The ongoing outbreak of Coronavirus Disease 2019 has become a global public health emergency. SARScoronavirus-2 (SARS-CoV-2), the causative pathogen of COVID-19, is a positive-sense single-stranded RNA virus belonging to the family Coronaviridae. For RNA viruses, virus-encoded RNA helicases have long been recognized to play pivotal roles during viral life cycles by facilitating the correct folding and replication of viral RNAs. Here, our studies show that SARS-CoV-2-encoded nonstructural protein 13 (nsp13) possesses the nucleoside triphosphate hydrolase (NTPase) and RNA helicase activities that can hydrolyze all types of NTPs and unwind RNA helices dependently of the presence of NTP, and further characterize the biochemical characteristics of these two enzymatic activities associated with SARS-CoV-2 nsp13. Moreover, we found that some bismuth salts could effectively inhibit both the NTPase and RNA helicase activities of SARS-CoV-2 nsp13 in a dose-dependent manner. Thus, our findings demonstrate the NTPase and helicase activities of SARS-CoV-2 nsp13, which may play an important role in SARS-CoV-2 replication and serve as a target for antivirals.

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Odor-preferences are usually influenced by life experiences. However, the neural circuit mechanisms remain unclear. The medial olfactory tubercle (mOT) is involved in both reward and olfaction, whereas the ventral tegmental area (VTA) dopaminergic (DAergic) neurons are considered to be engaged in reward and motivation. Here, we found that the VTA (DAergic)-mOT pathway could be activated by different types of naturalistic rewards as well as odors in DAT-cre mice. Optogenetic activation of the VTA-mOT DAergic fibers was able to elicit preferences for space, location and neutral odor, while pharmacological blockade of the dopamine receptors in the mOT fully prevented the odor-preference formation. Furthermore, inactivation of the mOT-projecting VTA DAergic neurons eliminated the previously formed odor-preference and strongly affected the Go-no go learning efficiency. In summary, our results revealed that the VTA (DAergic)-mOT pathway mediates a variety of naturalistic reward processes and different types of preferences including odor-preference in mice.

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Molybdenum disulfide (MoS 2) has been extensively for biomedical applications due to itsexcellent photothermal conversion ability. In this paper, we reported a nanoplatform based on folic acid (FA) targeted dual-stimuli responsive MoS 2 nanosheets (FA-BSA-PEI-LA-MoS 2-LA-PEG, FBPMP) and explore this for the treatment of FA-receptor positive human breast cancer. The nanocomposites had a uniform diameter (133 nm), and could be loaded with the anti-cancer drug doxorubicin (DOX) to a high capacity (151.4 mg/g). The release of DOX was greatly accelerated at pH 5.0 as compared to pH 7.4. In addition, it was found that drug release is enhanced under the near infrared laser (NIR) irradiation, showing that the composites can be used as dual responsive systems, with DOX release controllable through pH or NIR irradiation. MTT assays and confocal experiments showed that FBPMP nanoplatform could selectively target and kill FA-positive MDA-MB-231 cells (a human breast cancer cell line). The platform also allowed the combination of chemotherapy and photothermal therapy, which led to synergistic effects superior to either monotherapy. The functionalized MoS 2 nanoplatform developed in this work hence could be a potent system for targeted drug delivery and synergistic chemo-photothermal cancer therapy.

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