The global pandemic of coronavirus disease 2019 (COVID-19) is a disaster for human society. A convenient and reliable neutralization assay is very important for the development of vaccines and novel ...drugs. In this study, a G protein-deficient vesicular stomatitis virus (VSVdG) bearing a truncated spike protein (S with C-terminal 18 amino acid truncation) was compared to that bearing the full-length spike protein of SARS-CoV-2 and showed much higher efficiency. A neutralization assay was established based on VSV-SARS-CoV-2-Sdel18 pseudovirus and hACE2-overexpressing BHK21 cells (BHK21-hACE2 cells). The experimental results can be obtained by automatically counting the number of EGFP-positive cells at 12 h after infection, making the assay convenient and high-throughput. The serum neutralizing titer measured by the VSV-SARS-CoV-2-Sdel18 pseudovirus assay has a good correlation with that measured by the wild type SARS-CoV-2 assay. Seven neutralizing monoclonal antibodies targeting the receptor binding domain (RBD) of the SARS-CoV-2 S protein were obtained. This efficient and reliable pseudovirus assay model could facilitate the development of new drugs and vaccines.
Lung cancer is one of the greatest threats to human health, and is initially detected and attacked by the immune system through tumor‐reactive T cells. The aim of this study was to determine the ...basic characteristics and clinical significance of the peripheral blood T‐cell receptor (TCR) repertoire in patients with advanced lung cancer. To comprehensively profile the TCR repertoire, high‐throughput sequencing was used to identify hypervariable rearrangements of complementarity determining region 3 (CDR3) of the TCR β chain in peripheral blood samples from 64 advanced lung cancer patients and 31 healthy controls. We found that the TCR repertoire differed substantially between lung cancer patients and healthy controls in terms of CDR3 clonotype, diversity, V/J segment usage, and sequence. Specifically, baseline diversity correlated with several clinical characteristics, and high diversity reflected a better immune status. Dynamic detection of the TCR repertoire during anticancer treatment was useful for prognosis. Both increased diversity and high overlap rate between the pre‐ and post‐treatment TCR repertoires indicated clinical benefit. Combination of the diversity and overlap rate was used to categorize patients into immune improved or immune worsened groups and demonstrated enhanced prognostic significance. In conclusion, TCR repertoire analysis served as a useful indicator of disease development and prognosis in advanced lung cancer and may be utilized to direct future immunotherapy.
What's new?
T cells are essential players in the anti‐cancer immune response. Characterization of the T‐cell receptor (TCR) repertoire is a promising method for assessing tumor activity, directing therapy, and predicting prognosis; however, the importance of the TCR repertoire in lung cancer is unclear. This sequencing analysis found that the peripheral blood TCR repertoire of patients with advanced lung cancer was significantly different from that of healthy individuals. The peripheral blood TCR repertoire correlated with several clinical characteristics and patient immune status. Dynamic TCR repertoire analysis served as a useful indicator of disease development and may be utilized to direct future immunotherapy.
Inorganic perovskites such as CsPbX
(X=Cl, Br, I) have attracted attention due to their excellent thermal stability and high photoluminescence quantum efficiency. However, the electroluminescence ...quantum efficiency of their light-emitting diodes was <1%. We posited that this low efficiency was a result of high leakage current caused by poor perovskite morphology, high non-radiative recombination at interfaces and perovskite grain boundaries, and also charge injection imbalance. Here, we incorporated a small amount of methylammonium organic cation into the CsPbBr
lattice and by depositing a hydrophilic and insulating polyvinyl pyrrolidine polymer atop the ZnO electron-injection layer to overcome these issues. As a result, we obtained light-emitting diodes exhibiting a high brightness of 91,000 cd m
and a high external quantum efficiency of 10.4% using a mixed-cation perovskite Cs
MA
PbBr
as the emitting layer. To the best of our knowledge, this is the brightest and most-efficient green perovskite light-emitting diodes reported to date.
Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with ...HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.
Organic solar cells (OSCs) based on bulk heterojunction structures are promising candidates for next‐generation solar cells. However, the narrow absorption bandwidth of organic semiconductors is a ...critical issue resulting in insufficient usage of the energy from the solar spectrum, and as a result, it hinders performance. Devices based on multiple‐donor or multiple‐acceptor components with complementary absorption spectra provide a solution to address this issue. OSCs based on multiple‐donor or multiple‐acceptor systems have achieved power conversion efficiencies over 12%. Moreover, the introduction of an additional component can further facilitate charge transfer and reduce charge recombination through cascade energy structure and optimized morphology. This progress report provides an overview of the recent progress in OSCs based on multiple‐donor (polymer/polymer, polymer/dye, and polymer/small molecule) or multiple‐acceptor (fullerene/fullerene, fullerene/nonfullerene, and nonfullerene/nonfullerene) components.
This progress report provides an overview of the most impactful recent progress in high‐performance organic solar cells based on multiple‐donor (polymer/polymer, polymer/dye, and polymer/small molecule) or multiple‐acceptor (fullerene/fullerene, fullerene/nonfullerene, and nonfullerene/nonfullerene) components, focusing particularly on the interactions between different components from the perspective of morphology and photophysics.
Antimony trisulfide (Sb
S
) is considered to be a promising photovoltaic material; however, the performance is yet to be satisfactory. Poor power conversion efficiency and large open circuit voltage ...loss have been usually ascribed to interface and bulk extrinsic defects By performing a spectroscopy study on Sb
S
polycrystalline films and single crystal, we show commonly existed characteristics including redshifted photoluminescence with 0.6 eV Stokes shift, and a few picosecond carrier trapping without saturation at carrier density as high as approximately 10
cm
. These features, together with polarized trap emission from Sb
S
single crystal, strongly suggest that photoexcited carriers in Sb
S
are intrinsically self-trapped by lattice deformation, instead of by extrinsic defects. The proposed self-trapping explains spectroscopic results and rationalizes the large open circuit voltage loss and near-unity carrier collection efficiency in Sb
S
thin film solar cells. Self-trapping sets the upper limit on maximum open circuit voltage (approximately 0.8 V) and thus power conversion efficiency (approximately 16 %) for Sb
S
solar cells.
