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MoS2 nanosheets and a doxorubicin (DOX)-containing poly (lactic-co-glycolic acid) (PLGA)/MoS2 /DOX composite implant are successfully constructed based on the unique phase-changing behavior of PLGA/MoS2 /DOX oleosol within tumors. The fast phase transformation can firmly restrict MoS2 and DOX within tumors, and the integrated MoS2 and DOX can endow the implant with high synergistic photothermal and chemotherapeutic efficiency against tumors.

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BackgroundGa-[1,4,7,10-tetraazacyclododecane-N,N′,N″,N′″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE) positron emission tomography (PET) is commonly used for the visualization of somatostatin receptor (SSTR)-positive neuroendocrine tumors. SSTR is also known to be expressed on macrophages, which play a major role in inflammatory processes in the walls of coronary arteries and large vessels. Therefore, imaging SSTR expression has the potential to visualize vulnerable plaques. We assessed 68Ga-DOTATATE accumulation in large vessels in comparison to 18F-2-fluorodeoxyglucose (FDG) uptake, calcified plaques (CPs), and cardiovascular risk factors.MethodsSixteen consecutive patients with neuroendocrine tumors or thyroid cancer underwent both 68Ga-DOTATATE and 18F-FDG PET/CT for staging or restaging purposes. Detailed clinical data, including common cardiovascular risk factors, were recorded. For a separate assessment, they were divided into a high-risk and a low-risk group. In each patient, we calculated the maximum target-to-background ratio (TBR) of eight arterial segments. The correlation of the TBRmean of both tracers with risk factors including plaque burden was assessed.ResultsThe mean TBR of 68Ga-DOTATATE in all large arteries correlated significantly with the presence of CPs (r = 0.52; p < 0.05), hypertension (r = 0.60; p < 0.05), age (r = 0.56; p < 0.05), and uptake of 18F-FDG (r = 0.64; p < 0.01). There was one significant correlation between 18F-FDG uptake and hypertension (0.58; p < 0.05). Out of the 37 sites with the highest focal 68Ga-DOTATATE uptake, 16 (43.2%) also had focal 18F-FDG uptake. Of 39 sites with the highest 18F-FDG uptake, only 11 (28.2%) had a colocalized 68Ga-DOTATATE accumulation.ConclusionsIn this series of cancer patients, we found a stronger association of increased 68Ga-DOTATATE uptake with known risk factors of cardiovascular disease as compared to 18F-FDG, suggesting a potential role for plaque imaging in large arteries. Strikingly, we found that focal uptake of 68Ga-DOTATATE and 18F-FDG does not colocalize in a significant number of lesions.

Poor cell uptake of drugs is one of the major challenges for anticancer therapy. Moreover, the inability to release adequate drug at tumor sites and inherent multidrug resistance (MDR) may further limit the therapeutic effect. Herein, a delivery nanosystem with a charge‐reversal capability and self‐amplifiable drug release pattern is constructed by encapsulating β‐lapachone in pH/ROS cascade‐responsive polymeric prodrug micelle. The surface charge of this micellar system would be converted from negative to positive for enhanced tumor cell uptake in response to the weakly acidic tumor microenvironment. Subsequently, the cascade‐responsive micellar system could be dissociated in a reactive oxygen species (ROS)‐rich intracellular environment, resulting in cytoplasmic release of β‐lapachone and camptothecin (CPT). Furthermore, the released β‐lapachone is capable of producing ROS under the catalysis of nicotinamide adenine dinucleotide (NAD)(P)H:quinone oxidoreductase‐1 (NQO1), which induces the self‐amplifiable disassembly of the micelles and drug release to consume adenosine triphosphate (ATP) and downregulate P‐glycoprotein (P‐gp), eventually overcoming MDR. Moreover, the excessive ROS produced from β‐lapachone could synergize with CPT and further propagate tumor cell apoptosis. The studies in vitro and in vivo consistently demonstrate that the combination of the pH‐responsive charge‐reversal, upregulation of tumoral ROS level, and self‐amplifying ROS‐responsive drug release achieves potent antitumor efficacy via the synergistic oxidation‐chemotherapy.

Conventional embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) derived from primates resemble mouse epiblast stem cells, raising an intriguing question regarding whether the naive pluripotent state resembling mouse embryonic stem cells (mESCs) exists in primates and how to capture it in vitro. Here we identified several specific signaling modulators that are sufficient to generate rhesus monkey fibroblast-derived iPSCs with the features of naive pluripotency in terms of growth properties, gene expression profiles, self-renewal signaling, X-reactivation, and the potential to generate cross-species chimeric embryos. Interestingly, together with recent reports of naive human pluripotent stem cells, our findings suggest several conserved signaling pathways shared with rodents and specific to primates, providing significant insights for acquiring naive pluripotency from other species. In addition, the derivation of rhesus monkey naive iPSCs also provides a valuable cell source for use in preclinical research and disease modeling.

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