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Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with poor prognosis. Surgery, chemotherapy, and radiofrequency ablation are three conventional therapeutic options that will help only a limited percentage of HCC patients. Cancer immunotherapy has achieved dramatic advances in recent years and provides new opportunities to treat HCC. However, HCC has various etiologies and can evade the immune system through multiple mechanisms. With the rapid development of genetic engineering and synthetic biology, a variety of novel immunotherapies have been employed to treat advanced HCC, including immune checkpoint inhibitors, adoptive cell therapy, engineered cytokines, and therapeutic cancer vaccines. In this review, we summarize the current landscape and research progress of different immunotherapy strategies in the treatment of HCC. The challenges and opportunities of this research field are also discussed.

Information sharing has been regarded as a major way to promote collaboration or to optimize overall supply chain performance. Most of the literature has focused on unilateral information sharing in a supply chain with single or substitutable products. This paper investigates bilateral information sharing in two supply chains with complementary products, and formulates four decision models based on different information sharing patterns. Our results show that (i) information sharing always benefits the manufacturer, and benefits the retailer and the whole supply chain under certain conditions; (ii) information sharing increases/decreases the positive effect of the retailer’s/manufacturer’s forecast on the optimal pricing strategies in its own supply chain; however, its impact depends on the parameter conditions in the other complementary supply chain.

Background: Human glypican-3 (hGPC3) is a protein highly expressed in hepatocellular carcinoma (HCC) but limited in normal tissues, making it an ideal target for immunotherapy. The adoptive transfer of hGPC3-specific chimeric antigen receptor T (CAR-T) cells for HCC treatment has been conducted in clinical trials. Due to the rigid construction, conventional CAR-T cells have some intrinsic limitations, like uncontrollable overactivation and inducing severe cytokine release syndrome. Methods: We redesigned the hGPC3-specific CAR by splitting the traditional CAR into two parts. By using coculturing assays and a xenograft mouse model, the in vitro and in vivo cytotoxicity and cytokine release of the split anti-hGPC3 CAR-T cells were evaluated against various HCC cell lines and compared with conventional CAR-T cells. Results: In vitro data demonstrated that split anti-hGPC3 CAR-T cells could recognize and lyse hGPC3+ HepG2 and Huh7 cells in a dose-dependent manner. Impressively, split anti-hGPC3 CAR-T cells produced and released a significantly lower amount of proinflammatory cytokines, including IFN-γ, TNF-α, IL-6, and GM-CSF, than conventional CAR-T cells. When injected into immunodeficient mice inoculated subcutaneously with HepG2 cells, our split anti-hGPC3 CAR-T cells could suppress HCC tumor growth, but released significantly lower levels of cytokines than conventional CAR-T cells. Conclusions: We describe here for the first time the use of split anti-hGPC3 CAR-T cells to treat HCC; split anti-hGPC3 CAR-T cells could suppress tumor growth and reduce cytokine release, and represent a more versatile and safer alternative to conventional CAR-T cells treatment.

This paper studies the manufacturer's and retailer's integration strategies in a supply chain with complementary products and examines the effects of downstream, upstream and vertical integrations ...

This paper investigates the pricing problem of complementary products in a supply chain with two manufacturers and one retailer, one of the two manufacturers uses dual channels including an online channel and a traditional retail channel to sell its product. We formulate four pricing game models through considering different market power structures of channel members, and derive the corresponding optimal pricing strategies. Based on the theoretical and numerical analysis, we study the effects of consumer channel loyalty, the level of complementarity, and the market power structures on the pricing strategies and the maximal profits of two complementary products. Some interesting and valuable managerial insights are obtained.

Lipoteichoic acid (LTA), a major component of the cell wall of Staphylococcus aureus (S. aureus), is not generally considered as an ideal vaccine candidate since it is a thymus-independent antigen. In this study, we screened a 12-mer phage peptide library and identified a series of peptide sequences that can mimic the epitope of LTA. A tetra-branched multiple antigenic peptide, named MAP2-3, comprising one of the positive peptide sequences (GHKEDRQWCQHS), was synthesized. Immunization with MAP2-3 induced LTA-specific IgG antibodies, prolonged the survival time, and decreased the bacterial burden in organs of mice infected with S. aureus. Moreover, passive immunization with polyclonal anti-MAP2-3 sera reduced bacterial load in organs of mice with bacteremia, alleviated acute lung injury in mice with pneumonia, and decreased the size of lesions in mice with skin infection. The number of LTA-specific antibody-secreting cells in the spleen of MAP2-3 immunized mice were significantly higher than that in the control mice. In summary, as a surrogate of LTA, vaccination with MAP2-3 elicited humoral immune response and protected mice from S. aureus infection. This study provides a new option to design vaccines against S. aureus.

RE/Yb co-doped Y 2 O 3 transparent ceramics (RE=Er, Ho, Pr, Tm) were fabricated and characterized from the point of up-conversion luminescence. All the samples exhibit high transparence not only in near-infrared band (NIR) band but also in visible region, which ensures the output of the up-conversion luminescence. Under 980 nm excitation, green and red emissions were observed in Er, Yb:Y 2 O 3 transparent ceramic, while green emission was detected in Ho, Yb and Pr, Yb co-doped Y 2 O 3 transparent ceramics. In Tm, Yb co-doped Y 2 O 3 ceramic, very intense blue up-conversion luminescence was detected. The dependence of up-conversion emission intensity on the pumping power was measured for each RE/Yb co-doped Y 2 O 3 transparent ceramic, and the up-conversion mechanism was discussed in detail. Meanwhile, the energy transfer efficiency was calculated.

