Hypoxia-related prognostic model in bladder urothelial reflects immune cell infiltration.

Hypoxia is a common feature of tumor microenvironment (TME). This study aims to establish the genetic features related to hypoxia in Bladder urothelial carcinoma (BLCA) and investigate the potential correlation with hypoxia in the TME and immune cells. We established a BLCA outcome model using the hypoxia-related genes from The Cancer Genome Atlas using regression analysis and verified the model using the Gene Expression Omnibus GSE32894 cohort. We measured the effect of each gene in the hypoxia-related risk model using the Human Protein Atlas website. The predictive abilities were compared using the area under the receiver operating characteristic curves. Gene Set Enrichment Analysis was utilized for indicating enrichment pathways. We analyzed immune cell infiltration between risk groups using the CIBERSORT method. The indicators related to immune status between the two groups were also analyzed. The findings indicated that the high-risk group had better outcomes than the low-risk group in the training and validation sets. Each gene in the model affected the survival of BLCA patients. Our hypoxia-related risk model had better performance compared to other hypoxia-related markers (HIF-1α and GLUT-1). The high-risk group was enriched in immune-related pathways. The expression of chemokines and immune cell markers differed significantly between risk groups. Immune checkpoints were more highly expressed in the high-risk group. These findings suggest that the hypoxia-related risk model predicts patients' outcomes and immune status in BLCA risk groups. Our findings may contribute to the treatment of BLCA.

Recent progress on MHC-I epitope prediction in tumor immunotherapy.

Tumor immunotherapy has now become one of the most potential therapy for those intractable cancer diseases. The antigens on the cancer cell surfaces are the keys for the immune system to recognize and eliminate them. As reported, the immunogenicity of the tumor antigens could be determined by the binding between the key epitope peptides and MHC molecules. In recent years, the approaches to anticipate the peptides from the candidate epitopes have gradually changed into more efficient methods. Including the improved conventional methods, more diverse methods were coming into view. Here we review the anticipated methods of the tumor associated epitopes that specifically bind with major histocompatibility complex (MHC) class I molecules, and the recent advances and applications of those epitope prediction methods.

Integrated microenvironment-associated genomic profiles identify LRRC15 mediating recurrent glioblastoma-associated macrophages infiltration.

Glioblastoma (GBM) is the most common malignant intracranial tumour with intrinsic infiltrative characteristics, which could lead to most patients eventually relapse. The prognosis of recurrent GBM patients remains unsatisfactory. Cancer cell infiltration and their interaction with the tumour microenvironment (TME) could promote tumour recurrence and treatment resistance. In our study, we aimed to identify potential tumour target correlated with rGBM microenvironment based on the gene expression profiles and clinical information of rGBM patients from The Cancer Genome Atlas (TCGA) database. LRRC15 gene with prognostic value was screened by univariate and multivariate analysis, and the correlation between macrophages and LRRC15 was identified as well. Furthermore, the prognosis correlation and immune characteristics of LRRC15 were validated using the Chinese Glioma Genome Atlas (CGGA) database and our clinical tissues by immunochemistry assay. Additionally, we utilized the transwell assay and carboxy fluorescein succinimidyl ester (CFSE) tracking to further confirm the effects of LRRC15 on attracting microglia/macrophages and tumour cell proliferation in the TME. Gene profiles-based rGBM microenvironment identified that LRRC15 could act in collusion with microglia/macrophages in the rGBM microenvironment to promote the poor prognosis, especially in mesenchymal subtype, indicating the strategies of targeting LRRC15 to improve macrophages-based immunosuppressive effects could be promising for rGBM treatments.

HLA-A2.1-restricted ECM1-derived epitope LA through DC cross-activation priming CD8+ T and NK cells: a novel therapeutic tumour vaccine.

