Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer

Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment.

SciCN:A Scientific Dataset for Chinese Named Entity Recognition

Named entity recognition(NER)is a fundamental task of information extraction(IE),and it has attracted considerable research attention in recent years.The abundant annotated English NER datasets have significantly promoted the NER research in the English field.By contrast,much fewer efforts are made to the Chinese NER research,especially in the scientific domain,due to the scarcity of Chinese NER datasets.To alleviate this problem,we present aChinese scientificNER dataset–SciCN,which contains entity annotations of titles and abstracts derived from 3,500 scientific papers.We manually annotate a total of 62,059 entities,and these entities are classified into six types.Compared to English scientific NER datasets,SciCN has a larger scale and is more diverse,for it not only contains more paper abstracts but these abstracts are derived from more research fields.To investigate the properties of SciCN and provide baselines for future research,we adapt a number of previous state-of-theart Chinese NER models to evaluate SciCN.Experimental results show that SciCN is more challenging than other Chinese NER datasets.In addition,previous studies have proven the effectiveness of using lexicons to enhance Chinese NER models.Motivated by this fact,we provide a scientific domain-specific lexicon.Validation results demonstrate that our lexicon delivers better performance gains than lexicons of other domains.We hope that the SciCN dataset and the lexicon will enable us to benchmark the NER task regarding the Chinese scientific domain and make progress for future research.The dataset and lexicon are available at:https://github.com/yangjingla/SciCN.git.

An Ethogram of the Toad-headed Lizard Phrynocephalus vlangalii during the Breeding Season

In this study, we intended to construct an ethogram of the toad-headed lizard Phrynocephalus vlangalii by classifying and describing its behaviors using the Posture-act-environment （PAE） method. Through direct field observation and video recording, we obtained eight postures, sixty-two acts and ten environments, and thus we formed an ethogram consisting of eighty-three behaviors encoded with PAE. A complete ethogram for a species could provide systematic behavioral information which helps to understand the connections among related behaviors and provides background information for specific behavioral study, hence the present ethogram will be greatly useful for future behavioral studies on P. vlangalii as well as other Phrynocephalus species.

A Two-Phase Paradigm for Joint Entity-Relation Extraction

An exhaustive study has been conducted to investigate span-based models for the joint entity and relation extraction task.However,these models sample a large number of negative entities and negative relations during the model training,which are essential but result in grossly imbalanced data distributions and in turn cause suboptimal model performance.In order to address the above issues,we propose a two-phase paradigm for the span-based joint entity and relation extraction,which involves classifying the entities and relations in the first phase,and predicting the types of these entities and relations in the second phase.The two-phase paradigm enables our model to significantly reduce the data distribution gap,including the gap between negative entities and other entities,aswell as the gap between negative relations and other relations.In addition,we make the first attempt at combining entity type and entity distance as global features,which has proven effective,especially for the relation extraction.Experimental results on several datasets demonstrate that the span-based joint extraction model augmented with the two-phase paradigm and the global features consistently outperforms previous state-ofthe-art span-based models for the joint extraction task,establishing a new standard benchmark.Qualitative and quantitative analyses further validate the effectiveness the proposed paradigm and the global features.

Effect of Empowering Education on Refined Nursing of Patients with Internal Double J Tubes after Surgery for Ureteral Stricture

Objective: To investigate the effect of the theory of enabling education on the fine management of patients with internal double J tubes after ureteral stricture. Methods: Eighty patients with built-in double J tubes after ureteral stricture were selected from the urology department of a grade a hospital in Guangzhou. The patients were divided into control group and observation group by random number method, with 40 patients in each group. The control group received refined nursing after surgery, while the observation group received refined nursing including the theory of empowerment education after surgery on the basis of the control group. Results: After the intervention, the observation group had a higher standard rate of quality indicators, higher self-efficacy score than the control group (P ≤ 0.05), lower scores of ureteral stent-related symptoms, urinary system symptoms, pain symptoms, total health status, job performance, additional problems and total scores than the control group (P ≤ 0.05), and statistically significant differences were found in the total health status dimension and total scores (P ≤ 0.01). The nursing satisfaction survey, the scores of clinical nursing, health education, psychological counseling and nurse-patient communication were all higher than those in the control group (P ≤ 0.05), and the differences in health education and nurse-patient communication were statistically significant (P ≤ 0.01). Conclusion: The theory of enabling education can improve patients’ self-nursing level, promote the implementation of refined nursing quantitative indicators and nursing measures, relieve the poor symptoms of ureteral stricture patients, and improve patients’ satisfaction with nursing work.

