There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as ...a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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•Development of LNP-encapsulated mRNA vaccine (ARCoV) targeting the RBD of SARS-CoV-2•ARCoV induces neutralizing antibodies and T cell immunity in mice and NHPs•ARCoV vaccination confers full protection against SARS-CoV-2 challenge in mice•ARCoV is a thermostable vaccine candidate for phase I studies
ARCoV is an LNP-encapsulated mRNA vaccine platform that is highly immunogenic and safe in mice and non-human primates, conferring protection against challenge with a SARS-CoV-2 mouse-adapted strain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Superlattices have considerable potential as sonosensitizers for cancer therapy because of their flexible and tunable band gaps, although they have not yet been reported. In this study, a Ti‐based ...organic–inorganic superlattice with good electron–hole separation was synthesized, which consisted of orderly layered superlattices of 2,2′‐bipyridine‐5,5′‐dicarboxylic acid (BPDC) and Ti−O layers. In addition, the superlattice was coordinated with Fe(III) and encapsulated doxorubicin (DOX) to prepare Ti‐BPDC@Fe@DOX@PEG (TFDP) after biocompatibility modification. TFDP can realize the simultaneous generation of reactive oxygen species and release of DOX under ultrasound irradiation. Moreover, adjusting the Fe(III) content can effectively modulate the band gap of the superlattice and increase the efficiency of sonodynamic therapy (SDT). The mechanisms underlying this modulation were explored. TFDP with Fe(III) can also be used as a contrast agent for magnetic resonance imaging (MRI). Both in vitro and in vivo experiments demonstrated the ability of TFDP to precisely treat cancer using MRI‐guided SDT/chemotherapy. This study expands the applications of superlattices as sonosensitizers with flexible and tailored modifications and indicates that superlattices are promising for precise and customized treatments.
In this study, we developed a sonosensitizer by using superlattices for sonodynamic therapy (SDT) with sonication‐triggered drug release. Introducing Fe(III) through coordinated interactions and changing the Fe(III) content can efficiently enhance and modulate the band gap and improve the outcomes of SDT. Benefiting from the use of Fe(III) as a contrast agent, magnetic resonance imaging‐guided and synergistic therapy can be realized.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary
The filamentous fungus Beauveria bassiana, an insect fungal pathogen, is widely used for pest biocontrol. Aerial conidia are infectious propagules, and their yield and viability greatly ...affect the field application of this fungus; however, little is known about the molecular regulatory mechanism of the triggered conidiation. In the present study, we find that the secondary metabolite regulator BbSmr1 is involved in the regulation of asexual conidiation development and stress response in B. bassiana. A deficiency in Bbsmr1 results in a prominent fluffy‐like phenotype on solid medium, decreased conidial yield, accelerated conidial germination, as well as increased tolerance to H2O2 stress and cell wall inhibitors. The deletion of Bbsmr1 also leads to thickened conidial cell walls and changed cell epitopes. Overexpressing either BbbrlA or BbabaA in the ∆Bbsmr1 strain can rescue the phenotypes of conidial development and stress response. BbSmr1 activates BbbrlA transcription by directly binding to the A4GA3 sequence of the BbbrlA promoter. BbBrlA in turn binds to the promoter of Bbsmr1 and negatively regulates the expression of Bbsmr1. These results indicate that BbSmr1 positively regulates conidial development in B. bassiana by activating the central development pathway BrlA‐AbaA‐WetA and provides insights into the developmental regulatory mechanism of entomopathogenic fungi.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The electrochemical transformation of biomass to high value‐added products is attractive. Herein, Cu sulfide‐mediated in‐situ synthesis of Cu oxide was achieved for efficient electro‐oxidation of ...biomass derived 5‐hydroxymethylfurfural (HMF) to 2,5‐furandicarboxylic acid (FDCA). The copper foam‐supported Cu sulfide (Cu−S/CF) was in‐situ converted to Cu oxide during the electro‐oxidation process. The in‐situ formed Cu oxide presented high HMF conversion, FDCA yield, and faradaic efficiency in 1 m KOH with HMF concentration up to 100 mm. The oxidation of HMF on Cu oxide started with the formation of high‐valence Cu species with the assistance of OH−, which then oxidized HMF spontaneously. An anion exchange membrane (AEM) electrolyzer with Cu−S/CF as the anode was assembled to continuously produce FDCA with H2 generation at the cathode. The AEM electrolyzer ran stably for 60 h with FDCA content higher than 85 % at a cell voltage between 1.50 and 1.60 V.
