Enhancing Adhesion and Reducing Ohmic Contact through Nickel-Silicon Alloy Seed Layer in Electroplating Ni/Cu/Ag.

Due to the lower cost compared to screen-printed silver contacts, the Ni/Cu/Ag contacts formed by plating have been continuously studied as a potential metallization technology for solar cells. To address the adhesion issue of backside grid lines in electroplated n-Tunnel Oxide Passivating Contacts (n-TOPCon) solar cells and reduce ohmic contact, we propose a novel approach of adding a Ni/Si alloy seed layer between the Ni and Si layers. The metal nickel layer is deposited on the backside of the solar cells using electron beam evaporation, and excess nickel is removed by H2SO4:H2O2 etchant under annealing conditions of 300-425 °C to form a seed layer. The adhesion strength increased by more than 0.5 N mm-1 and the contact resistance dropped by 0.5 mΩ cm2 in comparison to the traditional direct plating Ni/Cu/Ag method. This is because the resulting Ni/Si alloy has outstanding electrical conductivity, and the produced Ni/Si alloy has higher adhesion over direct contact between the nickel-silicon interface, as well as enhanced surface roughness. The results showed that at an annealing temperature of 375 °C, the main compound formed was NiSi, with a contact resistance of 1 mΩ cm-2 and a maximum gate line adhesion of 2.7 N mm-1. This method proposes a new technical solution for cost reduction and efficiency improvement of n-TOPCon solar cells.

Antigen presentation by dendritic cells in tumors is disrupted by altered metabolism that involves pyruvate kinase M2 and its interaction with SOCS3.

Dendritic cell (DC) function is negatively affected by tumors and tumor-derived factors, but little is known about the underlying mechanisms. Here, we show that intracellular SOCS3 in DCs binds to pyruvate kinase type M2 (M2-PK), which plays a critical role in ATP production through glycolysis. The interaction of SOCS3 with M2-PK reduced ATP production and impaired DC-based immunotherapy against tumors. Thus, SOCS3, which has been shown to be upregulated by tumor-derived factors, interacts with M2-PK to decrease ATP production, causing DC dysfunction. These dysfunctional DCs have a reduced ability to present antigens. Alteration of DC metabolism mediated by SOCS3 represents a novel mechanism for DC dysfunction in the tumor microenvironment.

AA28-67 domain within MyD88 suppresses c-myc activity and expression to regulate differentiation and function of dendritic cells.

The mechanism by which c-myc expression in undifferentiated cells rapidly declines following induction of differentiation is poorly characterized. We demonstrate here that MyD88, which can activate NF-kappaB and MAPK, also suppresses c-myc activity and expression. The aa 28-67 domain, a highly conserved region within MyD88, plays a critical role in the MyD88-mediated inhibition. Indeed, deletion of the aa 28-67 domain (MyD88 Delta 28-67) or mutation of the highly conserved amino acid residue phenylalanine (aa 36) to aspartic acid (MyD88 Delta F36D) significantly promoted c-myc activity and expression. Additionally, we found that MyD88 Delta 28-67-mediated c-myc activity and expression could be abrogated using PI3K inhibitor, suggesting that the PI3K/Akt signaling pathway may be involved in MyD88-mediated suppression of c-myc. Compared to MyD88-transduced DCs, MyD88 Delta 28-67- and MyD88 Delta F36D-transduced DCs derived from MyD88-/- bone marrow cells had lower antigen-presenting ability. Thus, MyD88 induces the differentiation and maturation of DCs not only by activating NF-kappaB and MAPK but also via suppressing c-myc activity and expression.

Suppressor of cytokine signaling 3 promotes bone marrow cells to differentiate into CD8+ T lymphocytes in lung tissue via up-regulating Notch1 expression.

Suppressor of cytokine signaling 3 (SOCS3) expression in bone marrow cells (BMC) was up-regulated upon exposure to interleukin 6, lipopolysaccharide, or tumor-associated factors. But, how the up-regulated SOCS3 affects differentiation of BMCs is incompletely characterized. Here, we showed that SOCS3 promoted BMCs to intently differentiate into CD8 T cells. Importantly, lung can be as one athymus tissue for the BMCs to differentiate into CD8(+) T cells. Notch1 plays a critical role in the differentiation from SOCS3-transfected BMCs to CD8(+) T cells. We conclude that the up-regulated SOCS3 in some pathologic conditions, such as tumor and inflammation, might promote BMCs to differentiate into CD8(+) T lymphocytes in lung tissue via up-regulating Notch1 expression. This may represent a new mechanism against diseases such as tumor.

Regulation of arginase I activity and expression by both PD-1 and CTLA-4 on the myeloid-derived suppressor cells.

An elevated number of Gr-1(+)CD11b(+) myeloid-derived suppression cells (MDSCs) has been described in mice and human bearing tumor and associated with immune suppression. Arginase I production by MDSCs in the tumor environment may be a central mechanism for immunosuppression and tumor evasion. In this study and before, we found that Gr-1(+)CD11b(+) MDSCs from ascites and spleen of mice bearing ovarian 18D carcinoma express a high level of PD-1, CTLA-4, B7-H1 and CD80 while other co-stimulatory molecules, namely CD40, B7-DC and CD86 are not detected. Further studies showed that PD-1 and CTLA-4 on the Gr-1(+)CD11b(+) MDSCs regulated the activity and expression of arginase I. The blockage and silencing of PD-1, CTLA-4 or both PD-1 and CTLA4 molecules could significantly reduce arginase I activity and expression induced with tumor-associated factor. Similar results were also observed while their ligands B7-H1 and/or CD80 were blocked or silenced. Furthermore, CD80 deficiency also decreased the arginase I expression and activity. Antibody blockade or silencing of PD-1, CTLA-4 or both reduced the suppressive potential of PD-1+CTLA-4+MDSCs. Blockade of PD-1, CTLA-4 or both also slowed tumor growth and improved the survival rate of tumor-bearing mice. Thus, there may exist a coinhibitory and costimulatory molecules-based immuno-regulating net among MDSCs.

