Arabidopsis mutants produced by constitutive overexpression of the CRISPR/Cas9 genome editing system are usually mosaics in the T1 generation. In this study, we used egg cell-specific promoters to ...drive the expression of Cas9 and obtained non-mosaic T1 mutants for multiple target genes with high efficiency. Comparisons of 12 combinations of eight promoters and two terminators found that the efficiency of the egg cell-specific promoter-controlled CRISPR/Cas9 system depended on the presence of a suitable terminator, and the composite promoter generated by fusing two egg cell-specific promoters resulted in much higher efficiency of mutation in the T1 generation compared with the single promoters.
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.
.
Hepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one of the most severe forms of ...the chronic viral hepatitis. However, there is a scarcity of data on the global burden of HDV infection.
We searched PubMed, Embase, Cochrane Library and China Knowledge Resource Integrated databases from 1 January 1977 to 31 December 2016. We included studies with a minimum sample size of 50 patients. Our study analysed data from a total of 40 million individuals to estimate the prevalence of HDV by using Der-Simonian Laird random-effects model. The data were further categorised according to risk factors.
From a total of 2717 initially identified studies, only 182 articles from 61 countries and regions met the final inclusion criteria. The overall prevalence of HDV was 0.98% (95% CI 0.61 to 1.42). In HBsAg-positive population, HDV pooled prevalence was 14.57% (95% CI 12.93 to 16.27): Seroprevalence was 10.58% (95% CI 9.14 to 12.11) in mixed population without risk factors of intravenous drug use (IVDU) and high-risk sexual behaviour (HRSB). It was 37.57% (95% CI 29.30 to 46.20) in the IVDU population and 17.01% (95% CI 10.69 to 24.34) in HRSB population.
We found that approximately 10.58% HBsAg carriers (without IVDU and HRSB) were coinfected with HDV, which is twofold of what has been estimated before. We also noted a substantially higher HDV prevalence in the IVDU and HRSB population. Our study highlights the need for increased focus on the routine HDV screening and rigorous implementation of HBV vaccine programme.
Single atom catalysts (SACs) with the maximized metal atom efficiency have sparked great attention. However, it is challenging to obtain SACs with high metal loading, high catalytic activity, and ...good stability. Herein, we demonstrate a new strategy to develop a highly active and stable Ag single atom in carbon nitride (Ag‐N2C2/CN) catalyst with a unique coordination. The Ag atomic dispersion and Ag‐N2C2 configuration have been identified by aberration‐correction high‐angle‐annular‐dark‐field scanning transmission electron microscopy (AC‐HAADF‐STEM) and extended X‐ray absorption. Experiments and DFT calculations further verify that Ag‐N2C2 can reduce the H2 evolution barrier, expand the light absorption range, and improve the charge transfer of CN. As a result, the Ag‐N2C2/CN catalyst exhibits much better H2 evolution activity than the N‐coordinated Ag single atom in CN (Ag‐N4/CN), and is even superior to the Pt nanoparticle‐loaded CN (PtNP/CN). This work provides a new idea for the design and synthesis of SACs with novel configurations and excellent catalytic activity and durability.
A new Ag single atom in carbon nitride (Ag‐N2C2/CN) photocatalyst with Ag‐N2C2 configuration is developed. It affords fast charge transfer, high Ag loading, and good stability. Noteworthily, the Ag‐N2C2/CN exhibits much better hydrogen evolution activity than Ag‐N4/CN, and even superior to the platinum‐loaded CN.
Scutellaria baicalensis root is traditionally used for the treatment of common cold, fever and influenza. Flavonoids are the major chemical components of S. baicalensis root.
To evaluate the ...therapeutic effects and action mechanism of flavonoids-enriched extract from S. baicalensis root (FESR) on acute lung injury (ALI) induced by influenza A virus (IAV) in mice.
