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We present predictions for neutron star tidal deformabilities obtained from a Bayesian analysis of the nuclear equation of state, assuming a minimal model at high-density that neglects the ...possibility of phase transitions. The Bayesian posterior probability distribution is constructed from priors obtained from microscopic many-body theory based on realistic two- and three-body nuclear forces, while the likelihood functions incorporate empirical information about the equation of state from nuclear experiments. The neutron star crust equation of state is constructed from the liquid drop model, and the core-crust transition density is found by comparing the energy per baryon in inhomogeneous matter and uniform nuclear matter. From the cold
β
-equilibrated neutron star equation of state, we then compute neutron star tidal deformabilities as well as the mass-radius relationship. Finally, we investigate correlations between the neutron star tidal deformability and properties of finite nuclei.
Total phenolic content (TPC) and ascorbic acid equivalent antioxidant capacity (AEAC) of leaves of 26 ginger species belonging to nine genera and three tribes were screened. For 14 species, TPC and ...AEAC of rhizomes were also assessed. Ferrous ion-chelating (FIC) abilities of leaves and rhizomes of eight species were compared. Leaves of five species of
Etlingera were analysed for tyrosinase inhibition activity. Of the 26 species, leaves of
Etlingera species had the highest TPC and AEAC. Eleven of the 14 species had significantly higher TPC and/or AEAC in leaves than in rhizomes. Values of leaves of
Etlingera elatior and
Etlingera maingayi were seven to eight times higher than those of rhizomes. In terms of FIC ability, six of the eight species clearly showed higher values in leaves than in rhizomes. The most outstanding was the FIC value of
Alpinia galanga leaves which was more than 20 times higher than that of rhizomes. Of the five species of
Etlingera, leaves of
E. elatior displayed the strongest tyrosinase inhibition activity, followed by leaves of
Etlingera fulgens and
E. maingayi. Values of their inhibition activity were significantly higher than or comparable to the positive control. Besides promising tyrosinase inhibition ability, leaves of these three
Etlingera species also have high antioxidant activity and antibacterial properties.
A novel strategy for the recognition of anions in water using charge-neutral σ-hole halogen and chalcogen bonding acyclic hosts is demonstrated for the first time. Exploiting the intrinsic ...hydrophobicity of halogen and chalcogen bond donor atoms integrated into a foldamer structural molecular framework containing hydrophilic functionalities, a series of water-soluble receptors was constructed for an anion recognition investigation. Isothermal titration calorimetry (ITC) binding studies with a range of anions revealed the receptors to display very strong and selective binding of large, weakly hydrated anions such as I– and ReO4 –. This is achieved through the formation of 2:1 host–guest stoichiometric complex assemblies, resulting in an encapsulated anion stabilized by cooperative, multidentate, convergent σ-hole donors, as shown by molecular dynamics simulations carried out in water. Importantly, the combination of multiple σ-hole–anion interactions and hydrophobic collapse results in I– affinities in water that exceed all known σ-hole receptors, including cationic systems (β2 up to 1.68 × 1011 M–2). Furthermore, the anion binding affinities and selectivity trends of the first example of an all-chalcogen bonding anion receptor in pure water are compared with halogen bonding and hydrogen bonding receptor analogues. These results further advance and establish halogen and chalcogen bond donor functions as new tools for overcoming the challenging goal of anion recognition in pure water.
The culture of bone marrow derived mesenchymal stem cells (MSCs), as well as the control of its differentiation toward different tissue lineage, is a very important part of tissue engineering, where ...cells are combined with artificial scaffold to regenerate tissues. Graphene (G) and graphene oxide (GO) sheets are soft membranes with high in-plane stiffness and can potentially serve as a biocompatible, transferable, and implantable platform for stem cell culture. While the healthy proliferation of stem cells on various carbon platforms has been demonstrated, the chemical role of G and GO, if any, in guiding uncommitted stem cells toward differentiated cells is not known. Herein, we report that the strong noncovalent binding abilities of G allow it to act as a preconcentration platform for osteogenic inducers, which accelerate MSCs growing on it toward the osteogenic lineage. The molecular origin of accelerated differentation is investigated by studying the binding abilities of G and GO toward different growth agents. Interestingly, differentiation to adipocytes is greatly suppressed on G because insulin, which is a key regulator for the synthesis of fatty acids, is denatured upon π–π adsorption on G; in contrast, GO does not interfere with adipogenesis due to electrostatic binding with insulin. The different binding interactions and their subsequent influence on stem cell growth and differentiation are ascribed to different degrees of π–π stacking and electrostatic and hydrogen bonding mediated by G and GO.
