Recent researches of the novel 4
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Einstein–Gauss–Bonnet (EGB) gravity have attracted great attention. In this paper, we investigate the validity of the weak cosmic censorship conjecture for a novel ...4
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charged EGB black hole with test charged scalar field and test charged particle respectively. For the test charged field scattering process, we find that both extremal and near-extremal black holes cannot be overcharged. For the test charged particle injection, to first order, an extremal black hole cannot be overcharged while a near-extremal 4
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charged EGB black hole can be destroyed. To second order, however, both extremal and near-extremal 4
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charged EGB black holes can be overcharged for positive Gauss–Bonnet coupling constant; for negative Gauss–Bonnet coupling constant, an extremal black hole cannot be overcharged and the validity of the weak cosmic censorship conjecture for a near-extremal black hole depends on the Gauss–Bonnet coupling constant.
Improving the antibacterial activity of H2O2 and reducing its usage are requirements for wound disinfection. Nanomaterials with intrinsic peroxidase‐like properties are developed to enhance the ...antibacterial performance of H2O2 and avoid the toxicity seen with high H2O2 levels. Here, Pd–Pt core–frame nanodendrites consist of a dense array of platinum (Pt) branches on a Pd core are synthesized, and subsequently converted to Pt hollow nanodendrites by selective removal of the Pd cores by wet etching. The fabricated Pt hollow nanodendrites exert striking peroxidase‐like activity due to the maximized utilization efficiency of the Pt atoms and the presence of high‐index facets on their surfaces. By catalyzing the decomposition of H2O2 into more toxic hydroxyl radicals (•OH), Pt hollow nanodendrites exhibit excellent bactericidal activity against both Gram‐negative and Gram‐positive bacteria with the assistance of low concentrations of H2O2. Furthermore, Pt hollow nanodendrites accelerate wound healing in the presence of low doses of H2O2. In addition, no obvious adverse effects are observed at the given dose of nanodendrites. These findings can be used to guide the design of noble metal‐based nanomaterials as potential enzyme‐mimetic systems and advance the development of nanoenzymes to potentiate the antibacterial activity of H2O2.
Platinum (Pt) hollow nanodendrites are fabricated, which exert striking peroxidase‐like activity due to the maximized efficiency of Pt atoms and the presence of high‐index facets. By catalyzing the decomposition of H2O2 into more toxic •OH, Pt hollow nanodendrites show excellent bactericidal activity with the assistance of low concentrations of H2O2 and potently accelerated wound healing in actual wound infections.
The development of versatile nanotheranostic platforms that integrate both diagnostic and therapeutic functions have always been an intractable challenge in precise cancer treatment. Herein, an ...aptamer‐tethered deoxyribonucleic acids‐gold particle (Apt‐DNA‐Au) nanomachine has been developed for in situ imaging and targeted multimodal synergistic therapy of mammary carcinoma. Upon specifically internalized into MCF‐7 cells, the tumor‐related TK1 mRNA activates the Apt‐DNA‐Au nanomachine by DNA strand displacement cascades, resulting in the release of the fluorophore and antisense DNA as well as the aggregation of AuNPs for in situ imaging, suppression of survivin expression and photothermal therapy, respectively. Meanwhile, the controlled released drugs are used for chemotherapy, while under the laser irradiation the loaded photosensitizer produces reactive oxygen species (ROS) for photodynamic therapy. The results confirm that the proposed Apt‐DNA‐Au nanomachine provides a powerful nanotheranostic platform for in situ imaging‐guided combinatorial anticancer therapy.
A multifunctional DNA‐Au nanomachine which can be triggered by endogenous tumor growth‐related TK1 mRNA has been devised as the combinatorial theranostic agent for fluorescence imaging‐guided chemo, genic, photodynamic, and photothermal synergistic targeted therapy of breast cancer. This theranostic nanoplatform achieves the significant inhibition of tumor growth and improvement of therapeutic efficacy through in situ imaging.
With the assistance of microwave irradiation, greenish‐yellow luminescent graphene quantum dots (gGQDs) with a quantum yield (QY) up to 11.7% are successfully prepared via cleaving graphene oxide ...(GO) under acid conditions. The cleaving and reduction processes are accomplished simultaneously using microwave treatment without additional reducing agent. When the gGQDs are further reduced with NaBH4, bright blue luminescent graphene quantum dots (bGQDs) are obtained with a QY as high as 22.9%. Both GQDs show well‐known excitation‐dependent PL behavior, which could be ascribed to the transition from the lowest unoccupied molecular orbital (LUMO) to the highest occupied molecular orbital (HOMO) with a carbene‐like triplet ground state. Electrochemiluminescence (ECL) is observed from the graphene quantum dots for the first time, suggesting promising applications in ECL biosensing and imaging. The ECL mechanism is investigated in detail. Furthermore, a novel sensor for Cd2+ is proposed based on Cd2+ induced ECL quenching with cysteine (Cys) as the masking agent.
