The methyltransferase like 3 （METTL3）-containing methyltransferase complex catalyzes the N6-methyladenosine （m6A） formation, a novel epitranscriptomic marker; however, the nature of this complex ...remains largely unknown. Here we report two new components of the human m6A methyltransferase complex, Wilms＇ tumor 1-associating protein （WTAP） and methyltransferase like 14 （METTL14）. WTAP interacts with METTL3 and METTL14, and is required for their localization into nuclear speckles enriched with pre-mRNA processing factors and for catalytic ac- tivity of the m6A methyltransferase in vivo. The majority of RNAs bound by WTAP and METTL3 in vivo represent mRNAs containing the consensus m6A motif. In the absence of WTAP, the RNA-binding capability of METTL3 is strongly reduced, suggesting that WTAP may function to regulate recruitment of the m6A methyltransferase complex to mRNA targets. Furthermore, transcriptomic analyses in combination with photoactivatable-ribonucleoside-en- hanced crosslinking and immunoprecipitation （PAR-CLIP） illustrate that WTAP and METTL3 regulate expression and alternative splicing of genes involved in transcription and RNA processing. Morpholino-mediated knockdown targeting WTAP and/or METTL3 in zebrafish embryos caused tissue differentiation defects and increased apoptosis. These findings provide strong evidence that WTAP may function as a regulatory subunit in the m6A methyltransferase complex and play a critical role in epitranscriptomic regulation of RNA metabolism.
Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes ...an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model.
A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively.
The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 μmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect EC50 of 0.98 μmol/L. The viral RNA yield in cells treated with 10 μmol/L CEP was 15,393-fold lower than in cells without CEP treatment (6.48 ± 0.02 × 10vs. 1.00 ± 0.12, t = 150.38, P < 0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 μmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46 ± 0.12, vs.1.00 ± 0.37, t = 2.42, P < 0.05) and viral replication (6.18 ± 0.95 × 10vs. 1.00 ± 0.43, t = 3.98, P < 0.05).
Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.
Antibiotic resistance in bacteria has become a great threat to global public health. Tigecycline is a next‐generation tetracycline that is the final line of defense against severe infections by ...pan‐drug‐resistant bacterial pathogens. Unfortunately, this last‐resort antibiotic has been challenged by the recent emergence of the mobile Tet(X) orthologs that can confer high‐level tigecycline resistance. As it is reviewed here, these novel tetracycline destructases represent a growing threat to the next‐generation tetracyclines, and a basic framework for understanding the molecular epidemiology and resistance mechanisms of them is presented. However, further large‐scale epidemiological and functional studies are urgently needed to better understand the prevalence and dissemination of these newly discovered Tet(X) orthologs among Gram‐negative bacteria in both human and veterinary medicine.
The novel mobile tetracycline‐inactivating enzymes, Tet(X3)–Tet(X5), could confer high‐level tigecycline resistance. They have been disseminated in diverse bacterial hosts from a wide range of ecological niches through promiscuous plasmids and ISCR2. This complex dissemination can be driven by selective pressure from the massive use of the early tetracyclines.
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). ...Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
A
bstract
The anomalous magnetic moments of the electron and the muon are interesting observables, since they can be measured with great precision and their values can be computed with excellent ...accuracy within the Standard Model (SM). The current experimental measurement of this quantities show a deviation of a few standard deviations with respect to the SM prediction, which may be a hint of new physics. The fact that the electron and the muon masses differ by two orders of magnitude and the deviations have opposite signs makes it difficult to find a common origin of these anomalies. In this work we introduce a complex singlet scalar charged under a Peccei-Quinn-like (PQ) global symmetry together with the electron transforming chirally under the same symmetry. In this realization, the CP-odd scalar couples to electron only, while the CP-even part can couple to muons and electrons simultaneously. In addition, the CP-odd scalar can naturally be much lighter than the CP-even scalar, as a pseudo-Goldstone boson of the PQ-like symmetry, leading to an explanation of the suppression of the electron anomalous magnetic moment with respect to the SM prediction due to the CP-odd Higgs effect dominance, as well as an enhancement of the muon one induced by the CP-even component.
