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Puromycin is covalently added to the nascent chain of proteins by the peptidyl transferase activity of the ribosome and this event is normally followed by the dissociation of the puromycylated peptide. It was postulated that blocking the translocation of the ribosome with emetine could trap the puromycylated peptide on the ribosome, but evidence against this has recently been published (Hobson et al., 2020https://doi.org/10.7554/eLife.60048;Enam et al., 2020https://doi.org/10.7554/eLife.60303). In neurons, puromycylated nascent chains appear to remain in the ribosome even in the absence of emetine, yet direct evidence for this had been lacking. Using biochemistry and cryo-electron microscopy, we show that the puromycylated peptides remain in the ribosome exit channel in the large subunit in a subset of neuronal ribosomes stalled in the hybrid state. These results validate previous experiments to localize stalled polysomes in neurons and provide insight into how neuronal ribosomes are stalled. Moreover, in these hybrid-state ribosomes, anisomycin, which normally blocks puromycylation, competes poorly with puromycin in the puromycylation reaction, allowing a simple assay to determine the proportion of nascent chains in neurons stalled in this state. In early hippocampal neuronal cultures, over 50% of all nascent peptides are found in these stalled polysomes. These results provide new insights into the stalling mechanisms of neuronal ribosomes and suggest that puromycylated peptides can be used to reveal subcellular sites of hybrid-state stalled ribosomes in neurons.Significance StatementPuromycin can be covalently linked to the nascent polypeptide chain on ribosomes, followed by dissociation of the puromycylated polypeptide. Here we conclusively show that in stalled polysomes isolated from neuronal RNA granules, the puromycylated peptide instead remains in the polypeptide exit tunnel of the ribosome. This validates previous data using this technique to localize stalled polysomes in neurons and suggests a unique ribosomal conformation in these cells. Further evidence for the unique state of these ribosomes is the resistance of puromycylation to the inhibitor anisomycin, which prevents puromycylation in all other cellular contexts. These results provide insight into mechanism underlying neuronal ribosome stalling and resolve a controversy about the use of puromycin to localize translation in neurons.

A series of twelve two-coordinate coinage metal, Cu, Ag and Au, complexes with carbene-metal-amide structures were prepared and used to study the correlation of the overlap between the hole and electron NTOs with the electronic and photophysical properties of these TADF emitters.

Thermally activated delayed fluorescence (TADF) from linear two-coordinate coinage metal complexes is sensitive to the geometric arrangement of the ligands. Herein we realize the tuning of configuration from coplanar to orthogonal gradually by variation of substituents. In a complex with confined twist configuration, its blue emission peaking at 458 nm presents a high ΦPL of 0.74 and a short τTADF of 1.9 μs, which indicates a fast enough kr,TADF of 3.9×105 s-1 and a depressed knr of 1.4×105 s-1. Such outstanding luminescent properties are attributed to the proper overlap of HOMO and LUMO on Cu(I) d orbitals that guarantees not only small ΔEST but also sufficient transition oscillator strength for fast [[EQUATION]] . Vacuum-deposited blue OLEDs with either doped or host-free emissive layer present external quantum efficiencies over 20% and 10%, respectively, demonstrating the practicality of the configurationally confined strategy for efficient linear Cu(I) TADF emitters.

The chemical constituent investigation on the root bark of

We introduce a modified QHSS (MQHSS) iteration method for solving a class of complex symmetric linear systems, and prove that this MQHSS iteration method is convergent under certain conditions. We also consider acceleration of the MQHSS iteration by Krylov subspace methods. Numerical experiments show the good performance of the MQHSS iteration method.

A luminescent bimetallic AuI complex comprised of N-heterocyclic carbene (NHC) and carbazole (Cz) ligands, that is, (NHC')Au(NHC)AuCz has been synthesized and studied. Both carbene ligands in the bimetallic complex act as electron acceptors in tandem to increase the energy separation between the ground and excited state, which is higher than those found in either monometallic analogue, (NHC)AuCz and (NHC')AuCz. A coplanar geometry designed into the tandem complex ensures sufficient electronic coupling between the π-orbitals of the ligands to impart a strong oscillator strength to the singlet intra-ligand charge-transfer (1 ICT) transition. Theoretical modelling indicates that the emissive ICT excited state involves both NHC ligands. The tandem complex gives blue luminescence (λmax =480 nm) with a high photoluminescent quantum yield (ΦPL =0.80) with a short decay lifetime (τ=0.52 μs). Temperature-dependent photophysical studies indicate that emission is via thermally assisted delayed fluorescence (TADF) and give a small singlet-triplet energy difference (ΔEST =50 meV, 400 cm-1 ) consistent with the short TADF lifetime.

