The SARS-CoV-2 Omicron variant has become the dominant infective strain. We report the structures of the Omicron spike trimer on its own or in complex with ACE2 or an anti-Omicron antibody. Most Omicron mutations are located on the surface of the spike protein, which change binding epitopes to many current antibodies. In the ACE2 binding site, compensating mutations strengthen RBD binding to ACE2. Both the RBD and the apo form of the Omicron spike trimer are thermodynamically unstable. An unusual RBD-RBD interaction in the ACE2-spike complex supports the open conformation and further reinforces ACE2 binding to the spike trimer. A broad-spectrum therapeutic antibody, JMB2002, which has completed a Phase 1 clinical trial, maintains neutralizing activity against Omicron. JMB2002 binds to RBD differently from other characterized antibodies and inhibits ACE2 binding.
Tea tree oil (TTO) is a yellow liquid extracted from Melaleuca alternifolia. Although the antimicrobial activity of TTO has been known for a long time, its specific antimicrobial effects and mechanism underlying these remain poorly characterized. The present study investigated the chemical composition of TTO and the dynamics and mechanism of its antimicrobial activities in two bacterial and two fungal strains. Gas chromatography-mass spectrometry analysis identified alkenes and alcohols as the main constituents of TTO. Terpinen-4-ol was the most abundant individual component, accounting for approximately 23 % of the TTO. Poisoned food technique assessment showed that the minimum inhibitory concentrations of TTO for bacterial strains (Escherichia coli and Staphylococcus aureus) and fungal strains (Candida albicans and Aspergillus niger) were 1.08 and 2.17 mg/mL, respectively. Antimicrobial dynamic curves showed that with increasing concentrations of TTO, the rate of cell killing and the duration of growth lag phase increased correspondingly. These data indicated that TTO produced concentration and time-dependent antimicrobial effects. The minimum bactericidal and fungicidal concentrations of TTO were 2.17, 4.34, and 4.34 against E. coli, S. aureus, and C. albicans, respectively. However, A. niger conidia were not completely eradicated, even after 3 days in the presence of 17.34 mg/mL TTO. Transmission electron microscopy images indicated that TTO penetrated the cell wall and cytoplasmic membrane of all the tested bacterial and fungal strains. TTO may also penetrate fungal organelle membrane. These findings indicated that TTO maybe exerts its antimicrobial effects by compromising the cell membrane, resulting in loss of the cytoplasm and organelle damage, which ultimate leads to cell death.
Thelephora austrosinensis is described as a new species from southern China. Morphologically, it is closely related to T. ganbajun and T. vialis but is distinguished by its relatively smaller basidiomata with a thinner and more serrate or lobed margin, obviously longitudinally rugulose hymenial surface, and habitat in the broad-leaved forests. Based on the molecular phylogenetic analyses, sequences of the new species form a distinct clade which is close to T. ganbajun and T. vialis. Detailed morphological descriptions, colour photographs of the new species and comparisons with similar taxa are presented.
The Omicron variant of SARS-CoV-2 has rapidly become the dominant infective strain and the focus efforts against the ongoing COVID-19 pandemic. Here we report an extensive set of structures of the Omicron spike trimer by its own or in complex with ACE2 and an anti-Omicron antibody. These structures reveal that most Omicron mutations are located on the surface of the spike protein, which confer stronger ACE2 binding by nearly 10 folds but become inactive epitopes resistant to many therapeutic antibodies. Importantly, both RBD and the closed conformation of the Omicron spike trimer are thermodynamically unstable, with the melting temperature of the Omicron RBD decreased by as much as 7 degree, making the spiker trimer prone to random open conformations. An unusual RBD-RBD interaction in the ACE2-spike complex unique to Omicron is observed to support the open conformation and ACE2 binding, serving the basis for the higher infectivity of Omicron. A broad-spectrum therapeutic antibody JMB2002, which has completed Phase 1 clinical trial, is found to interact with the same two RBDs to inhibit ACE2 binding, in a mode that is distinguished from all previous antibodies, thus providing the structural basis for the potent inhibition of Omicron by this antibody. Together with biochemical data, our structures provide crucial insights into higher infectivity, antibody evasion and inhibition of Omicron.
Cordyceps guangdongensis can potently alleviate fatigue through reducing the accumulation of BLC; a functional constituent was the refined polysaccharide. This might become a new functional food for fatigue resistance.
In dense canopy, a reduction in red to far-red (R/FR) light ratio triggers shade avoidance responses (SARs) in Arabidopsis thaliana, a shade avoiding plant. Two red/far-red (R/FR) light photoreceptors, PHYB and PHYA, were reported to be key negative regulators of the SARs. PHYB represses the SARs under normal light conditions; however, the role of PHYA in the SARs remains elusive. We set up two shade conditions: Shade and strong Shade (s-Shade) with different R/FR ratios (0.7 and 0.1), which allowed us to observe phenotypes dominated by PHYB-and PHYA-mediated pathway, respectively. By comparing the hypocotyl growth under these two conditions with time, we found PHYA was predominantly activated in the s-Shade after prolonged shade treatment. We further showed that under s-Shade, PHYA inhibits hypocotyl elongation partially through repressing the brassinosteroid (BR) pathway. COP1 and PIF4,5 act downstream of PHYA. After prolonged shade treatment, the nuclear localization of COP1 was reduced, while the PIF4 protein level was much lower in the s-Shade than that in Shade. Both changes occurred in a PHYA-dependent manner. We propose that under deep canopy, the R/FR ratio is extremely low, which promotes the nuclear accumulation of PHYA. Activated PHYA reduces COP1 nuclear speckle, which may lead to changes of downstream targets, such as PIF4,5 and HY5. Together, these proteins regulate the BR pathway through modulating BES1/BZR1 and the expression of BR biosynthesis and BR target genes.
Materials with negative thermal expansion (NTE), which contract upon heating, are of great interest both technically and fundamentally. Here, we report giant NTE covering room temperature in mechanically milled antiperovksite GaN x Mn 3 compounds. The micrograin GaN x Mn 3 exhibits a large volume contraction at the antiferromagnetic (AFM) to paramagnetic (PM) (AFM-PM) transition within a temperature window (ΔT) of only a few kelvins. The grain size reduces to ~ 30 nm after slight milling, while ΔT is broadened to 50K. The corresponding coefficient of linear thermal expansion (α) reaches ~ -70 2 ppm/K, which is almost two times larger than those obtained in chemically doped antiperovskite compounds. Further reducing grain size to ~ 10 nm, ΔT exceeds 100 K and α remains as large as -30 ppm/K (-21 ppm/K) for x = 1.0 (x = 0.9). Excess atomic displacements together with the reduced structural coherence, revealed by high-energy Xray pair distribution functions, are suggested to delay the AFM-PM transition. By controlling the grain size via mechanically alloying or grinding, giant NTE may also be achievable in other materials with large lattice contraction due to electronic or magnetic phase transitions.
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