Highly responsive organic image sensors are crucial for medical imaging applications. To enhance the pixelwise photoresponse in an organic image sensor, the integration of an organic photodetector ...with amplifiers, or the use of a highly responsive organic photodetector without an additional amplifying component, is required. The use of vertically stacked, two‐terminal organic photodetectors with photomultiplication is a promising approach for highly responsive organic image sensors owing to their simple two‐terminal structure and intrinsically large responsivity. However, there are no demonstrations of an imaging sensor array using organic photomultiplication photodetectors. The main obstacle to a sensor array is the weak‐light sensitivity, which is limited by a relatively large dark current. Herein, a highly responsive organic image sensor based on monolithic, vertically stacked two‐terminal pixels is presented. This is achieved using pixels of a vertically stacked diode‐type organic photodetector with photomultiplication. Furthermore, applying an optimized injection electrode and additionally stacked rectifying layers, this two‐terminal device simultaneously demonstrates a high responsivity (>40 A W−1), low dark current, and high rectification under illumination. An organic image sensor based on this device with an extremely simple architecture exhibits a high pixel photoresponse, demonstrating a weak‐light imaging capability even at 1 µW cm−2.
A highly responsive organic image sensor based on vertically stacked two‐terminal pixels is achieved with pixels of a diode‐type organic photodetector through photomultiplication. With an optimized injection electrode and additionally stacked rectifying layers, the organic image sensor with an extremely simple architecture exhibits a high pixel photoresponse and demonstrates a weak‐light imaging capability at 1 µW cm−2.
The contact system, also named as plasma kallikrein-kinin system, consists of three serine proteinases: coagulation factors XII (FXII) and XI (FXI), and plasma prekallikrein (PK), and the ...nonenzymatic cofactor high molecular weight kininogen (HK). This system has been investigated actively for more than 50 years. The components of this system and their interactions have been elucidated from in vitro experiments, which indicates that this system is prothrombotic by activating intrinsic pathway, and proinflammatory by producing bioactive peptide bradykinin. Although the activation of the contact system have been implicated in various types of human disease, in only a few instances is its role clearly defined. In the last 10 years, our understanding of the contact system, particularly its biology and (patho)physiology has greatly increased through investigations using gene-modified animal models. In this review we will describe a revitalized view of the contact system as a critical (patho)physiologic mediator of coagulation and inflammation.
The influenza virus hemagglutinin (HA) and coronavirus spike (S) protein mediate virus entry. HA and S proteins are heavily glycosylated, making them potential targets for carbohydrate binding agents ...such as lectins. Here, we show that the lectin FRIL, isolated from hyacinth beans (Lablab purpureus), has anti-influenza and anti-SARS-CoV-2 activity. FRIL can neutralize 11 representative human and avian influenza strains at low nanomolar concentrations, and intranasal administration of FRIL is protective against lethal H1N1 infection in mice. FRIL binds preferentially to complex-type N-glycans and neutralizes viruses that possess complex-type N-glycans on their envelopes. As a homotetramer, FRIL is capable of aggregating influenza particles through multivalent binding and trapping influenza virions in cytoplasmic late endosomes, preventing their nuclear entry. Remarkably, FRIL also effectively neutralizes SARS-CoV-2, preventing viral protein production and cytopathic effect in host cells. These findings suggest a potential application of FRIL for the prevention and/or treatment of influenza and COVID-19.
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•FRIL is a plant lectin with potent anti-influenza and anti-SARS-CoV-2 activity•FRIL preferentially binds to complex-type N-glycans on viral glycoproteins•FRIL inhibits influenza virus entry by sequestering virions in late endosomes•Intranasal administration of FRIL protects against lethal H1N1 challenge in mice
Liu et al. demonstrate that FRIL, a plant lectin isolated from the hyacinth bean, has potent antiviral activity against SARS-CoV-2 and diverse influenza virus strains. FRIL is effective in vivo against H1N1. FRIL’s antiviral activity is mediated by binding to complex-type N-glycans on viral glycoproteins, interfering with viral entry.
Zirconium‐based metal‐organic framework materials (Zr−MOFs) have more practical usage over most conventional benchmark porous materials and even many other MOFs due to the excellent structural ...stability, rich coordination forms, and various active sites. However, their mass‐production and application are restricted by the high‐cost raw materials, complex synthesis procedures, harsh reaction conditions, and unexpected environmental impact. Based on the principles of “Green Chemistry”, considerable efforts have been done for breaking through the limitations, and significant progress has been made in the sustainable synthesis of Zr−MOFs over the past decade. In this review, the advancements of green raw materials and green synthesis methods in the synthesis of Zr−MOFs are reviewed, along with the corresponding drawbacks. The challenges and prospects are discussed and outlooked, expecting to provide guidance for the acceleration of the industrialization and commercialization of Zr−MOFs.
The production and application of Zirconium‐based metal‐organic framework materials are restricted by numerous factors. By embracing green chemistry, green raw materials and green synthesis methods are the keys in sustainable synthesis of Zr−MOFs over last decade. This review summarizes the achievements and looks forward to the future industrialization and commercialization of Zr−MOFs.
Fabrication of hybrid MOF‐on‐MOF heteroarchitectures can create novel and multifunctional platforms to achieve desired properties. However, only MOFs with similar crystallographic parameters can be ...hybridized by the classical epitaxial growth method (EGM), which largely suppressed its applications. A general strategy, called internal extended growth method (IEGM), is demonstrated for the feasible assembly of MOFs with distinct crystallographic parameters in an MOF matrix. Various MOFs with diverse functions could be introduced in a modular MOF matrix to form 3D core–satellite pluralistic hybrid system. The number of different MOF crystals interspersed could be varied on demand. More importantly, the different MOF crystals distributed in individual domains could be used to further incorporate functional units or enhance target functions.