Biomass electrochemical oxidation: Copper foam‐supported Cu sulfide (Cu−S/CF) is in‐situ converted to Cu oxide during electrochemical oxidation of 5‐hydroxymethylfurfural. The anion exchange membrane electrolyzer with Cu−S/CF as the anode can work stably for at least 60 h, and the 2,5‐furandicarboxylic acid content in the product can be higher than 90 %.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
We aim to familiarize the application status of metagenomic sequencing in diagnosing pulmonary infections, to compare metagenomic sequencing with traditional diagnostic methods, to conclude ...the advantages and limitations of metagenomic sequencing, and to provide some advice for clinical practice and some inspiration for associated researches.
Data Sources
The data were obtained from peer‐reviewed literature, white papers, and meeting reports.
Results
This review focused on the applications of untargeted metagenomic sequencing in lungs infected by bacteria, viruses, fungi, chlamydia pneumoniae, Mycoplasma pneumoniae, parasites, and other pathogens. Compared with conventional diagnostic methods, metagenomic sequencing is better in detecting novel, rare, and unexpected pathogens and being applied in co‐infections. Meanwhile, it can also provide more comprehensive information about pathogens. However, metagenomic sequencing still has limitations. Also, the situations that should be applied in and how the results should be interpreted are discussed in this review.
Conclusion
Metagenomic sequencing improves efficiency to identify pathogens compared with traditional diagnostic methods and can be applied in clinical diagnosis. However, the technology of metagenomic sequencing still needs to be improved. Also, clinicians should learn more about when to use metagenomic sequencing and how to interpret its results.
Compared with conventional diagnostic methods, metagenomic sequencing is more sensitive and better in detecting novel, rare, and unexpected pathogens. Meanwhile, it can provide more comprehensive information about pathogens. However, many challenges exist when using metagenomic sequencing. By Figdraw (www.figdraw.com).
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Enantioselective hydroarylation of unactivated terminal akenes constitutes a prominent challenge in organic chemistry. Herein, we reported a Cp*Co(III)-catalyzed asymmetric hydroarylation of ...unactivated aliphatic terminal alkenes assisted by a new type of tailor-made amino acid ligands. Critical to the chiral induction was the engaging of a novel noncovalent interaction (NCI), which has seldomly been disclosed in the C–H activation area, arising from the molecular recognition among the organocobalt(III) intermediate, the coordinated alkene, and the well-designed chiral ligand. A broad range of C2-alkylated indoles were obtained in high yields and excellent enantioselectivities. DFT calculations revealed the reaction mechanism and elucidated the origins of chiral induction in the stereodetermining alkene insertion step.
