Anti-infective immune functions of type Ⅳ interferon in grass carp(Ctenopharyngodon idella):A novel antibacterial and antiviral interferon in lower vertebrates

Type Ⅳ interferon(IFN-υ)is a recently discovered cytokine crucial for host defense against viral infections.However,the role and mechanisms of IFN-υin bacterial infections remain unexplored.This study investigated the antibacterial and antiviral functions and mechanisms of grass carp(Ctenopharyngodon idella)IFN-υ(CiIFN-υ)both in vivo and in vitro.The CiIFN-υgene was first identified and characterized in grass carp.Subsequently,the immune expression of CiIFN-υsignificantly increased following bacterial challenge,indicating its response to bacterial infections.The eukaryotic recombinant expression plasmid of CiIFN-υwas then constructed and transfected into fathead minnow(FHM)cells.Supernatants were collected and incubated with four bacterial strains,followed by plate spreading and colony counting.Results indicated that CiIFN-υexhibited more potent antibacterial activity against gram-negative bacteria compared to gram-positive bacteria and aggregated gram-negative bacteria but not gram-positive bacteria.In vivo experiments further confirmed the antibacterial function,showing high survival rates,low tissue edema and damage,reduced tissue bacterial load,and elevated proinflammatory response at the early stages of bacterial infection.In addition,the antiviral function of CiIFN-υwas confirmed through in vitro and in vivo experiments,including crystal violet staining,survival rates,tissue viral burden,and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR).This study highlights the antibacterial function and preliminary mechanism of IFN-υ,demonstrating that IFN-υpossesses dual functions against bacterial and viral infections.

Multi-modal knowledge graph inference via media convergence and logic rule

Media convergence works by processing information from different modalities and applying them to different domains.It is difficult for the conventional knowledge graph to utilise multi-media features because the introduction of a large amount of information from other modalities reduces the effectiveness of representation learning and makes knowledge graph inference less effective.To address the issue,an inference method based on Media Convergence and Rule-guided Joint Inference model(MCRJI)has been pro-posed.The authors not only converge multi-media features of entities but also introduce logic rules to improve the accuracy and interpretability of link prediction.First,a multi-headed self-attention approach is used to obtain the attention of different media features of entities during semantic synthesis.Second,logic rules of different lengths are mined from knowledge graph to learn new entity representations.Finally,knowledge graph inference is performed based on representing entities that converge multi-media features.Numerous experimental results show that MCRJI outperforms other advanced baselines in using multi-media features and knowledge graph inference,demonstrating that MCRJI provides an excellent approach for knowledge graph inference with converged multi-media features.

The Effects of Infrastructure Projects on House Prices and Rents:Evidence from the HS2 Extension Cancellation in the UK

This paper uses the HS2 extension cancellation in November 2021 as a quasi-experiment to study its impact on house prices and rents in Leeds.Using a DiD approach on repeat sales and monthly rents,I compare property values near the HS2 station and proposed construction site before and after the announcement.Results show a 3.6%decrease in house prices and a 3.9%decline in rents near the station,while properties near the construction site experienced a 2.4%increase in prices and a 2.1%rise in rents.This is the first paper to analyse the HS2 cancellation effect using panel data methods.

CSN6 promotes tumorigenesis of gastric cancer by ubiquitin-independent proteasomal degradation of p16INK4a

Objective: CSN6 is a vital subunit of the constitutive photomorphogenesis 9(COP9) signalosome(CSN), which is responsible for development disorders and promotes ubiquitin-26 S proteasome-dependent degradation in vitro and vivo.Its role in the tumor development of gastric cancer remains unclear.In this study, we investigated the role of CSN6 in gastric cancer progression.Methods: Human gastric cancer samples were collected and immunohistochemistry was performed to identify the role of CSN6 in gastric cancer.The cell proliferation was measured by CCK-8 and the EdU incorporation method.Immunofluorescence localization and a co-immunoprecipitation study were used to show the interaction between the protein CSN6 and p16.Ubiquitination assay was performed to validate whether ubiquitination is involved in CSN6-mediated p16 degradation.BALB/c nude mice were used to produce a tumor model in order to test the effect of CSN6 on cancer growth in vivo.Results: CSN6 expression was dramatically increased in gastric cancer tissues compared with paired adjacent non-tumor tissues and CSN6 was correlated with worse overall and disease-specific survival.Additionally, we also found that CSN6 downregulated p16 protein expression, thereby promoting gastric cancer cell growth and proliferation.Moreover, CSN6 interacted with p16 and a proteasome activator REGγ(PA28γ), thereby facilitating ubiquitin-independent degradation of p16.Conclusions: CSN6 promoted the loss of p16-mediated tumor progression and played an important role in regulating ubiquitin-independent proteasomal degradation of p16.