A general strategy, the internal extended growth method (IEGM), was applied to design modular hierarchically structured MOF composites, thereby overcoming the limitation of lattice matching. The number of MOF crystals interspersed and the size of the MOF matrix can be well‐controlled. IEGM can optimize the design of novel multicompositional MOFs systems with great flexibility. TTIP=Ti(OiPr4), BDC=benzenedicarboxylic acid.
Objectives
Tanshinone I (Tan‐I) is one of the vital fatsoluble monomer components, which extracted from Chinese medicinal herb Salvia miltiorrhiza Bunge. It has been shown that Tan‐I exhibited ...anti‐tumour activities on different types of cancers. However, the underlying mechanisms by which Tan‐Ⅰ regulates apoptosis and autophagy in ovarian cancer remain unclear. Thus, this study aimed to access the therapy effect of Tan‐Ⅰ and the underlying mechanisms.
Methods
Ovarian cancer cells A2780 and ID‐8 were treated with different concentrations of Tan‐Ⅰ (0, 1.2, 2.4, 4.8 and 9.6 μg/mL) for 24 hours. The cell proliferation was analysed by CCK8 assay, EdU staining and clone formation assay. Apoptosis was assessed by the TUNEL assay and flow cytometry. The protein levels of apoptosis protein (Caspase‐3), autophagy protein (Beclin1, ATG7, p62 and LC3II/LC3I) and PI3K/AKT/mTOR pathway were determined by Western blot. Autophagic vacuoles in cells were observed with LC3 dyeing using confocal fluorescent microscopy. Anti‐tumour activity of Tan‐Ⅰ was accessed by subcutaneous xeno‐transplanted tumour model of human ovarian cancer in nude mice. The Ki67, Caspase‐3 level and apoptosis level were analysed by immunohistochemistry and TUNEL staining.
Results
Tan‐Ⅰ inhibited the proliferation of ovarian cancer cells A2780 and ID‐8 in a dose‐dependent manner, based on CCK8 assay, EdU staining and clone formation assay. In additional, Tan‐Ⅰ induced cancer cell apoptosis and autophagy in a dose‐dependent manner in ovarian cancer cells by TUNEL assay, flow cytometry and Western blot. Tan‐Ⅰ significantly inhibited tumour growth by inducing cell apoptosis and autophagy. Mechanistically, Tan‐Ⅰ activated apoptosis‐associated protein Caspase‐3 cleavage to promote cell apoptosis and inhibited PI3K/AKT/mTOR pathway to induce autophagy.
Conclusions
This is the first evidence that Tan‐Ⅰ induced apoptosis and promoted autophagy via the inactivation of PI3K/AKT/mTOR pathway on ovarian cancer and further inhibited tumour growth, which might be considered as effective strategy.
Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which ...subtype patients will be responsive to checkpoint blockade are not fully understood.
We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic, and clinical data from cohorts of lung adenocarcinoma public (discovery set) and internal (validation set) database and immunotherapeutic patients. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups.
We observed that
mutation significantly increased expression of immune checkpoints and activated T-effector and interferon-γ signature. More importantly, the
comutated subgroup manifested exclusive increased expression of PD-L1 and a highest proportion of
Meanwhile,
or
-mutated tumors showed prominently increased mutation burden and specifically enriched in the transversion-high (TH) cohort. Further analysis focused on the potential molecular mechanism revealed that
or
mutation altered a group of genes involved in cell-cycle regulating, DNA replication and damage repair. Finally, immunotherapeutic analysis from public clinical trial and prospective observation in our center were further confirmed that
or
mutation patients, especially those with co-occurring
mutations, showed remarkable clinical benefit to PD-1 inhibitors.
This work provides evidence that
and
mutation in lung adenocarcinoma may be served as a pair of potential predictive factors in guiding anti-PD-1/PD-L1 immunotherapy.
.
A
bstract
Signals of heavy particle production during inflation are encoded as nonanalytic momentum scaling in primordial non-Gaussianity. These non-analytic signatures can be sourced by Standard ...Model particles with a modified Higgs scale uplifted by the slow-roll dynamics of inflation. We show that such a lifting mechanism becomes more efficient with the presence of a strong Higgs-inflaton mixing, where the Higgs mass scale is further increased by a small speed of sound in the effective theory of inflation. As a primary step towards detecting new particles in the cosmological collider program, non-Gaussianity due to heavy Higgs production in the strong-mixing regime can act as important background signals to be tested by future cosmological surveys.
Recent transcriptome analyses have revealed that noncoding RNAs (ncRNAs) are broadly expressed in mammalian cells and abundant in the CNS, with tissue and cell type-specific expression patterns. ...Moreover, ncRNAs have been found to intricately and dynamically regulate various signaling pathways in neurodegeneration. As such, some antisense transcripts and microRNAs are known to directly affect neurodegeneration in disease contexts. The functions of ncRNAs in pathogenesis are unique for each disorder, as are the pertinent networks of ncRNA/miRNA/mRNA that mediate these functions. Thus, further understanding of ncRNA biogenesis and effects might aid the discovery of diagnostic biomarkers or development of effective therapeutics for neurodegenerative disorders. Here, we review the ncRNAs that have so far been identified in major neurodegenerative disease etiology and the mechanisms that link ncRNAs with disease-specific phenotypes, such as HTT aggregation in HD, α-synuclein in PD, and Aβ plaques and hyperphosphorylated Tau in AD. We also summarize the known lncRNA/miRNA/mRNA networks that participate in neurodegenerative diseases, and we discuss ncRNA-related treatments shown to delay disease onset and prolong lifespan in rodent models.
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