B7-H1 on myeloid-derived suppressor cells in immune suppression by a mouse model of ovarian cancer.

Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and are associated with immune suppression. Here, we described high level of expression of B7-H1 (CD274), PD-1 (CD279) and CTLA4 (CD152) by Gr-1(+)CD11b(+) MDSCs obtained from both ascites and spleens of mice bearing the 1D8 ovarian carcinoma, whereas B7-DC (CD273), CD40 and CD86 were absent. In contrast, B7-H1, PD-1 and CTLA-4 expression was not detected on Gr-1(+)CD11b(+) cells from naive mice. Expression of B7-H1 by Gr-1(+)CD11b(+) cells from naive mice could be induced by co-culture with 1D8 ovarian carcinoma cells. Gr-1(+)CD11b(+) cells derived from 1D8 tumor-bearing mice markedly suppressed antigen-specific immune responses, whereas Gr-1(+)CD11b(+) cells from naive mice did not. siRNA-mediated knockdown of B7-H1 in Gr-1(+)CD11b(+) cells of 1D8 tumor-bearing mice alleviated suppression of antigen-specific immune responses. Suppression of antigen-specific immune responses via B7-H1 on Gr-1(+)CD11b(+) myeloid cells was mediated by CD4(+)CD25(+) Foxp3(+) T regulatory cells and required PD-1. Antibody blockade of either B7-H1 or PD-1 retarded the growth of 1D8 tumor in mice. This suggests that expression of B7-H1 on Gr-1(+)CD11b(+) myeloid cells triggered by the 1D8 mouse model of ovarian carcinoma suppresses antigen-specific immunity via interaction with PD-1 on CD4(+)CD25(+) Foxp3(+) regulatory T cells.

Tumor-induced suppressor of cytokine signaling 3 inhibits toll-like receptor 3 signaling in dendritic cells via binding to tyrosine kinase 2.

The suppressor of cytokine signaling (SOCS) family of negative regulatory proteins is up-regulated in response to several cytokines and pathogen-associated molecular patterns (PAMP) and suppresses cellular signaling responses by binding receptor phosphotyrosine residues. Exposure of bone marrow-derived dendritic cells (BMDC) to 1D8 cells, a murine model of ovarian carcinoma, suppresses their ability to express CD40 and stimulate antigen-specific responses in response to PAMPs and, in particular, to polyinosinic acid:poly-CMP (polyI:C) with the up-regulated SOCS3 transcript and protein levels. The ectopic expression of SOCS3 in both the macrophage cell line RAW264.7 and BMDCs decreased signaling in response to both polyI:C and IFNalpha. Further, knockdown of SOCS3 transcripts significantly enhanced the responses of RAW264.7 and BMDCs to both polyI:C and IFNalpha. Immunoprecipitation and pull-down studies show that SOCS3 binds to the IFNalpha receptor tyrosine kinase 2 (TYK2). Because polyI:C triggers autocrine IFNalpha signaling, binding of SOCS3 to TYK2 may thereby suppress the activation of BMDCs by polyI:C and IFNalpha. Thus, elevated levels of SOCS3 in tumor-associated DCs may potentially resist the signals induced by Toll-like receptor 3 ligands and type I IFN to decrease DC activation via binding with IFNalpha receptor TYK2.

Delivery of telomerase reverse transcriptase small interfering RNA in complex with positively charged single-walled carbon nanotubes suppresses tumor growth.

PURPOSE: To determine whether -CONH-(CH(2))(6)-NH(3)(+)Cl(-) functionalized single-walled carbon nanotubes (SWNT) carrying complexed small interfering RNA (siRNA) can enter into tumor cells, wherein they release the siRNA to silence the targeted gene. EXPERIMENTAL DESIGN: -CONH-(CH(2))(6)-NH(3)(+)Cl(-) was used to mediate the conjugation of telomerase reverse transcriptase (TERT) siRNA to SWNTs. The ability of TERT siRNA delivered via SWNT complexes to silence the expression of TERT was assessed by their effects on the proliferation and growth of tumor cells both in vitro and in mouse models. RESULTS: The functionalized SWNTs -CONH-(CH(2))(6)-NH(3)(+)Cl(-) could facilitate the coupling of siRNAs that specifically target murine TERT expression to form the mTERT siRNA:SWNT+ complex. These functionalized SWNTs rapidly entered three cultured murine tumor cell lines, suppressed mTERT expression, and produced growth arrest. Injection of mTERT siRNA:SWNT+ complexes into s.c. Lewis lung tumors reduced tumor growth. Furthermore, human TERT siRNA:SWNT+ complexes also suppressed the growth of human HeLa cells both in vitro and when injected into tumors in nude mice. CONCLUSIONS: -CONH-(CH(2))(6)-NH(3)(+)Cl(-) functionalized SWNTs carry complexed siRNA into tumor cells, wherein they release the siRNA from the nanotube sidewalls to silence the targeted gene. The -CONH-(CH(2))(6)-NH(3)(+)Cl(-) functionalized SWNTs may represent a new class of molecular transporters applicable for siRNA therapeutics.