The emergence of human infection with a novel H7N9 influenza virus in China raises a pandemic concern. Chicken H9N2 viruses provided all six of the novel reassortant’s internal genes. However, it is not fully understood how the prevalence and evolution of these H9N2 chicken viruses facilitated the genesis of the novel H7N9 viruses. Here we show that over more than 10 y of cocirculation of multiple H9N2 genotypes, a genotype (G57) emerged that had changed antigenicity and improved adaptability in chickens. It became predominant in vaccinated farm chickens in China, caused widespread outbreaks in 2010–2013 before the H7N9 viruses emerged in humans, and finally provided all of their internal genes to the novel H7N9 viruses. The prevalence and variation of H9N2 influenza virus in farmed poultry could provide an important early warning of the emergence of novel reassortants with pandemic potential.

The integration of reactive oxygen species (ROS)-involved photodynamic therapy (PDT) and chemodynamic therapy (CDT) holds great promise for enhanced anticancer effects. Herein, we report biodegradable cancer cell membrane-coated mesoporous copper/manganese silicate nanospheres (mCMSNs) with homotypic targeting ability to the cancer cell lines and enhanced ROS generation through singlet oxygen ( 1 O 2 ) production and glutathione (GSH)-activated Fenton reaction, showing excellent CDT/PDT synergistic therapeutic effects. We demonstrate that mCMSNs are able to relieve the tumor hypoxia microenvironment by catalytic decomposition of endogenous H 2 O 2 to O 2 and further react with O 2 to produce toxic 1 O 2 with a 635 nm laser irradiation. GSH-triggered mCMSNs biodegradation can simultaneously generate Fenton-like Cu + and Mn 2+ ions and deplete GSH for efficient hydroxyl radical (•OH) production. The specific recognition and homotypic targeting ability to the cancer cells were also revealed. Notably, relieving hypoxia and GSH depletion disrupts the tumor microenvironment (TME) and cellular antioxidant defense system, achieving exceptional cancertargeting therapeutic effects in vitro and in vivo. The cancer cells growth was significantly inhibited. Moreover, the released Mn 2+ can also act as an advanced contrast agent for cancer magnetic resonance imaging (MRI). Thus, together with photosensitizers, Fenton agent provider and MRI contrast effects along with the modulating of the TME allow mCMSNs to realize MRI-monitored enhanced CDT/PDT synergistic therapy. It provides a paradigm to rationally design TMEresponsive and ROS-involved therapeutic strategies based on a single polymetallic silicate nanomaterial with enhanced anticancer effects.

Cellular-membrane-coated nanoparticles have increasingly been pursued to leverage the natural cell functions for enhancing biocompatibility and improved therapeutic efficacy. Taking advantage of specialized cell membranes or combining functions from different membrane types facilitates the strengthening of their functionality. Herein, we fuse membrane materials derived from red blood cells (RBCs) and melanoma cells (B16-F10 cells) to create a hybrid biomimetic coating (RBC-B16), and RBC-B16 hybrid membrane camouflaged doxorubicin (DOX)-loaded hollow copper sulfide nanoparticles (DCuS@[RBC-B16] NPs) are fabricated for combination therapy of melanoma. The DCuS@[RBC-B16] NPs are comprehensively characterized, showing the inherent properties of the both source cells. Compared to the bare CuS NPs, the DCuS@[RBC-B16] NPs exhibit highly specific self-recognition to the source cell line in vitro and achieve markedly prolonged circulation lifetime and enhanced homogeneous targeting abilities in vivo inherited from the source cells. Thus, the DOX-loaded [RBC-B16]-coated CuS NP platform exhibits excellent synergistic photothermal/chemotherapy with about 100% melanoma tumor growth inhibition rate. The reported strategy may contribute to personalized nanomedicine of various tumors by combining the RBCs with a homotypic cancer membrane accordingly on the surface of the nanoparticle.

Outbreaks of diarrhea in newborn piglets without detection of transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV), have been recorded in a pig farm in southern China since February 2017. Isolation and propagation of the pathogen in cell culture resulted in discovery of a novel swine enteric alphacoronavirus (tentatively named SeACoV) related to the bat coronavirus HKU2 identified in the same region a decade ago. Specific fluorescence signal was detected in Vero cells infected with SeACoV by using a positive sow serum collected in the same farm, but not by using TGEV-, PEDV- or PDCoV-specific antibody. Electron microscopy observation demonstrated that the virus particle with surface projections was 100-120nm in diameter. Complete genomic sequencing and analyses of SeACoV indicated that the extreme amino-terminal domain of the SeACoV spike (S) glycoprotein structurally similar to the domain 0 of the alphacoronavirus NL63, whereas the rest part of S structurally resembles domains B to D of the betacoronavirus. The SeACoV-S domain 0 associated with enteric tropism had an extremely high variability, harboring 75-amino-acid (aa) substitutions and a 2-aa insertion, compared to that of HKU2, which is likely responsible for the extended host range or cross-species transmission. The isolated virus was infectious in pigs when inoculated orally into 3-day-old newborn piglets, leading to clinical signs of diarrhea and fecal virus shedding. These results confirmed that it is a novel swine enteric coronavirus representing the fifth porcine coronavirus.

