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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A high‐performance hybrid white organic light‐emitting device (WOLED) is demonstrated based on an efficient novel thermally activated delayed fluorescence (TADF) blue exciplex system. This device ...shows a low turn‐on voltage of 2.5 V and maximum forward‐viewing external quantum efficiency of 25.5%, which opens a new avenue for achieving high‐performance hybrid WOLEDs with simple structures.
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Since bacterial infections seriously threaten human's health, considerable attention is devoted to the design of nanoscale antibacterial materials. Among them, metal nanoparticles cannot meet the ...requirements of durable antibacterial effects and are harmful to biological environments. In this study, environmentally friendly nanogels with durable antibacterial and antiadhesion properties are prepared by copolymerization of styrene, polycaprolactone‐hydroxyethyl methacrylate, and polyhexamethylene guanidine hydrochloride methacrylate. The resultant nanogels possess regular spherical morphologies with the size of about 200 nm. The nanogels exhibit a strong ability to kill bacteria and the mechanism is different from that of conventional antibacterial agent loaded nanoparticles. In addition, anti‐infection experiments explored by a wound model confirm the nanogels have the capability to prevent infection. Furthermore, the nanogels grafted on the surface of cotton fibers display good thermal stability, which is essential for finishing of fabrics. The cotton fabrics finished with nanogels can prevent the adhesion of bacteria by enhancing the hydrophobicity and the bacteriostatic rate. The antibacterial fabrics against Staphylococcus aureus and Escherichia coli are still more than 86% active after 50 times of mechanical washing. The biocompatible nanogels are unleachable from the antibacterial fabrics which demonstrate that they are ideal candidates for durable and environmental‐friendly nanoscaled antimicrobial materials.
In this study, environmentally friendly nanogels with durable antibacterial and antiadhesion properties are prepared by copolymerization of guanidine groups based monomers. The resultant inherent guanidine spherical nanogels can kill bacteria effectively and have the capability to prevent infection. Furthermore, the nanogels grafted on cotton fibers display good thermal stability. The cotton fabrics finished with nanogels can prevent the adhesion of bacteria permanently.
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Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this ...study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hindered by spectral broadening issues with redshifted emission, long‐wavelength (e.g., maxima beyond 570 nm) multiple resonance (MR) emitters with full width at half maxima (FWHMs) below 20 nm ...remain absent. Herein, by strategically embedding diverse boron (B)/nitrogen (N) atomic pairs into a polycyclic aromatic hydrocarbon (PAH) skeleton, we propose a hybrid pattern for the construction of a long‐wavelength narrowband MR emitter. The proof‐of‐concept emitter B4N6‐Me realized orange‐red emission with an extremely small FWHM of 19 nm (energy unit: 70 meV), representing the narrowest FWHM among all reported long‐wavelength MR emitters. Theoretical calculations revealed that the cooperation of the applied para B‐π‐N and para B‐π‐B/N‐π‐N patterns is complementary, which gives rise to both narrowband and redshift characteristics. The corresponding organic light‐emitting diode (OLED) employing B4N6‐Me achieved state‐of‐the‐art performance, e.g., a narrowband orange‐red emission with an FWHM of 27 nm (energy unit: 99 meV), an excellent maximum external quantum efficiency (EQE) of 35.8 %, and ultralow efficiency roll‐off (EQE of 28.4 % at 1000 cd m−2). This work provides new insights into the further molecular design and synthesis of long‐wavelength MR emitters.
A hybrid pattern strategy is proposed, and a proof‐of‐concept multiple resonance emitter containing four boron atoms and six nitrogen atoms, namely, B4N6‐Me, is designed. B4N6‐Me realizes narrowband orange‐red emission with an extremely narrow full width at half maximum of 19 nm (energy unit: 70 meV) and delivers state‐of‐the‐art device performance with a maximum external quantum efficiency of 35.8 %.
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The low electrocatalytic activity of pristine graphite felt (GF) electrodes toward V(II)/V(III) and V(IV)/V(V) redox couples is a major concern in vanadium redox flow batteries (VRFBs). For ...overcoming this challenge, herein a novel composite electrode is proposed comprising of two components: multidimensional frame carbon (MFC) derived from edge‐rich carbon and GF that serves as the frame for the in situ growth of MFC. The high electrocatalytic activity, rapid charge migration, and reduced local current emanating from the 0D, 2D, and 3D coexistent structures of the MFC material, respectively, enhance the performance of the GF. Consequently, the battery assembled using the MFC GF electrode achieves a maximum current density of 500 mA cm−2, along with high stability and preeminent energy efficiency at a current density of 200 mA cm−2 for over 400 cycles. For the first time via density functional theory analysis on VRFBs, this study reveals that the edge‐rich carbon atoms possess higher electrocatalytic activity in both positive and negative electrolytes than the plane carbon atoms and heteroatoms. Therefore, this study is of immense significance in guiding and promoting the application of edge‐rich carbon in the battery‐based energy storage industry.