BACKGROUND: CD8+ T cell-mediated adaptive cellular immunity and natural killer (NK) cell-mediated innate immunity both play important roles in tumour immunity. This study aimed to develop therapeutic tumour vaccines based on double-activation of CD8+ T and NK cells. METHODS: The immune Epitope database, Molecular Operating Environment software, and enzyme-linked immunosorbent assay were used for epitope identification. Flow cytometry, confocal microscopy, UPLC-QTOF-MS, and RNA-seq were utilized for evaluating immunity of PBMC-derived DCs, CD8+ T or NK cells and related pathways. HLA-A2.1 transgenic mice combined with immunologically reconstituted tumour-bearing mice were used to examine the antitumour effect and safety of epitope vaccines. RESULTS: We identified novel HLA-A2.1-restricted extracellular matrix protein 1(ECM1)-derived immunodominant epitopes in which LA induced a potent immune response. We also found that LA-loaded DCs upregulated the frequency of CD3+/CD8+ T cells, CD45RO+/CD69+ activated memory T cells, and CD3-/CD16+/CD56+ NK cells. We demonstrated cytotoxic granule release of LA/DC-CTLs or LA/DC-NK cells and cytotoxicity against tumour cells and microtissue blocks via the predominant IFN-γ/perforin/granzyme B cell death pathway. Further investigating the mechanism of LA-mediated CD8+ T activation, we found that LA could be internalized into DCs through phagocytosis and then formed a LA-MHC-I complex presented onto the DC surface for recognition of the T cell receptor to upregulate Zap70 phosphorylation levels to further activate CD8+ T cells by DC-CTL interactions. In addition, LA-mediated DC-NK crosstalk through stimulation of the TLR4-p38 MAPK pathway increased MICA/B expression on DCs to interact with NKG2D for NK activation. Promisingly, LA could activate CD8+ T cells and NK cells simultaneously via interacting with DCs to suppress tumours in vivo. Moreover, the safety of LA was confirmed. CONCLUSIONS: LA-induced immune antitumour activity through DC cross-activation with CD8+ T and NK cells, which demonstrated proof-of-concept evidence for the capability and safety of a novel therapeutic tumour vaccine.

Peptide-based therapeutic cancer vaccine: Current trends in clinical application.

The peptide-based therapeutic cancer vaccines have attracted enormous attention in recent years as one of the effective treatments of tumour immunotherapy. Most of peptide-based vaccines are based on epitope peptides stimulating CD8+ T cells or CD4+ T helper cells to target tumour-associated antigens (TAAs) or tumour-specific antigens (TSAs). Some adjuvants and nanomaterials have been exploited to optimize the efficiency of immune response of the epitope peptide to improve its clinical application. At present, numerous peptide-based therapeutic cancer vaccines have been developed and achieved significant clinical benefits. Similarly, the combination of peptide-based vaccines and other therapies has demonstrated a superior efficacy in improving anti-cancer activity. We delve deeper into the choices of targets, design and screening of epitope peptides, clinical efficacy and adverse events of peptide-based vaccines, and strategies combination of peptide-based therapeutic cancer vaccines and other therapies. The review will provide a detailed overview and basis for future clinical application of peptide-based therapeutic cancer vaccines.

Silencing KIF18B enhances radiosensitivity: identification of a promising therapeutic target in sarcoma.

