Alternative polyadenylation (APA), which induces shortening of the 3′‐UTR, is emerging as an important feature in cancer development and progression. Nevertheless, the effects and mechanisms of ...APA‐induced 3′‐UTR shortening in nasopharyngeal carcinoma (NPC) remain largely unclear. Fibronectin type III domain containing 3B (FNDC3B) tended to use proximal polyadenylation site and produce shorter 3′‐UTR according to our previous sequencing study. Herein, we found that FNDC3B with shorter 3′‐UTR could escape from miRNA‐mediated gene repression, and caused its increased expression in NPC. Knocking down of FNDC3B inhibited NPC cell proliferation, migration, invasion, and metastasis in vitro and in vivo. Overexpression of FNDC3B, especially those with shorter 3′‐UTR, promoted NPC progression. Furthermore, the mechanism study revealed that FNDC3B could bind to and stabilize myosin heavy chain 9 (MYH9) to activate the Wnt/β‐catenin signaling pathway. In addition, MYH9 could reverse the inhibitory effects of FNDC3B knockdown in NPC. Altogether, our results suggested that the 3′‐UTR shortening of FNDC3B mRNA mediated its overexpression in NPC and promoted NPC progression by targeting MYH9. This newly identified FNDC3B‐MYH9‐Wnt/β‐catenin axis could represent potential targets for individualized treatment in NPC.
FNDC3B tended to use proximal polyadenylation site and produced shorter 3′‐UTR. FNDC3B with shorter 3′‐UTR could escape from microRNA‐mediated gene repression, and caused its increased expression in nasopharyngeal carcinoma (NPC) and promoted NPC progression by targeting MYH9.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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
Developing red thermally activated delayed fluorescence (TADF) emitters, attainable for both high‐efficient red organic light‐emitting diodes (OLEDs) and non‐doped deep red/near‐infrared (NIR) OLEDs, ...is challenging. Now, two red emitters, BPPZ‐PXZ and mDPBPZ‐PXZ, with twisted donor–acceptor structures were designed and synthesized to study molecular design strategies of high‐efficiency red TADF emitters. BPPZ‐PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED. Its non‐doped OLED has an EQE of 2.5 % owing to unavoidable intermolecular π–π interactions. mDPBPZ‐PXZ releases two pyridine substituents from its fused acceptor moiety. Although mDPBPZ‐PXZ realizes a lower EQE of 21.7 % in the doped OLED, its non‐doped device shows a superior EQE of 5.2 % with a deep red/NIR emission at peak of 680 nm.
Two red emitters, BPPZ‐PXZ and mDPBPZ‐PXZ, with twisted donor–acceptor structures were designed and synthesized to study molecular design strategies of high‐efficiency red TADF emitters. BPPZ‐PXZ employs the strictest molecular restrictions to suppress energy loss and realizes red emission with a photoluminescence quantum yield (ΦPL) of 100±0.8 % and external quantum efficiency (EQE) of 25.2 % in a doped OLED.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Recently, more than 300 Chinese patients with psychiatric disorders were diagnosed with the 2019 novel coronavirus disease (COVID-19). Possible reasons quoted in the report were the lack of caution ...regarding the COVID-19 outbreak in January and insufficient supplies of protective gear. We outlined major challenges for patients with psychiatric disorders and mental health professionals during the COVID-19 outbreak, and also discussed how to manage these challenges through further mental health service reform in China.
The photocatalytic reduction of N2 to NH3 is considered a promising strategy to alleviate human need for accessible nitrogen and environmental pollution, for which developing a photocatalyst is an ...effective method to complete the transformation of this process. We firstly design a series of highly efficient and stable polyoxometalates (POMs)‐based zeolitic imidazolate framework‐67 (ZIF‐67) photocatalysts for N2 reduction. ZIF‐67 can effectively fix N2 owing to its porosity. Integration of POMs cluster contributes enormous advantages in terms of broadening the absorption spectrum to improve sunlight utilization, enhance the stability of the materials, effectively inhibit the recombination of photo‐generated electron–hole pairs, and reduce charge‐transfer impedance. POMs can absorb light to convert into reduced POMs, which have stronger reducing ability to provide ample electrons to reduce N2. The reduced POMs can recover their oxidation state through contact with an oxidant, which forms a self‐recoverable and recyclable photocatalytic fixing N2 system. The photocatalytic activity enhances with the increasing number V substitutions in the POMs. Satisfactorily, ZIF‐67@K11PMo4V8O40 (PMo4V8) displays the most significant photocatalytic N2 activity with a NH3 yield of 149.0 μmol L−1 h−1, which is improved by 83.5 % (ZIF‐67) and 78.9 % (PMo4V8). The introduction of POMs provides new insights for the design of high‐performance photocatalyst nanomaterials to reduce N2.
New applications of old inorganic oxygen clusters: Five kinds of V‐substituted Keggin‐type polyoxometalates (POMs) and ZIF‐67 composite nanomaterials exhibit outstanding photocatalytic fixed‐N2 activities at room temperature and atmospheric pressure using illumination as the sole source of energy for the first time. The presence of both POMs and ZIF‐67 in the catalyst promote a synergistic effect, yielding a self‐healing, recyclable N2‐fixing catalytic system.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Early detection and accurate monitoring of chronic kidney disease (CKD) could improve care and retard progression to end-stage renal disease. Here, using untargeted metabolomics in 2155 participants ...including patients with stage 1-5 CKD and healthy controls, we identify five metabolites, including 5-methoxytryptophan (5-MTP), whose levels strongly correlate with clinical markers of kidney disease. 5-MTP levels decrease with progression of CKD, and in mouse kidneys after unilateral ureteral obstruction (UUO). Treatment with 5-MTP ameliorates renal interstitial fibrosis, inhibits IκB/NF-κB signaling, and enhances Keap1/Nrf2 signaling in mice with UUO or ischemia/reperfusion injury, as well as in cultured human kidney cells. Overexpression of tryptophan hydroxylase-1 (TPH-1), an enzyme involved in 5-MTP synthesis, reduces renal injury by attenuating renal inflammation and fibrosis, whereas TPH-1 deficiency exacerbates renal injury and fibrosis by activating NF-κB and inhibiting Nrf2 pathways. Together, our results suggest that TPH-1 may serve as a target in the treatment of CKD.
High‐efficiency, thermally activated delayed‐fluorescence organic light‐emitting diodes based on exciplex emitters are demonstrated. The best device, based on a TAPC:DPTPCz emitter, shows a high ...external quantum efficiency of 15.4%. Strategies for predicting and designing efficient exciplex emitters are also provided. This approach allow prediction and design of efficient exciplex emitters for achieving high‐efficiency organic light‐emitting diodes, for future use in displays and lighting applications.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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