Tracking of Labelled Stem Cells Using Molecular MR Imaging in a Mouse Burn Model <i>in Vivo</i>as an Approach to Regenerative Medicine

Therapies based on stem cell transplants offer significant potential in the field of regenerative medicine. Monitoring the fate of the transplanted stem cells in a timely manner is considered one of the main limitations for long-standing success of stem cell transplants. Imaging methods that visualize and track stem cells in vivo non-invasively in real time are helpful towards the development of successful cell transplantation techniques. Novel molecular imaging methods which are non-invasive particularly such as MRI have been of great recent interest. Hence, mouse models which are of clinical relevance have been studied by injecting contrast agents used for labelling cells such as super-paramagnetic iron-oxide (SPIO) nanoparticles for cellular imaging. The MR techniques which can be used to generate positive contrast images have been of much relevance recently for tracking of the labelled cells. Particularly when the off-resonance region in the vicinity of the labeled cells is selectively excited while suppressing the signals from the non-labeled regions by the method of spectral dephasing. Thus, tracking of magnetically labelled cells employing positive contrast in vivo MR imaging methods in a burn mouse model in a non-invasive way has been the scope of this study. The consequences have direct implications for monitoring labeled stem cells at some stage in wound healing. We suggest that our approach can be used in clinical trials in molecular and regenerative medicine.

High-throughput sequencing exclusively identified a novel Torque teno virus genotype in serum of a patient with fatal fever

Torque teno virus(TTV) has been found to be prevalent world-wide in healthy populations and in patients with various diseases, but its etiological role has not yet been determined. Using high-throughput unbiased sequencing to screen for viruses in the serum of a patient with persistent high fever who died of suspected viral infection and prolonged weakness, we identified the complete genome sequence of a TTV(isolate Hebei-1). The genome of TTV-Hebei-1 is 3649 bp in length, encoding four putative open reading frames, and it has a G+C content of 49%. Genomic comparison and a BLASTN search revealed that the assembled genome of TTV-Hebei-1 represented a novel isolate, with a genome sequence that was highly heterologous to the sequences of other reported TTV strains. A phylogenetic tree constructed using the complete genome sequence showed that TTV-Hebei-1 and an uncharacterized Taiwan Residents strain, TW53A37, constitute a new TTV genotype. The patient was strongly suspected of carrying a viral infection and died eventually without any other possible causes being apparent. No virus other than the novel TTV was identified in his serum sample. Although a direct causal link between the novel TTV genotype infection and the patient's disease could not be confirmed, the findings suggest that surveillance of this novel TTV genotype is necessary and that its role in disease deserves to be explored.

Passively Q-switched diode-pumped Tm,Ho:LuVO4 laser with a black phosphorus saturable absorber

We presented a passively Q-switched(PQS) diode-pumped c-cut Tm, Ho:LuVO_4 laser with a black phosphorus saturable absorber for the first time.Under PQS mode, an average output power of 0.86 W and a peak power of 2.32 W were acquired from the Tm, Ho:LuVO4 laser with the pump power of 14.55 W, corresponding to a pulse width of 2.89 μs,a pulse repetition rate of 71.84 kHz, and a pulse energy of about 6.70 μJ.

Nonhuman primate models of focal cerebral ischemia

Rodents have been widely used in the production of cerebral ischemia models. However, successful therapies have been proven on experimental rodent stroke model, and they have often failed to be effective when tested clinically. Therefore, nonhuman primates were recommended as the ideal alternatives, owing to their similarities with the human cerebrovascular system, brain metabolism, grey to white matter ratio and even their rich behavioral repertoire. The present review is a thorough summary of ten methods that establish nonhuman primate models of focal cerebral ischemia; electrocoagulation, endothelin-1-induced occlusion, microvascular clip occlusion, autologous blood clot embolization, balloon inflation, microcatheter embolization, coil embolization, surgical suture embolization, suture, and photochemical induction methods. This review addresses the advantages and disadvantages of each method, as well as precautions for each model, compared nonhuman primates with rodents, different species of nonhuman primates and different modeling methods. Finally it discusses various factors that need to be considered when modelling and the method of evaluation after modelling. These are critical for understanding their respective strengths and weaknesses and underlie the selection of the optimum model.

