Neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability

Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when activated.Sprague-Dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour intervals.At 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated p66ShcA.We found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 hours.The same procedure was performed on a different group of rats.At the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water maze.Latency to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was similar.These findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal period.This may have contributed to the deficit in spatial learning and memory that persisted into adulthood.The experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval No.A13.008) on January 22,2013.

A Prognostic Biomarker for Bladder Cancer Correlated with Immune Infiltration Is PAEP

Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.

Glaucoma surgery experiments using digital microscope-integrated optical coherence tomography and OCT-compatible instruments

There is a certain failure rate in traditional glaucoma surgery because of the lack of depth information in microscope images.In this work,we present a digital microscope-integrated optical coherence tomography(MIOCT)system and several custom-made OCT-compatible instruments for glaucoma surgery.Sixteen ophthalmologists were asked to perform trabeculectomy and canaloplasty on live porcine eyes using the system and instruments.After surgery,a subjective feedback survey about the user experience was taken.The experiment results showed that our system can help surgeons easily locate important tissue structures during surgery.The custom-made instruments also solved the shadowing problem in OCT imaging.Surgeons preferred to use the system in their future practice.

Chromosome-level assembly of triploid genome of Sichuan pepper(Zanthoxylum armatum)

As an important spice species in Rutaceae, the Sichuan pepper (Zanthoxylum armatum) can provide pungent and numbing taste, as well as aroma in its mature fruit. Here we assembled a chromosome-level genome of green prickly ash which was widely cultivated in a major production area including Chongqing and Sichuan province, China. We generated 712 Gb (~112×) PacBio long reads and 511 Gb (~82×) Hi-C data, and yielded an assembly of 99 pseudochromosomes with total size of 5.32 Gb and contig N50 of 796 kb. The genomic analyses and cytogenetic experiments both indicated that the cultivarZhuye Huajiao’ was a triploid. We identified a Zanthoxylum-specific whole genome duplication event emerging about 24.8 million years ago (Mya). We also detected a transposition burst event (0.3-0.4 Mya) responsible for the large genome size of Z. armatum. Metabolomic analysis of the Zanthoxylum fruits during development stages revealed profiles of39 volatile aroma compounds and 528 secondary metabolites, from which six types of sanshools were identified. Based on metabolomic and transcriptomic network analysis, we screened candidate genes encoding long chain acyl-CoA synthetase, fatty acid desaturase,branched-chain amino acid aminotransferase involved in sanshool biosynthesis and three genes encoding terpene synthase during fruit development. The multi-omics data provide insights into the evolution of Zanthoxylum and molecular basis of numbing and aroma flavor of Sichuan pepper.

Progress in efficient doping of Al-rich AlGaN

The development of semiconductors is always accompanied by the progress in controllable doping techniques.Taking AlGaN-based ultraviolet(UV)emitters as an example,despite a peak wall-plug efficiency of 15.3%at the wavelength of 275 nm,there is still a huge gap in comparison with GaN-based visible light-emitting diodes(LEDs),mainly attributed to the inefficient doping of AlGaN with increase of the Al composition.First,p-doping of Al-rich AlGaN is a long-standing challenge and the low hole concentration seriously restricts the carrier injection efficiency.Although p-GaN cladding layers are widely adopted as a compromise,the high injection barrier of holes as well as the inevitable loss of light extraction cannot be neglected.While in terms of n-doping the main issue is the degradation of the electrical property when the Al composition exceeds 80%,resulting in a low electrical efficiency in sub-250 nm UV-LEDs.This review summarizes the recent advances and outlines the major challenges in the efficient doping of Al-rich AlGaN,meanwhile the corresponding approaches pursued to overcome the doping issues are discussed in detail.

Potential pharmacological mechanisms of digallate in the treatment of enteritis based on network pharmacology and molecular docking

Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.

