Choline kinase catalyzes the initial reaction step of choline metabolism that produces phosphocholine, a prerequisite for the biosynthesis of a primary phospholipid phosphatidylcholine. However, the ...primary choline kinase and its role in plant growth remained elusive in seed plants.
Here, we showed that Arabidopsis CHOLINE/ETHANOLAMINE KINASE 1 (CEK1) encodes functional CEK that prefers choline than ethanolamine as a substrate in vitro and affects contents of choline and phosphocholine but not phosphatidylcholine in vivo.
CEK1 is localized at endoplasmic reticulum (ER); upon tunicamycin-induced ER stress, a null mutant of CEK1 showed hypersensitive phenotype in seedlings, albeit with no enhanced choline kinase activity.
Our results demonstrate that CEK1 is a primary ER-localized choline kinase in vivo that is required for ER stress tolerance possibly through the modulation of choline metabolites.
Mesenchymal stem cells (MSCs) and regulatory T cells (Tregs) are both potent immune-modulators. The aberrant proliferation and function of Tregs plays an important role in the development of asthma. ...Our previous studies have demonstrated the role of MSCs in promoting proliferation and immune-modulating of Tregs, as well as alleviating airway inflammation of asthmatic mice. In the present study, we isolated exosomes secreted by MSCs and investigated their immunomodulation effect on peripheral blood mononuclear cells (PBMCs) of asthmatic patient. We found that MSC exosomes upregulated IL-10 and TGF-β1 from PBMCs, thus promoting proliferation and immune-suppression capacity of Tregs. Furthermore, antigen presenting cells (APCs) but not CD4+ T cells-dependent pathway was shown to be possible mechanism involved in MSC exosome-mediated regulation. Our data elucidated the key role of exosomes in immune-modulation of MSCs, and suggested the therapeutic potential of MSC exosomes for asthma.
•MSC exosomes promote Tregs proliferation by upregulating IL-10 and TGF-β1 in asthma.•MSC exosomes enhance immunosuppression capacity of Tregs from asthmatic patient.•The effect of MSC exosomes on Tregs may be mediated by APCs.
The protein activator of protein kinase R (PKR) (PACT) has been shown to play a crucial role in stimulating the host antiviral response through the activation of PKR, retinoic acid‐inducible gene I, ...and melanoma differentiation‐associated protein 5. Whether PACT can inhibit viral replication independent of known mechanisms is still unrevealed. In this study, we show that, like many viruses, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) hijacks GSK‐3β to facilitate its replication. GSK‐3β‐induced phosphorylation on N protein increased the interaction between N protein and nsp3. Thus, GSK‐3β‐N‐nsp3 cascade promotes viral replication. Although SARS‐CoV‐2 can sabotage the activation of AKT, the upstream proteins suppressing the activation of GSK‐3β, we found that the host can use PACT, another protein kinase, instead of AKT to decrease the activity of GSK‐3β and the interaction between PACT and GSK‐3β is enhanced upon viral infection. Moreover, PACT inhibited the activity of GSK‐3β independent of its well‐studied double‐stranded RNA binding and PKR activating ability. In summary, this study identified an unknown function of PACT in inhibiting SARS‐CoV‐2 replication through the blockage of GSK‐3β‐N‐nsp3 cascade.
Multiple exopolysaccharides (EPSs) have been isolated from various organisms in extreme environments and have yielded a variety of activities. The present study evaluated the immunomodulatory ...capabilities of an EPS (termed PH‑EPS) derived from the fungus Paecilomyces lilacinus PH0016, which was isolated from a tropical and hyperhaline environment in southern China. The macrophage RAW 264.7 cell line was used to investigate the mechanism of PH‑EPS‑induced macrophage activation. The results indicated that RAW 264.7 macrophages were activated by PH‑EPS, in an effect slightly inferior to lipopolysaccharide (LPS), as evidenced by secretion of interleukin (IL)‑1β, tumor necrosis factor (TNF)‑α and nitric oxide (NO), and by significantly increased phagocytosis in the cells treated with PH‑EPS. Nuclear factor (NF)‑κB p65 was significantly translocated into the nucleus in the PH‑EPS‑treated cells. In addition, expression of inducible NO synthase (iNOS) and IκB‑α degradation were enhanced in PH‑EPS‑treated cells. The phosphorylation levels of p38, JNK and ERK were also significantly increased in the PH‑EPS‑treated cells. Furthermore, IL‑1β and TNF‑α production was markedly decreased in PH‑EPS‑treated cells when the mitogen‑activated protein kinase (MAPK) pathways were blocked by the inhibitor Dectin‑1 and by antibodies against Toll‑like receptor 4 (TLR4). The present results indicated that PH‑EPS from Paecilomyces lilacinus possessed the capability of activating RAW 264.7 cells via the TLR4/NF‑κB/MAPKs signaling pathway.
Sixth-generation (6G) mobile networks will have to cope with diverse threats on a space-air-ground integrated network environment, novel technologies, and an accessible user information explosion. ...However, for now, security and privacy issues for 6G remain largely in concept. This survey provides a systematic overview of security and privacy issues based on prospective technologies for 6G in the physical, connection, and service layers, as well as through lessons learned from the failures of existing security architectures and state-of-the-art defenses. Two key lessons learned are as follows. First, other than inheriting vulnerabilities from the previous generations, 6G has new threat vectors from new radio technologies, such as the exposed location of radio stripes in ultra-massive MIMO systems at Terahertz bands and attacks against pervasive intelligence. Second, physical layer protection, deep network slicing, quantum-safe communications, artificial intelligence (AI) security, platform-agnostic security, real-time adaptive security, and novel data protection mechanisms such as distributed ledgers and differential privacy are the top promising techniques to mitigate the attack magnitude and personal data breaches substantially.
