The radiation of electromagnetic and mechanical waves depends not only on the intrinsic properties of the emitter but also on the surrounding environment. This principle has laid the foundation for ...the development of lasers, quantum optics, sonar, musical instruments and other fields related to wave–matter interaction. In the conventional wisdom, the environment is defined exclusively by its eigenstates, and an emitter radiates into and interacts with these eigenstates. Here we show experimentally that this scenario breaks down at a non-Hermitian degeneracy known as an exceptional point. We find a chirality-reversal phenomenon in a ring cavity where the radiation field reveals the missing dimension of the Hilbert space, known as the Jordan vector. This phenomenon demonstrates that the radiation field of an emitter can become fully decoupled from the eigenstates of its environment. The generality of this striking phenomenon in wave–matter interaction is experimentally confirmed in both electromagnetic and acoustic systems. Our finding transforms the fundamental understanding of light–matter interaction and wave–matter interaction in general, and enriches the intriguing physics of exceptional points.The modes of the radiation field generated from an emitter are usually determined by the eigenstates of the surrounding environment. However, this scenario breaks down in a non-Hermitian system, at the spectral degeneracy known as an exceptional point.
•Ocalcitinib insets into the hydrophobic pocket in the central beta barrel of HAG.•Binding between ocalcitinib and HAG has a moderate affinity.•The driven forces include mainly van der Waals forces, ...hydrogen bonding and hydrophobic interactions.•The alteration in the conformation of HAG occurred after binding with ocalcitinib.•The contribution of key residues to forming the stable ocalcitinib-HAG complex was discussed.
A powerful Janus kinase (JAK) inhibitor, ocalcitinib has been authorized for controlling pruritus and atopic dermatitis from canine allergic dermatitis and many kinds of cytokines. To further understand the drug action, the interaction between ocalcitinib and HAG was explored using multi-spectroscopic approaches combined with theoretical calculations. The results demonstrated that ocalcitinib effectively quenched the intrinsic fluorescence of HAG protein through a mixed quenching and formed a stable ocalcitinib–HAG complex that had the association constant of 104–105M−1, outlining that ocalcitinib binding to HAG protein had a moderate affinity. In the ocalcitinib–HAG complex, ocalcitinib implanted into the bucket-shaped hydrophobic chamber of HAG, leading to the slight variety in the hydrophobicity of the microenvironment encircled Trp-and Tyr-resides as well as the secondary structure of HAG. And, the driving forces that forms the ocalcitinib-HAG complex were mainly the hydrogen bonding interaction, Van der Waals forces, and hydrophobic interaction. It is also confirmed that the common metal ions like Ca2+, Mg2+, Fe3+, Zn2+, Cu2+, Co2+, Ni2+ ions) except K+ ion had a greater negative influence on the complexation between ocalcitinib and HAG. This study should conducive to estimating the pharmacological natures of ocalcitinib, comprehending the distribution and operation of the drug in the body, and developing novel medication devise.
Display omitted
Polypyrimidine tract-binding protein 1 (PTBP1) plays an essential role in splicing and is expressed in almost all cell types in humans, unlike the other proteins of the PTBP family. PTBP1 mediates ...several cellular processes in certain types of cells, including the growth and differentiation of neuronal cells and activation of immune cells. Its function is regulated by various molecules, including microRNAs (miRNAs), long non-coding RNAs (IncRNAs), and RNA-binding proteins. PTBP1 plays roles in various diseases, particularly in some cancers, including colorectal cancer, renal cell cancer, breast cancer, and glioma. In cancers, it acts mainly as a regulator of glycolysis, apoptosis, proliferation, tumorigenesis, invasion, and migration. The role of PTBP1 in cancer has become a popular research topic in recent years, and this research has contributed greatly to the formulation of a useful therapeutic strategy for cancer. In this review, we summarize recent findings related to PTBP1 and discuss how it regulates the development of cancer cells.
Integrated radar and communications (IRC) technology has become very important for civil and military applications in recent years, and IRC waveform design is a major challenge for IRC development. ...In this paper, we focus on the IRC waveform design based on the multi-symbol orthogonal frequency division multiplexing (OFDM) technique. In view of the defects resulting from high peak-to-mean envelope power ratios (PMEPRs) and high range sidelobes in IRC systems, an intelligent and effective IRC waveform design method jointly optimized with the PMEPR and peak-to-sidelobe ratio (PSLR) is proposed. Firstly, a flexible tone reservation (TR)-based IRC waveform structure is applied in both temporal and frequency domains, i.e., multi-symbol OFDM waveform. Secondly, the optimization problem considering PMEPR and PSLR and extending them to the Lp-norm form is reformulated. Then, the conjugate gradient of the objective function is analytically derived and the conjugate gradient algorithm (CGA) is presented to simultaneously improve the PMEPR and PSLR. Finally, the simulation results show that the proposed algorithm can efficiently generate IRC waveforms with an excellent PMEPR, PSLR, radar signal-to-noise ratio (SNR), and bit error rate (BER) performance.
TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise ...mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.