黄芪建中汤肠内灌注对抗生素相关性腹泻患者肠道菌群、粘膜功能及炎性因子表达的影响

背景临床对抗生素相关性腹泻(antibiotic-associated diarrhea,AAD)尚无特效疗法,一般采用支持治疗与重建正常菌群-微生物制剂,但疗效不理想.黄芪建中汤源自张仲景《金匮要略》,为温阳健脾代表方,具有和胃止痛、温中健脾等功效.目的分析黄芪建中汤肠内灌注对抗生素相关性腹泻患者肠道菌群结构、肠粘膜功能损伤及炎性因子表达的影响.方法选取2016-12/2018-12于本院接受治疗的脾胃虚寒型AAD患者148例,随机数字表法将患者分成2组,分别为对照组(74例)口服双歧杆菌四联活菌片,观察组(74例)在对照组基础上采用黄芪建中汤肠内灌注.观察患者临床疗效、血清炎性因子含量、T淋巴细胞亚群、肠道菌群结构及肠粘膜屏障功能改善情况.结果观察组患者总有效率为94.59%,高于对照组79.73%,差异有统计学意义(P<0.05);治疗后2组患者血清白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、降钙素原(procalcitonin,PCT)及C反应蛋白(C-reactive protein,CRP)含量较治疗前降低,且观察组血清IL-6、TNF-α、PCT及CRP含量低于对照组,差异有统计学意义(P<0.05);治疗后2组患者粪便内双歧杆菌、肠杆菌及乳杆菌较治疗前升高,观察组粪便内双歧杆菌、肠杆菌及乳杆菌高于对照组,差异有统计学意义(P<0.05);治疗后2组患者血清细菌内毒素(endotoxin,BT)、D-乳酸(D-lactic acid,D-LC)及二胺氧化酶(diamine oxidase,DAO)含量较治疗前降低,观察组患者血清BT、D-LC及DAO含量低于对照组,差异有统计学意义(P<0.05).结论黄芪建中汤肠内灌注治疗AAD有效率高于双歧杆菌四联活菌片,能够可降低AAD患者血清炎性因子水平,加强机体免疫力,改善患者肠粘膜屏障功能与肠道菌群结构.

SlMYB75,an MYB-type transcription factor,promotes anthocyanin accumulation and enhances volatile aroma production in tomato fruits

Genetic manipulation of genes to upregulate specific branches of metabolic pathways is a method that is commonly used to improve fruit quality.However,the use of a single gene to impact several metabolic pathways is difficult.Here,we show that overexpression of the single gene SlMYB75(SlMYB75-OE)is effective at improving multiple fruit quality traits.In these engineered fruits,the anthocyanin content reached 1.86mg g−1 fresh weight at the red-ripe stage,and these SlMYB75-OE tomatoes displayed a series of physiological changes,including delayed ripening and increased ethylene production.In addition to anthocyanin,the total contents of phenolics,flavonoids and soluble solids in SlMYB75-OE fruits were enhanced by 2.6,4,and 1.2 times,respectively,compared to those of wild-type(WT)fruits.Interestingly,a number of aroma volatiles,such as aldehyde,phenylpropanoid-derived and terpene volatiles,were significantly increased in SlMYB75-OE fruits,with some terpene volatiles showing more than 10 times higher levels than those in WT fruits.Consistent with the metabolic assessment,transcriptomic profiling indicated that the genes involved in the ethylene signaling,phenylpropanoid and isoprenoid pathways were greatly upregulated in SlMYB75-OE fruits.Yeast one-hybrid and transactivation assays revealed that SlMYB75 is able to directly bind to the MYBPLANT and MYBPZM cis-regulatory elements and to activate the promoters of the LOXC,AADC2 and TPS genes.The identification of SlMYB75 as a key regulator of fruit quality attributes through the transcriptional regulation of downstream genes involved in several metabolic pathways opens new avenues towards engineering fruits with a higher sensory and nutritional quality.

