Hypoxia, a quite universal feature in most solid tumors, has been considered as the "Achilles' heel" of traditional photodynamic therapy (PDT) and substantially impairs the overall therapeutic efficacy. Herein, we develop a near-infrared (NIR) light-triggered molecular superoxide radical (O 2 −• ) generator (ENBS-B) to surmount this intractable issue, also reveal its detailed O 2 −• action mechanism underlying the antihypoxia effects, and confirm its application for in vivo targeted hypoxic solid tumor ablation. Photomediated radical generation mechanism study shows that, even under severe hypoxic environment (2% O 2 ), ENBS-B can generate considerable O 2 −• through type I photoreactions, and partial O 2 −• is transformed to high toxic OH• through SODmediated cascade reactions. These radicals synergistically damage the intracellular lysosomes, which subsequently trigger cancer cell apoptosis, presenting a robust hypoxic PDT potency. In vitro coculture model shows that, benefiting from biotin ligand, ENBS-B achieves 87-fold higher cellular uptake in cancer cells than normal cells, offering opportunities for personalized medicine. Following intravenous administration, ENBS-B is able to specifically target to neoplastic tissues and completely suppresses the tumor growth at a low light-dose irradiation. As such, we postulated this work will extend the options of excellent agents for clinical cancer therapy.

Strong oxygen dependence, poor tumor targeting, and limited treatment depth have been considered as the “Achilles’ heels” facing the clinical usage of photodynamic therapy (PDT). Different from common approaches, here, we propose an innovative tactic by using photon-initiated dyad cationic superoxide radical (O2 –•) generator (ENBOS) featuring “0 + 1 > 1” amplification effect to simultaneously overcome these drawbacks. In particular, by taking advantage of the Förster resonance energy transfer theory, the energy donor successfully endows ENBOS with significantly enhanced NIR absorbance and photon utility, which in turn lead to ENBOS more easily activated and generating more O2 –• in deep tissues, that thus dramatically intensifies the type I PDT against hypoxic deep tumors. Moreover, benefiting from the dyad cationic feature, ENBOS achieves superior “structure-inherent targeting” abilities with the signal-to-background ratio as high as 25.2 at 48 h post intravenous injection, offering opportunities for accurate imaging-guided tumor treatment. Meanwhile, the intratumoral accumulation and retention performance are also markedly improved (>120 h). On the basis of these unique merits, ENBOS selectively inhibits the deep-seated hypoxic tumor proliferation at a low light-dose irradiation. Therefore, this delicate design may open new horizons and cause a paradigm change for PDT in future cancer therapy.

Much remains unknown about how the nervous system of an animal generates behaviour, and even less is known about the evolution of behaviour. How does evolution alter existing behaviours or invent novel ones? Progress in computational techniques and equipment will allow these broad, complex questions to be explored in great detail. Here we present a method for tracking each leg of a fruit fly behaving spontaneously upon a trackball, in real time. Legs were tracked with infrared-fluorescent dyes invisible to the fly, and compatible with two-photon microscopy and controlled visual stimuli. We developed machine-learning classifiers to identify instances of numerous behavioural features (for example, walking, turning and grooming), thus producing the highest-resolution ethological profiles for individual flies.

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