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Cell‐penetrating peptides (CPPs) with better biomolecule delivery properties will expand their clinical applications. Using the MLCPP2.0 machine algorithm, we screened multiple candidate sequences with potential cellular uptake ability from the nuclear localization signal/nuclear export signal database and verified them through cell‐penetrating fluorescent tracing experiments. A peptide (NCR) derived from the Rev protein of the caprine arthritis‐encephalitis virus exhibited efficient cell‐penetrating activity, delivering over four times more EGFP than the classical CPP TAT, allowing it to accumulate in lysosomes. Structural and property analysis revealed that a high hydrophobic moment and an appropriate hydrophobic region contribute to the high delivery activity of NCR. Trastuzumab emtansine (T‐DM1), a HER2‐targeted antibody‐drug conjugate, could improve its anti‐tumor activity by enhancing targeted delivery efficiency and increasing lysosomal drug delivery. This study designed a new NCR vector to non‐covalently bind T‐DM1 by fusing domain Z, which can specifically bind to the Fc region of immunoglobulin G and effectively deliver T‐DM1 to lysosomes. MTT results showed that the domain Z‐NCR vector significantly enhanced the cytotoxicity of T‐DM1 against HER2‐positive tumor cells while maintaining drug specificity. Our results make a useful attempt to explore the potential application of CPP as a lysosome‐targeted delivery tool. [ABSTRACT FROM AUTHOR]

Targeted therapy has attracted more and more attention in cancer treatment in recent years. However, due to the diversity of tumor types and the mutation of target sites on the tumor surface, some existing targets are no longer suitable for tumor therapy. In addition, the long‐term administration of a single targeted drug can also lead to drug resistance and attenuate drug potency, so it is important to develop new targets for tumor therapy. The expression of Type III transforming growth factor β receptor (TGFBR3) is upregulated in colon, breast, and prostate cancer cells, and plays an important role in the occurrence and development of these cancers, so TGFBR3 may be developed as a novel target for tumor therapy, but so far there is no report on this research. In this study, the structure of bone morphogenetic protein 4 (BMP4), one of the ligands of TGFBR3 was analyzed through the docking analysis with TGFBR3 and sequence charge characteristic analysis, and a functional tumor‐targeting penetrating peptide T3BP was identified. The results of fluorescent labeling experiments showed that T3BP could target and efficiently enter tumor cells with high expression of TGFBR3, especially A549 cells. When the expression of TGFBR3 on the surface of tumor cells (HeLa) was knocked down by RNA interference, the high delivery efficiency of T3BP was correspondingly reduced by 40%, indicating that the delivery was TGFBR3‐dependent. Trichosanthin (TCS, a plant‐derived ribosome inactivating protein) fused with T3BP can enhance the inhibitory activity of the fusion protein on A549 cells by more than 200 times that of TCS alone. These results indicated that T3BP, as a novel targeting peptide that can efficiently bind TGFBR3 and be used for targeted therapy of tumors with high expression of TGFBR3. This study enriches the supply of tumor‐targeting peptides and provides a new potential application option for the treatment of tumors with high expression of TGFBR3. [ABSTRACT FROM AUTHOR]

Most tumors are resistant to programmed cell death protein 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) checkpoint inhibitors, which may be due to impaired antigen presentation resulting from the downregulation of major histocompatibility complex class I (MHC‐I) expression on tumor cells. We observed that platycodin D (PD), polygalacin D, and platycodin D2, which are plant‐derived triterpenoid saponins, significantly reduced PD‐L1 levels. RNA sequencing and the PharmMapper database analysis identified liver X receptor β (LXR‐β) as a potential PD target. Further studies showed that PD reduces PD‐L1 levels by binding to LXR‐β and inhibiting LXR‐β activity. Coadministration of PD and nintedanib, known to upregulate MHC‐I expression, enhanced tumor recognition and killing by T cells. This study provides new insights into PD applications and mechanisms. [ABSTRACT FROM AUTHOR]

Copper chromium chalcospinel (CuCr2S4) is a metallic ferromagnet with high Curie temperature and large magnetization. Due to these characteristics and highly spin-polarized electronic structure near the Fermi level, it has been considered as an attractive candidate for spintronic application. By using the first-principle calculations based on density functional theory, we discovered that a complete spin polarization, or the so-called half-metallicity, can be realized in (100) CuCr2S4 film. The results of electronic structure show that by decreasing the film thickness, the delocalized hybridization between Cu-d and S-p states is weakened, which shifts the valence band maximum of the minority spin to lower energy, and thus leads to the half-metallicity. Furthermore, the half-metallicity of the CuCr2S4 film is found to be robust with respect to different terminations and surface vacancies. [ABSTRACT FROM PUBLISHER]

Background: Knee osteoarthritis (KOA) is a major public health issue causing chronic disability as well as a burden on healthcare resources. In China, a herbal drug tablet has been used as an effective and conventional therapy to alleviate clinical symptoms caused by KOA. However, evidence gathered from systematic reviews or randomized controlled trials that validated herbal drugs for the management of osteoarthritic pain is weak. The purpose of this study is to explore the efficacy and safety of the Shaoyao Shujin tablet for the management of KOA in a short-term study.Methods/design: This trial is a multicenter randomized, double-blind, placebo-controlled study. A total of 276 patients will be randomized into 3 groups: (1) the high-dose Shaoyao Shujin tablet group (HD group), (2) the low-dose Shaoyao Shujin tablet group (LD group), and (3) the placebo tablet group (control group). In the three groups, four tablets will be administered three times per day for 6 weeks. Follow-up will be at regular intervals during a 10-week period with the Western Ontario and McMaster Universities Index (WOMAC) score, visual analog scale (VAS) score, and rescue medication use assessed as outcome measures.Discussion: This study will provide clinical evidence on the efficacy and safety of the Shaoyao Shujin tablet in treating KOA.Trial Registration: Chinese Cochrane Center ChiCTR-IPR- 15006194 , registered 4 April 2015. [ABSTRACT FROM AUTHOR]