High-entropy amorphous NbTiAlSiWxNy films (x = 0 or 1, i.e., NbTiAlSiNy and NbTiAlSiWNy) were prepared by magnetron sputtering method in the atmosphere of a mixture of N2 + Ar (N2 + Ar = 24 standard ...cubic centimeter per minute (sccm)), where N2 = 0, 4, and 8 sccm). All the as-deposited films present amorphous structures, which remain stable at 700 °C for over 24 h. After heat treatment at 1000 °C the films began to crystalize, and while the NbTiAlSiNy films (N2 = 4, 8 sccm) exhibit a face-centered cubic (FCC) structure, the NbTiAlSiW metallic films show a body-centered cubic (BCC) structure and then transit into a FCC structure composed of nanoscaled particles with increasing nitrogen flow rate. The hardness and modulus of the as-deposited NbTiAlSiNy films reach maximum values of 20.5 GPa and 206.8 GPa, respectively. For the as-deposited NbTiAlSiWNy films, both modulus and hardness increased to maximum values of 13.6 GPa and 154.4 GPa, respectively, and then decrease as the N2 flow rate is increased. Both films could be potential candidates for protective coatings at high temperature.
Near infrared photoimmunotherapy (NIR-PIT) is a newly developed molecular targeted cancer treatment, which selectively kills cancer cells or immune-regulatory cells and induces therapeutic host ...immune responses by administrating a cancer targeting moiety conjugated with IRdye700. The local exposure to near-infrared (NIR) light causes a photo-induced ligand release reaction, which causes damage to the target cell, resulting in immunogenic cell death (ICD) with little or no side effect to the surrounding normal cells. Moreover, NIR-PIT can generate an immune response in distant metastases and inhibit further cancer attack by combing cancer cells targeting NIR-PIT and immune regulatory cells targeting NIR-PIT or other cancer treatment modalities. Several recent improvements in NIR-PIT have been explored such as catheter-driven NIR light delivery, real-time monitoring of cancer, and the development of new target molecule, leading to NIR-PIT being considered as a promising cancer therapy. In this review, we discuss the progress of NIR-PIT, their mechanism and design strategies for cancer treatment. Furthermore, the overall possible targeting molecules for NIR-PIT with their application for cancer treatment are briefly summarised.
Traditional immunohistochemistry (IHC) has already become an essential method of diagnosis and therapy in cancer management. However, this antibody-based technique is limited to detecting a single ...marker per tissue section. Since immunotherapy has revolutionized the antineoplastic therapy, developing new immunohistochemistry strategies to detect multiple markers simultaneously to better understand tumor environment and predict or assess response to immunotherapy is necessary and urgent. Multiplex immunohistochemistry (mIHC)/multiplex immunofluorescence (mIF), such as multiplex chromogenic IHC and multiplex fluorescent immunohistochemistry (mfIHC), is a new and emerging technology to label multiple biomarkers in a single pathological section. The mfIHC shows a higher performance in cancer immunotherapy. This review summarizes the technologies, which are applied for mfIHC, and discusses how they are employed for immunotherapy research.
Recently, humidity sensors have been investigated extensively due to their broad applications in chip fabrication, health care, agriculture, amongst others. We propose a capacitive humidity sensor ...with a shielding electrode under the interdigitated electrode (SIDE) based on polyimide (PI). Thanks to the shielding electrode, this humidity sensor combines the high sensitivity of parallel plate capacitive sensors and the fast response of interdigitated electrode capacitive sensors. We use COMSOL Multiphysics to design and optimize the SIDE structure. The experimental data show very good agreement with the simulation. The sensitivity of the SIDE sensor is 0.0063% ± 0.0002% RH. Its response/recovery time is 20 s/22 s. The maximum capacitance drift under different relative humidity is 1.28% RH.
