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.
Although the basic principles of fibrous filters have been well understood for capture of micron and submicron sized particles, questions arise when they are applied to nanoscale particles. In the ...first part of this review, the classical theory of fibrous filters is described with focus on the principles that are applicable to nanoparticle collection. The areas of recent developments reviewed include thermal rebound of nanoparticles and the effects of particle shape, aggregate morphology, flow regime, humidity, fiber size, and particle loading. One of the outstanding questions in nanoparticle collection is the particle size at which the effect of thermal rebound on collection efficiency can be observed. Theoretical calculations indicate that the effect probably can be observed only for particles smaller than 1 nm, but experimental confirmation is difficult at present because of lack of instruments for classifying and counting subnanoscale particles. Two promising devices based on filtration principles have been studied in recent years: multilayer filters and inertial fibrous filters. Multilayer filters, which are composed of nanofiber and microfiber mats, have potential to become an efficient and economical device for removing nanoparticles from gas streams. The inertial fibrous filter operates at high flow rates and relatively low pressure drop, thereby offering an attractive alternative to low-pressure impactors for nanoparticle sampling. Further development of these two types of filtration devices is needed to make them simple and reliable.
•Supercritical carbon dioxide Brayton/organic flash cycle is proposed and analyzed.•Exergoeconomic analysis and optimization are conducted.•Supercritical carbon dioxide Brayton/organic flash cycle ...enhances the system performances.•Several organic flash cycle working fluids are investigated.
A novel combined supercritical carbon dioxide recompression Brayton/organic flash cycle is investigated by means of exergoeconomic analysis. The supercritical carbon dioxide recompression Brayton/organic flash cycle is a combination of a supercritical carbon dioxide recompression Brayton cycle and an organic flash cycle where the organic flash cycle absorbs waste heat from the supercritical carbon dioxide recompression Brayton cycle for power generation. Seven different organic flash cycle working fluids are examined, including n-Nonane, n-Octane, n-Heptane, n-Hexane, n-Pentane, R365mfc and R245fa. Parametric study is employed to investigate the effects of the some decision variables on the first and second law efficiencies and the total product unit cost of the supercritical carbon dioxide recompression Brayton/organic flash cycle and the supercritical carbon dioxide recompression Brayton cycle. The performances of the supercritical carbon dioxide recompression Brayton/organic flash cycle and the supercritical carbon dioxide recompression Brayton cycle are optimized and then compared from the perspective of thermodynamics and exergoeconomics. The results show that the second law efficiency and the total product unit cost of the supercritical carbon dioxide recompression Brayton/organic flash cycle are up to 6.57% higher and up to 3.75% lower than those of the supercritical carbon dioxide recompression Brayton cycle, respectively. Compared with the supercritical carbon dioxide recompression Brayton/organic Rankine cycle, the supercritical carbon dioxide recompression Brayton/organic flash cycle can obtain slightly higher second law efficiency, and comparable or slightly lower total product unit cost. It can also be concluded that the highest second law efficiency and the lowest total product unit cost for the supercritical carbon dioxide recompression Brayton/organic flash cycle are achieved when the n-Nonane is used as the organic flash cycle working fluid.
As the conversion of methanol to olefins (MTO) over a zeolite catalyst is conducted on acid sites derived from framework aluminum (AlF), it is possible to enhance the catalytic performance by ...altering the siting of AlF if one knows the catalytic behavior of specified AlF located at certain sites. In this work, two series of H-ZSM-5 zeolites, viz., S-HZ-m and T-HZ-m, were synthesized with silica sol and tetraethyl orthosilicate, respectively, as the silicon source. Both series of H-ZSM-5 zeolites exhibit similar acidity, morphology, and textual properties. However, they are quite different with respect to AlF siting, as determined by UV–vis–DRS of Co(II) ions and 27Al MAS NMR; AlF of S-HZ-m is enriched in the sinusoidal and straight channels, whereas AlF of T-HZ-m is concentrated in the channel intersections. When they are used as the catalyst in MTO, T-HZ-m gives higher selectivity to ethene and aromatics and a larger hydrogen transfer index (HTI) than S-HZ-m, whereas S-HZ-m exhibits higher selectivity to propene and higher olefins. Moreover, the 13C/12C-methanol-switching experiments indicate that the incorporation of 12C into pentamethylbenzene and hexamethylbenzene is faster on T-HZ-m, whereas the scramble of 12C for C3–C5 olefins is speedier on S-HZ-m. All of these illustrate that AlF in the channel intersections of H-ZSM-5 is probably more favorable to the propagation of the aromatic-based cycle, whereas AlF in the sinusoidal and straight channels is more encouraging for the alkene-based cycle. These results help to clarify the catalytic behavior of given framework acid sites of H-ZSM-5 in MTO and then bring forward an effective approach to improving the catalytic performance by regulating the framework aluminum siting.