BACKGROUND: Sarcomas are rare heterogeneous tumours, derived from primitive mesenchymal stem cells, with more than 100 distinct subtypes. Radioresistance remains a major clinical challenge for sarcomas, demanding urgent for effective biomarkers of radiosensitivity. METHODS: The radiosensitive gene Kinesin family member 18B (KIF18B) was mined through bioinformatics with integrating of 15 Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database. We used radiotherapy-sh-KIF18B combination to observe the anti-tumour effect in sarcoma cells and subcutaneous or orthotopic xenograft models. The KIF18B-sensitive drug T0901317 (T09) was further mined to act as radiosensitizer using the Genomics of Drug Sensitivity in Cancer (GDSC) database. FINDINGS: KIF18B mRNA was significantly up-regulated in most of the subtypes of bone and soft tissue sarcoma. Multivariate Cox regression analysis showed that KIF18B high expression was an independent risk factor for prognosis in sarcoma patients with radiotherapy. Silencing KIF18B or using T09 significantly improved the radiosensitivity of sarcoma cells, delayed tumour growth in subcutaneous and orthotopic xenograft model, and elongated mice survival time. Furthermore, we predicted that T09 might bind to the structural region of KIF18B to exert radiosensitization. INTERPRETATION: These results indicated that sarcomas with low expression of KIF18B may benefit from radiotherapy. Moreover, the radiosensitivity of sarcomas with overexpressed KIF18B could be effectively improved by silencing KIF18B or using T09, which may provide promising strategies for radiotherapy treatment of sarcoma. FUNDINGS: A full list of funding can be found in the Funding Sources section.

Core-shell ZnO@C:N hybrids derived from MOFs as long-cycling anodes for lithium ion batteries.

A core-shell hybrid of ZnO and nitrogen-doped carbon (ZnO@C:N) is designed as a long-cycling anode for LIBs. The ZnO@C:N hybrid has a high initial capacity of 1116 mA h g-1 and a reversible capacity of 608 mA h g-1 after 500 cycles at 0.1 A g-1. The unique core-shell structure, high conductivity due to nitrogen doping, and uniform solid electrolyte interphase (SEI) film formed in the electrode are revealed to result in the remarkable electrochemical performances of the ZnO@C:N electrodes.

TEX19 promotes ovarian carcinoma progression and is a potential target for epitope vaccine immunotherapy.

AIMS: Testis Expressed 19 (TEX19) is one of cancer/testis antigens identified in recent years and is related to the oncogenesis and progress of several cancers. This study aimed to reveal the role of TEX19 in ovarian cancer (OC) and searched for potential candidate epitope peptides of TEX19 to facilitate clinical application. MAIN METHODS: TEX19 levels were evaluated by immunohistochemistry (IHC) in 98 human ovarian tissue samples. The correlation of TEX19 levels with patients' clinicopathological features was assessed. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting analysis were utilized to detect TEX19 levels in ovarian cell lines and TEX19-deficient cells. The level of TEX19 in OVCAR-3 and A2780 was knocked down by small interfering RNA (siRNA), and loss-of-function assays were used to determine the biological effects of TEX19 on the proliferation, migration, and invasion of OC cells. Subsequently, candidate epitope peptides from TEX19 were predicted and verified by the IEDB database, pepsite2 website, MOE software, and T2 cell binding assay. KEY FINDINGS: TEX19 was significantly upregulated in OC which correlated to higher TNM stage, lymph node involvement, and invasiveness. Knockdown of TEX19 inhibited proliferation, migration, and invasion of OC cells. Additionally, we screened four peptides derived from TEX19 and found TL to be the dominant peptide with the greatest affinity with HLA-A*0201. SIGNIFICANCE: Our data indicated a cancer-promoting effect of TEX19 in OC and demonstrated that TL could be a potential candidate for an anti-tumor epitope vaccine of OC, suggesting that TEX19 is a promising biomarker and immunotherapeutic target for OC.