Triple-negative breast cancer (TNBC) is a group of heterogeneous and refractory breast cancers with the absence of estrogen receptor (ER), progesterone receptor (PgR) and epidermal growth factor ...receptor 2 (HER2). Over the past decade, antibody drug conjugates (ADCs) have ushered in a new era of targeting therapy. Since the epidermal growth factor receptor (EGFR) and epithelial cell adhesion molecule (EpCAM) are over expressed on triple-negative breast cancer, we developed novel ADCs by conjugating benzylguanine (BG)-modified monomethyl auristatin E (MMAE) to EpCAM- and EGFR-specific SNAP-tagged single chain antibody fragments (scFvs). Rapid and efficient conjugation was achieved by SNAP-tag technology. The binding and internalization properties of scFv-SNAP fusion proteins were confirmed by flow cytometry and fluorescence microscopy. The dose-dependent cytotoxicity was evaluated in cell lines expressing different levels of EGFR and EpCAM. Both ADCs showed specific cytotoxicity to EGFR or EpCAM positive cell lines via inducing apoptosis at a nanomolar concentration. Our study demonstrated that EGFR specific scFv-425-SNAP-BG-MMAE and EpCAM-specific scFv-EpCAM-SNAP-BG-MMAE could be promising ADCs for the treatment of TNBC.
In the last few decades, antibody-based diagnostic and therapeutic applications have been well established in medicine and have revolutionized cancer managements by improving tumor detection and ...treatment. Antibodies are unique medical elements due to their powerful properties of being able to recognize specific antigens and their therapeutic mechanisms such as blocking specific pathways, antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity. Furthermore, modification techniques have paved the way for improving antibody properties and to develop new classes of antibody-conjugate-based diagnostic and therapeutic agents. These techniques allow arming antibodies with various effector molecules. However, these techniques are utilizing the most frequently used amino acid residues for bioconjugation, such as cysteine and lysine. These bioconjugation approaches generate heterogeneous products with different functional and safety profiles. This is mainly due to the abundance of lysine and cysteine side chains. To overcome these limitations, different site-direct conjugation methods have been applied to arm the antibodies with therapeutic or diagnostics molecules to generate unified antibody conjugates with tailored properties. This review summarizes some of the enzyme-based site-specific conjugation approaches.
Cloud computing is now being used by more and more enterprises and individuals. To protect the privacy of outsourced data in the cloud, the searchable symmetric encryption is adopted. However, ...verifying search results to detect whether there is malicious behavior in the cloud server is still a challenge. In order to overcome this problem, we propose an efficient verifiable search scheme (EVSS), which allows users to retrieve ciphertext and verify the search result efficiently. A novel RSA accumulator-based Patricia tree (RAP-tree) is designed as the search index, where the token of a keyword and the proof evidence of documents containing the keyword are taken as the key-value pair to be placed in a node of the tree. By using the RAP-tree index, the efficient verifiable keyword search over encrypted data is realized. The security of the proposed scheme is analyzed by theoretical proofs. Experimental results on real data sets show that the proposed scheme is efficient and effective in terms of search processing and result verification.
This study was designed to investigate the effect of different concentrations of Hyperin and Icariin (ICA)on proliferation and the secretion of estrogen (E2), and progesterone (P) in granulosa cells, ...and to explore the effect of Hyperin and Icariin on the expression of CYP17 and CYP19.
Rat ovary granulosa cells were cultured in vitro and treated with different concentrations of Hyperin and Icariin. The proliferation of ovarian granulosa cells was measured with the MTT assay. The concentration of estradiol was measured with a magnetic particle-based enzyme-linked immunosorbent assay (ELISA) kit. The CYP17 and CYP19 mRNA expression was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). The CYP17 and CYP19 protein expression was determined with Western blotting.
Hyperin (50 μg/l) and Icariin (10 μg/l) significantly increased proliferation of ovarian granulosa cells and secretion of estrogen and progesterone. Hyperin and Icariin stimulated the mRNA and protein expression of CYP17 and CYP19.
These results showed that Hyperin and Icariin can promote the secretion of E2 and P through up-regulation of CYP17 and CYP19. Frequently used Chinese herbs like Cuscuta Chinensis Lam and Epimedium Brevicornu maxim, which contain Hyperin and Icariin, could improve the ovarian endocrine function through these effects.
•Hyperin and Icariin increase the viability of granulosa cells.•Estrogen and progesterone secretion was increased by Hyperin and Icariin treatment.•Hyperin and Icariin promote the secretion of E2 and P by up-regulating CYP17 and CYP19.