The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT). Here, we report a H 2 O 2 /O 2 self-supplying nanoagent, (MSNs@CaO 2 -ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO 2 ) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO 2 reacts with water to produce O 2 and H 2 O 2 for hypoxia-relieved ICG-mediated PDT and H 2 O 2 -supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies.

The limited penetration depth of photothermal agents (PTAs) active in the NIR-I biowindow and the thermoresistance caused by heat shock protein (HSP) significantly limit the therapeutic efficiency of photothermal therapy (PTT). To address the problem, we introduce a strategy of low-temperature nucleus-targeted PTT in the NIR-II region achieving effective tumor killing by combining the vanadium carbide quantum dots (V2C QDs) PTA and an engineered exosomes (Ex) vector. The small fluorescent V2C QDs with good photothermal effect in the NIR-II region were modified with TAT peptides and packaged into Ex with RGD modification (V2C-TAT@Ex-RGD). The resulting nanoparticles (NPs) exhibited good biocompatibility, long circulation time, and endosomal escape ability, and they could target the cell and enter into the nucleus to realize low-temperature PTT with advanced tumor destruction efficiency. The fluorescent imaging, photoacoustic imaging (PAI), and magnetic resonance imaging (MRI) capability of the NPs were also revealed. The low-temperature nucleus-targeted PTT in the NIR-II region provides more possibilities toward successful clinical application of PTT.

Nanozymes that integrate the advantages of both nanomaterials and natural enzymes have accumulated enormous research interest over the past decades because of the opportunity it provides to appreciate and further cultivate artificial enzymes with comparable property. By mimicking the coordination environments of the catalytic sites in natural enzymes, nanozymes with confined nanostructures can serve as substitutes for many catalytic processes with comparable activity and robust stability even in harsh conditions. Since the pioneered report about peroxidase-mimicking ferromagnetic nanoparticles in 2007, the nanozymes are specialized for nanomaterials with intrinsic enzyme-mimicking property. With the rapid development in nanoscience and nanotechnology, nanomaterials with superior advantages such as large-scale production, desired activity, and robust stability can bridge the natural enzymes with nanozymes.Metal-organic frameworks (MOFs) and their derivatives hold a great promise to serve as direct surrogates of conventional enzymes for enzymatic reactions. According to the chemical nature, MOF-based nanozymes can be divided into three main categories: pristine MOFs, enzyme-encapsulated MOF composites, and MOF-based derivatives. Due to the versatility of metallic nodes and bridging linkers together with the feasibility of post-synthetic engineering and modification, MOFs and their derivatives are envisioned as one of the most appropriate surrogates for this purpose. Using MOFs as precursors or sacrificial templates, multiple MOF-based derivatives including carbon-based nanomaterials (e.g., heteroatom-doped carbon or carbon with M-N-C moiety), metal oxide/carbon nanoparticles, and metal/carbon nanomaterials can be rationally synthesized through one-step direct carbonization/oxidation or indirect post-treatments of MOFs (e.g., bridging linker-exchange and metallic node-doping). Compared with the existing nanozymes, MOF-based derivatives open up a new avenue for constructing mesoporous nanozymes. In this way, the intrinsic mesoporous property of MOFs can still be maintained, while the stability and activity can be largely improved. In this Account, we highlight some important research advances in MOF-based derivatives (including M-N-C moiety (M = single metal atom), metal oxide/carbon, metal/carbon, and MOF derivatives obtained through post-synthetic linker exchange and metal doping strategies) with enzyme-mimicking activity. We also portray that, through integrating physicochemical properties of mesoporous nanomaterials and enzymatic activities of natural enzymes, MOF-derived nanozymes can provide multifunctional platforms in biomedical community such as anti-bacteria, biosensor, imaging, cancer therapy, and environmental protection. Finally, we propose future design principles and possible research approaches for deeper understanding of mechanisms, thus pointing out future research directions to offer more opportunities for conventional enzyme-engineering industry.

The tumor microenvironment (TME) with the characteristics of severe hypoxia, overexpressed glutathione (GSH), and high levels of hydrogen peroxide (H2O2) dramatically limits the antitumor efficiency by monotherapy. Herein, a novel TME‐modulated nanozyme employing tin ferrite (SnFe2O4, abbreviated as SFO) is presented for simultaneous photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT). The as‐fabricated SFO nanozyme demonstrates both catalase‐like and GSH peroxidase‐like activities. In the TME, the activation of H2O2 leads to the generation of hydroxyl radicals (•OH) in situ for CDT and the consumption of GSH to relieve antioxidant capability of the tumors. Meanwhile, the nanozyme can catalyze H2O2 to generate oxygen to meliorate the tumor hypoxia, which is beneficial to achieve better PDT. Furthermore, the SFO nanozyme irradiated with 808 nm laser displays a prominent phototherapeutic effect on account of the enhanced photothermal conversion efficiency (η = 42.3%) and highly toxic free radical production performance. This “all in one” nanozyme integrated with multiple treatment modalities, computed tomography, and magnetic resonance imaging properties, and persistent modulation of TME exhibits excellent tumor theranostic performance. This strategy may provide a new dimension for the design of other TME‐based anticancer strategies.