基于hACE2转导建立SARS-CoV-2 spike假病毒感染病证结合的小鼠病毒肺炎模型

目的建立与评价一种安全、经济、有效的病证结合小鼠新冠病毒感染肺炎模型。方法30只KM种小鼠随机分为空白组、对照组及实验1组、实验2组、实验3组,每组各6只。每天把KM小鼠置于模拟寒湿环境中4 h,将表达hACE2的重组腺相关病毒(pAAV-hACE2)采用改良悬挂法气管内给药转导至肺组织,继以新型冠状病毒(SARS-CoV-2)spike假病毒采用相同的气管内给药方式造模。观察各组小鼠一般情况,检测体重变化、肺指数、血清炎性因子及肺部病理变化。结果免疫组化法显示h ACE2在小鼠肺组织中有效表达;在寒湿环境中给予SARS-CoV-2 spike假病毒后,实验组小鼠表现出类似疫毒犯肺证候的体征;且同样喂养条件和时间下,与空白组和对照组小鼠比较,实验组小鼠出现体重下降;实验1、2、3组小鼠出现肺指数显著增大(P<0.05或P<0.01),血清炎性因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)显著升高(P<0.01),肺组织病理改变明显。结论本研究成功建立了一种安全、经济、有效的病证结合小鼠新冠病毒感染肺炎模型。

The first factor affecting dryland winter wheat grain yield under various mulching measures: Spike number

Water is the key factor limiting dryland wheat grain yield.Mulching affects crop yield and yield components by affecting soil moisture.Further research is needed to determine the relationships between yield components and soil moisture with yield,and to identify the most important factor affecting grain yield under various mulching measures.A long-term 9-yearifeld experiment in the Loess Plateau of Northwest China was carried out with three treatments:no mulch (CK),plastic mulch (M_(P)) and straw mulch (M_(S)).Yield factors and soil moisture were measured,and the relationships between them were explored by correlation analysis,structural equation modeling and significance analysis.The results showed that compared with CK,the average grain yields of M_(P) and M_(S) increased by 13.0and 10.6%,respectively.The average annual grain yield of the M_(P) treatment was 134 kg ha^(–1) higher than the M_(S) treatment.There were no significant differences in yield components among the three treatments (P<0.05).Soil water storage of the M_(S) treatment was greater than the M_(P) treatment,although the differences were not statistically signifiant.Soil water storage during the summer fallow period (SWSSF) and soil water storage before sowing (SWSS) of M_(S) were significantly higher than in CK,which increased by 38.5 and 13.6%,respectively.The relationship between M_(P) and CK was not statistically significant for SWSSF,but the SWSS in M_(P) was significantly higher than in CK.In terms of soil water storage after harvest (SWSH) and water consumption in the growth period(ET),there were no signi?cant differences among the three treatments.Based on the three analysis methods,we found that spike number and ET were positively correlated with grain yield.However,the relative importance of spike number to yield was the greatest in the M_(P )and M_(S) treatments,while that of ET was the greatest in CK.Suifcient SWSSF could indirectly increase spike number and ET in the three treatments.Based on these results,mulch can improve yield and soil water storage.The most important factor affecting the grain yield of dryland wheat was spike number under mulching,and ET with CK.These findings may help us to understand the main factors influencing dryland wheat grain yield under mulching conditions compared to CK.

Spike蛋白介导细胞融合程度定量方法的建立及其在药物筛选中的应用

新型冠状病毒Spike蛋白(S蛋白)与受体ACE2结合介导细胞融合的发生,为进一步探究新冠感染合胞体发生、发展的规律及致病机制,明确关键蛋白靶点,筛选干预合胞体形成的药物,笔者拟构建新冠S蛋白介导的细胞融合程度的定量方法.利用pCDH-CMV-MCS-EF1-Puro、pLV-CMV-MCS-3FLAG-IRES-Bla、S蛋白基因序列、ACE2基因序列、LacZ基因序列、EcoRⅠ限制性内切酶及同源重组酶构建慢病毒穿梭质粒pCDH-S,pCDH-ACE2,pLV-α与pLV-ω,利用该慢病毒质粒分别构建稳定表达S蛋白与ACE2蛋白的293FT和A549细胞系,随后利用pLV-α与pLV-ω慢病毒质粒分别感染上述稳定细胞系,构建出可以定量细胞融合程度的细胞系293FT-S_(1-56),A549-S_(1-56),293FT-ACE2△_(11-41),A549-ACE2△_(11-41).最后采用Western Blot蛋白免疫印迹技术鉴定上述融合定量细胞系中S蛋白与ACE2蛋白的过表达效果,并通过细胞共培养确定融合效果,用β-半乳糖苷酶报告基因检测试剂盒定量细胞融合程度.结果显示,慢病毒载体和稳定细胞系构建成功,时间梯度、转染梯度实验显示该系统具有良好的定量灵敏度,并能用于卡莫司他(Camostat mesylate)和氯硝柳胺(Niclosamide)等药物抗融合效果的定量评价.成功构建的新冠病毒Spike蛋白介导细胞融合程度定量系统,可用于不同S蛋白突变体致融合能力评价和抗融合药物筛选评价,可为进一步的研究奠定技术基础.

