Tumor hypoxia, the “Achilles’ heel” of current cancer therapies, is indispensable to drug resistance and poor therapeutic outcomes especially for radiotherapy. Here we propose an in situ catalytic ...oxygenation strategy in tumor using porphyrinic metal‐organic framework (MOF)‐gold nanoparticles (AuNPs) nanohybrid as a therapeutic platform to achieve O2‐evolving chemoradiotherapy. The AuNPs decorated on the surface of MOF effectively stabilize the nanocomposite and serve as radiosensitizers, whereas the MOF scaffold acts as a container to encapsulate chemotherapeutic drug doxorubicin. In vitro and in vivo studies verify that the catalase‐like nanohybrid significantly enhances the radiotherapy effect, alleviating tumor hypoxia and achieving synergistic anticancer efficacy. This hybrid nanomaterial remarkably suppresses the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theranostic nanomedicines.
A catalase‐like nanohybrid based on AuNPs/gold(III) porphyrinic metal‐organic frameworks is fabricated for O2 self‐supported chemoradiotherapy. Such an all‐in‐one nanohybrid holds advantages of modulating tumor hypoxia, amplifying radiation effect, regulating drug release and combining chemotherapy with radiotherapy, which will be a paradigm in O2‐elevated radiochemotherapy that offers a novel strategy in multimodal cancer therapy.
Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short‐chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies ...mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs‐mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.
Short‐chain fatty acids (SCFAs) produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch that escape absorption in the small intestine, and serve as a major source of energy for colonocytes. SCFAs are microbial‐derived metabolites, which are readily absorbed and used as an energy source by colonocytes. Several mechanisms have been proposed to underlie the anticancerous mechanisms of SCFAs. SCFAs reduce epithelial inflammation and trigger cancer cell apoptosis via p21 activity, providing an important defensive capacity against colorectal carcinogenesis.
Recent researches of the novel 4
D
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
D
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
D
charged EGB black hole can be destroyed. To second order, however, both extremal and near-extremal 4
D
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.
Room temperature phosphorescence (RTP) materials with long persistent luminescence (LPL) have raised particular attention among researchers for their potential uses in chemical sensing, optical ...recording devices, biological imaging, and security systems applications, due to the long‐lived triplet states. In this study, one‐pot method of reaction of appropriate ratio of crown ether ligand (15‐Crown‐5) and metallic salts (CdX2) is utilized to yield three metal halide‐based complexes (namely 15‐5‐CdCl2, 15‐5‐CdBr2, and 15‐5‐CdI2). In solid state, three complexes exhibit nearly standard white light emission with CIE coordinates of (0.28, 0.32), (0.31, 0.39), (0.30, 0.34) at room temperature under UV radiation of 340 nm. Meanwhile, they display the excitation‐dependent room temperature phosphorescence from blue/cyan to green/yellow, especially, 15‐5‐CdCl2 and 15‐5‐CdBr2 exhibit color‐tunable and visible LPL with time‐resolved luminescence lifetime as high as 1–2 s. Single‐crystal X‐ray diffraction analysis and theoretical calculations reveal that the bright LPL of 15‐5‐CdCl2 and 15‐5‐CdBr2 arise from the crown ether ligand and aggregation state induced by halogen‐bond. The thus obtained LPL provides potentials in lighting and displaying devices, optical recording devices, security systems and so on.
A macrocyclic molecule 15‐crown‐5 with CdX2 was hydrothermally constructed into metal‐organic linker, which was built into 2D metal‐organic frameworks with metal halide chains that play an external heavy atom effect to achieve long persistent luminescence at room temperature. Near white light emission is achieved in a single component, moreover adjustable phosphorescence is realized with longest visual time of 1‐2 s at ambient conditions.
Abstract
The dispersion measure (DM)–redshift relation of fast radio bursts (FRBs) has been proposed as a potential new tool for probing the intergalactic medium (IGM) and for studying cosmology. ...However, poor knowledge of the baryon fraction in the IGM (
f
IGM
) and its degeneracy with cosmological parameters impose restrictions on the cosmological applications of FRBs. Furthermore, DMs contributed by the IGM (DM
IGM
) and host galaxy (DM
host
), important cosmological quantities, cannot be exactly extracted from observations, which would bring uncontrolled systematic uncertainties in FRB cosmology. In this work, we use 17 localized FRBs to constrain
f
IGM
and its possible redshift evolution. Other cosmological probes such as type Ia supernovae, baryon acoustic oscillations, and cosmic microwave background radiation are combined to break parameter degeneracy. Taking into account the probability distributions of DM
IGM
and DM
host
derived from the IllustrisTNG simulation, we obtain a robust measurement of
f
IGM
= 0.927 ± 0.075, representing a precision of 8.0%. We find that there is no strong evidence for the redshift dependence of
f
IGM
at the current observational data level. The rapid progress in localizing FRBs will significantly improve the constraints on
f
IGM
.