Phytochemical investigation on the rhizomes of Paris fargesii var. petiolata (Baker ex C. H. Wright) Wang et Tang led to the isolation of five previously undescribed steroidal saponins, parpetiosides A-E (1-5), and six known analogs (6-11). Their structures were established by extensive spectroscopic data analysis and chemical methods. Compound 5 was a rare steroidal saponin with disaccharide moiety linked at C-26 of dehydrokryptogenin that was hardly seen in the genus Paris. The cytotoxicities of the isolated compounds against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated, and compound 1 displayed certain inhibitory effect with IC

For the discrete linear system resulted from the considered steady-state space-fractional diffusion equations, we propose an improved scaled HSS (ISHSS) iteration method and discuss its convergence theory. Then, we construct a fast ISHSS (FISHSS) preconditioner to accelerate the convergence rates of the Krylov subspace iteration methods. We discuss the spectral properties of the FISHSS preconditioning matrix. Numerical experiments show the good performance of the FISHSS preconditioner.

A series of (carbene)Au(I)(aryl) complexes are reported. The nature of the lowest excited state in these complexes changes character from metal-to-ligand charge transfer (MLCT) to interligand charg...

The chemical constituent investigation on the root bark of Ailanthus altissima leads to the isolation of a new β-carboline alkaloid, 14(S),15-dihydroxy-6-methoxy-β-carboline (1), along with nine known alkaloids. The structure of new compound was elucidated on basis of extensive spectroscopic analysis, especially two-dimensional (2D) NMR techniques and the absolute configuration of C-14 was determined by ECD calculation. The neuroprotective effect of the isolated compounds on PC12 cells against the serum deprivation injury was evaluated by MTT method. As a result, compound 7 revealed protective effect on PC12 cells and the cell survival rate was significantly increased.

This study aimed to clarify the characteristics of Tn7-derivatives transposons in MDR Proteus mirabilis strains isolated from anal swabs of chicken and swine in China from 2015-2020.The Tn7 tnsA gene was screened in 207 P. mirabilis isolates by polymerase chain reaction (PCR). These strains were subjected to antimicrobial susceptibility testing. Illumina Hiseq (200 × coverage) was used for genome sequencing. Transposon maps were completed by PCR and Sanger sequencing and analysed by BLAST.The Tn7 tnsA gene was detected in 21 strains by PCR. Eight novel Tn7-derivatives, named Tn6667, Tn6668, Tn6669, Tn6670, Tn7095, Tn7096, Tn7097 and Tn7098, were characterised. Three types of hybrid class 2/1 integrons were found at the right end of Tn7 derivatives. A novel Tn7-like transposon Tn6666 with an active integrase gene intI2, whose transposition module shows 93% nucleotide identity to the corresponding region of Tn7, was characterised in three strains. Tn6666 is also found next to Tn7097 or Tn7098 in the chromosomes of two clonally related P. mirabilis strains. The number of resistance genes carried by the novel transposons varied from 1 to 18. A novel variant of class A extended-spectrum beta-lactamase gene, blaOur study characterised diverse novel Tn7-derivatives and a new Tn7-like transposon in P. mirabilis. An active integrase gene intI2 might promote the diversification of Tn7-like transposons. More attention should be paid to the prevalence and evolution of Tn7-derivatives and Tn7-like transposons and antimicrobial resistance genes they carry.