Structure and properties of CIGS films based on one-stage RF-sputtering process at low substrate temperature

Currently, Nanjing South Railway Stationplanning to implement slate roof renovation is integratingsolar cell modules into traditional roof materials to generateclean energy. Copper–indium–gallium diselenide（CuIn1-xGaxSe2, CIGS） is one of the most promisingmaterials for thin film solar cells. Cu（In1-xGax）Se2 filmswere deposited by a one-step radio frequency magnetronsputtering process at low substrate temperature. X-raydiffraction, Raman, scanning electron microscopy, energydispersiveX-ray spectroscopy, and electrical and opticalmeasurements were carried out to investigate the depositedfilms. The results reveal that a temperature of 320 C iscritical for near-stoichiometric CIGS films with uniformsurface morphology. Cu-rich phase particulates are foundat less than this temperature. The sample deposited at380 C gives well-crystalline single-phase CIGS film.Furthermore, the electrical and optical performances of theabsorber layer are improved significantly with theincreasing substrate temperature.

Seeding Performance Simulations and Experiments for a Spoon- Wheel Type Precision Cottonseed-Metering Device Based on EDEM

To study the effects of seed metering on seeding performance under different motion parameters,a simulation model for a spoonwheel type seeder was established.A seed meter was tested by using EDEM(Engineering Discrete Element Method)software to simulate its working process at different speeds and tilt angles.The trajectories of individual cottonseeds in the seed-metering device were obtained,concurrently,the stress trend in the grain group was determined as a function of time.The simulation results suggest that at larger speeds,the metering index of the seed meter gradually decreases,while the index and the missing index gradually increase.As the tilt angle increased,the multiples index and missing index gradually decreased,while the multiples index gradually increased.When the seed meter speed reached 50 r/min and the tilt angle was 15°,the seed meter had a relatively good working performance with a seed spacing acceptance index of 92.59%,a multiples index of 1.85%,and a missing rate index of 5.56%.The seed meter was tested on a bench by using a JPS-12 performance-tester bench.At the aforementioned speed and angle,the coefficient of variation for the cottonseed spacing was 2.1%.The field trial results indicated that the multiples and the missing rates were higher than those for the tester bench but still met a passing rate of more than 90%.The coefficient of variation for the seed spacing was less than 10%,suggesting that the design could be used for field sowing.The resulting seeding uniformity was higher under these conditions,which indicates that the seed meter has a better working performance and the bench has a good seeding effect.

Central swallowing in normal adults using functional magnetic resonance imaging

BACKGROUND： While brain-imaging studies in healthy adults have indicated that multiple cortical regions are involved in swallowing, these functional imaging techniques have not been extensively applied to the complete understand neurophysiology of swallowing in China. A full understanding of normal swallowing neurophysiology is important for improving functional outcomes for dysphagia due to neurologic disorders or damage with increasing age. Thus the interpretations of the functional contributions of various brain areas in swallowing should be scientifically researched. OBJECTIVE： To identify the activation and characteristic of swallowing center in healthy adults using functional magnetic resonance imaging. DESIGN, TIME AND SETTING： An uncontrolled neuroimaging study was performed at the Outpatient Clinic, Department of Radiology, West China Hospital of Sichuan University between March and November 2008. PARTICIPANTS： Ten healthy right-handed volunteers, aged over 20 years with a mean age of （34.2 ＋ 8.1） years, a range of 25-45 years and including five males and five females participated. A medical history was obtained from all potential subjects and all subjects were free of systemic diseases and neurological disorders. METHODS： The healthy volunteers were examined with event-related functional magnetic resonance imaging of blood oxygenation level-dependent while laryngeal swallow-related movements were recorded. Subjects were scanned during voluntary saliva swallowing and water bolus swallowing activation tasks. Data was processed using the General Linear Model. A voxel by voxel group comparison was performed using random effect analysis. Any cluster with a corrected P 〈 0.05 for spatial extent was considered significant. MAIN OUTCOME MEASURES： The cerebral cortical activation maps of voluntary swallowing of saliva and swallowing of water bolus in healthy adults were observed. RESULTS： A multifocal cortical representation of swallowing was in the precentral gyrus, postcentral gyrus, insula, anterior cingulate gyrus, thalamus, basal ganglia and cerebellum, in a bilateral and asymmetrical manner, predominantly on the left hemisphere in the volunteers （P 〈 0.05）. CONCLUSION： Activation of the cortex during normal swallowing tasks may be functionally linked to basal nuclei, thalamus, and cerebellum, greatly appearing in the left hemisphere.

