•Successful synthesis of Sudan I MMIPs by the RAFT polymerization.•The prepared MMIPs were characterized by TEM, FT-IR, XPS, VSM, and XRD.•The MMIPs possess high selectivity and good recoveries for ...Sudan dyes.•Used as the SPE sorbent to enrichment Sudan dyes in chili powder samples.
Magnetic molecularly imprinted polymers (MMIPs) have become a hotspot owing to the dual functions of target recognition and magnetic separation. In this study, the MMIPs were obtained by the surface-initiated reversible addition fragmentation chain transfer (RAFT) polymerization using Sudan I as the template. The resultant MMIPs were characterized by transmission electron microscope, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, vibrating sample magnetometer, and X-ray diffraction. Benefiting from the controlled/living property of the RAFT strategy, the uniform MIP layer was successfully grafted on the surface of RAFT agent-modified Fe3O4@SiO2 nanoparticles, favoring the fast mass transfer and rapid binding kinetics. The developed MMIPs were used as the solid-phase extraction sorbents to selectively extract four Sudan dyes (Sudan I, II, III, and IV) from chili powder samples. The recoveries of the spiked samples in chili powder samples ranged from 74.1 to 93.3% with RSD lower than 6.4% and the relative standard uncertainty lower than 0.029. This work provided a good platform for the extraction and removal of Sudan dyes in complicated matrixes and demonstrated a bright future for the application of the well-constructed MMIPs in the field of solid-phase extraction.
A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is ...an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARSCoV-2 papain-like protease (PLpro). Together with main protease (Mpro), PLpro is responsible for processing the viral replicase polyprotein into functional units. Therefore, it is an attractive target for antiviral drug development. Here we discovered four compounds, YM155, cryptotanshinone, tanshinone I and GRL0617 that inhibit SARS-CoV-2 PLpro with IC50 values ranging from 1.39 to 5.63 μmol/L. These compounds also exhibit strong antiviral activities in cell-based assays. YM155, an anticancer drug candidate in clinical trials, has the most potent antiviral activity with an EC50 value of 170 nmol/L. In addition, we have determined the crystal structures of this enzyme and its complex with YM155, revealing a unique binding mode. YM155 simultaneously targets three "hot" spots on PLpro, including the substratebinding pocket, the interferon stimulating gene product 15 (ISG15) binding site and zinc finger motif. Our results demonstrate the efficacy of this screening and repurposing strategy, which has led to the discovery of new drug leads with clinical potential for COVID-19 treatments.
The scarcity of donor organs may be addressed in the future by using pigs to grow humanized organs with lower potential for immunological rejection after transplantation in humans. Previous studies ...have demonstrated that interspecies complementation of rodent blastocysts lacking a developmental regulatory gene can generate xenogeneic pancreas and kidney
. However, such organs contain host endothelium, a source of immune rejection. We used gene editing and somatic cell nuclear transfer to engineer porcine embryos deficient in ETV2, a master regulator of hematoendothelial lineages
. ETV2-null pig embryos lacked hematoendothelial lineages and were embryonic lethal. Blastocyst complementation with wild-type porcine blastomeres generated viable chimeric embryos whose hematoendothelial cells were entirely donor-derived. ETV2-null blastocysts were injected with human induced pluripotent stem cells (hiPSCs) or hiPSCs overexpressing the antiapoptotic factor BCL2, transferred to synchronized gilts and analyzed between embryonic day 17 and embryonic day 18. In these embryos, all endothelial cells were of human origin.
Coronavirus disease 2019 (COVID-19) is a current global health threat caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that ...SARS-CoV-2 elicits a dysregulated immune response and a delayed interferon (IFN) expression in patients, which contribute largely to the viral pathogenesis and development of COVID-19. However, underlying mechanisms remain to be elucidated. Here, we report the activation and repression of the innate immune response by SARS-CoV-2. We show that SARS-CoV-2 RNA activates the RIG-I-MAVS-dependent IFN signaling pathway. We further uncover that ORF9b immediately accumulates and antagonizes the antiviral type I IFN response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells. ORF9b targets the nuclear factor κB (NF-κB) essential modulator NEMO and interrupts its K63-linked polyubiquitination upon viral stimulation, thereby inhibiting the canonical IκB kinase alpha (IKKα)/β/γ-NF-κB signaling and subsequent IFN production. Our findings thus unveil the innate immunosuppression by ORF9b and provide insights into the host-virus interplay during the early stage of SARS-CoV-2 infection.
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•SARS-CoV-2 RNA activates the RIG-I-MAVS antiviral signaling pathway•ORF9b from SARS-CoV-2 antagonizes IFN-β and pro-inflammatory cytokines production•N-terminal motif of ORF9b mediates its interaction with NEMO upon viral infection•ORF9b interrupts the K63-linked polyubiquitination of NEMO
The reason why COVID-19 patients experience innate immunosuppression at the early stage of SARS-CoV-2 infection is unclear. Wu et al. report that ORF9b accumulates immediately during SARS-CoV-2 infection and antagonizes the RIG-I-MAVS antiviral type I interferon response by interrupting the K63-linked polyubiquitination of the interferon signaling modulator NEMO.