Aiming at the complex structure, small output displacement, and low positioning accuracy of the two-degree-of-freedom (2-DOF) precision positioning platform, theoretical analyses and experimental tests are carried out so that the platform has the characteristics of compact structure, large output stroke, and high positioning accuracy. First, to optimize the structural parameters of the positioning platform, a modeling method to improve the modeling accuracy of the compliant mechanism of the positioning platform is proposed. A static model of the positioning platform based on Euler–Bernoulli beam theory and the sixth-order compliance matrix method is established, and the accuracy of the model is verified by simulation. In addition, the single-objective genetic optimization algorithm is used to optimize the structural size parameters of the positioning platform, and the optimal solution set of the structural size parameters of the positioning platform is obtained by taking the displacement amplification rate of the positioning platform as the optimization target. Finally, according to theoretical and simulation analysis and optimization results, an experimental prototype was fabricated, and a series of experimental tests were carried out on the working stroke, displacement magnification, and output stiffness. The experimental results show that the displacement magnification of the positioning platform reaches 3.39, the positioning stroke is 89.2 × 85.9 µm2, and the displacement resolutions of the x-axis and y-axis are 35 and 31 nm, respectively. The positioning platform designed in this paper meets the requirements of large output stroke and high positioning accuracy.

To investigate whether Hydrolyzed Seawater Pearl tablet (HSPT) could modulate the Th1/Th2 imbalance in an immunosuppressed mouse model with Th1 to Th2 shift induced by Cyclosporine A (CsA) which can be used in the clinical treatment of Th2 to Th1 shift diseases, and explore the possible mechanism for the adjuvant therapeutic efficacy of HSPT on recurrent respiratory infections (RRI) and acquired immune deficiency syndrome (AIDS).The mice were randomly divided into six groups of five animals each, namely normal group, model group, lentinan polysaccharide tablet (LPT) group and three HPST treated groups. HPST treated groups were administered with HPST (0.51, 1.02, 2.04 g/kg) via intragastric gavage (i.g) for 30 consecutive days. LPT used as reference drug for positive control, LPT group was administered with LPT (8.2 mg/kg) for 30 consecutive days. Normal group and model group were received distilled water. The animals in model group, LPT group and HPST treated groups were injected intraperitoneally with CsA (50 mg/kg) to establish the immunosuppressed mice model with Th1 to Th2 shift on the 20th, 22nd and 24th day, one hour after the administration of the respective treatment. Animals were sacrificed one hour after the last administration to collect blood and splenic tissue. The proportion of T cells including CD8+ and CD4+ T cells, Th1 and Th2 in peripheral blood of experimental mice were measured by flow cytometric. The protein level in serum and mRNA level in splenic tissue of experimental mice for interleukin (IL)-2, IL-12, interferon-γ (IFN-γ), IL-4, IL-6, IL-10 and IL-13 were measured by enzyme linked immunosorbent assay and fluorescence quantitative polymerase chain reaction respectively.HSPT elevated the proportion of T cells including both CD8+ and CD4+ T cells, in which the proportion of Th1 and Th2 cells increased, while the ratio of Th1/Th2 cells decreased in peripheral blood of the immunosuppressed mouse model with Th1 to Th2 shift induced by CsA. Furthermore, HSPT elevated both protein and mRNA level of Th1-type cytokines IL-2 and IFN-γ, while had no significant effect on protein and mRNA level of Th1-type cytokine IL-12 and Th2-type cytokines IL-4, IL-6, IL-10, IL- 13 in mouse model.Our findings suggest that HSPT can increase proportion of T cells including both CD8+ and CD4+ T cells and induce Th2 to Th1 shift in both cells and cytokines, which probably was the mechanism to account for the adjuvant therapeutic efficacy of HSPT on RRI and AIDS.

For the discrete linear system resulting from certain steady-state space-fractional diffusion equations, we construct a lopsided scaled HSS (LSHSS) iteration method and establish its convergence theory. From the LSHSS, we obtain the corresponding matrix splitting preconditioner. By further replacing the involved Toeplitz matrix with certain circulant matrix, we construct a fast LSHSS (FLSHSS) preconditioner in order to accelerate the convergence rates of the Krylov subspace iteration methods. Theoretical analyses and numerical experiments show good performance of the FLSHSS preconditioning.