Two‐color graphene quantum dots are prepared using a facile microwave‐assisted approach to have fluorescent quantum yields as high as 22.9%. The graphene quantum dots are demonstrated to be electrochemiluminescent. A novel electrochemiluminescence sensor for Cd2+ is proposed based on the competitive coordination between cysteine and graphene quantum dots for metal ions.
During photodynamic therapy (PDT), severe hypoxia often occurs as an undesirable limitation of PDT owing to the O2‐consuming photodynamic process, compromising the effectiveness of PDT. To overcome ...this problem, several strategies aiming to improve tumor oxygenation are developed. Unlike these traditional approaches, an opposite method combining hypoxia‐activated prodrug and PDT may provide a promising strategy for cancer synergistic therapy. In light of this, azido‐/photosensitizer‐terminated UiO‐66 nanoscale metal–organic frameworks (UiO‐66‐H/N3 NMOFs) which serve as nanocarriers for the bioreductive prodrug banoxantrone (AQ4N) are engineered. Owing to the effective shielding of the nanoparticles, the stability of AQ4N is well preserved, highlighting the vital function of the nanocarriers. By virtue of strain‐promoted azide–alkyne cycloaddition, the nanocarriers are further decorated with a dense PEG layer to enhance their dispersion in the physiological environment and improve their therapeutic performance. Both in vitro and in vivo studies reveal that the O2‐depleting PDT process indeed aggravates intracellular/tumor hypoxia that activates the cytotoxicity of AQ4N through a cascade process, consequently achieving PDT‐induced and hypoxia‐activated synergistic therapy. Benefiting from the localized therapeutic effect of PDT and hypoxia‐activated cytotoxicity of AQ4N, this hybrid nanomedicine exhibits enhanced therapeutic efficacy with negligible systemic toxicity, making it a promising candidate for cancer therapy.
Nanoscale metal–organic frameworks‐based nanohybrids capable of protecting prodrugs from degradation are engineered for photodynamic therapy and hypoxia‐triggered cascade chemotherapy. The nanovehicles with good stability, favorable photodynamic therapy (PDT) performance, and on‐demand prodrug release take advantage of the hypoxia generated by PDT to activate cascade chemotherapy, achieving enhanced tumor suppression as well as negligible systemic toxicity.
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.
Here, the electrocatalytic activity of a single graphene sheet is mapped using electrochemiluminescence (ECL) microscopy with a nanometer resolution. The achievement of this high-spatial imaging ...relies on the varied adsorption of hydrogen peroxide at different sites on the graphene surface, leading to unsynchronized ECL emission. By shortening the exposure time to 0.2 ms, scattered ECL spots are observed in the ECL image that are not overlaid with the spots in the consecutive images. Accordingly, after stacking all the images into a graph, the ECL intensity of each pixel could be used to reflect the electrocatalytic features of the graphene surface with a resolution of 400 nm. This novel ECL method efficiently avoids the long-standing problem of classic ECL microscopy regarding the overlap of ECL emissions from adjacent regions and enables the nanometer spatial resolution of ECL microscopy for the first time.
High spatial electrochemiluminescence microscopy is established to map the electrocatalytic activity of a single graphene sheet with a nanometer resolution.
Engineering of efficient and safe materials remains a challenge for cancer therapy. Here, the lipid droplet, an organelle in adipocytes, is demonstrated to be a controllable and biocompatible vehicle ...to deliver anticancer drugs. It is validated that isolated lipid droplets maintain their key physiological functions to interact with other organelles and augment the therapeutic effect of cancer photodynamic therapy by encapsulation with a lipid‐conjugated photosensitizer (Pyrolipid) through a variety of pathways, including generation of reactive oxygen species (ROS); lipid peroxidation; and endoplasmic reticulum (ER) stress. As such, the IC50 value of Pyrolipid is reduced by 6.0‐fold when loaded into the lipid droplet. Of note, in vivo results demonstrate that engineered lipid droplets induce significant inhibition of tumor growth with minimal side effects.
The lipid droplet, an organelle in adipocytes, is engineered to be a controllable, effective, and biocompatible drug delivery system for cancer therapy. It is demonstrated that the lipid droplet can augment the therapeutic performance of an encapsulated drug via several pathways, including generation of reactive oxygen species, lipid peroxidation, and endoplasmic reticulum stress, providing a promising material with clinical translation potential.
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