Poly(1,2‐dithiolane)s are a family of intrinsically recyclable polymers due to their dynamic covalent disulfide linkages. Despite the common use of thiolate‐initiated anionic ring‐opening ...polymerization (ROP) under basic condition, cationic ROP is still not exploited. Here we report that disulfide bond can act as a proton acceptor, being protonated by acids to form sulfonium cations, which can efficiently initiate the ROP of 1,2‐dithiolanes and result in high‐molecular‐weight (over 1000 kDa) poly(disulfide)s. The reaction can be triggered by adding catalytic amounts of acids and non‐coordinating anion salts, and completed in few minutes at room temperature. The acidic conditions allow the applicability for acidic monomers. Importantly, the reaction condition can be under open air without inert protection, enabling the nearly quantitative chemical recycling from bulk materials to original monomers.
Acid can catalyze the reversible polymerization of cyclic disulfides, enabling a robust methodology that produces long poly(disulfide)s within a few minutes under open‐air condition. High‐yield chemical recycling from materials to monomers is achieved at gram scale, showing the capability of intrinsic dynamic polymers toward sustainable materials.
As post-lithium ion batteries, both sodium ion batteries (SIBs) and potassium ion batteries (PIBs) possess great potential for large scale energy storage. However, the improvements of both SIBs and ...PIBs for practical applications are facing great challenges in the development of high-performance electrode materials. Here, we demonstrate the fabrication of alkalized Ti3C2 (a-Ti3C2) MXene nanoribbons attained by continuous shaking treatment of pristine Ti3C2 MXene in aqueous KOH solution. Benefited from the expanded interlayer spacing of a-Ti3C2, narrow widths of nanoribbons as well as three-dimensional interconnected porous frameworks for enhanced ion reaction kinetics and improved structure stability, the resulting a-Ti3C2 anodes showed excellent sodium/potassium storage performance, for example, high reversible capacities of 168 and 136mAhg−1 at 20mAg−1 and 84 and 78mAhg−1 at 200mAg−1 were obtained for SIBs and PIBs, respectively. Notably, a-Ti3C2 possessed outstanding long-term cyclability at high current density of 200mAg−1, delivering a capacity of ~ 50mAhg−1 for SIBs and ~ 42mAhg−1 for PIBs after 500 cycles, which outperformed most of reported MXene based anodes for SIBs and PIBs. Moreover, this alkalization strategy could be extended as a universal approach for fabricating various alkalized MXene-based frameworks derived from a large family of MAX phases for numerous applications, such as catalysis, energy storage and conversion.
Alkalized Ti3C2 (a-Ti3C2) MXene nanoribbons were successfully synthesized by shaking treatment of Ti3C2 in KOH solution. Benefited from the expanded interlayer spacing, narrow widths of nanoribbons as well as 3D interconnected porous frameworks for enhanced ion reaction kinetics and improved structure stability, the resulting a-Ti3C2 anodes showed excellent sodium/potassium storage performance. Display omitted
•Alkalized Ti3C2 MXene nanoribbons (a-Ti3C2) with expanded interlayer spacing is synthesized by shaking treatment of Ti3C2 MXene in KOH solution.•a-Ti3C2 shows narrow widths of nanoribbons (6–22nm) as well as 3D interconnected porous frameworks.•a-Ti3C2 displays high capacities and superior cycling stability over 500 cycles for sodium/ potassium storage.
Nanometer‐sized hydroxide active centers are uniformly and strongly hybridized into a graphene framework by means of defect‐anchored nucleation and spatially confined growth, resulting in a superior ...electrocatalyst for oxygen evolution reaction. This family of strongly coupled complexes and the topology‐assisted fabrication strategy is expected to open up new avenues of research. It sheds light on a novel branch of advanced nano‐architectured materials.
