The contrast and sensitivity of in vivo fluorescence imaging has been revolutionized by molecular fluorophores operating in the second near-infrared window (NIR-II; 1000-1700 nm), but an ongoing challenge is the solvatochromism-caused quenching in aqueous solution for the long-wavelength absorbing fluorophores. Herein, we develop a series of anti-quenching pentamethine cyanine fluorophores that significantly overcome the severe solvatochromism, thus affording stable absorption/emission beyond 1000 nm with up to ~ 44-fold enhanced brightness and superior photostability in aqueous solution. These advantages allow for deep optical penetration (8 mm) as well as high-contrast and highly-stable lymphatic imaging superior to clinical-approved indocyanine green. Additionally, these fluorophores exhibit pH-responsive fluorescence, allowing for noninvasive ratiometric fluorescence imaging and quantification of gastric pH in vivo. The results demonstrate reliable accuracy in tissue as deep as 4 mm, comparable to standard pH electrode method. This work unlocks the potential of anti-quenching pentamethine cyanines for NIR-II biological applications.

Experimental data reveal that the incorporation of carbonyl groups into polymer matrix can significantly enhance singlet oxygen ((1) O2 ) generation and suppress production of other reactive oxygen species. Excitonic processes investigated by phosphorescence spectroscopy reveal enhanced triplet-exciton generation in the modified g-C3 N4 , which facilitate (1) O2 generation through an energy transfer process. Benefiting from this, the modified g-C3 N4 shows excellent conversion and selectivity in organic synthesis.

Homeobox (HOX) transcript antisense RNA (HOTAIR) is a long intergenic noncoding RNA (lincRNA) that is significantly overexpressed in breast and hepatocellular cancers. It remains unclear, however, whether HOTAIR plays an oncogenic role in human laryngeal squamous cell cancer (LSCC). We therefore investigated the expression and functional role of HOTAIR in LSCC. HOTAIR levels were significantly higher in LSCC than in corresponding adjacent non-neoplastic tissues, and patients with poor histological grade or advanced clinical stage had higher HOTAIR expression. Log-rank test showed a significant association between high levels of HOTAIR and poor prognosis in LSCC patients. Multivariate Cox analysis suggested that HOTAIR is an independent prognostic factor of LSCC. siRNA-mediated knockdown of HOTAIR led to reduced invasion and increased apoptosis of Hep-2 cells in vitro and significantly reduced growth of LSCC xenograft tumors in mice. Moreover, PTEN methylation was significantly reduced in Hep-2 cells depleted of HOTAIR. Taken together, these results suggest that the oncogenic role of HOTAIR in LSCC is related to promotion of PTEN methylation. HOTAIR could serve as a marker for LSCC prognosis and a potential target for therapeutic intervention.

As next-generation artificial enzymes, nanozymes have shown great promise for tumor catalytic therapy. In particular, their peroxidase-like activity has been employed to catalyze hydrogen peroxide (H 2 O 2 ) to produce highly toxic hydroxyl radicals ( • OH) to kill tumor cells. However, limited by the low affinity between nanozymes with H 2 O 2 and the low level of H 2 O 2 in the tumor microenvironment, peroxidase nanozymes usually produced insufficient • OH to kill tumor cells for therapeutic purposes. Herein, we present a pyrite peroxidase nanozyme with ultrahigh H 2 O 2 affinity, resulting in a 4144-and 3086-fold increase of catalytic activity compared with that of classical Fe 3 O 4 nanozyme and natural horseradish peroxidase, respectively. We found that the pyrite nanozyme also possesses intrinsic glutathione oxidase-like activity, which catalyzes the oxidation of reduced glutathione accompanied by H 2 O 2 generation. Thus, the dual-activity pyrite nanozyme constitutes a self-cascade platform to generate abundant • OH and deplete reduced glutathione, which induces apoptosis as well as ferroptosis of tumor cells. Consequently, it killed apoptosis-resistant tumor cells harboring KRAS mutation by inducing ferroptosis. The pyrite nanozyme also exhibited favorable tumor-specific cytotoxicity and biodegradability to ensure its biosafety. These results indicate that the high-performance pyrite nanozyme is an effective therapeutic reagent and may aid the development of nanozyme-based tumor catalytic therapy.

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