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Subcellular targeted cancer therapy and in situ monitoring of therapeutic effect are highly desirable for clinical applications. Herein, we report a series of probes by conjugating zero (TPECM-2Br), one (TPECM-1TPP) and two (TPECM-2TPP) triphenylphosphine (TPP) ligands to a fluorogen with aggregation-induced emission (AIE) characteristics. The probes are almost non-emissive as molecularly dissolved species, but they can light up in cell cytoplasm or mitochondria. TPECM-2TPP is found to be able to target mitochondria, depolarize mitochondria membrane potential and selectively exert potent chemo-cytotoxicity on cancer cells. Furthermore, it can efficiently generate singlet oxygen with strong photo-toxicity upon light illumination, which further enhances its anti-cancer effect. On the other hand, TPECM-1TPP can also target mitochondria and generate singlet oxygen to trigger cancer cell apoptosis, but it shows low cytotoxicity in dark. Meanwhile, TPECM-1TPP can report the cellular oxidative stress by visualizing the morphological changes of mitochondria. However, TPECM-2Br does not target mitochondria and shows no obvious anticancer effect either in dark or under light illumination. This study thus highlights the importance of molecular probe design, which yields a new generation of subcellular targeted molecular theranostic agents with multi-function, such as cancer cell imaging, chemotherapy, photodynamic therapy, and in situ monitoring of the therapeutic effect in one go.

Modeling and theoretical prediction of thermal expansion property of particulate reinforced polymer composite are important hot issues in composite science and engineering. In this article, the thermomechanical interaction between spherical particle and polymer matrix and its contribution to the thermal expansion behavior of spherical particle reinforced polymer composite have been studied theoretically. A mechanical interphase resulted from the thermomechanical interaction is observed in radial distribution of effective coefficient of thermal expansion (CTE) around the particle with an isotropic assumption of the particle and polymer matrix, and with necessary simplification of the thermomechanical interference among particles, an analytical equation for predicting the CTE of the composite has been proposed. Compared with other models, good fits by this model with finite element (FE) simulated CTE value of particle reinforced composite and previously reported CTE data of particulate reinforced epoxy composites with particle size from micron to nanometer scale are observed. This study would deepen the understanding of the interphase in particle reinforced composites and be favorable for mechanism analysis of other physical properties of polymer composites. Highlights: Thermomechanical interaction between spherical particle and matrix is studiedA new model for the CTE of particle reinforced polymer composite is proposedFE simulation been carried out to examine the reasonability of the proposed modelPresent model well fits the reported reinforced epoxy composites CTE dataA new perspective for analyzing other properties of reinforced composites [ABSTRACT FROM AUTHOR]

Background: Hyperlipidemia is characterized by abnormally elevated blood lipids. Quinoa saponins (QS) have multiple pharmacological activities, including antitumor, bactericidal and immune‐enhancing effects. However, the lipid‐lowering effect and mechanisms of QS in vivo have been scarcely reported. Methods: The effect of QS against hyperlipidemia induced by high‐fat diet in rats was explored based on gut microbiota and serum non‐targeted metabolomics. Results: The study demonstrated that the supplementation of QS could reduce serum lipids, body weight, liver injury and inflammation. 16S rRNA sequencing demonstrated that QS mildly increased alpha‐diversity, altered the overall structure of intestinal flora, decreased the relative richness of Firmicutes, the ratio of Firmicutes/Bacteroidetes (P < 0.05) and increased the relative richness of Actinobacteria, Bacteroidetes, Bifidobacterium, Roseburia and Coprococcus (P < 0.05). Simultaneously, metabolomics analysis showed that QS altered serum functional metabolites with respect to bile acid biosynthesis, arachidonic acid metabolism and taurine and hypotaurine metabolism, which were closely related to bile acid metabolism and fatty acid β‐oxidation. Furthermore, QS increased protein levels of farnesoid X receptor, peroxisome proliferator‐activated receptor α and carnitine palmitoyltransferase 1, which were related to the screened metabolic pathways. Spearman correlation analysis showed that there was a correlation between gut microbiota and differential metabolites. Conclusion: QS could prevent lipid metabolism disorders in hyperlipidemic rats, which may be closely associated with the regulation of the gut microbiota and multiple metabolic pathways. This study may provide new evidence for QS as natural active substances for the prevention of hyperlipidemia. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Purpose: Non‐operating revenue (NOR), derived from investments, contributions, government appropriations, and medical space rentals, can contribute to financial stability of hospitals by offsetting operating losses and improving profitability. NOR might benefit rural hospitals that often face intense financial pressures. However, little is known about how much rural hospitals rely on NOR and if certain organizational characteristics are associated with differences in NOR. Methods: Healthcare Cost Report Information System data from 2011 to 2019 were used to analyze sources of revenue among Critical Access Hospitals (CAHs) and Rural Prospective Payment System (R‐PPS) hospitals through descriptive statistics and regression models. Reliance on NOR was measured by the percentage of total revenue from non‐operating sources. Findings: Results indicate that both CAHs and R‐PPS hospitals rely on NOR; however, CAHs have a higher percentage of total revenue derived from non‐operating sources (3.2%) as compared to R‐PPS hospitals (1.9%) (p < 0.001). Government‐owned hospitals have significantly higher reliance on NOR than other ownership types. System affiliation also influences reliance on NOR. Lastly, results suggest that NOR may play a role in improving overall profit margins. Conclusions: As rural hospitals disproportionately face challenges related to declining profitability and the risk for closure, they may rely on NOR to continue to strengthen financial performance and provide health care to their communities. However, NOR is not guaranteed, and reliance on NOR further reiterates the value of stable, adequate reimbursement to guard against fluctuations in NOR. [ABSTRACT FROM AUTHOR]