Multi-objective Trajectory Planning Method based on the Improved Elitist Non-dominated Sorting Genetic Algorithm

Robot manipulators perform a point-point task under kinematic and dynamic constraints.Due to multi-degreeof-freedom coupling characteristics,it is difficult to find a better desired trajectory.In this paper,a multi-objective trajectory planning approach based on an improved elitist non-dominated sorting genetic algorithm(INSGA-II)is proposed.Trajectory function is planned with a new composite polynomial that by combining of quintic polynomials with cubic Bezier curves.Then,an INSGA-II,by introducing three genetic operators:ranking group selection(RGS),direction-based crossover(DBX)and adaptive precision-controllable mutation(APCM),is developed to optimize travelling time and torque fluctuation.Inverted generational distance,hypervolume and optimizer overhead are selected to evaluate the convergence,diversity and computational effort of algorithms.The optimal solution is determined via fuzzy comprehensive evaluation to obtain the optimal trajectory.Taking a serial-parallel hybrid manipulator as instance,the velocity and acceleration profiles obtained using this composite polynomial are compared with those obtained using a quintic B-spline method.The effectiveness and practicability of the proposed method are verified by simulation results.This research proposes a trajectory optimization method which can offer a better solution with efficiency and stability for a point-to-point task of robot manipulators.

Generalized Kinematics Analysis of Hybrid Mechanisms Based on Screw Theory and Lie Groups Lie Algebras

Advanced mathematical tools are used to conduct research on the kinematics analysis of hybrid mechanisms,and the generalized analysis method and concise kinematics transfer matrix are obtained.In this study,first,according to the kinematics analysis of serial mechanisms,the basic principles of Lie groups and Lie algebras are briefly explained in dealing with the spatial switching and differential operations of screw vectors.Then,based on the standard ideas of Lie operations,the method for kinematics analysis of parallel mechanisms is derived,and Jacobian matrix and Hessian matrix are formulated recursively and in a closed form.Then,according to the mapping relationship between the parallel joints and corresponding equivalent series joints,a forward kinematics analysis method and two inverse kinematics analysis methods of hybrid mechanisms are examined.A case study is performed to verify the calculated matrices wherein a humanoid hybrid robotic arm with a parallel-series-parallel configuration is considered as an example.The results of a simulation experiment indicate that the obtained formulas are exact and the proposed method for kinematics analysis of hybrid mechanisms is practically feasible.

Establishment of nude mice model of human osteosarcoma cell MG63 with different potential of metastasis

Objective: To establish a nude mice model of human osteosarcoma lung metastasis. Methods: The growth of human osteosarcoma cell sublines M8 and M6 was determined by MTT assay. 2 × 107 cells were injected into the tail vein of nude mice. Mice were sacrificed started on week 4 after injection, and lung metastases were evaluated under both mac-roscopic and microscopic observation with HE staining. Results: The growth of low-metastatic subline M6 was lower than high-metastatic sublines M8. Seventeen mice after injected M8 had occurred lung metastases while only one mice had oc-curred in M6 group. Moreover, M8 cells within metastases were arrangement disorder with variable nuclear hyperchromasia. Conclusion: A mouse model for human osteosarcoma cancer lung metastasis can be established by injection different ability of metastasis MG63 cells into tail vein.

Modeling hydrogen exchange of proteins by a multiscale method

We proposed a practical way for mapping the results of coarse-grained molecular simulations to the observables in hydrogen change experiments.By combining an atomic-interaction based coarse-grained model with an all-atom structure reconstruction algorithm,we reproduced the experimental hydrogen exchange data with reasonable accuracy using molecular dynamics simulations.We also showed that the coarse-grained model can be further improved by imposing experimental restraints from hydrogen exchange data via an iterative optimization strategy.These results suggest that it is feasible to develop an integrative molecular simulation scheme by incorporating the hydrogen exchange data into the coarse-grained molecular dynamics simulations and therefore help to overcome the accuracy bottleneck of coarse-grained models.

