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Highlights d Discovery of prognosis-associated proteins and pathways at early stage of LUAD d Proteomics revealed three subtypes related to clinical and molecular features d Identification of subtype-specific kinases and cancerassociated phosphoproteins d Identification of potential prognostic biomarkers and drug targets in LUAD

Tumor infiltrated type II (M2) macrophages promote tumorigenesis by suppressing immune clearance, promoting proliferation, and stimulating angiogenesis. Interestingly, macrophages were also found to enrich in small foci of altered hepatocytes containing liver tumor-initiating cells (TICs). However, whether and how TICs specifically recruit macrophages and the function of these macrophages in tumor initiation remain unknown due to technical difficulties. In this study, by generating genetically defined liver TICs, we demonstrate that TICs actively recruit M2 macrophages from as early as the single-cell stage. Elimination of TIC-associated macrophages (TICAMs) abolishes tumorigenesis in a manner dependent on the immune system. Mechanistically, activation of the Hippo pathway effector Yes-associated protein (YAP) underlies macrophage recruitment by TICs. These results demonstrate for the first time that macrophages play a decisive role in the survival of single TICs in vivo and provide a proof of principle for TIC elimination by targeting YAP or M2 macrophages.

Graphical Abstract Highlights d We designed ocular injectable photoreceptor-binding upconversion nanoparticles d The nanoparticles are safe and enable NIR light sensation and pattern vision d This NIR pattern vision is compatible with native daylight vision d This method offers options for mammalian vision repair and enhancement SUMMARY Mammals cannot see light over 700 nm in wavelength. This limitation is due to the physical thermodynamic properties of the photon-detecting opsins. However, the detection of naturally invisible nearinfrared (NIR) light is a desirable ability. To break this limitation, we developed ocular injectable photoreceptor-binding upconversion nanoparticles (pbUCNPs). These nanoparticles anchored on retinal photoreceptors as miniature NIR light transducers to create NIR light image vision with negligible side effects. Based on single-photoreceptor recordings, electroretinograms, cortical recordings, and visual behavioral tests, we demonstrated that mice with these nanoantennae could not only perceive NIR light, but also see NIR light patterns. Excitingly, the injected mice were also able to differentiate sophisticated NIR shape patterns. Moreover, the NIR light pattern vision was ambient-daylight compatible and existed in parallel with native daylight vision. This new method will provide unmatched opportunities for a wide variety of emerging bio-integrated nanodevice designs and applications. Continued REAGENT or RESOURCE SOURCE IDENTIFIER Other 65 RN 5uL SYR W/O NEEDLE Hamilton, Switzerland Cat# 7633-01 RN Needle (34/8 mm/3)

Tissue penetration depth is a major challenge in practical photodynamic therapy (PDT). A biocompatible and highly effective near infrared (NIR)-light-absorbing carbazole-substituted BODIPY (Car-BDP) molecule is reported as a class of imaging-guidable deep-tissue activatable photosensitizers for PDT. Car-BDP possesses an intense, broad NIR absorption band (600-800 nm) with a remarkably high singlet oxygen quantum yield (Φ = 67%). After being encapsulated with biodegradable PLA-PEG-FA polymers, Car-BDP can form uniform and small organic nanoparticles that are water-soluble and tumor-targetable. Rather than using laser light, such nanoparticles offer an unprecedented deep-tissue, tumor targeting photodynamic therapeutic effect by using an exceptionally low-power-density and cost-effective lamp light (12 mW cm). In addition, these nanoparticles can be simultaneously traced in vivo due to their excellent NIR fluorescence. This study signals a major step forward in photodynamic therapy by developing a new class of NIR-absorbing biocompatible organic nanoparticles for effective targeting and treatment of deep-tissue tumors. This work also provides a potential new platform for precise tumor-targeting theranostics and novel opportunities for future affordable clinical cancer treatment.

Spatial transcriptome technique was applied to decipher the spatial architecture and TME characteristics of liver cancers.

A strategy to expand anti-Stokes shifting from the far-red to deep-blue region in metal-free triplet–triplet annihilation upconversion (TTA-UC) is presented and its utility in the in vivo titration of the photorelease of an anticancer prodrug is demonstrated. This new TTA system has robust brightness and the longest anti-Stokes shift of any reported TTA system. TTA core-shell-structured prodrug delivery capsules that benefit from these properties are developed; they can operate with low-power-density far-red light-emitting diode (LED) light. These capsules contain mesoporous silica nanoparticles preloaded with TTA molecules as the core and amphiphilic polymers encapsulating anticancer prodrug molecules as the shell. When stimulated by far-red light, the intense TTA upconversion blue emssison in the system activates the anticancer prodrug molecules and shows effective tumor growth inhibition in vivo. This work paves the way for the design of new organic TTA upconversion with regard to in vivo photocontrollable drug release and other biophotonic applications.

Graphical abstract Resonance energy transfer constructed NIR-absorbing BODIPY-based photosensitized dyad (RET-BDP) nanoparticles are developed. These nanoparticles enable targeted photodynamic therapy upon application of low-power NIR LED light irradiation. This work provides a new concept for the design of biocompatible nanoparticles with significantly improved NIR sensitivity, which is key to PDT development.