Bioinformatics Analysis Suggests the Combined Expression of AURKB and KIF18B Being an Important Event in the Development of Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma with high metastatic rate and high mortality rate, needing to find potential therapeutic targets and develop new therapy methods. The bioinformatics analysis was used in this study to find the targets. Firstly, the expression profile of ccRCC obtained from The Cancer Genome Atlas (TCGA) database and GSE53757 dataset were used to identify the significant up-regulated genes. IL20RB, AURKB and KIF18B with the top efficiency of capable of diagnosis ccRCC from para cancer tissue, were over-expressed in ccRCC samples, and expressed increasedly with the development of ccRCC. There was the closest correlation between AURKB and KIF18B in these three over-expressed genes. AURKB (high) or KIF18B (high) were all significantly correlated with higher T, N, M stage, G grade and shorter overall survival (OS) of ccRCC patients. Furthermore, the ccRCC patients with AURKB (high) + KIF18B (high) showed worse clinical characteristics and prognosis. Multivariate COX regression analysis indicated AURKB (high) and KIF18B (high) were all the independent prognostic risk factor without considering the interaction of AURKB and KIF18B. Moreover, considering the combination of each other, only AURKB (high) + KIF18B (high) expression was an independent prognostic risk factor for ccRCC patients, but not other situations. Collectively, AURKB was closely associated with KIF18B, and the combined expression of AURKB and KIF18B may be of great significance in ccRCC.

Speckle pattern shifting deflectometry based on digital image correlation.

A method based on digital image correlation (DIC) for the surface shape measurement of specular surface by shifting a speckle pattern, which is displayed on an LCD screen, is proposed in this paper. With this method, the deformed information of test surface is encoded within the displacement distribution between the two recorded speckle images before and after the speckle pattern shifted. The displacement distribution is calculated by the DIC algorithm, then the slope data and the surface shape are obtained. The principle and algorithm of speckle pattern shifting deflectometry (SPSD) are described in detail. The correctness and feasibility of the proposed method are verified by simulation, and the source of error is analyzed as well. Finally, the shape of an acrylic plastic plate and a silicon wafer are measured. The experimental result of the proposed method is compared with that of PMD, and the figure error is around 1µm RMS with a measured diameter of about 100mm. This method has the advantages of fast measurement, simple device, low cost and needlessness of reference element. It provides a new approach to measure the shape of specular surface.

FeSe2/carbon nanotube hybrid lithium-ion battery for harvesting energy from triboelectric nanogenerators.

FeSe2-carbon nanotube (FeSe2-CNT) hybrid microspheres are investigated as anode materials for lithium ion batteries (LIBs), exhibiting a high specific capacity of 571.2 mA h g-1 at 0.5 A g-1 with excellent rate performance and cycling stability. The FeSe2-CNT hybrid LIBs could withstand the high-voltage pulse of triboelectric nanogenerators (TENGs) and be charged by TENGs directly for harvesting energy with high stability.

The Analysis of Key Factors Related to ADCs Structural Design.

Antibody-drug conjugates (ADCs) have developed rapidly in recent decades. However, it is complicated to map out a perfect ADC that requires optimization of multiple parameters including antigens, antibodies, linkers, payloads, and the payload-linker linkage. The therapeutic targets of the ADCs are expected to express only on the surface of the corresponding target tumor cells. On the contrary, many antigens usually express on normal tissues to some extent, which could disturb the specificity of ADCs and limit their clinical application, not to mention the antibody is also difficult to choose. It requires to not only target and have affinity with the corresponding antigen, but it also needs to have a linkage site with the linker to load the payloads. In addition, the linker and payload are indispensable in the efficacy of ADCs. The linker is required to stabilize the ADC in the circulatory system and is brittle to release free payload while the antibody combines with antigen. Also, it is a premise that the dose of ADCs will not kill normal tissues and the released payloads are able to fulfill the killing potency in tumor cells at the same time. In this review, we mainly focus on the latest development of key factors affecting ADCs progress, including the selection of antibodies and antigens, the optimization of payload, the modification of linker, payload-linker linkage, and some other relevant parameters of ADCs.

Integrated System of Solar Cells with Hierarchical NiCo2O4 Battery-Supercapacitor Hybrid Devices for Self-Driving Light-Emitting Diodes.

