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This study was performed to compare the safety and efficacy of one-stage laparoscopic common bile duct exploration (LCBDE) plus laparoscopic cholecystectomy (LC) with those of endoscopic sphincterotomy (EST) plus LC for concomitant gallbladder (GB) and common bile duct (CBD) stones in elderly patients.This single-center retrospective study reviewed the medical records of patients aged80 years who were diagnosed with concomitant GB and CBD stones between January 2010 and December 2020.Of the 137 patients included in this study, 46 underwent one-stage LCBDE + LC and 91 underwent two-stage EST + LC. The frequency of previous gastrectomy (23.9% vs. 5.5%,One-stage LCBDE + LC is a safe and effective treatment for concomitant GB and CBD stones, even in elderly patients, and may be considered as the first treatment option in elderly patients with previous gastrectomy, multiple large (≥ 15 mm) CBD stones, or inability to cooperate with endoscopic procedures.

Supplementary Figure 6. Route-dependency of IL-7-Fc administration on recruitment of T cells in cervicovaginal tissue

PDF file - 58K, Dose-dependent induction of apoptosis by dodecameric TRAIL expressing MSCs

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Supplementary Figure 4. Comparison of Fc-fragment and IL-7-Fc on accumulation of T cells in cervicovaginal tissue

Supplementary Figure 1. Schematic diagram of Fc-fused IL-7 Supplementary Figure 2. FcRn-mediated transcytosis and transport of Fc-fused IL-7 into serum after intravaginal treatment Supplementary Figure 3. Distinct localization patterns of CD4 and CD8 T cells after intravaginal administration of IL-7-Fc Supplementary Figure 4. Comparison of Fc-fragment and IL-7-Fc on accumulation of T cells in cervicovaginal tissue Supplementary Figure 5. Abrogation of T cell accumulation after IL-7RÃŽ{plus minus} blocking Supplementary Figure 6. Route-dependency of IL-7-Fc administration on recruitment of T cells in cervicovaginal tissue

Supplementary Figure 5. Abrogation of T cell accumulation after IL-7Rα blocking

Purpose: Durable complete remission of metastatic renal cell carcinoma (RCC) has rarely been achieved with current treatment modalities. To solve this problem, alternative therapeutic options with high efficacy and minimal side effects are strongly needed.Experimental Design: Mesenchymal stem cells (MSC) were engineered to coexpress dodecameric TRAIL and herpes simplex virus thymidine kinase (MSC/dTRAIL-TK). The antitumor effects of MSCs expressing dTRAIL (MSC/dTRAIL) or HSV-TK alone (MSC/TK) and MSC/dTRAIL-TK were compared with murine RCC cells using in vitro coculture system and in vivo experimental lung metastasis model. The effects of different doses and schedules of engineered MSCs on mice survival were also evaluated.Results: MSC/dTRAIL-TK exerted stronger apoptotic response in Renca cells than did MSC/TK or MSC/dTRAIL after ganciclovir (GCV) treatment. In vivo imaging results suggest that MSCs reside longer in the lungs of metastatic tumor-bearing mice, compared with that of control mice, regardless of genetic engineering. In addition, MSC/dTRAIL-TK treatment followed by ganciclovir administrations significantly decreased the number of tumor nodules in the lung, to a greater degree than MSC/dTRAIL or MSC/TK, and led to a prolonged survival. More importantly, the antimetastatic effect of MSC/dTRAIL-TK was markedly enhanced by repeated injections but not by increased dose, and resulted in 100% survival of tumor-bearing mice after three injections.Conclusion: Sequential combination gene therapy using MSC/dTRAIL-TK achieved long-term remission of metastatic RCC without noticeable toxicity. Our findings provide an innovative therapeutic approach to completely eradicate metastatic tumors by simple, repeated administrations of MSC/dTRAIL-TK. Clin Cancer Res; 19(2); 415–27. ©2012 AACR.

Supplementary Table 1. Tolerable toxicity after repeated intravaginal administration of IL-7-Fc. Information of detailed materials and methods, and supplementary figure legends are contained.

Supplementary Figure 3. Distinct localization patterns of CD4 and CD8 T cells after intravaginal administration of IL-7-Fc

Supplementary Figure 1. Schematic diagram of Fc-fused IL-7

Supplementary Figure 2. FcRn-mediated transcytosis and transport of Fc-fused IL-7 into serum after intravaginal treatment

Purpose: The induction of tissue-localized virus-specific CD8 T-cell response is essential for the development of an effective therapeutic vaccine against genital diseases, such as cervical cancer and genital herpes. Here, we aimed to elucidate the immunologic role of IL7 in the induction of mucosal cellular immunity.Experimental Design: IL7 was engineered through Fc fusion to enhance mucosal delivery across the genital epithelial barrier. The immunomodulatory role of IL7 was evaluated by monitoring the kinetics of various immune cells and measuring the expression of chemokines and cytokines after intravaginal administration of Fc-fused IL7 (IL7-Fc). The antitumor effects of intramuscular human papillomavirus (HPV) DNA vaccine or topical IL7-Fc alone or in a combinational regimen on mice survival were compared using a orthotopic cervical cancer model.Results: Intravaginal treatment of IL7-Fc, but not native IL7, induces upregulation of chemokines (CXCL10, CCL3, CCL4, and CCL5), cytokines (IFNγ, TNFα, IL6, and IL1β), and an adhesion molecule (VCAM-1) in the genital tract, leading to the recruitment of several leukocytes, including CD4, CD8, γδ T cells, and dendritic cells. Importantly, in this murine cervical cancer model, topical administration of IL7-Fc after intramuscular HPV DNA vaccination increases the number of HPV-specific CD8 T cells in the genital mucosa, but not in the spleen, leading to stronger antitumor activity than the HPV DNA vaccine alone.Conclusions: Our findings provide an important insight into the immunomodulatory role of IL7-Fc via topical application and the design of therapeutic vaccine regimen that induces effective genital–mucosal CD8 T-cell responses. Clin Cancer Res; 22(23); 5898–908. ©2016 AACR.