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IJS, KILJ, NUK, PNG, UL, UM
This study evaluated the effects of pretransplantation minimal residual disease (pre‐MRD) on outcomes of patients with acute lymphoblastic leukemia (ALL) who underwent unmanipulated haploidentical ...stem cell transplantation (haplo‐SCT). A retrospective study including 543 patients with ALL was performed. MRD was determined using multiparametric flow cytometry. Both in the entire cohort of patients and in subgroup cases with T‐ALL or B‐ALL, patients with positive pre‐MRD had a higher incidence of relapse (CIR) than those with negative pre‐MRD in MSDT settings (P < 0.01 for all). Landmark analysis at 6 months showed that MRD positivity was significantly and independently associated with inferior rates of relapse (HR, 1.908; P = 0.007), leukemia‐free survival (LFS) (HR, 1.559; P = 0.038), and OS (HR, 1.545; P = 0.049). The levels of pre‐MRD according to a logarithmic scale were also associated with leukemia relapse, LFS, and OS, except that cases with MRD <0.01% experienced comparable CIR and LFS to those with negative pre‐MRD. A risk score for CIR was developed using the variables pre‐MRD, disease status, and immunophenotype of ALL. The CIR was 14%, 26%, and 59% for subjects with scores of 0, 1, and 2‐3, respectively (P < 0.001). Three‐year LFS was 75%, 64%, and 42%, respectively (P < 0.001). Multivariate analysis confirmed the association of the risk score with CIR and LFS. The results indicate that positive pre‐MRD, except for low level one (MRD < 0.01%), is associated with poor outcomes in patients with ALL who underwent unmanipulated haplo‐SCT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Claudin-7 knockout (CLDN7
) mice display renal salt wasting and dehydration phenotypes. To address the role of CLDN7 in kidneys, we established collecting duct (CD) cell lines from CLDN7
and CLDN7
...mouse kidneys. We found that deletion of CLDN7 increased the transepithelial resistance (TER) and decreased the paracellular permeability for Cl
and Na
in CLDN7
CD cells. Inhibition of transcellular Cl
and Na
channels has no significant effect on TER or dilution potentials. Current-voltage curves were linear in both CLDN7
and CLDN7
CD cells, indicating that the ion flux was through the paracellular pathway. The impairment of Cl
and Na
permeability phenotype can be rescued by CLDN7 re-expression. We also found that WNK4 (its mutations lead to hypertension) expression, but not WNK1, was significantly increased in CLDN7
CD cell lines as well as in primary CLDN7
CD cells, suggesting that the expression of WNK4 was modulated by CLDN7. In addition, deletion of CLDN7 upregulated the expression level of the apical epithelial sodium channel (ENaC), indicating a potential cross-talk between paracellular and transcellular transport systems. This study demonstrates that CLDN7 plays an important role in salt balance in renal CD cells and modulating WNK4 and ENaC expression levels that are vital in controlling salt-sensitive hypertension.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A novel Lewis base-catalyzed 4 + 3 annulation process for the construction of benzoboxepine scaffolds has been developed. 1,4-Diazabicyclo2.2.2octane (DABCO) promotes the union of o-QMs and ...Morita–Baylis–Hillman carbonates in reasonable to excellent yields and good stereoselectivities (dr > 20:1). This straightforward, catalytic approach offers access to a variety of synthetically useful benzoboxepine derivatives bearing oxindole scaffolds containing all-carbon spiro-quaternary stereocenters.
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IJS, KILJ, NUK, PNG, UL, UM
Background & Aims
T‐cell receptor (TCR) repertoire is ambiguously changed in chronic hepatitis B (CHB) patients during antivirus therapy. We tried to assess TCR repertoire dynamics and its clinical ...significance upon HBeAg seroconversion in CHB patients.
Methods
Twenty CHB patients undergoing 1‐year entecavir (ETV) treatment were enrolled, including 10 complete response (CR) vs 10 non‐complete response (NCR) patients based on HBeAg seroconversion at week 48. The TCRβ complementarity‐determining region 3 (CDR3) of peripheral CD4+ and CD8+ T cells at weeks 0, 12 and 48 was analyzed by unbiased high‐throughput sequencing. The TCR repertoire profiles and their correlations with serological parameters were analyzed.
Results
The diversity of TCRβ repertoires was decreasing in CR patients but increasing in NCR patients. The distribution pattern of TCR repertoires stratified according to clonotype frequencies changed in the opposite direction between CR and NCR patients. Narrow amounts of newly appearing clonotypes in CR patients experienced a more intensive and robust expansion and this phenomenon could occur as early as week 12 for the CD4+ subset but later at week 48 for the CD8+ subset. There existed some CR‐exclusive clonotypes with a relatively low but increasing frequency at week 48. The number of unique TCRβ clonotypes was positively correlated with the ALT or HBV DNA level in CR patients but showed no or negative correlation in NCR patients.
Conclusion
Distinct TCR profiles contribute to predicting HBeAg seroconversion in CHB patients during ETV treatment and certain TCRβ CDR3 motif may be utilized for CHB immunotherapy in the future.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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