Tm3+/Er3+/Yb3+ triply doped Y2O3 transparent ceramics were fabricated by solid state reaction and characterized from the point of view of white light upconversion luminescence. All the samples exhibited high transparency not only in near-infrared band but also in visible region. Strong red (Er3+: 4F9/2 → 4I15/2), green (Er3+: 2H11/2, 4S3/2 → 4I15/2) and blue (Tm3+: 1G4 → 3H6) upconversion emissions have been observed under 980 nm excitation at room temperature. By varying the concentration of Er3+ ion, various colors of upconversion luminescence (pure blue, bluish green, pure green and yellowish green), including white light with CIE-X = 0.295 and CIE-Y = 0.312, can be easily achieved.

A-plane GaN films are deposited on (302) \gamma-LiAlO2 substrates by metalorganic chemical vapor deposition (MOCVD). The X-ray diffraction (XRD) results indicate that the in-plane orientation relationship between GaN and LAO substrates is [010]LAO//[0001]GaN and [203]LAO//[1100]GaN with 0.03% and 2.85% lattice mismatch, respectively. Raman scattering results indicate that the strain in the films decreases along with the increase in the thickness of the films. In addition to the band edge emission at 3.42 eV, defects-related luminescence at 3.35 eV is observed in the photoluminescence (PL) spectra. The cathodoluminescence (CL) spectra indicate that the 3.35-eV emission is related to the V pits.

(Y 0.97− x Zr 0.03 Yb x ) 2 O 3 ( x = 0–0.15) transparent ceramics were fabricated by solid-state reaction. As ZrO 2 was introduced as additive, the transmittance of yttria ceramic was improved greatly. The optical measurements such as absorption, fluorescence spectrum and lifetime of Yb 3+ ion were carried out at room temperature. The intensities of the absorption peaks (904 and 973 nm) increase linearly with Yb 3+ ion concentration. The absorption cross-section at 973 nm and stimulated emission cross-section at 1032 nm are calculated to be 1.175 × 10 −20 and 1.767 × 10 −20 cm 2 , respectively. The lifetime of 5.0 at.% Yb:Y 2 O 3 ceramic is measured to be 0.93 ms. According to the emission spectra and measured lifetime, the optimum doping concentration of Yb 3+ ion in Y 2 O 3 transparent ceramic is in the range of 5.0–8.0 at.%. Meanwhile the up-conversion luminescence is also investigated.

Er3+/Yb3+-codoped Y2O3 transparent ceramics were fabricated and characterized from the point of up-conversion luminescence. All the samples exhibit high transparency not only in the near-infrared band but also in the visible region. Under 980 nm excitation, the ceramics gave up-conversion luminescence with very intense green (525–560 nm), red (around 660 nm), and considerably intense blue (405 nm) emissions. It is worthwhile to point out that the blue emission, which only appears in halide, was clearly observed in Y2O3 transparent ceramic. The emission bands at 405, 525, 560, and 660 nm are attributed to the transitions from excited states 2H9/2, 2H11/2, 4S3/2, and 4F9/2 to the ground state 4I15/2 of Er3+ ions, respectively. For nearly all samples, the green emissions were stronger than red emissions, and the maximal emission intensities were obtained with (Er0.025Yb0.05Y0.938Zr0.01)2O3 ceramic (Yb/Er=20). The red and green luminescence result from a two-photon process, while the blue emission is due to a three-photon process.

C-axis preferred oriented ZnO thin films were prepared on quartz substrates by RF sputtering. Photoconductive ultraviolet detector with planar interdigital electrodes was fabricated on ZnO thin film by the lift off technique. Linear I-V characteristic was observed under dark or 365 nm UV light illumination and has obvious difference. The photoresponsivity of 365 nm at 5 V bias is 18 A/W. The response time measure set mainly contains KrF excimer laser with the pulse width of 30 ns and the oscillograph with the bandwidth of 200 MHz. The result shows fast photoresponse with a rise time of 100 ns and fall time of 1.5 mu s. (c) 2005 Elsevier B.V. All rights reserved.

Down-conversion from blue to near infrared (NIR) has been demonstrated in Tm3+-Yb3+ codoped Y2O3 transparent ceramics. Upon the 464-nm excitation, the energy transfer (ET) mechanisms consisted of the Tm3+ : 1G4 → 2Yb3+ : 2F5/2 cooperative down-conversion and the phonon assisted Tm3+ : 1G4 + Yb3+ : 2F7/2 → Tm3+ : 3H5 + Yb3+ : 2F5/2 cross relaxation. The low quantum yield of the latter process, together with the low absorption cross section of Tm3+ at 464 nm and the low quenching concentration of Yb3+ in the Y2O3 host, made the Yb3+ 1030-nm NIR emission too weak for practical application.

The last process of the (1 0 0) γ-LiAlO 2 (LAO) wafer polishing has been investigated by adopting two different sizes (20 nm and 40 nm) SiO 2 suspension. Atomic force microscopy images show that the suspension with 20 nm SiO 2 particles tends to introduce a set of parallel trenches to the wafer surface and the suspension with 40 nm SiO 2 particles can provide a relative smooth surface. The following epitaxial ZnO films grown on the two as-prepared wafers demonstrate that the trench structure of the wafer surface will lead to mixed orientations of the ZnO film and single phase m -plane ZnO film can be obtained on the (1 0 0) LAO with a smooth surface.