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      • Intracellular Mechanistic Understanding of 2D MoS<sub>2</sub> Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy

        Zhu, Xianbing,Ji, Xiaoyuan,Kong, Na,Chen, Yunhan,Mahmoudi, Morteza,Xu, Xiaoding,Ding, Li,Tao, Wei,Cai, Ting,Li, Yujing,Gan, Tian,Barrett, Austin,Bharwani, Zameer,Chen, Hongbo,Farokhzad, Omid C. American Chemical Society 2018 ACS NANO Vol.12 No.3

        <P>Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenide (TMD) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials (<I>i</I>.<I>e</I>., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS<SUB>2</SUB>) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy. MoS<SUB>2</SUB> NSs were found to be internalized through three pathways: clathrin → early endosomes → lysosomes, caveolae → early endosomes → lysosomes, and macropinocytosis → late endosomes → lysosomes. We also observed autophagy-mediated accumulation in the lysosomes and exocytosis-induced efflux of MoS<SUB>2</SUB> NSs. Based on these findings, we developed a strategy to achieve effective and synergistic <I>in vivo</I> cancer therapy with MoS<SUB>2</SUB> NSs loaded with low doses of drug through inhibiting exocytosis pathway-induced loss. To the best of our knowledge, this is the first systematic experimental report on the nano-bio interaction of 2D nanomaterials in cells and their application for anti-exocytosis-enhanced synergistic cancer therapy.</P> [FIG OMISSION]</BR>

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        The associations of obesity phenotypes with the risk of hypertension and its transitions among middle-aged and older Chinese adults

        Ziyue Sheng,Shang Lou,Jin Cao,Weidi Sun,Yaojia Shen,Yunhan Xu,Ziyang Ren,Wen Liu,Qian Yi,Peige Song 한국역학회 2023 Epidemiology and Health Vol.45 No.-

        OBJECTIVES: This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese. METHODS: Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex. RESULTS: NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages. CONCLUSIONS: This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.

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