The wheat sucrose synthase gene TaSus1 is a determinant of grain number per spike

Some haplotypes of the sucrose synthase gene TaSus1 are associated with thousand-grain weight(TGW)in wheat(Triticum aestivum L.).However,no mutations have been identified within the gene to test this association.The effects of TaSus1 on grain number per spike(GNS)also are largely unknown.Our previous genome-wide association study identified TaSus-A1 as a candidate gene controlling fertile spikelet number per spike(FSN).In the present study,we generated two independent mutants for the three TaSus1 homoeologs by CRISPR/Cas9-mediated genome editing.The triple mutants displayed lower FSN,GNS,grain number per spikelet(GNST),and TGW than wild-type plants.In 306 hexaploid wheat accessions,two single-nucleotide polymorphisms in TaSus-A1 contributed differently to GNS.Introgression of the two alleles into a wheat genetic background confirmed their effects.The alleles differed in geographical distribution among the accessions.

Estimating wheat spike-leaf composite indicator(SLI)dynamics by coupling spectral indices and machine learning

The contribution of spike photosynthesis to grain yield(GY)has been overlooked in the accurate spectral prediction of yield.Thus,it’s essential to construct and estimate a yield-related phenotypic trait considering spike photosynthesis.Based on field and spectral reflectance data from 19 wheat cultivars under two nitrogen fertilization conditions in two years,our objectives were to(i)construct a yield-related phenotypic trait(spike–leaf composite indicator,SLI)accounting for the contribution of the spike to photosynthesis,(ii)develop a novel spectral index(enhanced triangle vegetation index,ETVI3)sensitive to SLI,and(iii)establish and evaluate SLI estimation models by integrating spectral indices and machine learning algorithms.The results showed that SLI was sensitive to nitrogen fertilizer and wheat cultivar variation as well as a better predictor of yield than the leaf area index.ETVI3 maintained a strong correlation with SLI throughout the growth stage,whereas the correlations of other spectral indices with SLI were poor after spike emergence.Integrating spectral indices and machine learning algorithms improved the estimation accuracy of SLI,with the most accurate estimates of SLI showing coefficient of determination,root mean square error(RMSE),and relative RMSE values of 0.71,0.047,and 26.93%,respectively.These results provide new insights into the role of fruiting organs for the accurate spectral prediction of GY.This high-throughput SLI estimation approach can be applied for wheat yield prediction at whole growth stages and may be assisted with agronomical practices and variety selection.

Translocation of a fish spike from the pharynx to the thyroid gland:A case report

BACKGROUND A fish spike stuck in the throat is a common ear,nose,and throat(ENT)emergency.However,it is very rare for a fish spike to reach the thyroid tissue through the throat,which is very dangerous and can lead to pharyngeal fistula,cervical abscess,mediastinal abscess,and thyroid abscess.Proper and timely management can help reduce complications,especially in elderly patients.CASE SUMMARY In the case presented here,the causative factor was dentures,but improper management aggravated the condition.In the case presented here,an elderly woman with a history of accidentally swallowing fish bones for 20 d had a sensation of foreign bodies in her throat.Eventually,computed tomography(CT)of the neck showed that the left side of the thyroid gland had a dense shadow in the form of a stripe.CONCLUSION If a fishbone foreign body is not visible during endoscopic examination but the patient has significant symptoms,the surgeon should be aware that the fishbone may be lodged in the thyroid.To avoid a misdiagnosis,ultrasound,CT,and other tests can be used to clarify the diagnosis.T The first step in treating a fish bone in the thyroid gland is to determine the position of the foreign body and the extent of the infection,and to develop a personalized surgical plan for its removal.At the same time,scientific information should be made available to the general public so that people know that if a fish bone is accidentally lodged,they should not force it to be swallowed or be spit out by inducing vomiting,which are incorrect methods and may aggravate the condition or even cause it to migrate outside the cavity,leading to serious complications,as in this reported case.

Innovative COVID-19 Screening: RT-LAMP Assay for Spike and NSP1 Proteins

Coronavirus disease(COVID-19)is a serious respiratory disease that spreads through the coronavirus globally.It soon became a pandemic after its appearance in 2019 and demanded new techniques for its identification and detection.Owing to this situation,RT-LAMP appears to be a novel method for the identification of COVID-19 because of its vast applications,including cost-effectiveness and time-saving.This research highlights the use of RT-LAMP,a more sensitive test than RT-PCR,for the assessment of SARS-CoV-2,the severe acute respiratory illness.To identify the spike(S)and NSP1 protein using RT-LAMP,170 total samples of coronavirus-suspected patients were served in this research.Health certifications and bioethical considerations were taken into consideration.After the sample was extracted from the patient's swabs,RNA was isolated,extracted,and purified.The response was then run on the RT-LAMP at the ideal temperature,and the outcomes could be observed with the unaided eye as they changed from pink to yellow.It is a simple method of determining if the test is positive or negative.For this purpose,both RT-LAMP and RT-PCR tests are used during these procedures.Genes linked with COVID-19 testing including S,nspl,and ORF are suited to coronavirus testing;they have 100%specificity and low sensitivity,but S has more specificity and sensitivity than nspl and ORF,respectively.Out of the 95 positive samples,89(93.68%)samples yielded favorable outcomes utilizing RT-LAMP,while 55 negative samples yielded 100%positive results.The present research demonstrates that RT-LAMP is less sensitive yet more selective for coronavirus detection.

