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Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle‐mediated DNA vaccine containing an activated factor L‐Myc and a tumor‐specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS‐pL‐Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS‐pL‐Myc/pCAIX co‐immunization group. The increased proportion and mature of CD11c+ DCs, CD8+CD11c+ DCs and CD103+CD11c+ DCs were observed in the splenocytes from CS‐pL‐Myc/pCAIX co‐immunized mice. Furthermore, the enhanced antigen‐specific CD8+ T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi‐functional CD8+ T cell induction were detected in CS‐pL‐Myc/pCAIX co‐immunization group compared with CS‐pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8+ T cells or CD8+CD11c+ DCs and the loss of anti‐tumor efficacy induced by CS‐pL‐Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8+ DCs and CD103+ DCs mediated CD8+ T cells responses. Likewise, CS‐pL‐Myc/pCAIX co‐immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi‐functional CD8+ T cell responses. Therefore, these results indicated that CS‐pL‐Myc/pCAIX vaccine could effectively induce CD8+ DCs and CD103+ DCs mediated tumor‐specific multi‐functional CD8+ T cell responses and exert the anti‐tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment., CS‐p‐L‐Myc/pCAIX vaccine activated the CD8+CD11c+ DCs and CD103+CD11c+ DCs, and activated CAIX‐specific CD8+ T cell proliferation, CTL responses, and multi‐functional CD8+ T cells (expressing TNF‐α, IL‐2, and IFN‐γ) in mouse tumor models. Moreover, the CD8+ T cell depletion resulted in the reduction of CD8+CD11c+ DCs and the loss of anti‐tumor activity of vaccine, suggesting that this therapeutic efficacy was required for CD8+CD11c+ DCs‐mediated multi‐functional CD8+ T cell responses. Therefore, this vaccine strategy may be a potential approach for primary solid or metastasis tumor therapy.

Interferon-induced protein 35 (IFI35), is currently acknowledged to govern the virus-related immune inflammatory responses. However, the biological significance and function of IFI35 in renal cell cancer (RCC) is still not well understood. Here, IFI35 expression and function were investigated in RCC tissues, renal cancer cells, and animal models. The results showed that IFI35 expression was significantly increased in 200 specimens of RCC patients. We found that higher IFI35 levels were significantly correlated with poor RCC prognosis. In human cell lines, the knockdown of IFI35 suppressed the malignant behavior of renal cancer cells. Similarly, the IFI35 knockdown resulted in significant inhibition of tumor progression in the subcutaneous or lung metastasis mouse model. Furthermore, the knockdown of IFI35 promoted the induction of autophagy by enhancing the autophagy-related gene expression (LC3-II, Beclin-1, and ATG-5). Additionally, blockade of STAT1/STAT6 phosphorylation (pSTAT1/pSTAT6) abrogated the induced autophagy by IFI35 knockdown in renal cancer cells. The autophagy inhibitor 3-MA also abolished the prevention of tumor growth by deleting IFI35 in renal cancer models. The above results suggest that the knockdown of IFI35 suppressed tumor progression of renal cancer by pSTAT1/pSTAT6-dependent autophagy. Our research revealed that IFI35 may serve as a potential diagnosis and therapeutic target for RCC.

We report the high stability and reversibility of disordered graphitic nanocarbon (DGN) under high pressure. No bonding change can be observed in DGN even up to 52.0 GPa and it fully recovers upon decompression. The high stability and reversibility should be related to its unique highly disordered structure which consists of nanosized wavy graphene layers, making the DGN elastic upon compression. Combined with high temperature, DGN is transformed into polycrystalline nanodiamonds with average grain size smaller than the pristine nanoparticles.

Developing a universal strategy to design piezochromic luminescent materials with desirable properties remains challenging. Here, we report that insertion of a non-emissive molecule into a donor (perylene) and acceptor (1,2,4,5-tetracyanobezene) binary cocrystal can realize fine manipulation of intermolecular interactions between perylene and 1,2,4,5-tetracyanobezene (TCNB) for desirable piezochromic luminescent properties. A continuous pressure-induced emission enhancement up to 3 GPa and a blue shift from 655 to 619 nm have been observed in perylene-TCNB cocrystals upon THF insertion, in contrast to the red-shifted and quenched emission observed when compressing perylene-TCNB cocrystals and other cocrystals reported earlier. By combining experiment with theory, it is further revealed that the inserted non-emissive THF forms blue-shifting hydrogen bonds with neighboring TCNB molecules and promote a conformation change of perylene molecules upon compression, causing the blue-shifted and enhanced emission. This strategy remains valid when inserting other molecules as non-emissive component into perylene-TCNB cocrystals for abnormal piezochromic luminescent behaviors., The design of piezochromic luminescent materials with desirable stimuliresponsive properties remains challenging. Here, the authors report the insertion of a non-emissive molecule into a donor and acceptor binary cocrystal and realize desirable piezochromic luminescent properties by manipulation of intermolecular interactions between the donor and acceptor molecules.