An Organic Solvent-Assisted Intercalation and Collection (OAIC) for Ti_(3)C_(2)T_(x) MXene with Controllable Sizes and Improved Yield

A good method of synthesizing Ti_(3)C_(2)T_(x)(MXene)is critical for ensuring its success in practical applications,e.g.,electromagnetic interference shielding,electrochemical energy storage,catalysis,sensors,and biomedicine.The main concerns focus on the moderation of the approach,yield,and product quality.Herein,a modified approach,organic solvent-assisted intercalation and collection,was developed to prepare Ti_(3)C_(2)T_(x) flakes.The new approach simultaneously solves all the concerns,featuring a low requirement for facility(centrifugation speed<4000 rpm in whole process),gram-level preparation with remarkable yield(46.3%),a good electrical conductivity(8672 S cm^(−1)),an outstanding capacitive performance(352 F g^(−1)),and easy control over the dimension of Ti_(3)C_(2)T_(x) flakes(0.47–4.60μm^(2)).This approach not only gives a superb example for the synthesis of other MXene materials in laboratory,but sheds new light for the future mass production of Ti_(3)C_(2)T_(x) MXene.

Decomposition of Polycyclic Aromatic Hydrocarbon (PAHs) on Mineral Surface under Controlled Relative Humidity

The fate of Polycyclic Aromatic Hydrocarbons （PAHs） residing in the atmosphere has received enormous attention in recent years due to their mutagenic and carcinogenic risks on human health. In this context, the stability of pyrene （as a representative PAHs） on quartz, alumina, montmorillonite, kaolinite, humic acid and quartz coated with sorbed humic acid was investigated at controlled relative humidity （RH： i.e. 5% and 30%） without light irradiation in order to detect the presence of catalytic effect of mineral surface on PAHs decomposition. The stability of pyrene was found to depend strongly on the physicochemical properties of the substrates. Quartz showed a strong catalytic effect for the decomposition of pyrene even though it was coated with sorbed humic acid. Pyrene sorbed on montmorillonite and humic acid remained stable during the experimental period （i.e. 3 days）. Moisture in the experimental cell also affected the stability of pyrene in particular minerals. Especially, pyrene sorbed on alumina was rapidly decomposed at higher RH. However, there were almost no effect in the case of quartz, kaolinite and humic acid. Depending on the physicochemical properties of aerosols and RH, PAHs associated with minerals in the atmosphere would be decomposed and/or stably reside in the atmosphere.

Ralstonia solanacearum type Ⅲ effector RipAS associates with potato type one protein phosphatase StTOPP6 to promote bacterial wilt

The bacterial pathogen Ralstonia solanacearum(R.solanacearum)delivered type III secretion effectors to inhibit the immune system and cause bacterial wilt on potato.Protein phosphatases are key regulators in plant immunity,which pathogens can manipulate to alter host processes.Here,we show that a type III effector RipAS can reduce the nucleolar accumulation of a type one protein phosphatase(PP1)StTOPP6 to promote bacterial wilt.StTOPP6 was used as bait in the Yeast two-Hybrid(Y2H)assay and acquired an effector RipAS that interacts with it.RipAS was characterized as a virulence effector to contribute to R.solanacearum infection,and stable expression of RipAS in potato impaired plant resistance against R.solanacearum.Overexpression of StTOPP6 showed enhanced disease symptoms when inoculated with wild strain UW551 but not the ripAS deletion mutant,indicating that the expression of StTOPP6 facilitates the virulence of RipAS.RipAS reduced the nucleolar accumulation of StTOPP6,which occurred during R.solanacearum infection.Moreover,the association also widely existed between other PP1s and RipAS.We argue that RipAS is a virulence effector associated with PP1s to promote bacterial wilt.

Nucleus Pulposus Cells from Calcified Discs Promote the Degradation of the Extracellular Matrix through Upregulation of the GATA3 Expression