Metal halide perovskites are emerging scintillator materials in X‐ray detection and imaging. However, the vulnerable structure of perovskites triggers unreliable performance when they are utilized in ...X‐ray detectors under cumulative dose irradiation. Herein, a self‐limited growth strategy is proposed to construct CsPbBr3 nanocrystals that are embedded in a transparent amorphous network structure, featuring X‐imaging with excellent resolution (≈16.8 lp mm−1), and fast decay time (τ = 27 ns). Interestingly, it is found that the performance degradation of the scintillator, caused by the damage from high‐dose X‐ray irradiation, can be fully recovered after a facile thermal treatment process. This indicates a superior recycling behavior of the explored perovskites scintillator for practical applications. The recoverability of the as‐explored scintillator is attributed to the low atom‐migration rate in the amorphous network with high‐viscosity (1 × 1014 cP). This result highlights the practical settlement of the promising perovskites for long‐term, cost‐effective scintillator devices.
A self‐limited growth strategy is proposed to construct CsPbBr3 nanocrystals, which features X‐imaging with excellent resolution (16.8 lp mm−1). More importantly, the blurred X‐ray images of the damaged perovskite NCs, due to irradiation at high dose rate, are well refreshed by a thermal treatment. This discovery broadens the research and application of the scintillators and opens a new chapter.
Abstract
By electronically wiring-up living cells with abiotic conductive surfaces, bioelectrochemical systems (BES) harvest energy and synthesize electric-/solar-chemicals with unmatched ...thermodynamic efficiency. However, the establishment of an efficient electronic interface between living cells and abiotic surfaces is hindered due to the requirement of extremely close contact and high interfacial area, which is quite challenging for cell and material engineering. Herein, we propose a new concept of a single cell electron collector, which is
in-situ
built with an interconnected intact conductive layer on and cross the individual cell membrane. The single cell electron collector forms intimate contact with the cellular electron transfer machinery and maximizes the interfacial area, achieving record-high interfacial electron transfer efficiency and BES performance. Thus, this single cell electron collector provides a superior tool to wire living cells with abiotic surfaces at the single-cell level and adds new dimensions for abiotic/biotic interface engineering.
Titanium metal–organic frameworks (Ti‐MOFs), as an appealing type of artificial photocatalyst, have shown great potential in the field of solar energy conversion due to their well‐studied photoredox ...activity (similar to TiO2) and good optical responsiveness of linkers, which serve as the antenna to absorb visible‐light. Although much effort has been dedicated to developing Ti‐MOFs with high photocatalytic activity, their solar energy conversion performances are still poor. Herein, we have implemented a covalent‐integration strategy to construct a series of multivariate Ti‐MOF/COF hybrid materials PdTCPP⊂PCN‐415(NH2)/TpPa (composites 1, 2, and 3), featuring excellent visible‐light utilization, a suitable band gap, and high surface area for photocatalytic H2 production. Notably, the resulting composites demonstrated remarkably enhanced visible‐light‐driven photocatalytic H2 evolution performance, especially for the composite 2 with a maximum H2 evolution rate of 13.98 mmol g−1 h−1 (turnover frequency (TOF)=227 h−1), which is much higher than that of PdTCPP⊂PCN‐415(NH2) (0.21 mmol g−1 h−1) and TpPa (6.51 mmol g−1 h−1). Our work thereby suggests a new approach to highly efficient photocatalysts for H2 evolution and beyond.
A series of covalently connected multivariate Ti‐MOF/COF hybrid materials were constructed demonstrating outstanding photocatalytic H2 evolution performance with a maximum H2 evolution rate of 13.98 mmol g−1 h−1 (TOF=227 h−1), much higher than the prototypical counterparts.
Despite intensive efforts to discover highly effective treatments to eradicate tuberculosis (TB), it remains as a major threat to global human health. For this reason, new TB drugs directed toward ...new targets are highly coveted. MmpLs (Mycobacterial membrane proteins Large), which play crucial roles in transporting lipids, polymers and immunomodulators and which also extrude therapeutic drugs, are among the most important therapeutic drug targets to emerge in recent times. Here, crystal structures of mycobacterial MmpL3 alone and in complex with four TB drug candidates, including SQ109 (in Phase 2b-3 clinical trials), are reported. MmpL3 consists of a periplasmic pore domain and a twelve-helix transmembrane domain. Two Asp-Tyr pairs centrally located in this domain appear to be key facilitators of proton-translocation. SQ109, AU1235, ICA38, and rimonabant bind inside the transmembrane region and disrupt these Asp-Tyr pairs. This structural data will greatly advance the development of MmpL3 inhibitors as new TB drugs.
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•The crystal structure of Mycobacterium smegmatis MmpL3 has been determined•Two Asp-Tyr pairs in the TM region of MmpL3 facilitate proton-translocation•SQ109, an anti-TB drug, binds inside the proton-translocation channel of MmpL3•Rimonabant, an antagonist for the cannabinoid receptor CB1, also inhibits MmpL3
MmpL3 has emerged as an important target for anti-tuberculosis drug discovery with inhibitors of this protein currently in clinical trials. Here, crystal structures of mycobacterial MmpL3 alone and in complex with four TB drug candidates have been determined. These data pave the way for the rational development of MmpL3 inhibitors as potent TB drugs.
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