There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness ...of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.
The methanolic fresh leaf extracts of
Macaranga gigantea, Macaranga pruinosa, Macaranga tanarius and
Macaranga triloba were screened for their antioxidant properties (AOP), tyrosinase inhibition and ...antibacterial activities. Total phenolic content (TPC), 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, ferric-ion reducing power (FRAP), ferrous-ion chelating (FIC) and lipid peroxidation inhibition (LPI) activities were used to evaluate the AOP. Modified 3,4-dihydroxy-
L-phenylalanine (
L-DOPA) method was used to determine tyrosinase inhibition activity, whereas antibacterial activity was determined using the disc-diffusion technique. TPC screening of the same species from different collection sites showed no significant difference between sites
. M.
triloba showed the highest ascorbic acid equivalent antioxidant activity (AEAC), FRAP and LPI values.
M. tanarius, which showed the lowest TPC, AEAC, FRAP and LPI activities, exhibited the best FIC activity.
M. pruinosa showed the best tyrosinase inhibition activity, whereas
M. triloba showed the best antibacterial activity against Gram-positive bacteria species, with minimal inhibition dosage (MID) values as low as 10
μg/disc.
Abstract
The human non-canonical inflammasome controls caspase-4 activation and gasdermin-D-dependent pyroptosis in response to cytosolic bacterial lipopolysaccharide (LPS). Since LPS binds and ...oligomerizes caspase-4, the pathway is thought to proceed without dedicated LPS sensors or an activation platform. Here we report that interferon-induced guanylate-binding proteins (GBPs) are required for non-canonical inflammasome activation by cytosolic
Salmonella
or upon cytosolic delivery of LPS. GBP1 associates with the surface of cytosolic
Salmonella
seconds after bacterial escape from their vacuole, initiating the recruitment of GBP2-4 to assemble a GBP coat. The GBP coat then promotes the recruitment of caspase-4 to the bacterial surface and caspase activation, in absence of bacteriolysis. Mechanistically, GBP1 binds LPS with high affinity through electrostatic interactions. Our findings indicate that in human epithelial cells GBP1 acts as a cytosolic LPS sensor and assembles a platform for caspase-4 recruitment and activation at LPS-containing membranes as the first step of non-canonical inflammasome signaling.
There have been limited data on the risk of onward transmission from individuals with Omicron variant infections who return to work after a 5-day isolation.
To evaluate the risk of transmission from ...healthcare workers (HCWs) with Omicron variant who returned to work after a 5-day isolation and the viable-virus shedding kinetics.
This investigation was performed in a tertiary care hospital, Seoul, South Korea. In a secondary transmission study, we retrospectively reviewed the data of HCWs confirmed as COVID-19 from March 14th to April 3rd, 2022 in units with five or more COVID-19-infected HCWs per week. In the viral shedding kinetics study, HCWs with Omicron variant infection who agreed with daily saliva sampling were enrolled between February and March, 2022.
Of the 248 HCWs who were diagnosed with COVID-19 within 5 days of the return of an infected HCW, 18 (7%) had contact with the returned HCW within 1–5 days after their return. Of these, nine (4%) had an epidemiologic link other than with the returning HCW, and nine (4%) had contact with the returning HCW, without any other epidemiologic link. In the study of the kinetics of virus shedding (N = 32), the median time from symptom onset to negative conversion of viable virus was four days (95% confidence interval: 3–5).
Our data suggest that the residual risk of virus transmission after 5 days of isolation following diagnosis or symptom onset is low.
The prevalence of depression may be affected by changes in psychiatric practices and the availability of online mental health information in the past two decades. This study aimed to evaluate the ...aggregate prevalence of depression in communities from different countries between 1994 and 2014 and to explore the variations in prevalence stratified by geographical, methodological and socio-economic factors. A total of 90 studies were identified and met the inclusion criteria (n = 1,112,573 adults) with 68 studies on single point prevalence, 9 studies on one-year prevalence, and 13 studies on lifetime prevalence of depression. A random-effects model meta-analysis that was performed to calculate the aggregate point, one-year and lifetime prevalence of depression calculated prevalences of 12.9%, 7.2% and 10.8% respectively. Point prevalence of depression was significantly higher in women (14.4%), countries with a medium human development index (HDI) (29.2%), studies published from 2004 to 2014 (15.4%) and when using self-reporting instruments (17.3%) to assess depression. Heterogeneity was identified by meta-regression and subgroup analysis, and response rate, percentage of women and year of publication, respectively, were determined contribute to depression prevalence. This meta-analysis allows benchmarking of the prevalence of depression during the era when online health information emerged, facilitating future comparisons.
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