Objective Disc calcification is strongly associated with disc degeneration;however,the underlying mechanisms driving its pathogenesis are poorly understood.This study aimed to provide a gene expression profile of nucleus pulposus cells(NPCs)from calcified discs,and clarify the potential mechanism in disc degeneration.Methods Primary NPCs were isolated from calcified and control discs(CAL-NPC and CON-NPC),respectively.The proliferation and extracellular matrix(ECM)metabolism capacities of the cells were evaluated using MTT and Western blotting,respectively.RNA sequencing was used to identify differentially expressed genes(DEGs)in the CAL-NPCs.The biological functions of the DEGs were analyzed using the Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)databases.The transcription factor database and Cytoscape software were used to construct the transcription factor-DEGs regulatory network.The role of the verified transcription factor in NPC proliferation and ECM metabolism was also investigated.Results The CAL-NPCs exhibited a lower proliferation rate and higher ECM degradation capacity than the CON-NPCs.In total,375 DEGs were identified in the CAL-NPCs.The GO and KEGG analyses showed that the DEGs were primarily involved in the regulation of ribonuclease activity and NF-kappa B and p53 signaling pathways.GATA-binding protein 3(GATA3)with the highest verified levels was selected for further studies.Overexpression of GATA3 in the CON-NPCs significantly inhibited their proliferation and promoted their ECM degradation function,while the knockdown of GATA3 in the CAL-NPCs resulted in the opposite phenotypes.Conclusion This study provided a comprehensive gene expression profile of the NPCs from the calcified discs and supported that GATA3 could be a potential target for reversing calcification-associated disc degeneration.

Spin injection into heavily-doped n-GaN via Schottky barrier

Spin injection and detection in bulk GaN were investigated by performing magnetotransport measurements at low temperatures.A non-local four-terminal lateral spin valve device was fabricated with Co/GaN Schottky contacts.The spin injection efficiency of 21%was achieved at 1.7 K.It was confirmed that the thin Schottky barrier formed between the heavily ndoped GaN and Co was conducive to the direct spin tunneling,by reducing the spin scattering relaxation through the interface states.

Intramolecular Hydrogen Bond Self-template Synthesis of Some New Robson-type Macrocyclic Ligands

The intramolecular hydrogen bond self-template effect was suggested in the process of directly synthesizing the first six chiral metal-free Robson-type macrocyclic ligands. These ligands were characterized by H-1 NMR, IR, FAB-MS.

Effect of polygonatum polysaccharide on the hypoxia-induced apoptosis and necrosis in in vitro cultured cerebral cortical neurons from neonatal rats