PDF file - 122K, Phenotype of na�ve and engineered MSCs

Engineering thermoplastics, such as poly(arylene ether sulfone), are more often synthesized using F-containing monomers rather than Cl-containing monomers because the F atom is considered more electronegative than Cl, leading to a better condensation polymerization reaction. In this study, the reaction’s spontaneity improved when Cl atoms were used compared to the case using F atoms. Specifically, sulfonated poly(arylene ether sulfone) was synthesized by reacting 4,4′-dihydroxybiphenyl with two types of biphenyl sulfone monomers containing Cl and F atoms. No significant difference was observed in the structural, elemental, and chemical properties of the two copolymers based on nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, transmission electron microscopy, and electrochemical impedance spectroscopy. However, the solution viscosity and mechanical strength of the copolymer synthesized with the Cl-terminal monomers were slightly higher than those of the copolymer synthesized with the F-terminal monomers due to higher reaction spontaneity. The first-principle study was employed to elucidate the underlying mechanisms of these reactions.

Graphene moire superlattices are outstanding platforms to study correlated electron physics and superconductivity with exceptional tunability. However, robust superconductivity has been measured only in magic-angle twisted bilayer graphene (MA-TBG) and magic-angle twisted trilayer graphene (MA-TTG). The absence of a superconducting phase in certain moire flat bands raises a question on the superconducting mechanism. In this work, we investigate electronic structure and electron-phonon coupling in graphene moire superlattices based on atomistic calculations. We show that electron-phonon coupling strength lambda is dramatically different among graphene moire flat bands. The total strength lambda is very large (lambda>1) for MA-TBG and MA-TTG, both of which display robust superconductivity in experiments. However, lambda is an order of magnitude smaller in twisted double bilayer graphene (TDBG) and twisted monolayer-bilayer graphene (TMBG) where superconductivity is reportedly rather weak or absent. We find that the Bernal-stacked layers in TDBG and TMBG induce sublattice polarization in the flat-band states, suppressing intersublattice electron-phonon matrix elements. We also obtain the nonadiabatic superconducting Tc that matches well with the experimental results. Our results clearly show a correlation between strong electron-phonon coupling and experimental observations of robust superconductivity., Comment: 6 pages for the main text (including 4 figures and 1 table) and 3 pages for Supplemental Material

We investigate the role of pseudospin structure of few-layer black phosphorus (BP) in interband tunneling properties in lateral BP junctions. We find that interband tunneling is critically dependent on junction directions because of the anisotropic pseudospin structure of BP. When the armchair direction of BP is normal to the interface, pseudospins of incident and transmitted carriers are nearly aligned so that interband tunneling is highly effective, analogous to the Klein tunneling in graphene. However, when the zigzag direction is normal to the interface, interband tunneling is suppressed by misaligned pseudospins. We also study junctions of band-gap inverted BP where the electronic structure is characterized by two Dirac cones. In this case, intervalley tunneling is prohibited either by momentum conservation or by pseudospin mismatch while intravalley tunneling is Klein-like irrespective of the junction direction. These results provide a foundation for developing high-performance devices from BP and other pseudospin materials., Comment: 6 pages, 4 figures

In this study, by treating not only the membrane but also the whole membrane electrode assembly (MEA) with KOH solution prior to incorporation in alkaline anion exchange membrane fuel cells, an ionic pathway for hydroxide conduction has optimized in the catalyst layer. This lowers the ohmic resistance of the KOH-treated MEA as detected by the polarization curve and impedance spectroscopy analysis. The process has greater advantage for non-platinum group metal (PGM) catalysts than PGM catalysts, because of the lower active site density and consequent high loading required for non-PGM catalysts.

Commercial ion-exchange membranes are usually thick, and have high electrical resistances that can reduce the adsorption capacity of electrodes in membrane capacitive deionization (MCDI) cells. In this study, porous polyethylene (PE) membranes, filled with a sulfonated monomer, crosslinking agent (5, 10, 15 wt%), and radical initiator, were subjected to polymerization and subsequent ion-exchange, to yield PE filled with crosslinked sulfonated polystyrene (PE-CSPS-5, 10, 15). PE-CSPS membranes were very thin (27 μm), and exhibited moderate water uptake (26–35 wt%) and ion-exchange capacity (0.70–1.0 meq/g), and low electrical resistances (0.33–0.62 Ω·cm 2 ) compared with commercial ones. MCDI cells were assembled with either a PE-CSPS-5 membrane or a commercial cation-exchange membrane (CMX, IEC 1.5–1.8 meq/g), and their performances studied using a 500 ppm solution of NaCl. The current efficiency of the PE-CSPS-5-based MCDI cell showed slightly higher than that of the commercial CMX-based MCDI cell, which was attributed to the considerably lower electrical resistance of the membrane (0.33 vs. 2.9 Ω·cm 2 ), even though its IEC value is smaller (1.0 vs. 1.5–1.8 meq/g). Our study reveals that supporting membranes filled with ion-exchange polymers have advantages over casting membranes in preparing membranes for MCDI application, with respect to dimentional stability and thickness.