The Solutions to Invoice Tax Affairs Sharing of Large and Medium- size Enterprises

Invoice tax affairs sharing, which is based on the relying on invoice tax information management system, with the aims of avoiding the risk of tax affairs, optimizing the organizational structure, standardizing the process, improving the efficiency, reducing the operating costs and supporting the planning of tax affairs, is dedicated to providing internal and external customers with specialized, centralized and shareable management services of invoice tax affairs.

Empirical Research on the Influence of Export Market Diversification on Total Factor Productivity: Based on the Perspective of Trade Protection

This paper mainly explores the impact of export market diversification as an important measure to deal with trade friction on firms total factor productivity.Firstly,this article focuses on the theoretical analysis of the impact mechanism,including risk diversification,reversal effect and spillover effect.Based on the sample data of Chinese manufacturing export enterprises from 2000 to 2007,this paper conducts an empirical test on the relationship between export market diversification and total factor productivity.The result indicates that export market diversification has a significant positive effect on the total factor productivity of enterprises.After considering the endogenous problem,by controlling the fixed effects,using the two-stage least square method and changing the duration of the sample for robustness analysis,the results are still consistent.In addition,the role of diversification policy in total factor productivity presents heterogeneous characteristics in terms of different types of enterprise ownership,export intensity,industry competition,trade methods,and the development degree of exporting market.Accordingly,this paper puts forward corresponding policy recommendations.

Electrocatalytic seawater splitting for hydrogen production:Recent progress and future prospects

Earth-abundant seawater resource has become an attractive candidate to produce hydrogen from electrolysis,which is of great significance to realize hydrogen economy and carbon neutrality.Nonetheless,developing highly active and stable electrocatalysts to meet the needs of highly effective seawater splitting is still challenging for the sluggish oxygen evolution dynamics and the existed competitive reaction of chlorine evolution reaction(CER).To this end,some newly-developed electrocatalysts with superior performance,such as noble metals,alloy,transition metals,oxides,carbides,nitrides,phosphides,and so on,have been synthesized for the seawater splitting in recent years.This review starts from the historical background and fundamental mechanisms,and summarizes the most recent progress in the development of seawater electrolysis technologies.Some existing issues in the process of seawater electrolysis are enumerated and the corresponded solutions are presented.The future of hydrogen production from seawater electrolysis,especially the design and synthesis of novel catalysts for seawater electrolysis,is prospected.

Porcine epidemic diarrhea virus nsp14 inhibits NF-κB pathway activation by targeting the IKK complex and p65

Coronaviruses(CoVs)are a group of related enveloped RNA viruses that have severe consequences in a wide variety of animals by causing respiratory,enteric or systemic diseases.Porcine epidemic diarrhea virus(PEDV)is an economically important CoV distributed worldwide that causes diarrhea in pigs.nsp14 is a nonstructural protein of PEDV that is involved in regulation of innate immunity and viral replication.However,the function and mechanism by which nsp14 modulates and manipulates host immune responses remain largely unknown.Here,we report that PEDV nsp14 is an NF-κB pathway antagonist.Overexpression PEDV nsp14 protein remarkably decreases SeV-,poly(I:C)-and TNF-α-induced NF-κB activation.Meanwhile,expression of proinflammatory cytokines is suppressed by nspl4.nsp14 inhibits the phosphorylation of IKKs by interacting with IKKs and p65.Furthermore,nsp14 suppresses TNF-α-induced phosphorylation and nuclear import of p65.Overexpression nsp14 considerably increases PEDV replication.These results suggest a novel mechanism employed by PEDV to suppress the host antiviral response,providing insights that can guide the development of antivirals against CoVs.

Breeding exceptionally fragrant soybeans for soy milk with strong aroma

Soybean(Glycine max(L.)Merr.)is a major source of vegetable protein and oil in human diet and animal nutrition.Soybean seeds have been extensively used in various food products and snacks.Taste quality,particularly the aroma,affects cooking and eating,and ultimately influences consumer preference.Soy milk is particularly popular in China and has been gaining popularity in many other countries in the world.