BACKGROUND： Cardiocerebrovascular diseases induced cerebral circulation insufficiency and senile vascular dementia can result in ischemic/hypoxic apoptosis of central neurons, which we should pay more attention to and prevent and treat as early as possible. Traditional Chinese medicine possesses the unique advantage in this field. Polygonatum, a Chinese herb for invigorating qi, may play a role against the hypoxic apoptosis of brain neurons. OBJECTIVE ： To observe the protective effect of polygonatum polysaccharide on hypoxia-induced apoptosis and necrosis in cerebral cortical neurons cultured in vitro. DESIGN： A comparative experiment.SETTING： Laboratory of Cell Biology, Institute of Basic Medical Sciences, Jiangxi Provincial Academy of Traditional Chinese Medicine. MATERIALS： The experiment was carried out in the Laboratory of Cell Biology, Institute of Basic Medical Sciences, Jiangxi Provincial Academy of Traditional Chinese Medicine from November 2003 to April 2005. Totally 218 Wistar rats （male or female） of clean degree within 24 hours after birth were purchased from the animal center of Jiangxi Medical College （certification number was 021-97-03）. METHODS：① Preparation of cerebral cortical neurons of rats： The cerebral cortical tissues were isolated from the Wistar rats within 24 hours after birth, and prepared to single cell suspension, and the cerebral cortical neurons of neonatal rats were in vitro cultured in serum free medium with Neurobasal plus B27 Supplement. ② Observation on the non-toxic dosage of polygonatum polysaccharide on neurons： After the neurons were cultured for 4 days, polygonatum polysaccharide of different dosages （1-20 g/L） was added for continuous culture for 48 hours, the toxicity and non-toxic dosage of polygonatum polysaccharide on neurons were observed and detected with trypan blue staining. ③Grouping： After hypoxia/reoxygenation, the cultured neurons were divided into normal control group, positive apoptotic group and polygonatum polysaccharide group. In the normal control group, the neurons were cultured at 37℃ in CO2 with the volume fraction of 0.05 under saturated humidity for 6 days. In the apoptotic positive group, the neurons were cultured with hypoxia for 12 hours after 4-day culture, and followed by reoxygenation for 48 hours. In the polygonatum polysaccharide group, polygonatum polysaccharide with the terminal concentration of 0.5, 1 and 1.5 g/L was added to some neurons at 10 hours before the hypoxia culture, and then the neurons were cultured with hypoxia for 12 hours, followed by reoxygenation for 48 hours; polygonatum polysaccharide with the terminal concentration of 0.5, 1 and 1.5 g/L was added to the other neurons at 12 hours after hypoxia followed by reoxygenation for 48 hours.④ The Hoechst33342 fluorescence staining, Annexin V/PI flow cytometer, appearance of DNA agarose gel electrophoresis gradient strap and immunohistochemical staining were used to observe the expressions of Bcl-2, Bax and Caspase-3 apoptotic and anti-apoptotic proteins and the ratio of Bcl-2/Bax, and observe the effect of polygonatum polysaccharide against the hypoxic apoptosis of cerebral cortical neurons of neonatal rats. MAIN OUTCOME MEASURES： ① Toxicity and non-toxic dosage of polygonatum polysaccharide on neurons;② Apoptotic rate of neurons detected with Hoechst33342 fluorescence staining;③ Early apoptotic rate and necrotic rate of neurons detected with Annexin V/PI flow cytometer; ④DNA agarose gel electrophoresis ladder-like strap appeared or not;⑤ Expressions of Bcl-2, Bax and Caspase-3 apoptotic and anti-apoptotic proteins and the ratio of Bcl-2/Bax. RESULTS：① Polygonatum polysaccharide within 6 g/L had no cytotoxicity on the normal cultured cerebral cortical neurons （P 〉 0.05）. ②The apoptotic rates of neurons detected with Hoechst33342 fluorescence staining had significant differences between the polygonatum polysaccharide groups and positive apoptosis group added to neurons at 10 hours before the hypoxia culture [（13.00±4.52）%,（12.72±2.15）%, （11.80±1.18）%,（38.03±1.05）%, P 〈 0.01], and had no significant differences between the polygonatum polysaccharide groups and positive apoptosis group added to neurons at 12 hours after the hypoxia culture （36.77±1.45）%, （36.60±1.61）%, （36.37±2.02）%, （38.03±1.05）%, P 〉 0.05].③ Annexin V/PI flow cytometer detected that the anti-necrotic effect was enhanced with the increased concentration of polygonatum polysaccharide within 0.5-1.5 g/L （P 〈 0.01）. Polygonatum polysaccharide of 0.5-1.5 g/L added before hypoxia could significantly decrease the apoptotic rate of neurons induced by hypoxia/reoxygenation （P 〈 0.01）. ④ No DNA agarose gel electrophoresis ladder-like strap appeared in the groups with polygonatum polysaccharide of 0.5-1.5 g/L added at 10 hours before hypoxia;⑤ After Polygonatum polysaccharide of 0.5-1.5 g/L was added before hypoxia, the expression of Bcl-2 protein of hypoxic neurons was increased （P 〈 0.01）, and those of Bax protein and Caspase-3 protein were reduced （P 〈 0.01）, and the ratio of Bcl-2/Bax was increased （P 〈 0.01）. CONCLUSION： Polygonatum polysaccharide within 6 g/L has no cytotoxicity on the normal cultured cerebral cortical neurons. Polygonatum polysaccharide of 0.5-1.5 g/L added before hypoxia plays a role agains necrosis of neurons induced by hypoxia. Polygonatum polysaccharide of 0.5-1.5 g/L can significantly reduce the apoptosis of neurons induced by hypoxia through up-regulating the expression of Bcl-2 protein, down-regulating the expressions of Bax protein and Caspase-3 protein, and increasing the ratio of Bcl-2/Bax.