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.
Recent advances in the fabrication of complex particles and particle‐based materials assisted by droplet‐based microfluidics are reviewed. Monodisperse particles with expected internal structures, ...morphologies, and sizes in the range of nanometers to hundreds of micrometers have received a good deal of attention in recent years. Due to the capability of generating monodisperse emulsions and of executing precise control and operations on the suspended droplets inside the microchannels, droplet‐based microfluidic devices have become powerful tools for fabricating complex particles with desired properties. Emulsions and multiple‐emulsions generated in the microfluidic devices can be composed of a variety of materials including aqueous solutions, gels, polymers and solutions containing functional nanoparticles. They are ideal microreactors or fine templates for synthesizing advanced particles, such as polymer particles, microcapsules, nanocrystals, and photonic crystal clusters or beads by further chemical or physical operations. These particles are promising materials that may be applicable for many fields, such as photonic materials, drug delivery systems, and bio‐analysis. From simple to complex, from spherical to nonspherical, from polymerization and reaction crystallization to self‐assembly, this review aims to help readers be aware of the many aspects of this field.
Droplet‐based microfluidic devices are powerful tools to generate emulsions and multiple‐emusions, which are fine templates for fabricating advanced particles and particle‐based materials. For instance, by further chemical or physical operations, multiple‐emulsions can be used to synthesize microcapsules that can be applied for drug delivery systems. By evaporating the solvent, photonic crystals can be fabricated through the self‐assembly of the colloidal particles suspended in the emulsion droplets.
Organic heterostructures (OHSs) integrating the intrinsic heterostructure characters as well as the organic semiconductor properties have attracted intensive attention in material chemistry. However, ...the precise bottom-up synthesis of OHSs is still challenging owing to the general occurrence of homogeneous-nucleation and the difficult manipulation of noncovalent interactions. Herein, we present the rational synthesis of the longitudinally/horizontally-epitaxial growth of one-dimensional OHSs including triblock and core/shell nanowires with quantitatively-manipulated microstructure via a hierarchical self-assembly method by regulating the noncovalent interactions: hydrogen bond (-15.66 kcal mol
) > halogen bond (-4.90 kcal mol
) > π-π interaction (-0.09 kcal mol
). In the facet-selective epitaxial growth strategy, the lattice-matching and the surface-interface energy balance respectively facilitate the realization of triblock and core/shell heterostructures. This hierarchical self-assembly approach opens up avenues to the fine synthesis of OHSs. We foresee application possibilities in integrated optoelectronics, such as the nanoscale multiple input/out optical logic gate with high-fidelity signal.
Perovskite photovoltaics are strong potential candidates to drive low‐power off‐grid electronics for indoor applications. Compared with rigid devices, flexible perovskite devices can provide a more ...suitable surface for indoor small electronic devices, enabling them have a broader indoor application prospect. However, the mechanical stability of flexible perovskite photovoltaics is an urgent issue solved. Herein, a kind of 3D crosslinking agent named borax is selected to carry out grain boundary penetration treatment on perovskite film to realize full‐dimensional stress release. This strategy improves the mechanical and phase stabilities of perovskite films subjected to external forces or large temperature changes. The fabricated perovskite photovoltaics deliver a champion power conversion efficiency (PCE) of 21.63% under AM 1.5G illumination, which is the highest one to date. The merit of low trap states under weak light makes the devices present a superior indoor PCE of 31.85% under 1062 lux (LED, 2956 K), which is currently the best flexible perovskite indoor photovoltaic device. This work provides a full‐dimensional grain boundary stress release strategy for highly stable flexible perovskite indoor photovoltaics.
A grain boundary stress release strategy is proposed for high‐stability flexible perovskite indoor photovoltaics by the grain boundary penetration with borax 3D stretchable molecules. The full‐dimensional grain boundary stress release enables the flexible perovskite photovoltaics deliver a champion power conversion efficiency (PCE) of 21.63% under AM 1.5G illumination and an indoor PCE of 31.85% under 1062 lux.
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