Nanotechnology has become more and more potentially used in diagnosis or treatment of diseases. Advances in nanotechnology have led to new and improved nanomaterials in biomedical applications. ...Common nanomaterials applicable in biomedical applications include liposomes, polymeric micelles, graphene, carbon nanotubes, quantum dots, ferroferric oxide nanoparticles, gold nanoparticles (Au NPs), and so on. Among them, Au NPs have been considered as the most interesting nanomaterial because of its unique optical, electronic, sensing and biochemical properties. Au NPs have been potentially applied for medical imaging, drug delivery, and tumor therapy in the early detection, diagnosis, and treatment of diseases. This review focuses on some recent advances in the use of Au NPs as drug carriers for the intracellular delivery of therapeutics and as molecular nanoprobes for the detection and monitoring of target molecules.
A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing ...the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 46%), fatigue (47 44%), headache (42 39%), and muscle pain (18 17%. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.
The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.
This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an ...appropriate dose of the candidate vaccine for an efficacy study.
This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.
603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.
The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.
National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
Adsorption technology based on ethane‐selective materials is a promising alternative to energy‐intensive cryogenic distillation for separating ethane (C2H6) and ethylene (C2H4). We employed a pore ...engineering strategy to tune the pore environment of a metal–organic framework (MOF) through organic functional groups and boosted the C2H6/C2H4 separation of the MOF. Introduction of amino (−NH2) groups into Tb‐MOF‐76 not only decreased pore sizes but also facilitated multiple guest‐host interactions in confined pores. The NH2‐functionalized Tb‐MOF‐76(NH2) has increased C2H6 and C2H4 uptakes and C2H6/C2H4 selectivity. The results of experimental and simulated transient breakthroughs reveal that Tb‐MOF‐76(NH2) has significantly improved one‐step separation performance for C2H6/C2H4 mixtures with a high C2H4 (>99.95 %) productivity of 17.66 L kg−1 compared to 7.53 L kg−1 by Tb‐MOF‐76, resulting from the suitable pore confinement and accessible −NH2 groups on pore surfaces.
By virtue of a pore engineering strategy based on isoreticular chemistry, an amino‐functionalized metal–organic framework (MOF) with suitable pore confinement and more binding sites improved the ethane/ethylene separation performance compared to the parent MOF.
One‐step C2H4 purification from ternary C2H6/C2H4/C2H2 mixtures by a single adsorbent is of great industrial significance, but few adsorbents achieve this separation. Herein, we report a robust ...metal–organic framework (MOF) that possesses methyl‐decorated nonpolar pores and shows one‐step C2H4 purification (purity >99.9 %) from binary C2H6/C2H4 mixtures and ternary C2H6/C2H4/C2H2 mixtures. The methyl groups in pores provide a suitable pore environment to simultaneously enhance the adsorption capacity for C2H2 and C2H6 compared to C2H4. Simulations revealed the multiple interactions between C2H6 or C2H2 molecules and the pore wall, while the interactions with C2H4 molecules are weak and also unfavorable due to the repulsion from methyl groups in pores. The MOF displays high C2H6 and C2H2 uptakes and benchmark C2H6/C2H4 selectivity (2.2), surpassing all of the reported MOFs for one‐step C2H4 purification from ternary C2H6/C2H4/C2H2 mixtures.
The combination of nonpolar pore environment and accessible active sites in a metal–organic framework affords benchmark C2H6/C2H4 selectivity and realizes one‐step C2H4 purification from ternary C2H6/C2H4/C2H2 mixtures.
A metal‐free 2+2 cycloaddition and 1,4‐addition sequence induced by S‐centered radicals has been achieved by treating benzene‐linked allene‐ynes with aryldiazonium tetrafluoroborates and ...DABCO‐bis(sulfur dioxide) in a one‐pot procedure. The reaction provides a greener and more practical access to functionalized cyclobutaanaphthalen‐4‐ols with valuable applications. More than 50 examples are demonstrated with excellent diastereoselectivity and chemical yields. The reaction pathway is proposed to proceed by the following steps:2+2 cycloaddition, insertion of SO2, 1,4‐addition, diazotization, and tautomerization.
Just a DAB: A new metal‐free 2+2 cycloaddition/S‐centered radical induced 1,4‐addition sequence of benzene‐linked allene‐ynes has been established by treatment with aryldiazonium tetrafluoroborates and DABCO‐bis(sulfur dioxide) under convenient reaction conditions, thus providing practical access to functionalized cyclobutaanaphthalen‐4‐ols of chemical and biomedical importance. DABCO=1,4‐diazabicyclo2.2.2octane.
A robust cluster-based Eu-MOF has been created by a tetrazolyl-carboxyl linker, which shows great chemical and thermal stability and multiple functions of fluorescent sensor for the detection of ...antibiotics (MDZ, DMZ) and pesticides (DCN).
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•A robust cluster-based Eu-MOF as a fluorescence probe.•Resistance to water, organic solvents and wide pH value range.•Selective detection of MDZ, DMZ and DCN with low detection limit, rapid response.•Detected MDZ and DMZ in calf serum and sensed DCN in lake water.•Combining experiments and calculations to study the sensing mechanism.