An edge‐rich multidimensional structure frame carbon originates from the in situ recrystallization and annealling of sodium citrate. With the help of density functional theory, this work reveals that the edge carbon atoms possess higher electrocatalytic activity than the plane carbon atom for V(II)/V(III) and V(IV)/V(V) redox couples in vanadium redox flow batteries.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The problems of soil quality degradation and environmental pollution caused by excessive use of nitrogen fertilizer seriously affect sustainable development of agriculture.
Aims
We ...investigated the effects of reduced nitrogen application with simultaneous full straw return on carbon input, aggregate size distribution, aggregate‐associated organic carbon and total nitrogen (TN), soil organic carbon (SOC) stock, SOC fractions, and crop yield.
Methods
A long‐term field experiment was performed in the dryland region of Guanzhong. The study involved three nitrogen fertilizer (NF) amounts: 337.5 (conventional NF, CNF), 286.4 (15%NF reduction, 15%RNF), and 236.3 (30%NF reduction, 30%RNF) kg N ha–1 y–1 with full straw return.
Results
Compared with CNF, 30%RNF increased the content of soil organic carbon by 5.7% and increased maize yield by 13.1%, under straw return conditions. The 30%RNF + straw application treatment promoted the formation of large macro‐aggregates more effectively than CNF application. The 30%RNF + straw treatment significantly increased SOC by 10.6% and 4.7%, respectively, in large and small macroaggregates relative to conventional NF. Moreover, the 30%RNF + straw treatment resulted in a significant increase in the SOC content in the density fractions of mineral soil organic matter (mSOM) for both small and large macro‐aggregates. This treatment also resulted in a significant increase in the content of TN in the mSOM and density fractions of particulate matter that had coarse and fine intra‐aggregates of the large macro‐aggregates.
Conclusion
Full straw return with reduced nitrogen (N) application could be a promising option to improve the structure of soil aggregates, soil organic carbon, and nitrogen sequestration.
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Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the ...registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.
This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response CR, partial response PR, stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR.
A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%-81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.
Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients.
ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621.
Machine-assisted pathological recognition has been focused on supervised learning (SL) that suffers from a significant annotation bottleneck. We propose a semi-supervised learning (SSL) method based ...on the mean teacher architecture using 13,111 whole slide images of colorectal cancer from 8803 subjects from 13 independent centers. SSL (~3150 labeled, ~40,950 unlabeled; ~6300 labeled, ~37,800 unlabeled patches) performs significantly better than the SL. No significant difference is found between SSL (~6300 labeled, ~37,800 unlabeled) and SL (~44,100 labeled) at patch-level diagnoses (area under the curve (AUC): 0.980 ± 0.014 vs. 0.987 ± 0.008, P value = 0.134) and patient-level diagnoses (AUC: 0.974 ± 0.013 vs. 0.980 ± 0.010, P value = 0.117), which is close to human pathologists (average AUC: 0.969). The evaluation on 15,000 lung and 294,912 lymph node images also confirm SSL can achieve similar performance as that of SL with massive annotations. SSL dramatically reduces the annotations, which has great potential to effectively build expert-level pathological artificial intelligence platforms in practice.
Building blocks and heteroatom alignments are two determining factors in designing multiple resonance (MR)‐type thermally activated delayed fluorescence (TADF) emitters. Carbazole‐fused MR emitters, ...represented by CzBN derivatives, and the heteroatom alignments of ν‐DABNA are two star series of MR‐TADF emitters that show impressive performances from the aspects of building blocks and heteroatom alignments, respectively. Herein, a novel CzBN analog, Π‐CzBN, featuring ν‐DABNA heteroatom alignment is developed via facile one‐shot lithium‐free borylation. Π‐CzBN exhibits superior photophysical properties with a photoluminescence quantum yield close to 100 % and narrowband sky blue emission with a full width at half maximum (FWHM) of 16 nm/85 meV. It also gives efficient TADF properties with a small singlet‐triplet energy offset of 40 meV and a fast reverse intersystem crossing rate of 2.9×105 s−1. The optimized OLED using Π‐CzBN as the emitter achieves an exceptional external quantum efficiency of 39.3 % with a low efficiency roll‐off of 20 % at 1000 cd m−2 and a narrowband emission at 495 nm with FWHM of 21 nm/106 meV, making it one of the best reported devices based on MR emitters with comprehensive performance.
Collocating carbazole building blocks with ν‐DABNA heteroatom alignment, a novel double boron‐embedded multiple resonance emitter Π‐CzBN is obtained and exhibits superior photophysical properties. The corresponding organic light‐emitting diodes based on Π‐CzBN achieve an exceptional efficiency of 39.3 % with a mild roll‐off and a narrow full width at half maximum of 21 nm/106 meV in the bluish‐green region.
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