Highlight • AIM2 expression in TAMs was negatively correlated with the percentages of M2-like polarization phenotype in renal cancer specimens. • Over-expression of AIM2 in macrophages reversed renal cancer cell-induced macrophage phenotype from M2 to M1. • The inflammasome activation is required for AIM2-mediated M1 macrophages in suppression of tumor malignant behaviors. • Administration of BMDMs-AIM2 reduced the tumor growth in subcutaneous tumor or lung metasis mice., Absent in melanoma 2 (AIM2) as an immune regulator for the regulation of tumor-associated macrophages (TAMs) function is unclear in tumor development. Here, the AIM2 function was investigated in TAMs-mediated malignant behaviors of renal carcinoma. The correlation analysis result showed that the AIM2 expression in TAMs was negatively correlated with the percentages of M2-like polarization phenotype in human or murine renal cancer specimens. By the cocultured assay with bone marrow-derived macrophages (BMDMs) and Renca cells, overexpression of AIM2 in macrophages enhanced the inflammasome activation and reversed the phenotype from M2 to M1. Compared with BMDMs-Ctrl cocultured group, BMDMs-AIM2 cocultured group showed reduced tumor cell proliferation and migration. The blockade of inflammasome activation by the inhibitor Ac-YVAD-CMK abrogated AIM2-mediated M1 polarization and the inhibition of tumor cell growth. To evaluate the therapeutic efficacy of AIM2-mediated M1 macrophages in vivo, BMDMs-AIM2 were intravenously injected into subcutaneous Renca-tumor mice. The results showed that the infiltration of M1 TAMs was increased and tumor growth was suppressed in BMDMs-AIM2-treated mice when compared with BMDMs-Ctrl-treat mice. Accordingly, the blockade of inflammasome activation reduced the anti-tumor activities of BMDMs-AIM2. Moreover, the lung metastases of renal carcinoma were suppressed by the administration of BMDMs-AIM2 accompanied with the reduced tumor foci. These results demonstrated that AIM2 enhanced TAMs polarization switch from anti-inflammatory M2 phenotypy to pro-inflammatory M1 through inflammasome signaling activation, thus exerting therapeutic intervention in renal carcinoma models. Our results provide a possible molecular mechanism for the modulation of TAMs polarization in tumor microenvironment and open a new potential therapeutic approach for renal cancer.

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIXpromotor )-controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIXpromotor -AIM2 adenoviruses (Ad-CAIXpromotor -AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad-CAIXpromotor , Ad-CAIXpromotor -AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786-O cells or OSRC-2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC-2-xenograft mice. The tumour growth was remarkably inhibited in Ad-CAIXpromotor -AIM2-treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD-CMK resulted in the reduction of anti-tumour activity by Ad-CAIXpromotor -AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad-CAIXpromotor -AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour-specific Ad-CAIXpromotor -AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2-based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.

Pressure generation to a higher pressure range in a large-volume press (LVP) denotes our ability to explore more functional materials and deeper Earth’s interior. Pressure generated by normal tungsten carbide (WC) anvils in a commercial way is mostly limited to 25GPa in LVPs due to the limitation of their hardness and design of cell assemblies. We adopt three newly developed WC anvils for ultrahigh pressure generation in a Walker-type LVP with a maximum press load of 1000 ton. The hardest ZK01F WC anvils exhibit the highest efficiency of pressure generation than ZK10F and ZK20F WC anvils, which is related to their performances of plastic deformations. Pressure up to 35GPa at room temperature is achieved at a relatively low press load of 4.5MN by adopting the hardest ZK01F WC anvils with three tapering surfaces in conjunction with an optimized cell assembly, while pressure above 35GPa at 1700K is achieved at a higher press load of 7.5MN. Temperature above 2000K can be generated by our cell assemblies at pressure below 30GPa. We adopt such high-pressure and high-temperature techniques to fabricate several high-quality and well-sintered polycrystalline minerals for practical use. The present development of high-pressure techniques expands the pressure and temperature ranges in Walker-type LVPs and has wide applications in physics, materials, chemistry, and Earth science.

The switching surges of a cable collector system can cause equipment failure in a wind power plant (WPP). The study on the switching over-voltage caused by operation of medium voltage breaker in the cable collector system is important. In this paper, a laboratory test system was set up to reproduce a part of a cable collector system in a WPP. Based on the way the load was connected to the cable collector, four test approaches were proposed to measure the switching over-voltage. A vacuum circuit breaker (VCB) with point on wave control was used in the circuit to study the effect of current chopping characteristics while breaking the inductive load. These switching tests were conducted to simulate the possible switching operations in a WPP. The test results have shown that the over-voltages caused in a cable system are closely related to the cable length and inductive load. The maximum over-voltage was observed during the breaking of the inductive load at zero phase voltage in which multi re-ignitions of the VCB were recorded.

Accepted manuscript