Precise control of solid-state elastic waves' mode content and coherence is of great use nowadays in reinforcing mechanical energy harvesting/storage, nondestructive material testing, wave-matter ...interaction, high sensitivity sensing, and information processing, etc. Its efficacy is highly dependent on having elastic transmission channels with lower loss and higher degree of freedom. Here, we demonstrate experimentally an elastic analog of the quantum spin Hall effects in a monolithically scalable configuration, which opens up a route in manipulating elastic waves represented by elastic pseudospins with spin-momentum locking. Their unique features including robustness and negligible propagation loss may enhance elastic planar-integrated circuit-level and system-level performance. Our approach promotes topological materials that can interact with solid-state phonons in both static and time-dependent regimes. It thus can be immediately applied to multifarious chip-scale topological phononic devices, such as path-arbitrary elastic wave-guiding, elastic splitters and elastic resonators with high-quality factors.
The exploration of quantum‐inspired symmetries in optical and photonic systems has witnessed immense research interest both fundamentally and technologically in a wide range of subject areas in ...physics and engineering. One of the principal emerging fields in this context is non‐Hermitian physics based on parity‐time symmetry, originally proposed in the studies pertaining to quantum mechanics and quantum field theory and recently ramified into a diverse set of areas, particularly in optics and photonics. The intriguing physical effects enabled by non‐Hermitian physics and PT symmetry have enhanced significant application prospects and engineering of novel materials. In addition, there has been increasing research interest in many emerging directions beyond optics and photonics. Here, the state‐of‐the art developments in the field of complex non‐Hermitian physics based on PT symmetry in various physical settings are brought together, and key concepts, a background, and a detailed perspective on new emerging directions are described. It can be anticipated that this trendy field of interest will be indispensable in providing new perspectives in maneuvering the flow of light in the diverse physical platforms in optics, photonics, condensed matter, optoelectronics, and beyond, and will offer distinctive application prospects in novel functional materials.
As a quantum‐inspired symmetry paradigm in optical and photonic systems, non‐Hermitian physics based on parity‐time symmetry has gained significant research interest in a wide range of subjects, enabling intriguing physical effects and significant application prospects. The state‐of‐the‐art developments in this trendy field in various physical settings are discussed, and key concepts, background, and a detailed perspective on new emerging directions are also provided.
A topological insulator is a material with an insulating interior but time-reversal symmetry-protected conducting edge states. Since its prediction and discovery almost a decade ago, such a ...symmetry-protected topological phase has been explored beyond electronic systems in the realm of photonics. Electrons are spin-1/2 particles, whereas photons are spin-1 particles. The distinct spin difference between these two kinds of particles means that their corresponding symmetry is fundamentally different. It is well understood that an electronic topological insulator is protected by the electron’s spin-1/2 (fermionic) time-reversal symmetry
T
f
2
=
−
1
. However, the same protection does not exist under normal circumstances for a photonic topological insulator, due to photon’s spin-1 (bosonic) time-reversal symmetry
T
b
2
=
−
1
. In this work, we report a design of photonic topological insulator using the Tellegen magnetoelectric coupling as the photonic pseudospin orbit interaction for left and right circularly polarized helical spin states. The Tellegen magnetoelectric coupling breaks bosonic time-reversal symmetry but instead gives rise to a conserved artificial fermionic-like-pseudo time-reversal symmetry,
T
p
(
T
p
2
=
−
1
)
, due to the electromagnetic duality. Surprisingly, we find that, in this system, the helical edge states are, in fact, protected by this fermionic-like pseudo time-reversal symmetry Tp
rather than by the bosonic time-reversal symmetry Tb
. This remarkable finding is expected to pave a new path to understanding the symmetry protection mechanism for topological phases of other fundamental particles and to searching for novel implementations for topological insulators.
Recent explorations of topology in physical systems have led to a new paradigm of condensed matters characterized by topologically protected states and phase transition, for example, topologically ...protected photonic crystals enabled by magneto-optical effects. However, in other wave systems such as acoustics, topological states cannot be simply reproduced due to the absence of similar magnetics-related sound-matter interactions in naturally available materials. Here, we propose an acoustic topological structure by creating an effective gauge magnetic field for sound using circularly flowing air in the designed acoustic ring resonators. The created gauge magnetic field breaks the time-reversal symmetry, and therefore topological properties can be designed to be nontrivial with non-zero Chern numbers and thus to enable a topological sonic crystal, in which the topologically protected acoustic edge-state transport is observed, featuring robust one-way propagation characteristics against a variety of topological defects and impurities. Our results open a new venue to non-magnetic topological structures and promise a unique approach to effective manipulation of acoustic interfacial transport at will.
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