The tone reservation (TR) approach is mainly adopted to reduce the peak-to-mean envelope power ratio (PMEPR) of orthogonal frequency division multiplexing (OFDM) waveform with low TR ratio (TRR) in ...classic 4G communication systems. However, for the OFDM integrated radar and communication waveform, high TRR is necessary to simultaneously maintain the radar detection performance as well as communication performance. For cases with high TRR, the traditional waveform optimization algorithms have low execution efficiency and a poor PMEPR convergence level, and thus a new algorithm is needed. This paper proposes a new PMEPR optimization algorithm based on conjugate gradient. Firstly, by introducing the concept of Lp-norm, the PMEPR of the OFDM waveform is accurately remodeled as the objective function of the waveform optimization problem. Secondly, the conjugate gradient of the objective function is analytically derived to form the basis of the efficient PMEPR optimization. Finally, a PMEPR optimization algorithm based on the Polak–Ribière–Polyak (PRP) conjugate gradient is proposed. The simulation results verified the proposed algorithm in terms of optimization efficiency, as well as convergence level, and the initial experimental results suggested the practicality of the proposed algorithm.
Oxaliplatin (L-OHP) is one of the effective chemotherapeutic drugs for colorectal cancer (CRC). Further investigation into the molecular mechanism of chemoresistance could improve outcomes for ...patients with colorectal cancer. Recently, microRNAs have been reported as a key in drug resistance of tumors. In this study, we aimed to investigate the effects of miR-153-5p in L-OHP-resistant CRC cells, and its underlying mechanism. Downregulation of miR-153-5p was observed in CRC cells, while upregulation of miR-153-5p enhances the chemosensitivity of CRC/L-OHP cells. The autophagy of CRC/L-OHP cells was markedly increased after exposure to L-OHP but abolished by the upregulation of miR-153-5p. Dual-luciferase reporter assays validated that Bcl-2 was a direct target of miR-153-5p. In conclusion, our data suggested that miR-153-5p was a mediator of cisplatin resistance in colorectal cancer by affecting Bcl-2-mediated autophagy, indicating a new therapeutic target for CRC treatment.
MiR-153-5p was a mediator of cisplatin resistance in colorectal cancer by affecting Bcl-2-mediated autophagy
Abstract Molecular doping plays an important role in controlling the carrier concentration of organic semiconductors. However, the introduction of dopant counterions often results in increased ...energetic disorder and traps due to the molecular packing disruption and Coulomb potential wells. To date, no general strategy has been proposed to reduce the counterion-induced structural and energetic disorder. Here, we demonstrate the critical role of non-covalent interactions (NCIs) between counterions and polymers. Employing a computer-aided approach, we identified the optimal counterions and discovered that NCIs determine their docking positions, which significantly affect the counterion-induced energetic disorder. With the optimal counterions, we successfully reduced the energetic disorder to levels even lower than that of the undoped polymer. As a result, we achieved a high n-doped electrical conductivity of over 200 S cm −1 and an eight-fold increase in the thermoelectric power factor. We found that the NCIs have substantial effects on doping efficiency, polymer backbone planarity, and Coulomb potential landscape. Our work not only provides a general strategy for identifying the most suitable counterions but also deepens our understanding of the counterion effects on doped polymeric semiconductors.
COVID-19 caused by SARS-CoV-2 is a great threat to public health. We present the safety and immunogenicity data from a phase I trial in China of an mRNA vaccine (LVRNA009).
In the single-centre, ...double-blind, placebo-controlled and dose-escalation study, 72 healthy unvaccinated adults aged 18-59 years were randomized (3:1) to receive LVRNA009 with one of three vaccine dosage (25, 50 and 100 μg) or placebo, to evaluate for the safety, tolerability and immunogenicity of LVRNA009.
All these participants received two injections 28 days apart. No adverse events higher than grade 2 were reported during the study. A total of 30 participants (42 %) reported solicited adverse reactions during the first 14 days after vaccinations. Of the events reported, fever (n = 11, 15 %) was the most common systemic adverse reaction, and pain at the injection site (n = 17, 24 %) was the most frequent solicited local adverse reaction. Anti-S-protein IgG and neutralising antibodies were observed to have been induced 14 days after the first dose, significantly increased 7 days after the second dose, and remained at a high level 28 days after the second dose. Specific T-cell responses peaked 7 days and persisted 28 days after second vaccination.
LVRNA009 has demonstrated promising results in safety and tolerability at all three dose levels among Chinese adults. LVRNA009 at three dose levels could rapidly induce strong humoral and cellular immune responses, including binding and neutralising antibody production and IFN- γ secretion, which showed good immunogenicity.
Clinicaltrials.gov NCT05364047; Chictr.org.cn ChiCTR2100049349.
Cyclic polymers exhibit fascinating crystallization behaviors owing to the absence of chain ends and more compact conformations. In the current simulation, dynamic Monte Carlo simulations were ...performed to reveal the underlying mechanism of the effect of chain topology and chain length on crystallization of polymer in solutions containing one-dimensional nanofiller. Simulation results suggested that the filled cyclic polymers exhibit higher melting temperature, higher crystallization temperature, and faster crystallization rate than the analogous linear polymers of identical chain length, especially in the systems with relatively short chains. Based on the Thomson-Gibbs equation, we theoretically analyzed the difference in the melting point between the cyclic and linear polymers under different chain lengths, and derived the dependence of the ratio of the melting point of the linear polymers to that of its cyclic analogs on chain length. In addition, it was also observed that the nanofiller can induce the formation of nanohybrid shish-kebab structure during isothermal crystallization of all systems.
PDF