As a hot issue of global concern, the abuse of organic pollutants, including pesticides and antibiotics poses a great threat to the human health and ecological environment. Effective and accurate detection of these species is of profound significance in many fields. In this work, a novel 3D metal-organic framework (MOF) Eu2(dtztp)(OH)2(DMF)(H2O)2.5·2H2O (1) was solvothermally synthesized. 1 is a three-dimensional framework based on tetranuclear Eu4(μ3-OH)4(μ2-OH2)8+ clusters, and reveals the great chemical stability and excellent tolerance in water and organic solvents. The MOF also shows strong fluorescence that was undisturbed by the pH in aqueous water (pH = 3–12). Importantly, 1 can quickly detect metronidazole (MDZ) and dimetridazole (DMZ) antibiotics as well as 2,6-dichloro-4-nitroaniline (DCN) pesticide in water with good recyclability and low detection limit. MDZ, DMZ and DCN were also successfully detected in calf serum and lake water, respectively. The mechanism of fluorescence quenching was disclosed through the combination of experiments and density functional theory calculations.
A new, complete sample of 14,584 broad-line active galactic nuclei (AGNs) at z < 0.35 is presented, which are uncovered homogeneously from the complete database of galaxies and quasars observed ...spectroscopically in the Sloan Digital Sky Survey Seventh Data Release. The stellar continuum is properly removed for each spectrum with significant host absorption line features, and careful analyses of the emission line spectra, particularly in the H and Hβ wavebands, are carried out. The broad Balmer emission line, particularly H , is used to indicate the presence of an AGN. The broad H lines have luminosities in a range of 1038.5- 1044.3 , and line widths (FWHMs) of 500-34,000 . The virial black hole masses, estimated from the broad-line measurements, span a range of 105.1- 1010.3 , and the Eddington ratios vary from −3.3 to 1.3 in logarithmic scale. Other quantities such as multiwavelength photometric properties and flags denoting peculiar line profiles are also included in this catalog. We describe the construction of this catalog and briefly discuss its properties. The catalog is publicly available online. This homogeneously selected AGN catalog, along with the accurately measured spectral parameters, provides the most updated, largest AGN sample data, which will enable further comprehensive investigations of the properties of the AGN population in the low-redshift universe.
The oncogene c‐Myc is aberrantly expressed and plays a key role in malignant transformation and progression of hepatocellular carcinoma (HCC). Here, we report that c‐Myc is significantly up‐regulated ...by tumor necrosis factor receptor–associated factor 6 (TRAF6), an E3 ubiquitin ligase, in hepatocarcinogenesis. High TRAF6 expression in clinical HCC samples correlates with poor prognosis, and the loss of one copy of the Traf6 gene in Traf6+/– mice significantly impairs liver tumorigenesis. Mechanistically, TRAF6 first interacts with and ubiquitinates histone deacetylase 3 (HDAC3) with K63‐linked ubiquitin chains, which leads to the dissociation of HDAC3 from the c‐Myc promoter and subsequent acetylation of histone H3 at K9, thereby epigenetically enhancing the mRNA expression of c‐Myc. Second, the K63‐linked ubiquitination of HDAC3 impairs the HDAC3 interaction with c‐Myc and promotes c‐Myc protein acetylation, which thereby enhances c‐Myc protein stability by inhibiting carboxyl terminus of heat shock cognate 70‐kDa–interacting protein–mediated c‐Myc ubiquitination and degradation. Importantly, TRAF6/HDAC3/c‐Myc signaling is also primed in hepatitis B virus–transgenic mice, unveiling a critical role for a mechanism in inflammation–cancer transition. In clinical specimens, TRAF6 positively correlates with c‐Myc at both the mRNA and protein levels, and high TRAF6 and c‐Myc expression is associated with an unfavorable prognosis, suggesting that TRAF6 collaborates with c‐Myc to promote human hepatocarcinogenesis. Consistently, curbing c‐Myc expression by inhibition of TRAF6 activity with a TRAF6 inhibitor peptide or the silencing of c‐Myc by small interfering RNA significantly suppressed tumor growth in mice. Conclusion: These findings demonstrate the oncogenic potential of TRAF6 during hepatocarcinogenesis by modulating TRAF6/HDAC3/c‐Myc signaling, with potential implications for HCC therapy.
Circ‐Foxo3 is a circRNA encoded by the human FOXO3 gene and works as a sponge for potential microRNAs (miRNAs) to regulate cancer progression. However, the role of circ‐Foxo3 in esophageal squamous ...cell cancer (ESCC) is not clear. In this study, circ‐Foxo3 was lowly expressed in cell lines and ESCC tissues. Meanwhile, overexpression of circ‐Foxo3 inhibited cell growth, migration, and invasion, whether in vivo or in vitro. Mechanically, we found a potential miRNA target, miR‐23a, which negatively correlated with circ‐Foxo3 in ESCC. Then, a luciferase assay confirmed the relationship between the circ‐Foxo3 and miRNA. Moreover, circ‐Foxo3 upregulation of PTEN occurred through “sponging” miR‐23a. Taken together, these results indicated that the circ‐Foxo3/miR‐23a/PTEN pathway was critical for inhibiting the ESCC progression. This may provide a promising target for treat ESCC.
The circ‐Foxo3/miR‐23a/PTEN pathway is possibly a critical factor in inhibiting esophageal squamous cell cancer (ESCC) progression. This may provide a promising target for treating ESCC.
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