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The self-assembling nanotoxin T22-PE24 that specifically targets CXCR4 was designed to selectively deliver the cytotoxic toxin PE24 to treat CXCR4+ melanoma via activating caspase 3/GSDME pathways in which initially “cold” tumors will become “hot”.

Hepatocellular carcinoma (HCC) is a common malignant tumor usually resistant to chemotherapy. MicroRNAs play important roles in modulation of carcinogenesis and chemoresistance, which miR-16 has been reported to mediate chemoresistance in many types of cancers. However, the role of miR-16 in HCC remains unknown. The aim of this study was to investigate whether miR-16 is participated in chemoresistance in HCC and shed light on the underlying molecular mechanisms. The findings of the current study discover that miR-16 is down-regulated in HCC tissue and cell lines. The results demonstrate that the inhibition of miR-16 renders resistance to paclitaxel in vitro and in vivo by targeting IKBKB via NF-κB signaling pathway, suggesting that miR-16 may be a meaningful therapeutic potential to overcome drug resistance in HCC.

Noble metals, such as platinum, ruthenium and iridium-group metals, are often used as oxygen reduction or evolution reaction (ORR/OER) electrocatalysts. To reduce the cost and provide an application of bifunctional catalysis, in this work, cobalt oxide supported on nitrogen and phosphorus co-doped carbon (Co 3 O 4 /NPC) was fabricated and examined as a bifunctional electrocatalyst for OER and ORR. To prepare Co 3 O 4 /NPC, NPC was pyrolyzed from melamine and phytic acid supported on carbon, followed by the solvothermal synthesis of Co 3 O 4 on NPC. Linear sweep voltammetry was used to evaluate the activity for OER and ORR. For OER, Co 3 O 4 /NPC showed an onset potential of 0.54 V (versus the saturated calomel electrode) and a current density of 21.95 mA/cm 2 at 0.80 V, which was better than both Co 3 O 4 /C and NPC. The high activity of Co 3 O 4 /NPC was attributed to a synergistic effect of the N, P co-dopants and Co 3 O 4 . For ORR, Co 3 O 4 /NPC exhibited an activity close to commercial Pt/C in terms of the diffusion limited current density (-4.49 vs -4.76 mA/cm 2 at -0.80 V), and Co 3 O 4 played the key role for the catalysis. Chronoamperometry (current versus time) was used to evaluate the stability, which showed that Co 3 O 4 /NPC maintained 46% current after the chronoamperometry test for OER and 95% current for ORR. Overall, Co 3 O 4 /NPC exhibited high activity and improved stability for both OER and ORR.

The performance of the cobalt-based spinel electrocatalysts (MCo2X4) is improved for oxygen reduction reaction (ORR) by simply optimizing solvothermal conditions via the orthogonal experiment L18 (2 × 37). Five conditions are investigated, and the order of significant factors for ORR efficiency is metal component > solvothermal temperature > calcining temperature > precipitant > solvent component. Mn, Ni, or S is considered as the factor of metal component or precipitant respectively and is introduced into the Co3O4 to find the best MCo2X4 for ORR. But, the pure Co3O4 exhibits the best performance among these cobalt-based catalysts. The optimized product, 9.6 wt.% Co3O4 supported on carbon (Co3O4/C), can reach 90 % of the 20 wt.% Pt/C in term of the limited diffusion current exhibiting the close efficiency of Co3O4/C to Pt/C. Methanol-poisoning tests performed by chronoamperometry show the Co3O4/C remained 95 % current after 6 h, exhibiting superior methanol resistance and long-time stability.

Liver regeneration (LR) is the result of a dynamic balance between the increased proliferation and decreased apoptosis of hepatocytes. However, the role of microRNA (miR)‑26a in regulating complex signalling networks involving E3 ubiquitin‑protein ligase Mdm2 (mdm2), p53, p21 and p27 in the process of LR is currently unclear. In the present study, it was hypothesized that miR‑26a may negatively regulate the mdm2/p53 signalling loop in response to LR. In vitro experiments were performed, whereby mouse liver cells were transfected with an miR‑26a vector or an anti/miR‑26a vector. Cell proliferation was analysed using an MTS assay and cell apoptosis, and cell cycle progression were analysed by flow cytometry. In addition, the expression of mdm2, p53, p21 and p27 were assessed using western blotting and reverse transcription‑quantitative polymerase chain reaction analyses. Dual‑luciferase reporter assays were also used to examine the association between mdm2 and miR‑26a. A 70% partial hepatectomy in C57BL/6J mice was then performed, which was followed by injection with an mdm2‑cDNA vector or an mdm2‑small interfering RNA vector. The liver‑to‑body weight ratio and liver function of mice were measured at 72 h following vector administration. The results demonstrated an increase in hepatocyte proliferation accompanied by decreased hepatocyte apoptosis levels. In addition, inhibition of miR‑26a expression was associated with a marked increase in mdm2 expression, while the expression of p53, p21 and p27 was decreased when compared with negative controls. The opposite effects were observed when miR‑26a was overexpressed. Notably, miR‑26a was demonstrated to target the 3'‑untranslated region of mdm2 directly. The results of the present study are the first to demonstrate as far as the authors are aware that the mdm2/p53 negative feedback loop may be targeted by miR‑26a directly in response to LR, and that mdm2 negatively regulates p53, p21 and p27 but not miR‑26a. miR‑26a may therefore function as an important factor that regulates the interaction between mdm2 and p53.