The anti-influenza, anti-inflammatory and anti-complementary properties of FESR and the main flavonoids were evaluated in vitro. Mice were challenged intranasally with influenza virus H1N1 (A/FM/1/47) 2 h before treatment. FESR (50, 100 and 200 mg/kg) was administrated intragastrically. Baicalin (BG), the most abundant compound in FESR was given as reference control. Survival rates, life spans and lung indexes of IAV-infected mice were measured. Histopathological changes, virus levels, inflammatory markers and complement deposition in lungs were analyzed.
Compared with the main compound BG, FESR and lower content aglycones (baicalein, oroxylin A, wogonin and chrysin) in FESR significantly inhibited H1N1 activity in virus-infected Madin-Darby canine kidney (MDCK) cells and markedly decreased nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In vitro assays showed that FESR and BG had no anti-complementary activity whereas baicalein, oroxylin A, wogonin and chrysin exhibited obvious anti-complementary activity.
Oral administration of FESR effectively protected the IAV-infected mice, increased the survival rate (FESR: 67%; BG: 33%), decreased the lung index (FESR: 0.90; BG: 1.00) and improved the lung morphology in comparing with BG group. FESR efficiently decreased lung virus titers, reduced haemagglutinin (HA) titers and inhibited neuraminidase (NA) activities in lungs of IAV-infected mice. FESR modulated the inflammatory responses by decreasing the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1), and increasing the levels of interferon-γ (IFN-γ) and interleukin-10 (IL-10) in lung tissues. Although showing no anti-complementary activity in vitro, FESR obviously reduced complement deposition and decreased complement activation product level in the lung .
FESR has a great potential for the treatment of ALI induced by IAV and the underlying action mechanism might be closely associated with antiviral, anti-inflammatory and anti-complementary properties. Furthermore, FESR resulted in more potent therapeutic effect than BG in the treatment of IAV-induced ALI.
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Chiral materials have been widely present in people's lives, and their in-depth application research is underway. Generally, the circularly polarized light obtained from nonpolarized light through ...filters would result in brightness loss. Scientists have found that chirality can be introduced into organic compounds to obtain circularly polarized luminescence (CPL). Chiral compounds with CPL properties have attracted great attention and interest in recent years for their wide potential applications in 3D information displays, quantum communication, spintronics information storage, CPL lasers, nonlinear optics, biological probes and other fields. It is worth noting that helicene derivatives with twisted extended π-conjugated molecular structures could exhibit special helical chirality and excellent CPL properties. A chiral helix has also proven to be a valuable structural design for exploring small organic molecules with CPL. This review summarizes the recent development of CPL based on helicene derivatives.
This review summarizes the recent research progress of helicenes and their derivatives with circularly polarized luminescence properties.
To accelerate the application of the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9) system to a variety of plant species, a toolkit with ...additional plant selectable markers, more gRNA modules, and easier methods for the assembly of one or more gRNA expression cassettes is required.
We developed a CRISPR/Cas9 binary vector set based on the pGreen or pCAMBIA backbone, as well as a gRNA (guide RNA) module vector set, as a toolkit for multiplex genome editing in plants. This toolkit requires no restriction enzymes besides BsaI to generate final constructs harboring maize-codon optimized Cas9 and one or more gRNAs with high efficiency in as little as one cloning step. The toolkit was validated using maize protoplasts, transgenic maize lines, and transgenic Arabidopsis lines and was shown to exhibit high efficiency and specificity. More importantly, using this toolkit, targeted mutations of three Arabidopsis genes were detected in transgenic seedlings of the T1 generation. Moreover, the multiple-gene mutations could be inherited by the next generation.
We developed a toolkit that facilitates transient or stable expression of the CRISPR/Cas9 system in a variety of plant species, which will facilitate plant research, as it enables high efficiency generation of mutants bearing multiple gene mutations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•The characteristics of low temperature oxidation kinetics of water-soaked coal samples were analyzed.•Find out the migration law of functional groups in the oxygen-lean combustion ...process of water-soaked coal.•The thermal evolution process of water-soaked coal samples in an oxygen-lean environment is proposed.•A micro-reaction mechanism of coal-oxygen-water molecular chemisorption was constructed.