A 61-mJ,1-kHz cryogenic Yb:YAG laser amplifier

We report a diode-pumped rod-type Yb:YAG laser amplifier operating at 1 kHz.Cryogenic cooling method was adopted to make the Yb:YAG crystal work with four-level behavior.A single-frequency fiber laser acts as the seed in an actively Q-switched Yb:YAG oscillator.The resonator delivers 5.75-mJ pulses at 1 kHz with a pulse duration of approximately 40 ns.The pulses were amplified to 61 mJ in a four-pass rod-type Yb:YAG amplifier with optical-to-optical efficiency of 24%in the main amplifier.The M^(2)parameter of the output laser is<1.4.

Effectiveness and safety of acupoint catgut embedding combined with Chinese herbal medicine in chronic urticaria: A systematic review of randomized controlled trials

Objective:To evaluate the effectiveness and safety of acupoint catgut embedding(ACE)in combination with Chinese herbal medicine(CHM)in treating chronic urticaria(CU).Methods:We thoroughly searched Embase,PubMed,Cochrane Library,Web of Science,China National Knowledge Infrastructure(CNKI),Wangfang database,Chinese Scientific Journal Database(VIP),and Chinese biomedical literature database(SinoMed)for relevant studies from inception until May 2022.Randomized controlled trials(RCTs)on ACE combined with CHM for CU were included.Literature search,data extraction,and risk of bias assessment were independently conducted by two authors.Results:A total of 15 RCTs with 1065 participants were included in this review.Five trials reported that the combined therapy showed a higher total effective rate,and four trials reported that the combined therapy was associated with a lower level of serum immunoglobulin E.Furthermore,two,four,and four trials reported that the combined therapy was more effective in reducing itching degree,size,and number of wheals,respectively.The combined therapy was reported to be associated with a lower recurrence rate in three trials,and with a fewer adverse reaction rate in two trials.Conclusions:ACE in combination with CHM appears to be a safe and effective therapy for patients with CU.Given the relatively low quality of the included trials,these findings should be interpreted cautiously.Further high-quality RCTs are needed to confirm our findings.

Effect of tumor suppressor in lung cancer-1 on growth inhibition of MG63 cell line

Objective： The aim of this study was to establish the osteosarcoma cell sublines which stably expressing tumor suppressor in lung cancer-1 （TSLC1） gene and evaluate its effect on growth inhibition of human osteosarcoma cell line MG63. Methods： The recombinant plasmid pCI-TSLC1 was stably transfected into MG63 cells with Lipofectamine 2000. The posi- tive clones were developed by selection by G418. Biological characteristics of one of the 6 cell lines which highly expressing TSLC1, namely, the M8T were studied. Cell growth was analyzed with MTT assay. 2 x 10^7cells suspended in 0.2 mL phosphate buffered saline （PBS） were injected into the two flanks of 5-6-week-old female BALB/C nu/nu athymic nude mice. The volumes of subcutaneous of tumor growth were evaluated and calculated by the formula V= Length x Width x Height x 0.5 once a week. Results： The MST cell subline which stably expressing TSLC1 was characterized by Western blot. The genetic stability and purity of M8T cells were stable. TSLC1 significantly suppressed the growth of M8T cells in vitro. Moreover, the tumorigenicity of MST cells was suppressed in vivo. Conclusion： The osteosarcoma cell sublines MST which stably expressing TSLC1 had been successfully established. The ability of growth and metastasis of MST was significantly suppressed both in vitro and in vivo.

Pre-mating nitenpyram exposure in male mice leads to depression-like behavior in offspring by affecting tryptophan metabolism in gut microbiota

Several studies have confirmed that the health status of the paternal affects the health of the offspring,however,it remains unknown whether paternal exposure to pesticides affect the offspring health.Here,we used untargeted metabolomics and 16S rRNA sequencing technology,combined with tail suspension test and RT-qPCR to explore the effects of paternal exposure to nitenpyram on the neurotoxicity of offspring.Our results found that the paternal exposure to nitenpyram led to the offspring’s depressive-like behaviors,accompanied by the reduction of tryptophan content and the disorder of microbial abundance in the gut of the offspring.Further,we determined the expression of tryptophan metabolism-related genes tryptophanase(tnaA)and tryptophan hydroxylase 1(TpH1)in gut bacteria and colonic tissues.We found that tryptophan is metabolized to indoles rather than being absorbed into colonocytes,which coursed the reduce of tryptophan availability after nitenpyram exposure.In conclusion,our study deepens our understanding of the intergenerational toxic effects of pesticides.