This study is to investigate whether astaxanthin could alleviate the oxidative stress damages of follicles induced by BPA and improve the development of the cultured follicles and oocytes. Compared ...with BPA group, the survival rate, antrum formation rate, oocyte maturation rate and adherence area of the D8 and D10 follicles of the BPA+Asta group were significantly higher. The estrogen and progesterone in the culture medium of BPA+Asta group were significantly higher. PCNA in D8 and D10 granulosa cells and ERα in D10 granulosa cells of follicles in BPA+Asta group were significantly higher. The levels of malondialdehyde in the follicle culture medium, levels of ROS in the oocytes, the expression levels of caspase 3 and cathepsin B in the oocytes of the BPA+Asta group were significantly lower. However, the mitochondrial membrane potential, and the expression levels of antioxidant genes (CAT, SOD1 and SOD2) and anti-apoptotic gene Bcl-2 in the oocytes in the BPA+Asta group were significantly higher. Astaxanthin improves the development of follicles and oocytes through increasing the antioxidant capacity of follicles and oocytes, and relieving the BPA-induced oxidative stress during follicular development and oocyte maturation.
Analyses of four endocrine disrupting chemicals (EDCs) in water and milk samples were undertaken by using magnetic molecularly imprinted polymers (MMIPs). These were prepared via the surface ...molecular imprinting technique using super paramagnetic core-shell nanoparticle as support. Diethylstilbestrol (DES), which is a typical EDC, was employed as the template molecule. The obtained MMIPs were characterized using transmission electron microscope, Fourier transform infrared, X-ray diffraction, and vibrating sample magnetometer. Accordingly, the adsorption capacity and selectivity of prepared MMIPs were investigated. The binding isotherms were obtained for DES and fitted by the Freundlich isotherm model. A corresponding analytical method to determine four EDCs was developed. The recoveries of the spiked samples in pond water and pure milk range from 67.8 to 93.2 % and from 65.3 to 92.5 %, respectively. Coupled with high-performance liquid chromatography analysis, the prepared MMIPs were successfully applied to the analysis of EDCs in water and milk samples.
Graphical Abstract
The construction and feature of magnetic molecularly imprinted polymers
Undiagnosed and untreated mpox infections may infect others through unprotected sex 21. Because of the fear of revealing personal privacy, the transmission of mpox among MSM is insidious, the source ...of infection is unclear, and prevention and control are difficult. ...over the past 50 years, the age distribution of mpox infections in Africa revealed that the susceptible population to mpox consisted mainly of children with weakened immune systems, not gay groups 23. ...mpox is not only transmitted sexually but also through prolonged face-to-face respiratory droplets or through direct or indirect contact with a patient’s body fluids, diseased tissues, and possibly through contaminated pollutants such as clothing and bed linen stained with fluids from ruptured patient’s rashes, and in addition, mpox can be transmitted vertically from mother to child 24. ...simply defining mpox as gay disease and the transmission mode as sexual transmission is incomplete and may mislead people’s perception of mpox, which is a barrier to preventing the disease or eliminating discrimination. ...mpox prevention should be integrated with HIV control efforts to develop interventions for high-risk groups.
Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the ...SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.
Soil nutrient balance is related to the interaction mechanism between soil fertilizer, soil water, climate change, and plant capability. This paper provides a perspective from bibliometric analysis ...based on data from the Web of Science core collection with software tools, including Vosviewer, HistCite Pro, and Citespace, in order to reveal the evolution of research trends in soil nutrients. The results show that publication outputs have increased exponentially from 1992 to 2020. The synthetic parameter of the sum of normalized data (SND), calculated from the default indicators of the bibliometric software tools, was used to rank the overall contribution of journal/authors/institutions/countries. The results demonstrate that Agriculture Ecosystems & Environment, Soil Biology & Biochemistry and Science of the Total Environment are the leading journals in the soil nutrient field. The Chinese Academy of Sciences had the highest total citations and collaborated most closely with other organizations, followed by United States Department of Agriculture (USDA) Agricultural Research Service (ARS) and Agr& Agri Food Canada. In addition, USA, China, and UK are the top three research centers for this topic. Moreover, Ken E Giller, Qirong Shen, and Rattan Lal were the top three authors, while Andrew Sharpley ranked the first depending on citations per publication. In terms of co-occurrence of keyword analysis, the results indicate that nitrogen fertilizer, green manure, and soil population have gained close attention from scholars, while soil amendment of biochar have evolved as a hot topic in recent years. Perspectives on future studies are also given.
Forkhead O transcription factors (FOXOs) have been implicated in glucose and lipid homeostasis; however, the role of FOXOs in the development of nonalcoholic fatty liver disease (NAFLD) is not well ...understood. In this study, we designed experiments to examine the effects of two different diets-very high fat diet (HFD) and moderately high fat plus cholesterol diet (HFC)-on wildtype (WT) and liver-specific Foxo1/3/4 triple knockout mice (LTKO). Both diets induced severe hepatic steatosis in the LTKO mice as compared to WT controls. However, the HFC diet led to more severe liver injury and fibrosis compared to the HFD diet. At the molecular levels, hepatic Foxo1/3/4 deficiency triggered a significant increase in the expression of inflammatory and fibrotic genes including Emr1, Ccl2, Col1a1, Tgfb, Pdgfrb, and Timp1. Thus, our data suggest that FOXO transcription factors play a salutary role in the protection against the diet-induced fatty liver disease.
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