We explored whether medical health workers had more psychosocial problems than nonmedical health workers during the COVID-19 outbreak.
An online survey was run from February 19 to March 6, 2020; a ...total of 2,182 Chinese subjects participated. Mental health variables were assessed via the Insomnia Severity Index (ISI), the Symptom Check List-revised (SCL-90-R), and the Patient Health Questionnaire-4 (PHQ-4), which included a 2-item anxiety scale and a 2-item depression scale (PHQ-2).
Compared with nonmedical health workers (n = 1,255), medical health workers (n = 927) had a higher prevalence of insomnia (38.4 vs. 30.5%, p < 0.01), anxiety (13.0 vs. 8.5%, p < 0.01), depression (12.2 vs. 9.5%; p< 0.04), somatization (1.6 vs. 0.4%; p < 0.01), and obsessive-compulsive symptoms (5.3 vs. 2.2%; p < 0.01). They also had higher total scores of ISI, GAD-2, PHQ-2, and SCL-90-R obsessive-compulsive symptoms (p ≤ 0.01). Among medical health workers, having organic disease was an independent factor for insomnia, anxiety, depression, somatization, and obsessive-compulsive symptoms (p < 0.05 or 0.01). Living in rural areas, being female, and being at risk of contact with COVID-19 patients were the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression (p < 0.01 or 0.05). Among nonmedical health workers, having organic disease was a risk factor for insomnia, depression, and obsessive-compulsive symptoms (p < 0.01 or 0.05).
During the COVID-19 outbreak, medical health workers had psychosocial problems and risk factors for developing them. They were in need of attention and recovery programs.
Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly ...conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.
Cell membrane–based nanosystems with desirable characteristics have been studied extensively for many therapeutic applications. However, current research has focused on single cell membrane, and ...multifunctional fused membrane materials from different membrane types are still rare. Herein, a platelet–cancer stem cell (CSC) hybrid membrane‐coated iron oxide magnetic nanoparticle (MN) {CSC‐PMN} is presented for the first time for the enhanced photothermal therapy of head and neck squamous cell carcinoma (HNSCC). Inherited from the original source cells, the platelet membrane shows immune evading ability due to the surface marker comprising a number of “don't eat me” signals, and the CSC membrane has homotypic targeting capabilities due to the specific surface adhesion molecules. The CSC‐PMNs possess superior characteristics for immune evasion, active cancer targeting, magnetic resonance imaging, and photothermal therapy. Compared with single cell membrane–coated MNs, CSC‐PMNs exhibit prolonged circulation times and enhanced targeting abilities. Moreover, the CSC‐PMNs exhibit a superior photothermal ability that provides excellent HNSCC tumor growth inhibition, particularly in an immunocompetent Tgfbr1/Pten conditional double knockout HNSCC mouse model that contains a more complex tumor microenvironment that is similar to the human HNSCC microenvironment. Collectively, this biomimetic multimembrane‐coated nanoplatform may provide enhanced antitumor efficacy in the complex tumor microenvironment.
A natural cancer stem cell‐platelet hybrid mimic membrane is collected from tumor‐bearing mice and further used for magnetic nanoparticle coating. The obtained biomimetic nanoparticles are then injected into the same mice for magnetic resonance imaging and photothermal therapy. The work presents a novel design strategy for personalized cancer theranostics.
A major challenge for traditional cancer therapy, including surgical resection, chemoradiotherapy, and immunotherapy, is how to induce tumor cell death and leverage the host immune system at the same ...time. Here, a myeloid‐derived suppressor cell (MDSC) membrane‐coated iron oxide magnetic nanoparticle (MNP@MDSC) to overcome this conundrum for cancer therapy is developed. In this study, MNP@MDSC demonstrates its superior performance in immune evasion, active tumor‐targeting, magnetic resonance imaging, and photothermal therapy (PTT)‐induced tumor killing. Compared with red blood cell membrane‐coated nanoparticles (MNPs@RBC) or naked MNPs, MNP@MDSCs are much more effective in active tumor‐targeting, a beneficial property afforded by coating MNP with membranes from naturally occurring MDSC, thus converting the MNP into “smart” agents that like to accumulate in tumors as the source MDSCs. Once targeted to the tumor microenvironment, MNPs@MDSC can act as a PTT agents for enhanced antitumor response by inducing immunogenic cell death, reprogramming the tumor infiltrating macrophages, and reducing the tumor's metabolic activity. These benefits, in combination with the excellent biocompatibility and pharmacological kinetics characteristics, make MNP@MDSC a promising, multimodal agent for cancer theranostics.
Myeloid‐derived suppressor cell (MDSC) membranes are collected from tumor‐bearing mice and further used for magnetic Fe3O4 nanoparticle (MNP) coating. The resulting MDSC‐mimicking nanoparticles (MNP@MDSC) demonstrate superior performance in immune evasion, active tumor‐targeting, magnetic resonance imaging, photothermal therapy‐induced tumor killing, and excellent biocompatibility and pharmacological kinetics characteristics. These benefits make MNP@MDSC a promising, multimodal agent for cancer theranostics.
For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have ...reported a phenomenon known as “accelerated blood clearance (ABC)” where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane‐coated Fe3O4 nanoparticles (Fe3O4@RBC NPs) rely on CD47, which is a “don't eat me” marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein‐alpha (SIRP‐α) receptor. Fe3O4@RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe3O4@RBC NPs does not elicit immune responses on neither the cellular level (myeloid‐derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane‐camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long‐existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.