Oxidative spontaneous combustion is likely to occur after long-term water immersion in the gob area of coal mines. Mostly, the oxidation process is slowly carried out under different air leakage conditions. This paper summarizes the four stages of the low-temperature oxidation of water-soaked coal samples through temperature-programmed experiments. Using infrared spectroscopy and thermal analysis experiments, the migration laws of the functional groups and the thermal reaction characteristics of the four stages were investigated. The results show that as the oxygen concentration increases, the gas product concentration increases, and the activation energy of the deep oxidation stage decreases. With the progress of the heating stage, when the oxygen concentration is higher than 10%, the change in each functional group is larger, and the conversion of the functional group and the intermediate complex is relatively closer at an oxygen concentration of 21%. The low-temperature oxidation reaction is a parallel process of the pyrolysis and micro-oxygen absorption, and the DTG size is not affected by the oxygen concentration at the critical temperature. The higher the oxygen concentration is, the lower the initial exothermic temperature is, which promotes the exothermic process in the deep oxidation and oxidation-limited stages. The microreaction mechanism among coal, oxygen and water molecular chemisorption is constructed. By controlling the coal oxidation reaction stages under different air leakage conditions, the spontaneous combustion of water-soaked coal in the goaf is avoided.
Background
Accurate glioma grading plays an important role in the clinical management of patients and is also the basis of molecular stratification nowadays.
Purpose/Hypothesis
To verify the ...superiority of radiomics features extracted from multiparametric MRI to glioma grading and evaluate the grading potential of different MRI sequences or parametric maps.
Study Type
Retrospective; radiomics.
Population
A total of 153 patients including 42, 33, and 78 patients with Grades II, III, and IV gliomas, respectively.
Field Strength/Sequence
3.0T MRI/T1‐weighted images before and after contrast‐enhanced, T2‐weighted, multi‐b‐value diffusion‐weighted and 3D arterial spin labeling images.
Assessment
After multiparametric MRI preprocessing, high‐throughput features were derived from patients' volumes of interests (VOIs). The support vector machine‐based recursive feature elimination was adopted to find the optimal features for low‐grade glioma (LGG) vs. high‐grade glioma (HGG), and Grade III vs. IV glioma classification tasks. Then support vector machine (SVM) classifiers were established using the optimal features. The accuracy and area under the curve (AUC) was used to assess the grading efficiency.
Statistical Tests
Student's t‐test or a chi‐square test were applied on different clinical characteristics to confirm whether intergroup significant differences exist.
Results
Patients' ages between LGG and HGG groups were significantly different (P < 0.01). For each patient, 420 texture and 90 histogram parameters were derived from 10 VOIs of multiparametric MRI. SVM models were established using 30 and 28 optimal features for classifying LGGs from HGGs and grades III from IV, respectively. The accuracies/AUCs were 96.8%/0.987 for classifying LGGs from HGGs, and 98.1%/0.992 for classifying grades III from IV, which were more promising than using histogram parameters or using the single sequence MRI.
Data Conclusion
Texture features were more effective for noninvasively grading gliomas than histogram parameters. The combined application of multiparametric MRI provided a higher grading efficiency. The proposed radiomic strategy could facilitate clinical decision‐making for patients with varied glioma grades.
Level of Evidence: 3
Technical Efficacy: Stage 2
J. Magn. Reson. Imaging 2018;48:1518–1528
The Advanced Space-based Solar Observatory (ASO-S) is a mission proposed for the 25th solar maximum by the Chinese solar community. The scientific objectives are to study the relationships between ...the solar magnetic field, solar flares and coronal mass ejections (CMEs). Three payloads are deployed: the Full-disk vector MagnetoGraph (FMG), the Lyman-α Solar Telescope (LST) and the Hard X-ray Imager (HXI). ASO-S will perform the first simultaneous observations of the photospheric vector magnetic field, non-thermal imaging of solar flares, and the initiation and early propagation of CMEs on a single platform. ASO-S is scheduled to be launched into a 720 km Sun-synchronous orbit in 2022. This paper presents an overview of the mission till the end of Phase-B and the beginning of Phase-C.
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