Ultrabroadband second-harmonic generation via spatiotemporal-coupled phase matching

We propose a spatially chirped quasi-phase-matching(QPM)scheme that enables ultrabroadband second-harmonic-generation(SHG)by using a fan-out QPM grating to frequency-convert a spatially chirped fundamental wave.A“zerodispersion”4f system maps the spectral contents of ultrabroadband fundamental onto different spatial coordinates in the Fourier plane,where the fundamental is quasi-monochromatic locally in picosecond duration,fundamentally canceling high-order phase mismatch.A fan-out QPM grating characterized by a linear variation of the poling period along the transverse direction exactly supports the QPM of the spatially chirped beam.We theoretically demonstrate the SHG of an 810-nm,12.1-fs pulse into a 405-nm,10.2-fs pulse with a conversion efficiency of 77%.

A novel bat coronavirus with a polybasic furin-like cleavage site

The current pandemic of COVID-19 caused by a novel coronavirus,severe acute respiratory syndrome coronavirus-2(SARS-CoV-2),threatens human health around the world.Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2;however,coronavirus ecology in bats is still nascent.Here,we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats,collected from Hainan Province,China.Three coronaviruses,namely bat betacoronavirus(Bat CoV)CD35,Bat CoV CD36 and bat alpha-coronavirus CD30 were identified.Bat CoV CD35 genome had 99.5%identity with Bat CoV CD36,both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013(71.4%),followed by SARS-CoV-2(54.0%).Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade,and together with Bat Hp-betacoronavirus Zhejiang2013,was basal to the lineage of SARS-CoV-1 and SARS-CoV-2.Notably,Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2.The furin cleavage sites between CD35 and CD36 are identical.In addition,the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2,especially in one binding loop.In conclusion,this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.

Salicylic acid biosynthesis is not from phenylalanine in Arabidopsis

The phytohormone salicylic acid(SA)regulates biotic and abiotic stress responses in plants.Two distinct biosynthetic pathways for SA have been well documented in plants:the isochorismate(IC)pathway in the chloroplast and the phenylalanine ammonia-lyase(PAL)pathway in the cytosol.However,there has been no solid evidence that the PAL pathway contributes to SA biosynthesis.Here,we report that feeding Arabidopsis thaliana with Ring-13C-labeled phenylalanine(13C6-Phe)resulted in incorporation of the13C label not into SA,but into its isomer 4-hydroxybenzoic acid(4-HBA)instead.We obtained similar results when feeding13C6-Phe to the SA-deficient ics1 ics2 mutant and the SA-hyperaccumulating mutant s3h s5h.Notably,we detected13C6-SA when13C6-benzoic acid(BA)was provided,suggesting that SA can be synthesized from BA.Furthermore,despite the substantial accumulation of SA upon pathogen infection,we did not observe incorporation of13C label from Phe into SA.We also did not detect13C6-SA in PAL-overexpressing lines in the kfb01 kfb02 kfb39 kfb50 background after being fed13C6-Phe,although endogenous PAL levels were dramatically increased.Based on these combined results,we propose that SA biosynthesis is not from Phe in Arabidopsis.These results have important implications for our understanding of the SA biosynthetic pathway in land plants.

Temperature-regulated typeⅡgrass carp reovirus establishes latent infection in Ctenopharyngodon idella brain

Grass carp reovirus(GCRV)causes extensive infection and death in grass carp and black carp fingerlings,with a highly seasonal prevalence.Previous studies suggested that GCRV can become latent after primary infection.In this study,we investigated type II GCRV(GCRV-II)latency in asymptomatic grass carp with GCRV infection or exposure history.We found that during latent infection,GCRV-II was detectable only in the brain of grass carp,unlike the multi-tissue distribution observed in natural infection.GCRV-II only caused damage to the brain during latent infection,while in natural infection,brain,heart,and eye tissues had relatively higher viral loads.We also discovered viral inclusion bodies in infected fish brains.Additionally,GCRV-II distribution in grass carp was notably affected by ambient temperature,with the virus targeting the brain only during low temperatures and multi-tissue distribution during high temperatures.This study provides insights into the mechanisms of GCRV-II latent infection and reactivation and contributes to the prevention and control of GCRV pandemics.

