Background As the number of patients increases, there is a growing understanding of the form of pneumonia sustained by the 2019 novel coronavirus (SARS-CoV-2), which has caused an outbreak in China. ...Up to now, clinical features and treatment of patients infected with SARS-CoV-2 have been reported in detail. However, the relationship between SARS-CoV-2 and coagulation has been scarcely addressed. Our aim is to investigate the blood coagulation function of patients with SARS-CoV-2 infection. Methods In our study, 94 patients with confirmed SARS-CoV-2 infection were admitted in Renmin Hospital of Wuhan University. We prospectively collect blood coagulation data in these patients and in 40 healthy controls during the same period. Results Antithrombin values in patients were lower than that in the control group (p < 0.001). The values of D-dimer, fibrin/fibrinogen degradation products (FDP), and fibrinogen (FIB) in all SARS-CoV-2 cases were substantially higher than those in healthy controls. Moreover, D-dimer and FDP values in patients with severe SARS-CoV-2 infection were higher than those in patients with milder forms. Compared with healthy controls, prothrombin time activity (PT-act) was lower in SARS-CoV-2 patients. Thrombin time in critical SARS-CoV-2 patients was also shorter than that in controls. Conclusions The coagulation function in patients with SARS-CoV-2 is significantly deranged compared with healthy people, but monitoring D-dimer and FDP values may be helpful for the early identification of severe cases.
Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress ...to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.
From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.
Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.
LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Based on the context of complexity = action (CA) conjecture, we calculate the holographic complexity of AdS black holes with planar and spherical topologies in Horndeski theory. We find that the rate ...of change of holographic complexity for neutral AdS black holes saturates the Lloyd’s bound. For charged black holes, we find that there exists only one horizon and thus the corresponding holographic complexity can’t be expressed as the difference of some thermodynamical potential between two horizons as that of Reissner–Nordstrom AdS black hole in Einstein–Maxwell theory. However, the Lloyd’s bound is not violated for charged AdS black hole in Horndeski theory.
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.
To fully exploit the microbial genome resources, a high-throughput experimental platform is needed to associate genes with phenotypes at the genome level. We present here a novel method that enables ...investigation of the cellular consequences of repressing individual transcripts based on the CRISPR interference (CRISPRi) pooled screening in bacteria. We identify rules for guide RNA library design to handle the unique structure of prokaryotic genomes by tiling screening and construct an E. coli genome-scale guide RNA library (~60,000 members) accordingly. We show that CRISPRi outperforms transposon sequencing, the benchmark method in the microbial functional genomics field, when similar library sizes are used or gene length is short. This tool is also effective for mapping phenotypes to non-coding RNAs (ncRNAs), as elucidated by a comprehensive tRNA-fitness map constructed here. Our results establish CRISPRi pooled screening as a powerful tool for mapping complex prokaryotic genetic networks in a precise and high-throughput manner.
•The multi-scale optimization strategy can serve as a conceptual material paradigm.•A giant Wrec of 5.02 J·cm−3 and a high η of ~ 90% can be obtained in the 0.5NBT-0.5SST ceramic.•The underlying ...mechanism of high energy storage properties has been visualized.
Dielectric ceramic materials with high power density and fast charge–discharge speed have attracted increasing attention in recent years. However, their mutually restricted energy density and efficiency as well as unsatisfactory temperature stability have been the main obstacles for their practical applications. Herein, a high recoverable energy density of 5.02 J·cm−3 and a high efficiency of ~ 90% can be obtained under 422 kV·cm−1 in the Sr0.85Sm0.1TiO3 (SST)-modified Na0.5Bi0.5TiO3 (NBT) ceramics via composition design and domain engineering strategy, and the excellent stability of energy storage properties in frequency (1–100 Hz) and temperature (20–180 °C) were also observed at 250 kV·cm−1 in the 0.50NBT-0.50SST ceramics, which are attributed to the improved breakdown strength (Eb) and the enhanced relaxation behavior. The increased band gap width and refined grain size are responsible for the significantly enhanced Eb of Na0.5Bi0.5TiO3-based solid solution, being confirmed by ultraviolet and visible (UV–vis) absorption spectra as well as scanning electron microscopy. The generation of polar nanoregions as demonstrated by piezoresponse force microscopy and transmission electron microscopy results in a negligible remanent polarization and thermally stable polarization-field response. It is worth noting that the energy density will be further greatly optimized due to the improvement of Eb if this ceramic composite is made into multilayer ceramic capacitor as a dielectric layer. Moreover, a large power density of 188.6 MW·cm−3 and a fast discharge speed of 70 ns can also be achieved in the optimized composition. The results show that the multi-scale optimization strategy is an effective way to realize excellent comprehensive energy storage performances in the Na0.5Bi0.5TiO3 based ceramics.
Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to ...increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
Visible‐light copper photocatalysis has recently emerged as a viable technology for building sustainable synthetic processes. To broaden the applications of phosphine‐ligated copper(I) complexes, we ...describe herein an effective metal‐organic framework (MOF)‐supported copper(I) photocatalyst for multiple iminyl radical‐mediated reactions. Due to site isolation, the heterogenized copper photosensitizer has a significantly higher catalytic activity than its homogeneous counterpart. Using a hydroxamic acid linker to immobilize copper species on MOF supports affords the heterogeneous catalysts with high recyclability. The post‐synthetic modification sequence on MOF surfaces allows for the preparation of previously unavailable monomeric copper species. Our findings highlight the potential of using MOF‐based heterogeneous catalytic systems to address fundamental challenges in the development of synthetic methodologies and mechanistic investigations of transition‐metal photoredox catalysis.
A binap‐ligated copper dimer has been heterogenized on a pillar‐layered MOF surface for the first time using a hydroxamic acid linker. This MOF‐supported dimeric copper photocatalyst demonstrates much higher activity and recyclability than its homogeneous counterparts in intra‐ and intermolecular radical reactions of N‐acyloxy imidates and O‐acyl oximes.
The up‐regulation and nuclear relocation of epithelial‐mesenchymal transition (EMT) regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). ...The term vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. However, the relationship between Twist1 and VM formation is not clear. In this study, we explored HCC as a VM and EMT model in order to investigate the role of Twist1 in VM formation. We first examined the expression of Twist1 in human HCC samples and cell lines and found that Twist1 was frequently overexpressed in the nuclear relocation occurring in VM‐positive HCCs (13/18 72%). Twist1 nuclear expression was likewise significantly associated with VM formation. Clinicopathological analysis revealed that both VM and Twist1 nuclear expressions present shorter survival durations than those without expression. We consistently demonstrated that an overexpression of Twist1 significantly enhanced cell motility, invasiveness, and VM formation in an HepG2 cell. Conversely, a knockdown of Twist1 by the short hairpin RNA approach remarkably reduced Bel7402 cell migration, invasion, and VM formation. Using chromatin immunoprecipitation, we also showed that Twist1 binds to the vascular endothelial (VE)‐cadherin promoter and enhances its activity in a transactivation assay. Conclusion: The results of this study indicate that Twist1 induces HCC cell plasticity in VM cells more through the suppression of E‐cadherin expression and the induction of VE‐cadherin up‐regulation than through the VM pattern in vivo and in a three‐dimensional in vitro system. Our findings also demonstrate a novel cogitation in cancer stem‐like cell differentiation and that related molecular pathways may be used as novel therapeutic targets for the inhibition of HCC angiogenesis and metastasis. (HEPATOLOGY 2009.)
Citrus is one of the most important fruit crops in the world, and it is worthy to conduct more research on artificially controlling citrus plant growth and development to adapt to different ...cultivation patterns and environmental conditions. The plant-specific TEOSINTE BRANCHED1, CYCOLOIDEA, and PROLIFERATING CELL FACTORS (TCP) transcription factors are crucial regulators controlling plant growth and development, as well as responding to abiotic stresses. However, the information about citrus TCP transcription factors remains unclear. In this study, twenty putative TCP genes (CsTCPs) with the TCP domain were explored from Citrus sinensis genome, of which eleven (CsTCP3, - 4, - 5, - 6, - 10, - 11, - 15, - 16, - 18, - 19, - 20), five (CsTCP1, - 2, - 7, - 9, - 13), and four genes (CsTCP8, - 12, - 14, - 17) were unevenly distributed on chromosomes and divided into three subclades. Cis-acting element analysis indicated that most CsTCPs contained many phytohormone- and environment-responsive elements in promoter regions. All of CsTCPs were predominantly expressed in vegetative tissues or organs (stem, leaf, thorn, and bud) instead of reproductive tissues or organs (flower, fruit, and seed). Combined with collinearity analysis, CsTCP3, CsTCP9, and CsTCP13 may take part in leaf development; CsTCP12 and CsTCP14 may function in shoot branching, leaf development, or thorn development; CsTCP15 may participate in the development of stem, leaf, or thorn. In mature leaf, transcript levels of two CsTCPs (CsTCP19, - 20) were significantly increased while transcript levels of eight CsTCPs (CsTCP2, - 5, - 6, - 7, - 8, - 9, - 10, - 13) were significantly decreased by shading; except for two CsTCPs (CsTCP11, - 19), CsTCPs' transcript levels were significantly influenced by low temperature; moreover, transcript levels of two CsTCPs (CsTCP11, - 12) were significantly increased while five CsTCPs' (CsTCP14, - 16, - 18, - 19, - 20) transcript levels were significantly reduced by drought. This study provides significant clues for research on roles of CsTCPs in regulating citrus plant growth and development, as well as responding to abiotic stresses.
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