FoxJ1 inhibits African swine fever virus replication and viral S273R protein decreases the expression of FoxJ1 to impair its antiviral effect

African swine fever(ASF)is a highly pathogenic swine infectious disease that affects domestic pigs and wild boar,which is caused by the African swine fever virus(ASFV).ASF has caused huge economic losses to the pig industry and seriously threatens global food security and livestock health.To date,there is no safe and effective commercial vaccine against ASF.Unveiling the underlying mechanisms of ASFV-host interplay is critical for developing effective vaccines and drugs against ASFV.In the present study,RNA-sequencing,RT-qPCR and Western blotting analysis revealed that the transcriptional and protein levels of the host factor FoxJ1 were significantly down-regulated in primary porcine alveolar macrophages(PAMs)infected by ASFV.RT-qPCR analysis showed that overexpression of FoxJ1 upregulated the transcription of type I interferon and interferon stimulating genes(ISGs)induced by poly(dA:dT).FoxJ1 revealed a function to positively regulate innate immune response,therefore,suppressing the replication of ASFV.In addition,Western blotting analysis indicated that FoxJ1 degraded ASFV MGF505-2R and E165R proteins through autophagy pathway.Meanwhile,RT-qPCR and Western blotting analysis showed that ASFV S273R inhibited the expression of FoxJ1.Altogether,we determined that FoxJ1 plays an antiviral role against ASFV replication,and ASFV protein impairs FoxJ1-mediated antiviral effect by degradation of FoxJ1.Our findings provide new insights into the antiviral function of FoxJ1,which might help design antiviral drugs or vaccines against ASFV infection.

促肿瘤长链非编码RNA LINC00973通过增强LDHA酶活促进肿瘤细胞有氧糖酵解

有氧糖酵解在肿瘤细胞内被特异激活的调控机制尚不清楚.本研究通过大规模的功能筛选,发现了一个能显著促肿瘤细胞增殖的长链非编码RNA LINC00973.敲低该RNA的表达,能够抑制多种肿瘤细胞的体外增殖及体内(动物)生长.LINC00973能够结合到糖酵解关键酶LDHA(乳酸脱氢酶A)上并增强其酶活,进而加速肿瘤细胞的有氧糖酵解,最终促进肿瘤细胞增殖.LINC00973在多种肿瘤的样本中显著高表达,且高表达LINC00973的病人预后较差.本研究提示在肿瘤细胞中高表达的LINC00973促进了肿瘤细胞中的有氧糖酵解的特异激活,揭示了肿瘤细胞中特异存在的糖酵解调控方式,为靶向糖酵解开发广谱抗肿瘤药物提供了新靶标.

中药蛴螬多肽Probrelin抗白色念珠菌活性研究

【目的】研究蛴螬多肽Probrelin对白色念珠菌的抗菌活性。【方法】采用肉汤稀释法测定蛴螬多肽Probrelin对正常菌株及临床耐药菌株的最小抑菌浓度,同时结合平板计数法测定最小杀真菌浓度;通过不同浓度多肽处理后经平板计数绘制时间-杀菌动力学曲线;通过PI吸收实验检测多肽对白色念珠菌细胞膜完整性的影响;通过核酸阻滞实验检测多肽与核酸间是否具有结合作用;通过扫描电子显微镜检测多肽对白色念珠菌形态的影响;通过结晶紫染色法检测多肽对生物膜生成及成熟生物膜的影响;通过显微镜观察多肽对白色念珠菌菌丝形成的影响;通过棋盘法检测多肽与抗真菌药物间的相互效应;通过小鼠皮下感染模型检测多肽在生理条件下的抗白色念珠菌活性。【结果】蛴螬多肽Probrelin对正常菌株及临床耐药菌株的最小抑菌浓度均为100μg/mL,最小杀真菌浓度为100–200μg/mL,且对白色念珠菌的杀菌动力学具有时间和浓度依赖性;该多肽以浓度依赖性的方式影响白色念珠菌细胞膜的完整性,并通过破坏白色念珠菌细胞壁的结构影响其形态,但与核酸间不具有结合作用;该多肽既可抑制白色念珠菌生物膜的形成,又可清除成熟生物膜,同时还可抑制白色念珠菌菌丝的形成;该多肽与抗真菌药物Clotrimazole间具有协同效应;在小鼠皮下感染模型中,该多肽可以有效杀灭白色念珠菌,进而抑制感染。【结论】蛴螬多肽Probrelin对白色念珠菌具有良好的抑制杀灭活性,可以作为新的药物分子或模板分子用于抗白色念珠菌药物的研发。