Red blood cell membrane‐camouflaged Fe3O4 nanoparticles (Fe3O4@RBC NPs) exhibit prolonged circulation time in the blood with no adverse effects. There is little change between a first and second dose, and no accelerated blood clearance is seen, as is generally the case for PEGylated nanomaterials. This is a significant advancement toward developing biomaterials that are able to resist both immune response and rapid clearance.
Whether tobacco carcinogens enable exposed cells immune escape resulting in carcinogenesis, and why patients who smoke respond better to immunotherapies than non-smokers, remains poorly understood. ...Here we report that cigarette smoke and the carcinogen benzo(a)pyrene (BaP) induce PD-L1 expression on lung epithelial cells in vitro and in vivo, which is mediated by aryl hydrocarbon receptor (AhR). Anti-PD-L1 antibody or deficiency in AhR significantly suppresses BaP-induced lung cancer. In 37 patients treated with anti-PD-1 antibody pembrolizumab, 13/16 (81.3%) patients who achieve partial response or stable disease express high levels of AhR, whereas 12/16 (75%) patients with progression disease exhibit low levels of AhR in tumor tissues. AhR inhibitors exert significant antitumor activity and synergize with anti-PD-L1 antibody in lung cancer mouse models. These results demonstrate that tobacco smoke enables lung epithelial cells to escape from adaptive immunity to promote tumorigenesis, and AhR predicts the response to immunotherapy and represents an attractive therapeutic target.
Here, we present a platelet‐facilitated photothermal tumor therapy (PLT‐PTT) strategy, in which PLTs act as carriers for targeted delivery of photothermal agents to tumor tissues and enhance the PTT ...effect. Gold nanorods (AuNRs) were first loaded into PLTs by electroporation and the resulting AuNR‐loaded PLTs (PLT‐AuNRs) inherited long blood circulation and cancer targeting characteristics from PLTs and good photothermal property from AuNRs. Using a gene‐knockout mouse model, we demonstrate that the administration of PLT‐AuNRs and localizing laser irradiation could effectively inhibit the growth of head and neck squamous cell carcinoma (HNSCC). In addition, we found that the PTT treatment augmented PLT‐AuNRs targeting to the tumor sites and in turn, improved the PTT effects in a feedback manner, demonstrating the unique self‐reinforcing characteristic of PLT‐PTT in cancer therapy.
Platelets (PLTs) are circulating sentinels that can accumulate in injured tissues to trigger the repair processes. Photothermal therapy (PTT) uses heat generated from light to ablate tumor tissues. Inspired by both observations, gold nanorods were loaded into PLTs for enhanced PTT of head and neck squamous cell carcinoma.
Cancer cell membrane‐coated upconversion nanoprobes (CC‐UCNPs) with immune escape and homologous targeting capabilities are used for highly specific tumor imaging. The combination of UCNPs with ...biomimetic cancer cell membranes embodies a novel materials design strategy and presents a compelling class of advanced materials.
Background and Purpose
The anthelmintic drug nitazoxanide has a mitochondrial uncoupling effect. Mitochondrial uncouplers have been proven to inhibit smooth muscle cell proliferation and migration, ...inhibit NLRP3 inflammasome activation of macrophages and improve dyslipidaemia. Therefore, we aimed to demonstrate that nitazoxanide would protect against atherosclerosis.
Experimental Approach
The mitochondrial oxygen consumption of cells was measured by using the high‐resolution respirometry system, Oxygraph‐2K. The proliferation and migration of A10 cells were measured by using Edu immunofluorescence staining, wound‐induced migration and the Boyden chamber assay. Protein levels were measured by using the western blot technique. ApoE (−/−) mice were fed with a Western diet to establish an atherosclerotic model in vivo.
Key Results
The in vitro experiments showed that nitazoxanide and tizoxanide had a mitochondrial uncoupling effect and activated cellular AMPK. Nitazoxanide and tizoxanide inhibited serum‐ and PDGF‐induced proliferation and migration of A10 cells. Nitazoxanide and tizoxanide inhibited NLRP3 inflammasome activation in RAW264.7 macrophages, the mechanism by which involved the AMPK/IκBα/NF‐κB pathway. Nitazoxanide and tizoxanide also induced autophagy in A10 cells and RAW264.7 macrophages. The in vivo experiments demonstrated that oral administration of nitazoxanide reduced the increase in serum IL‐1β and IL‐6 levels and suppressed atherosclerosis in Western diet‐fed ApoE (−/−) mice.
Conclusion and Implications
Nitazoxanide inhibits the formation of atherosclerotic plaques in ApoE (−/−) mice fed on a Western diet. In view of nitazoxanide being an antiprotozoal drug already approved by the FDA, we propose it as a novel anti‐atherosclerotic drug with clinical translational potential.
Adding small nanoparticles (NPs) into polymer melt can lead to a non-Einstein-like decrease in viscosity. However, the underlying mechanism remains a long-standing unsolved puzzle. Here, for an ...all-polymer nanocomposite formed by linear polystyrene (PS) chains and PS single-chain nanoparticles (SCNPs), we perform large-scale molecular dynamics simulations and experimental rheology measurements. We show that with a fixed (small) loading of the SCNP, viscosity reduction (VR) effect can be largely amplified with an increase in matrix chain length Formula: see text, and that the system with longer polymer chains will have a larger VR. We demonstrate that such Formula: see text-dependent VR can be attributed to the friction reduction experienced by polymer segment blobs which have similar size and interact directly with these SCNPs. A theoretical model is proposed based on the tube model. We demonstrate that it can well describe the friction reduction experienced by melt polymers and the VR effect in these composite systems.
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