The emergence of the phenicol-oxazolidinone-tetracycline resistance gene poxtA becomes a significant challenge for public health, since it confers a decreased susceptibility not only to the last resort drug linezolid, but also to florfenicol and doxycycline widely used in veterinary medicine. To determine the dissemination mechanism of poxtA in enterococci isolates from different healthy pigs in the swine farm, a total of 178 florfenicol-resistant enterococci isolates were collected from 400 fresh faecal swabs in a swine farm in China. The poxtA gene was detected in 11 (6.18 %) enterococci isolates, including 8 E. faecium, 2 E. hirae and 1 E. casseliflavus isolates. Whole genome sequencing indicated that the eight poxtA-harbouring E. faecium strains belonged to four different sequence types, including ST156 and three new STs, ST1818, ST1819 and ST1820. Five out of the 11 poxtA-positive enterococci isolates also harboured optrA gene. Moreover, E. casseliflavus strain DY31 co-harboured poxtA, optrA and cfr. Seven different poxtA-harbouring plasmids were obtained through Nanopore combined with Illumina sequencing. The poxtA-harbouring plasmids exhibited high genetic variation, six out of which belonged to rep2 plasmid of Inc18 family. The poxtA gene was flanked by IS1216E in the left and/or right ends.The optrA and cfr genes were located on different plasmids, respectively, but those genes could be co-transferred with poxtA gene into the recipient E. faecalis strain by electrotransformation. Our study highlights that both clonal spread and horizontal transfer mediated by Inc18 plasmid and IS1216E promote the dissemination of poxtA in enterococci isolates from different healthy pigs in the swine farm.

Objective To explore the change of intestinal microecology in patients with primary Sjogren's syndrome (pSS) and correlation with disease activity, and also discuss the therapy effect of Yangyin Yiqi Huoxue Recipe (, YYHD). Methods Sixteen pSS patients were enrolled in the present study, who received 3-month treatment of YYHR, 200 mL orally twice daily. Their pre-and post-test ESSDAI scores, erythrocyte sedimentation rate (ESR) and serum immunoglobulin G (IgG) levels were measured respectively. The 16SrDNA metagenomic sequencing was used to detect and analyze the abundance and diversity of intestinal bacteria flora and the proportion of bacteria at the levels of phylum, family, and genus, in comparision with those of 6 healthy subjects in the control group. Results The abundance and diversity of intestinal bacteria flora in pSS patients were lower than those of healthy subjects (P 0.05). Conclusions There exists an imbalance of intestinal microecology in pSS patients, which can be improved through the treatment with YYHD. Besides, such treatment can also improve the disease activity and adjust the diversity of intestinal bacteria flora, the composition and the abundance of intestinal flora.

An understanding of the factors limiting the open-circuit voltage (V-oc) and related photon energy loss mechanisms is critical to increase the power conversion efficiency (PCE) of small-molecule organic solar cells (OSCs), especially those with near-infrared (NIR) absorbers. In this work, two NIR boron dipyrromethene (BODIPY) molecules are characterized for application in planar (PHJ) and bulk (BHJ) heterojunction OSCs. When two H atoms are substituted by F atoms on the peripheral phenyl rings of the molecules, the molecular aggregation type in the thin film changes from the H-type to J-type. For PHJ devices, the nonradiative voltage loss of 0.35 V in the J-aggregated BODIPY is lower than that of 0.49 V in the H-aggregated device. In BHJ devices with a nonradiative voltage loss of 0.35 V, a PCE of 5.5% is achieved with an external quantum efficiency (EQE) maximum of 68% at 700 nm.

This review is an update on recent developments in emissive iridium(III) phosphorescent complexes and their applications in organic light-emitting diodes (OLEDs). The emphasis is focused on complexes with emission colors spanning the whole visible spectral region, which is extremely important for applications of OLEDs in display and white-light luminance. In each color section, materials are classified according to their coordination configuration, including homoleptic, heteroleptic and tridentate, trying to clarify the relationship between the molecular structure and the photophysical properties. Since the emission color, photoluminescence efficiency and carrier mobility of the phosphors are critical for device performances, we endeavor to dig out these values along with the measuring methods from the publications, and rational chemical modifications aiming for high efficiency and carrier mobility with different colors are also discussed.

