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Extranodal natural killer/T cell lymphoma (ENKTL) shows a high rate of recurrence after chemoradiotherapy. Drug resistance can be mediated by the cargo of small extracellular vesicles (sEVs). Here, we show that high abundance of the transmembrane glycoprotein CD98hc in tumor cells and serum sEVs was associated with ENKTL progression and drug resistance. Mechanistically, PEGylated-asparaginase (PEG-asp) treatment, a common therapy against ENKTL, promoted the translocation of the transcription factor ATF4 to the nucleus, where it was stabilized by USP1 and subsequently increased CD98hc expression. CD98hc delivered in tumor cell–derived sEVs increased tumor cell proliferation and drug resistance in a cultured human NK lymphoma cell line, animal models, and samples from patients with refractory/relapse ENKTL. Moreover, inhibiting both USP1 and EV secretion synergistically enhanced the cytotoxicity of PEG-asp. These data suggest that targeting CD98hc in the treatment of ENKTL may be beneficial in overcoming drug resistance. Editor's summary: Extranodal natural killer/T cell lymphoma (ENKTL) is treated with PEGylated asparaginase (PEG-asp), but drug resistance is common. Liao et al. found that limiting the trafficking of a glycoprotein could overcome drug resistance. Ubiquitin carboxyl-terminal hydrolase 1 (USP1) stabilized the transcription factor ATF4, which promoted CD98hc expression. Knocking out CD98hc in tumor cells and small extracellular vesicles (sEVs) sensitized cells to PEG-asp treatment, whereas CD98hc-enriched sEVs suppressed the effects of PEG-asp in mice, suggesting that targeting CD98hc may be explored in the treatment of ENKTL. —Amy E. Baek [ABSTRACT FROM AUTHOR]

Photo‐electrochemical (PEC) water splitting is a promising method for converting solar energy into clean energy, but the mechanism of improving PEC efficiency through the interfacial contact and defect strategy remains highly controversial. Herein, reduced graphene oxide (rGO) and oxygen vacancies are introduced into α‐Fe2O3 nanorod (NR) arrays using a simple spin‐coating method and acid treatment. The resultant oxygen vacancy–α‐Fe2O3/rGO‐integrated system exhibits a higher photocurrent, four times than the pristine α‐Fe2O3. It is well evidenced that the electronic interface interaction between α‐Fe2O3 and rGO is boosted with the oxygen vacancies, facilitating electron transfer from α‐Fe2O3 to rGO. Moreover, the oxygen vacancies not only create interband states in α‐Fe2O3 that can trap photogenerated holes and thus facilitate charge separation but significantly also strengthen the adsorption of oxidative intermediates and reduce the energy barrier of rate‐determining step during oxygen evolution reaction (OER). This study demonstrates an rGO–oxygen vacancy synergistic interfacial contact and defect modification approach to design semiconducting photocatalysts for high‐efficiency solar energy capture and conversion. The generated principle is expected to be extendable to another material system. [ABSTRACT FROM AUTHOR]

In a ZnO microcavity, the exciton-polariton effect with ultralarge Rabi splitting (can be as large as several hundreds of millielectron volts) may dominate the optical properties at the energies near the band edge. Due to the light-matter coupling, the renormalized energy states, i.e., the exciton-polariton states are expected to show very different dynamical behavior compared to the free exciton state. In this work, we used a femtosecond laser to pump a high-quality ZnO whispering gallery microcavity at room temperature. In the time-resolved photoluminescence measurements, we observed that both the fast and slow decay rates of the exciton-polaritons are faster than that of the free exciton due to the strong coupling between excitons and photons in a microcavity. The decay time constants are found to depend on the exciton-photon energy detuning (δ = E p h o t o n − E e x c i t o n ). [ABSTRACT FROM AUTHOR]

The DNA damage response (DDR) is essential for the maintenance of genomic stability. Protein posttranslational modifications play pivotal roles in regulating the DDR process. Here, we found that SUMOylated RNF168 undergoes liquid-liquid phase separation (LLPS), which restricts the recruitment of RNF168 to DNA damage sites, reduces RNF168-catalyzed H2A ubiquitination, restrains 53BP1 in nuclear condensates, and ultimately impairs nonhomologous DNA end joining repair efficiency. Sentrin/SUMO-specific protease 1 (SENP1) was identified as a specific deSUMOylase of RNF168, and it was highly expressed in colorectal adenocarcinoma. In response to DNA damage, SENP1 decreased RNF168 SUMOylation and prevented RNF168 from forming nuclear condensates, thus promoting damage repair efficiency and cancer cell resistance to DNA damaging agents. Moreover, high SENP1 expression correlated with poor prognosis in patients with cancer, and SENP1 depletion sensitized cancer cells to chemotherapy. In summary, these findings reveal DDR is suppressed by SUMOylation-induced LLPS of RNF168 and suggest that SENP1 is a potential target for cancer therapy., Significance: Sentrin/SUMO-specific protease 1 decreases RNF168 SUMOylation and liquid-liquid phase separation to promote DNA damage repair, safeguarding genomic integrity and driving chemotherapy resistance., (©2023 American Association for Cancer Research.)