A cascade nanosystem with "Triple-Linkage" effect for enhanced photothermal and activatable metal ion therapy for hepatocellular carcinoma.

Due to the limitations of single-model tumor therapeutic strategies, multimodal combination therapy have become a more favorable option to enhance efficacy by compensating for its deficiencies. However, in nanomaterial-based multimodal therapeutics for tumors, exploiting synergistic interactions and cascade relationships of materials to achieve more effective treatments is still a great challenge. Based on this, we constructed a nanoplatform with a "triple-linkage" effect by cleverly integrating polydopamine (PDA), silver nanoparticles (AgNPs), and glucose oxidase (GOx) to realize enhanced photothermal therapy (PTT) and activatable metal ion therapy (MIT) for hepatocellular carcinoma (HCC) treatment. First, the non-radiative conversion of PDA under light conditions was enhanced by AgNPs, which directly enhanced the photothermal conversion efficiency of PDA. In addition, GOx reduced the synthesis of cellular heat shock proteins by interfering with cellular energy metabolism, thereby enhancing cellular sensitivity to PTT. On the other hand, H2O2, a by-product of GOx-catalyzed glucose, could be used as an activation source to activate non-toxic AgNPs to release cytotoxic Ag+, achieving activatable Ag+-mediated MIT. In conclusion, this nanosystem achieved efficient PTT and MIT for HCC by exploiting the cascade effect among PDA, AgNPs, and GOx, providing a novel idea for the design of multimodal tumor therapeutic systems with cascade regulation.

Exosomal lncCRLA is predictive for the evolvement and development of lung adenocarcinoma.

Lung adenocarcinoma, the most common histological subtype of non-small cell lung cancer, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Our team uncovers that lncRNA related to chemotherapy resistance in lung adenocarcinoma (lncCRLA) is preferentially expressed in lung adenocarcinoma cells with the mesenchymal phenotype. lncCRLA can not enhance chemotherapy resistance in lung adenocarcinoma due to its binding to RIPK1 in exosomes, which is released into intercellular media and transferred by exosomes from mesenchymal-like to epithelial-like cells. However, plasmatic lncCRLA corresponding to tissue lncCRLA functions as a preferred biomarker to reflect the response to chemotherapy and disease progression of lung adenocarcinoma. Through single-cell sequencing, RNA-Mutect technique and spatial transcriptomics, a handful of hybrid EMT cells with elevated lncCRLA are characterized as the origin of lung adenocarcinoma, which are indiscriminated from hybrid EMT cells by the in-depth sequencing. Plasmatic lncCRLA is properly predictive for the preinvasive lesion of lung adenocarcinoma that would evolve to invasive lesion. That notion is confirmed by a brand-new transgenic mouse model in which EMT is tracked by Cre and Dre system. Dasatinib is potential to hinder the spontaneous progression from preinvasive to invasive lesion of lung adenocarcinoma. Together, plasmatic lncCRLA is defined as a brand-new circulating biomarker to predict the occurrence and evolvement of lung adenocarcinoma, a light for early detection of lung adenocarcinoma.

Pulse oximeter bench tests under different simulated skin tones.

Pulse oximeters' (POs) varying performance based on skin tones has been highly publicised. Compared to arterial blood gas analysis, POs tend to overestimate oxygen saturation (SpO2) values for people with darker skin (occult hypoxemia). The objective is to develop a test bench for assessing commercial home and hospital-based POs in controlled laboratory conditions. A laboratory simulator was used to mimic different SpO2 values (~ 70 to 100%). Different neutral density and synthetic melanin filters were used to reproduce low signal and varying melanin attenuation levels. Six devices consisting of commercial home (Biolight, N = 13; ChoiceMMed, N = 18; MedLinket, N = 9) and hospital-based (Masimo Radical 7 with Neo L, N = 1; GE B450 Masimo SET with LNCS Neo L, N = 1; Nonin 9550 Onyx II™, N = 1) POs were reviewed and their response documented. Significant variations were observed in the recorded SpO2 values among different POs when exposed to identical simulated signals. Differences were greatest for lower SpO2 (< 80%) where empirical data is limited. All PO responses under low signal and melanin attenuation did not change across various simulated SpO2 values. The bench tests do not provide conclusive evidence that melanin does not affect in vivo SpO2 measurements. Research in the areas of instrument calibration, theory and design needs to be further developed.