At the stage where China’s economic growth has shifted from high speed to high quality, how to build a sustainable development system with complementary high-quality resources through the integration of culture and tourism industries is the core issue. Since the 26 proposals for the integration of Beijing’s culture and tourism industries were put forward, Beijing is gradually building a sample of integrated culture and tourism development. In this paper, the theory of physics coupling is applied to the research on industrial integration, and a comprehensive evaluation index system is formulated. At the same time, the relative development model, coupling degree model, and coupling coordination degree model were used to empirically analyze the integrated development of the culture and tourism industries in Beijing from 2005 to 2017. The research results show that the degree of coupling and coordination of Beijing’s culture and tourism industry experienced three phases of mild imbalance, primary coordination, moderate coordination during the statistical period, and the integration effect gradually improved. Based on this, this article puts forward policy suggestions that are conducive to the further coordinated development of Beijing’s culture industry and tourism industry.

Purpose: To explore the main active ingredients and mechanism of Yangyin Yiqi Huoxue (YYYQHX) Recipe in treating Sjogren’s syndrome.Methods: The main active ingredients of Yangyin Yiqi Huoxue(YYYQHX) Recipe were obtained through UPLC-LTQ-Orbitrap-MSn research technical analysis. Subsequently, the main active ingredients were analyzed by network pharmacology to explore their important targets and biological processes. Finally, the important target M3 muscarinic acetylcholine receptor (CHRM3) gene was verified by cytological experiments.Results: We identified 41 active ingredients in the YYYQHX Recipe, and identified 26 potential targets through network pharmacology methods. According to the network analysis and literature research, CHRM3 is one of the main targets of YYYQHX in the treatment of Sjogren’s syndrome. We observed the effect of YYYQHX on the CHRM3 and aquaporin 5(AQP5) genes using cytological experiments. The results showed that YYYQHX significantly increased the expression of CHRM3 and AQP5 in submandibular gland cells. This may be the mechanism of YYYQHX Recipe in improving symptoms such as dry mouth in Sjogren’s syndrome.Conclusions: This study provides a strategy for understanding the mechanism of action of YYYQHX in treating Sjogren’s syndrome by combining UPLC-LTQ-Orbitrap-MS research, network pharmacology, and experimental validation.

For the saddle-point problems, we discuss and analyze the updated preconditioned Hermitian and skew-Hermitian splitting (UPHSS) iteration method in detail. On this basis, we introduce a two-stage iteration method for the UPHSS iteration method. Theoretical analysis shows that the UPHSS and two-stage UPHSS iteration methods are convergent to the unique solution of the saddle-point linear system when the parameter is suitably chosen. Numerical examples show the correctness of the theory and the effectiveness of these methods.

Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease with a long duration of illness, for which there is no cure. Patients often suffer from anxiety and depression due to various reasons, exhibiting a decline in their quality of life. Chinese medicine (CM) has certain advantages in the treatment of pSS, which not only helps relieve clinical symptoms and improve treatment outcomes, but also reduces anxiety and depression and improves the quality of life. Therefore, CM should be considered as early as possible given its effectiveness and synergistic effects in treating pSS.

Purpose To investigate the effect of total glucoside of paeony (TGP) on gut microbiota in NOD mice with Sjögren’s syndrome (SS), using high-throughput sequencing of 16SrRNA gene. Methods Twenty-four NOD mice were randomly assigned to 4 groups (n = 6 per group): sham group receiving deionized water (0.4 ml), hydroxychloroquin group receiving hydroxychloroquin (0.4 ml), TGP group receiving TGP (0.4 ml), and TGP + hydroxychloroquin group receiving 0.4 ml TGP and 0.4 ml hydroxychloroquin. Balb/c mice (n = 6) receiving 0.4 ml deionized water were used as a control group. After intragastric injection of drugs for 8 weeks, feces were collected for high-throughput sequencing of 16SrRNA gene. Results The sequencing of 16SrRNA gene resulted in 3686 OTUs, and 10 phyla and 69 genera were identified. Compared with the control group, the indices of Chao, Ace and Shannon in the other 4 groups were significantly lower (P Conclusions TGP increases the growth of many key beneficial bacteria, inhibits the growth of dominant pathogenic bacteria, and increases the diversity and abundance of gut microorganisms, especially when combined with hydroxychloroquine. Our findings suggest that TGP may be effective to treat SS by improving the microecological structure of the gut.