帕博利珠单抗联合化疗一线治疗晚期三阴性乳腺癌的成本-效果分析

本文旨在从中国卫生体系角度评价帕博利珠单抗联合化疗治疗晚期TNBC的成本-效果。建立具有三种健康状态的Markov模型,该模型的模拟时限为10年,循环周期为21天。通过单因素敏感性分析和概率敏感性分析来验证模型的稳健性,进行情景分析来探讨中国患者援助计划(PAP)下帕博利珠单联合化疗治疗晚期TNBC的经济性。基础分析结果表明,帕博利珠单抗联合化疗可多获得0.67 QALYs,增量成本为$77096.78,ICER为115896.30$/QALY。单因素敏感性分析结果显示,帕博利珠单抗成本对结果的影响最大。概率敏感性分析结果显示,在中国的意愿支付阈值下(33782.23$/QALY),帕博利珠单抗联合化疗具有经济性的概率为0。从中国卫生体系角度来看,与安慰剂联合化疗相比,帕博利珠单抗联合化疗一线治疗晚期TNBC不具有成本-效果优势。如果考虑帕博利珠单抗纳入PAP,虽仍然不具有经济性,但是ICER更加接近于中国3倍人均GDP。

Glycoside-specific metabolomics combined with precursor isotopic labeling for characterizing plant glycosyltransferases

Glycosylation by uridine diphosphate-dependent glycosyltransferases(UGTs)in plants contributes to the complexity and diversity of secondary metabolites.UGTs are generally promiscuous in their use of acceptors,making it challenging to reveal the function of UGTs in vivo.Here,we described an approach that combined glycoside-specific metabolomics and precursor isotopic labeling analysis to characterize UGTs in Arabidopsis.We revisited the UGT72E cluster,which has been reported to catalyze the glycosylation of monolignols.Glycoside-specific metabolomics analysis reduced the number of differentially accumulated metabolites in the ugt72e1e2e3 mutant by at least 90%compared with that from traditional untargeted metabolomics analysis.In addition to the two previously reported monolignol glycosides,a total of 62 glycosides showed reduced accumulation in the ugt72e1e2e3 mutant,22 of which were phenylalanine-derived glycosides,including 5-OH coniferyl alcohol-derived and lignan-derived glycosides,as confirmed by isotopic tracing of[^(13)C_(6)]-phenylalanine precursor.Our method revealed that UGT72Es could use coumarins as substrates,and genetic evidence showed that UGT72Es endowed plants with enhanced tolerance to low iron availability under alkaline conditions.Using the newly developed method,the function of UGT78D2 was also evaluated.These case studies suggest that this method can substantially contribute to the characterization of UGTs and efficiently investigate glycosylation processes,the complexity of which have been highly underestimated.

Beta-and Novel Delta-Coronaviruses Are Identified from Wild Animals in the Qinghai-Tibetan Plateau, China

Outbreaks of severe virus infections with the potential to cause global pandemics are increasingly concerning. One type of those commonly emerging and re-emerging pathogens are coronaviruses(SARS-Co V, MERS-Co V and SARS-Co V-2).Wild animals are hosts of different coronaviruses with the potential risk of cross-species transmission. However, little is known about the reservoir and host of coronaviruses in wild animals in Qinghai Province, where has the greatest biodiversity among the world's high-altitude regions. Here, from the next-generation sequencing data, we obtained a known beta-coronavirus(beta-Co V) genome and a novel delta-coronavirus(delta-Co V) genome from faecal samples of 29 marmots, 50 rats and 25 birds in Yushu Tibetan Autonomous Prefecture, Qinghai Province, China in July 2019. According to the phylogenetic analysis, the beta-Co V shared high nucleotide identity with Coronavirus HKU24. Although the novel delta-Co V(Mt Co V) was closely related to Sparrow deltacoronavirus ISU42824, the protein spike of the novel delta-Co V showed highest amino acid identity to Sparrow coronavirus HKU17(73.1%). Interestingly, our results identified a novel host(Montifringilla taczanowskii) for the novel delta-Co V and the potential cross-species transmission. The most recent common ancestor(t MRCA) of Mt Co Vs along with other closest members of the species of Coronavirus HKU15 was estimated to be 289 years ago. Thus, this study increases our understanding of the genetic diversity of beta-Co Vs and deltaCo Vs, and also provides a new perspective of the coronavirus hosts.

A Yb:KGW dual-crystal regenerative amplifier

This study develops a Yb:KGW dual-crystal based regenerative amplifier.The thermal lensing and gain-narrowing effects are compensated by the dual-crystal configuration.Sub-nanojoule pulses are amplified to 1.5 mJ with 9 nm spectral bandwidth and 1 kHz repetition rate using chirped pulse amplification technology.Consequently,1.2 m J pulses with a pulse duration of 227 fs are obtained after compression.Thanks to the cavity design,the output laser was a near diffraction limited beam with M2 around 1.1.The amplifier has the potential to boost energy above 2 m J after compression and act as a front end for a future kilohertz terawatt-class diode-pumped Yb:KGW laser system.