An integrated system has been provided with a-Si/H solar cells as energy conversion device, NiCo2O4 battery-supercapacitor hybrid (BSH) as energy storage device, and light emitting diodes (LEDs) as energy utilization device. By designing three-dimensional hierarchical NiCo2O4 arrays as faradic electrode, with capacitive electrode of active carbon (AC), BSHs were assembled with energy density of 16.6 Wh kg-1, power density of 7285 W kg-1, long-term stability with 100% retention after 15,000 cycles, and rather low self-discharge. The NiCo2O4//AC BSH was charged to 1.6 V in 1 s by solar cells and acted as reliable sources for powering LEDs. The integrated system is rational for operation, having an overall efficiency of 8.1% with storage efficiency of 74.24%. The integrated system demonstrates a stable solar power conversion, outstanding energy storage behavior, and reliable light emitting. Our study offers a precious strategy to design a self-driven integrated system for highly efficient energy utilization.

Three-Dimensional NiCo2O4@MnMoO4 Core-Shell Nanoarrays for High-Performance Asymmetric Supercapacitors.

Design of new materials with sophisticated nanostructure has been proven to be an efficient strategy to improve their properties in many applications. Herein, we demonstrate the successful combination of high electron conductive materials of NiCo2O4 with high capacitance materials of MnMoO4 by forming a core-shell nanostructure. The NiCo2O4@MnMoO4 core-shell nanoarrays (CSNAs) electrode possesses high capacitance of 1169 F g-1 (4.24 F cm-2) at a current density of 2.5 mA cm-2, obviously larger than the pristine NiCo2O4 electrode. The asymmetric supercapacitors (ASCs), assembled with NiCo2O4@MnMoO4 CSNAs as binder-free cathode and active carbon (AC) as anode, exhibit high energy density of 15 Wh kg-1 and high power density of 6734 W kg-1. Cycle performance of NiCo2O4@MnMoO4 CSNAs//AC ASCs, conducted at current density of 20 mA cm-2, remain 96.45% of the initial capacitance after 10,000 cycles, demonstrating its excellent long-term cycle stability. Kinetically decoupled analysis reveals that the capacitive capacitance is dominant in the total capacitance of NiCo2O4@MnMoO4 CSNAs electrode, which may be the reason for ultra long cycle stability of ASCs. Our assembled button ASC can easily light up a red LED for 30 min and a green LED for 10 min after being charged for 30 s. The remarkable electrochemical performance of NiCo2O4@MnMoO4 CSNAs//AC ASCs is attributed to its enhanced surface area, abundant electroactive sites, facile electrolyte infiltration into the 3D NiCo2O4@MnMnO4 nanoarrays and fast electron and ion transport path.

Excellent absorption properties of BaFe12-xNbxO19 controlled by multi-resonance permeability, enhanced permittivity, and the order of matching thickness.

For the sol-gel-derived BaFe12-xNbxO19 (x = 0-0.6), coercivity (Hc) and saturation magnetization (Ms) vary from 3.53-0.85 kOe and 70.3-53.8 emu g-1 to 1.02-0.22 kOe and 69.6-59.5 emu g-1, respectively, with an increase in sintering temperature from 1250 °C to 1350 °C. Moreover, ε' and ε'' increase from 4.13-4.04 and 0.0049-0.0045 to 7.64-6.93 and 1.50-0.97 over 26.5-40 GHz, and the multi-resonance peaks in permeability shift from ∼40+ GHz to ∼27 GHz. The bandwidth (BW) and reflection loss peak intensity (RLp) are broadened and enhanced from 0.8 GHz and -10.3 dB of the sample with x = 0.2 sintered at 1250 °C under 0.92 mm to 11.9+ GHz and -54 dB, respectively, of the sample with x = 0.6 sintered at 1350 °C under 0.86 mm around a millimeter-wave atmospheric window of 35 GHz. The effects of Nb5+ content (x) and sintering temperature on grain size, phase compositions, formations of Fe2+ and oxygen vacancy, and thus on static magnetism and EM parameters are investigated. The correlations of multi-resonance permeability, enhanced permittivity, and the order of matching thickness with absorption properties are also discussed in detail.