Endothelial cells (ECs) sense and respond to fluid flow and regulate immune cell trafficking in all organs. Despite sharing the same mesodermal origin, ECs exhibit heterogeneous tissue-specific ...characteristics. Human pluripotent stem cells (hPSCs) can potentially be harnessed to capture this heterogeneity and further elucidate endothelium behavior to satisfy the need for increased accuracy and breadth of disease models and therapeutics. Here, we review current strategies for hPSC differentiation to blood vascular ECs and their maturation into continuous, fenestrated, and sinusoidal tissues. We then discuss the contribution of hPSC-derived ECs to recent advances in organoid development and organ-on-chip approaches.
Human pluripotent stem cells (hPSCs) can be harnessed to capture the heterogeneous tissue-specific characteristics of endothelial cells (ECs) toward disease models and therapeutics. This review focuses on hPSC-EC derivation and maturation into continuous, fenestrated, and sinusoidal tissues and the contribution of hPSC-ECs to recent advances in organoid development and organ-on-chip approaches.
Abstract Objectives Although long non-coding RNAs (lncRNAs) are emerging as new regulators in the cancer paradigm, the involvement of lncRNAs in epithelial ovarian cancer (EOC) is just beginning to ...be studied. In this study, we focused on lncRNA HOX transcript antisense RNA (HOTAIR) and investigated its expression pattern, clinical significance, and biological function in EOC. Methods HOTAIR expression in EOC tissues was examined and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of in vitro and in vivo assays were performed to understand the role of HOTAIR in EOC metastasis. Results HOTAIR expression was elevated in EOC tissues, and HOTAIR levels were highly positively correlated with the FIGO stage, the histological grade of the tumor, lymph node metastasis, and reduced overall survival (OS) and disease-free survival (DFS). A multivariate analysis showed that HOTAIR expression is an independent prognostic factor of OS and DFS in patients with EOC. Additionally, the results of in vitro assays showed that the suppression of HOTAIR expression in the three highly metastatic EOC cell lines (SKOV3.ip1, HO8910-PM, and HEY-A8) significantly reduced cell migration/invasion. The results of in vivo assays further confirmed the pro-metastatic effects of HOTAIR. Moreover, the pro-metastatic effects of HOTAIR were partially mediated by the regulation of certain matrix metalloproteinases (MMPs) and epithelial-to-mesenchymal transition (EMT)-related genes. Conclusions Our data suggest that HOTAIR plays a vital role in EOC metastasis and could represent a novel prognostic marker and potential therapeutic target in patients with EOC.
A
bstract
We introduce spectral functions that capture the distribution of OPE coefficients and density of states in two-dimensional conformal field theories, and show that nontrivial upper and lower ...bounds on the spectral function can be obtained from semidefinite programming. We find substantial numerical evidence indicating that OPEs involving only scalar Virasoro primaries in a
c >
1 CFT are necessarily governed by the structure constants of Liouville theory. Combining this with analytic results in modular bootstrap, we conjecture that Liouville theory is the unique unitary
c >
1 CFT whose primaries have bounded spins. We also use the spectral function method to study modular constraints on CFT spectra, and discuss some implications of our results on CFTs of large
c
and large gap, in particular, to what extent the BTZ spectral density is universal.
Background
The emergence of the COVID-19 and its consequences has led to fears, worries, and anxiety among individuals worldwide. The present study developed the Fear of COVID-19 Scale (FCV-19S) to ...complement the clinical efforts in preventing the spread and treating of COVID-19 cases.
Methods
The sample comprised 717 Iranian participants. The items of the FCV-19S were constructed based on extensive review of existing scales on fears, expert evaluations, and participant interviews. Several psychometric tests were conducted to ascertain its reliability and validity properties.
Results
After panel review and corrected item-total correlation testing, seven items with acceptable corrected item-total correlation (0.47 to 0.56) were retained and further confirmed by significant and strong factor loadings (0.66 to 0.74). Also, other properties evaluated using both classical test theory and Rasch model were satisfactory on the seven-item scale. More specifically, reliability values such as internal consistency (
α
= .82) and test–retest reliability (ICC = .72) were acceptable. Concurrent validity was supported by the Hospital Anxiety and Depression Scale (with depression,
r
= 0.425 and anxiety,
r
= 0.511) and the Perceived Vulnerability to Disease Scale (with perceived infectability,
r
= 0.483 and germ aversion, r = 0.459).
Conclusion
The Fear of COVID-19 Scale, a seven-item scale, has robust psychometric properties. It is reliable and valid in assessing fear of COVID-19 among the general population and will also be useful in allaying COVID-19 fears among individuals.
Metalloproteins and metalloenzymes play important roles in biological systems by using the limited metal ions, complexes, and clusters that are associated with the protein matrix. The design of ...artificial metalloproteins and metalloenzymes not only reveals the structure and function relationship of natural proteins, but also enables the synthesis of artificial proteins and enzymes with improved properties and functions. Acknowledging the progress in rational design from single to multiple active sites, this review focuses on recent achievements in the design of artificial metalloproteins and metalloenzymes with metal clusters, including zinc clusters, cadmium clusters, iron-sulfur clusters, and copper-sulfur clusters, as well as noble metal clusters and others. These metal clusters were designed in both native and de novo protein scaffolds for structural roles, electron transfer, or catalysis. Some synthetic metal clusters as functional models of native enzymes are also discussed. These achievements provide valuable insights for deep understanding of the natural proteins and enzymes, and practical clues for the further design of artificial enzymes with functions comparable or even beyond those of natural counterparts.
PDF
