female ratio of 1.7:1. The age ranged from 1 month to 15 years 5 months with a median of 1.7 years. Infants (<1 year) constituted the largest group of patients (223,32.0%) and overall, 638 (91.7%) were younger than 5 years. Skin rash, conjunctivitis, and oral signs were among the principal clinical features present in over 80% of cases. Prominent cervical lymph nodes larger than 1.5 cm were less commonly found (24%). Coronary artery aneurysms or ectasia were present in 15.7% (109/696), 8.5% (59/696), and 5.0% (35/696) of patients at 2, 4, and 8 weeks, respectively. The incidence of Kawasaki disease per 100 000 children under 5 years was significantly higher in the prospective study period than in the retrospective period (39 vs 26, <0.001). CONCLUSION. The incidence of Kawasaki disease is high in Hong Kong and is 39 per 100 000 children below 5 years of age. The coronary artery aneurysm prevalence is 5%. Intravenous gamma-globulin and high-dose aspirin is the mainstay of treatment.published_or_final_versio

Thermoelectric materials by using two-dimensional materials with negative correlation between electrical and thermal conductivity

In general, in thermoelectric materials the electrical conductivity sigma and thermal conductivity kappa are related and thus cannot be controlled independently. Previously, to maximize the thermoelectric figure of merit in state-of-the-art materials, differences in relative scaling between sigma and kappa as dimensions are reduced to approach the nanoscale were utilized. Here we present an approach to thermoelectric materials using tin disulfide, SnS2, nanosheets that demonstrated a negative correlation between sigma and kappa. In other words, as the thickness of SnS2 decreased, sigma increased whereas kappa decreased. This approach leads to a thermoelectric figure of merit increase to 0.13 at 300 K, a factor similar to 1,000 times greater than previously reported bulk single-crystal SnS2. The Seebeck coefficient obtained for our two-dimensional SnS2 nanosheets was 34.7mVK(-1) for 16-nm-thick samples at 300 K.114330Ysciescopu

Structural modification of TiO2 nanorod films with an influence on the photovoltaic efficiency of a dye-sensitized solar cell (DSSC)

TiO2 nanorod films have been deposited on ITO substrates by dc reactive magnetron sputtering technique. The structures of these nanorod films were modified by the variation of the oxygen pressure during the sputtering process. Although all these TiO2 nanorod films deposited at different oxygen pressures show an anatase structure, the orientation of the nanorod films varies with the oxygen pressure. Only a very weak (101) diffraction peak can be observed for the TiO2 nanorod film prepared at low oxygen pressure. However, as the oxygen pressure is increased, the (220) diffraction peak appears and the intensity of this diffraction peak is increased with the oxygen pressure. The results of the SEM show that these TiO2 nanorods are perpendicular to the ITO substrate. At low oxygen pressure, these sputtered TiO2 nanorods stick together and have a dense structure. As the oxygen pressure is increased, these sputtered TiO2 nanorods get separated gradually and have a porous structure. The optical transmittance of these TiO2 nanorod films has been measured and then fitted by OJL model. The porosities of the TiO2 nanorod films have been calculated. The TiO2 nanorod film prepared at high oxygen pressure shows a high porosity. The dye-sensitized solar cells (DSSCs) have been assembled using these TiO2 nanorod films prepared at different oxygen pressures as photoelectrode. The optimum performance was achieved for the DSSC using the TiO2 nanorod film with the highest (220) diffraction peak and the highest porosity