Effectiveness of an Indoor Air Pollution (IAP) Intervention on Reducing IAP and Improving Women’s Health Status in Rural Areas of Gansu Province, China

Given the deleterious health effects associated with indoor air pollution (IAP), this study was conducted to evaluate an IAP intervention in rural areas in Gansu, one of the poorest provinces of China. We selected 371 rural households to take part in intervention measures including stove improvement and health education. Eight of 371 households were selected to conduct IAP sampling. Four hundred and thirteen women in these households completed a questionnaire and 49 women took part in lung function tests. After the intervention, PM4 levels reduced from 455 μg/m3 to 200 μg/m3 and CO reduced from 3.40 ppm to 2.90 ppm in indoor air. The percentage of predicted value of FEV1 and FVC improved to some degree after the intervention, but all the parameters of lung function assessment did not show a significant change. Prevalence rates of several symptoms associated with IAP significantly declined in the study population, compared with baseline levels. Intervention measures combining stove improvement with health education were effective in reducing IAP levels. Women’s health status, including eye and respiratory symptoms, also showed improvement. However, the effect on lung function was not apparent and warranted additional follow-up. Similarly, evaluation of the long term effects of the IAP intervention will require future studies.

Non-Markovian Dynamics of an Open Two-Level System with Amplitude-Phase Damping

By use of the measure, the backflow of information presented recently, we study the non-Markovianity of the dynamics for a two-level system interacting with a zero-temperature structured environment via amplitude-phase coupling. In the limit of weak coupling between the system and its reservoir, the time-local non-Markovian master equation for the reduced state of the system is derived. Under the secular approximation, the exact analytic solution is obtained. Numerical simulations show that the amplitude and phase dampings can produce destructive interference to the backflow of information, leading to the weaker non-Markovianity of the compound dynamics compared with the dynamics of a single amplitude or phase damping model. We also study the characteristics of the initial-state pairs that maximize the backflow of information.

Molecular mechanism of azvudine in the treatment of COVID-19 based on network pharmacology and molecular docking

Azvudine(FNC)is a nucleotide inhibitor with a wide antiviral drug.Azvudine was available for the treatment of HIV and corona virus disease(COVID-19)in 2019,but its efficacy and mechanism of action for the treatment of COVID-19 have not been evaluated.PharmMapper was used to predict 287 potentially relevant targets,and the OMIM and GeneCards databases yielded 2468 potential related targets.COVID-19 is linked to 72 FNC-related targets.Using gene ontology(GO)functional annotation and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment,binding protein-protein interaction(PPI)networks and cytoHubba plug-ins,10 relevant signaling pathways(Lipid and atherosclerosis,Pathways in cancer,Coronavirus disease COVID-19,T cell receptor signaling pathway,and so on.)and 10 hub genes were identified.FNC was shown to interact with MMP9,ALB,AKT1,EGFR,HRAS,MAPK14,MAPK8,PPARG,RHOA and NOS3 via molecular docking.This work investigated the key routes and targets of FNC in the treatment of COVID-19,as well as the possible anti-COVID-19 and anti-tumor targets and related signaling pathways of FNC,which provided references for us to locate and explore effective COVID-19 medications.

一株鸭源传染性支气管炎病毒的分离鉴定及结构蛋白基因和血清型分析

【目的】对从广西某鸭场发生呼吸道感染的11天龄樱桃谷肉鸭分离到的病毒株进行鉴定,并探索此鸭源病毒分离株的遗传变异情况。【方法】通过血凝试验、鸡胚接种实验、3?端非编码区(3'UTR)基因扩增与序列测定对分离株进行鉴定,并对该分离株的结构基因S1、E、M和N分别进行序列测定以及相似性、系统进化树分析和血清型鉴定。【结果】血凝试验为阴性,接种鸡胚盲传5代后出现侏儒胚,3?UTR基因测序结果表明为传染性支气管炎病毒(IBV)序列。该分离株S蛋白的裂解位点为RRSRR,S1、E、M和N基因与IBV毒株H120、4/91、LTD3核苷酸相似性分别为:78.6%–99.7%、85.4%–100.0%、91.6%–93.2%、86.7%–91.7%。除N基因存在点突变外,S1、E和M基因均存在氨基酸的突变、插入和(或)缺失。系统进化树分析显示,其S1基因属于4/91型,E、M和N基因均为LDT3型。血清型分析表明,该分离株的血清型不同于疫苗株H120和4/91。【结论】此鸭源病毒分离株为IBV,且该分离株的基因型与血清型均发生了变异。本研究结果暗示禽类传染性支气管炎的防控面临着更严峻的挑战。