Intrahepatic cholangiocarcinoma (ICC) is the second most common liver malignancy. ICC typically features remarkable cellular heterogeneity and a dense stromal reaction. Therefore, a comprehensive ...understanding of cellular diversity and the interplay between malignant cells and niche cells is essential to elucidate the mechanisms driving ICC progression and to develop therapeutic approaches.
Herein, we performed single-cell RNA sequencing (scRNA-seq) analysis on unselected viable cells from 8 human ICCs and adjacent samples to elucidate the comprehensive transcriptomic landscape and intercellular communication network. Additionally, we applied a negative selection strategy to enrich fibroblast populations in 2 other ICC samples to investigate fibroblast diversity. The results of the analyses were validated using multiplex immunofluorescence staining, bulk transcriptomic datasets, and functional in vitro and in vivo experiments.
We sequenced a total of 56,871 single cells derived from human ICC and adjacent tissues and identified diverse tumor, immune, and stromal cells. Malignant cells displayed a high degree of inter-tumor heterogeneity. Moreover, tumor-infiltrating CD4 regulatory T cells exhibited highly immunosuppressive characteristics. We identified 6 distinct fibroblast subsets, of which the majority were CD146-positive vascular cancer-associated fibroblasts (vCAFs), with highly expressed microvasculature signatures and high levels of interleukin (IL)-6. Functional assays indicated that IL-6 secreted by vCAFs induced significant epigenetic alterations in ICC cells, particularly upregulating enhancer of zeste homolog 2 (EZH2) and thereby enhancing malignancy. Furthermore, ICC cell-derived exosomal miR-9-5p elicited high expression of IL-6 in vCAFs to promote tumor progression.
Our single-cell transcriptomic dataset delineates the inter-tumor heterogeneity of human ICCs, underlining the importance of intercellular crosstalk between ICC cells and vCAFs, and revealing potential therapeutic targets.
Intrahepatic cholangiocarcinoma is an aggressive and chemoresistant malignancy. Better understanding the complex transcriptional architecture and intercellular crosstalk of these tumors will help in the development of more effective therapies. Herein, we have identified important interactions between cancer cells and cancer-associated fibroblasts in the tumor stroma, which could have therapeutic implications.
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•Single cell transcriptomic datasets are a valuable resource to dissect cellular diversity and intercellular crosstalk of human ICCs.•Malignant cells displayed remarkable inter-tumor heterogeneity and Tregs revealed highly immunosuppressive characteristics.•Six distinct fibroblast subsets were defined in ICCs and adjacent tissues.•CD146+ vCAFs, comprising most of the fibroblasts, had tight interactions with malignant cells through IL-6/IL-6R axis.•Tumor exosomal miR-9-5p elicited IL-6 expression in vCAFs, contributing to ICC progression via upregulation of EZH2.
Cisplatin (CDDP) treatment is one of the most predominant chemotherapeutic strategies for patients with gastric cancer (GC). A better understanding of the mechanisms of CDDP resistance can greatly ...improve therapeutic efficacy in patients with GC. Circular RNAs (circRNAs) are a class of noncoding RNAs whose functions are related to the pathogenesis of cancer, but, in CDDP resistance of GC remains unknown.
circAKT3 (hsa_circ_0000199, a circRNA originating from exons 8, 9, 10, and 11 of the AKT3 gene) was identified by RNA sequencing and verified by quantitative reverse transcription PCR. The role of circAKT3 in CDDP resistance in GC was assessed both in vitro and in vivo. Luciferase reporter assay, biotin-coupled RNA pull-down and fluorescence in situ hybridization (FISH) were conducted to evaluate the interaction between circAKT3 and miR-198. Functional experiments were measured by western blotting, a cytotoxicity assay, clonogenic assay and flow cytometry.
The expression of circAKT3 was higher in CDDP-resistant GC tissues and cells than in CDDP-sensitive samples. The upregulation of circAKT3 in GC patients receiving CDDP therapy was significantly associated with aggressive characteristics and was an independent risk factor for disease-free survival (DFS). Our data indicated that circAKT3 promotes DNA damage repair and inhibits the apoptosis of GC cells in vivo and in vitro. Mechanistically, we verified that circAKT3 could promote PIK3R1 expression by sponging miR-198.
circAKT3 plays an important role in the resistance of GC to CDDP. Thus, our results highlight the potential of circAKT3 as a therapeutic target for GC patients receiving CDDP therapy.
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