A method for testing drag-reduction on riblet surfaces based on the Spalding formula

This paper presents a method based on riblet surfaces. Its advantage lies in that it is more with testing methods using instruments such as a the Spalding formula for testing drag-reduction on convenient and yields more precise data compared scale. With this method, data is obtained from the velocity distribution within the inner layer, nearest the riblet surface. Precision of measurement of the velocity distribution is the key factor affecting the precision of the testing.

基于RISC-V架构的Spike缓存模型的设计和实现

使用基于精简指令集原则的指令架构(RISC-V)的指令集,针对现有Spike验证模型中的缓存写回功能的缺失问题,设计一种基于RISC-V指令集的现代超标量处理器缓存模型。基于现代高速缓存的基本原理,结合Spike验证模型,实现现代高速缓存的基本读写操作,并进行系统级芯片(SoC)环境下的仿真和验证,可作为微型电子芯片(IC)前端逻辑设计中的验证模型使用。该方案能够以较快的时间完成基于RISC-V指令集的大型SoC的设计与验证。

Twice-split phosphorus application alleviates low-temperature impacts on wheat by improved spikelet development and setting

Extreme low-temperature incidents have become more frequent and severe as climate change intensifies.In HuangHuai-Hai wheat growing area of China,the late spring coldness occurring at the jointing-booting stage(the anther interval stage)has resulted in significant yield losses of winter wheat.This study attempts to develop an economical,feasible,and efficient cultivation technique for improving the low-temperature(LT)resistance of wheat by exploring the effects of twice-split phosphorus application(TSPA)on wheat antioxidant characteristics and carbon and nitrogen metabolism physiology under LT treatment at the anther interval stage using Yannong 19 as the experimental material.The treatments consisted of traditional phosphorus application and TSPA,followed by a-4℃ LT treatment and natural temperature(NT)control at the anther interval stage.Our analyses showed that,compared with the traditional application,the TSPA increased the net photosynthetic rate(P_(n)),stomatal conductance(Gs),and transpiration rate(T_(r))of leaves and reduced the intercellular carbon dioxide concentration(C_(i)).The activity of carbon and nitrogen metabolism enzymes in the young wheat spikes was also increased by the TSPA,which promoted the accumulation of soluble sugar(SS),sucrose(SUC),soluble protein(SP),and proline(Pro)in young wheat spike and reduced the toxicity of malondialdehyde(MDA).Due to the improved organic nutrition for reproductive development,the young wheat spikes exhibited enhanced LT resistance,which reduced the sterile spikelet number(SSN)per spike by 11.8%and increased the spikelet setting rate(SSR)and final yield by 6.0 and 8.4%,respectively,compared to the traditional application.The positive effects of split phosphorus application became more pronounced when the LT treatment was prolonged.

Highly Sensitive Poly-N-isopropylacrylamide Microgel-based Electrochemical Biosensor for the Detection of SARS-COV-2 Spike Protein

Objective Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019(COVID-19),a new,highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,considerable attention has been paid to the development of new diagnostic tools for the early detection of SARS-CoV-2.Methods In this study,a new poly-N-isopropylacrylamide microgel-based electrochemical sensor was explored to detect the SARS-CoV-2 spike protein(S protein)in human saliva.The microgel was composed of a copolymer of N-isopropylacrylamide and acrylic acid,and gold nanoparticles were encapsulated within the microgel through facile and economical fabrication.The electrochemical performance of the sensor was evaluated through differential pulse voltammetry.Results Under optimal experimental conditions,the linear range of the sensor was 10-13-10-9 mg/m L,whereas the detection limit was 9.55 fg/mL.Furthermore,the S protein was instilled in artificial saliva as the infected human saliva model,and the sensing platform showed satisfactory detection capability.Conclusion The sensing platform exhibited excellent specificity and sensitivity in detecting spike protein,indicating its potential application for the time-saving and inexpensive detection of SARS-CoV-2.

Bifurcations for counterintuitive post-inhibitory rebound spike related to absence epilepsy and Parkinson disease

Seizures are caused by increased neuronal firing activity resulting from reduced inhibitory effect and enhancement of inhibitory modulation to suppress this activity is used as a therapeutic tool.However,recent experiments have shown a counterintuitive phenomenon that inhibitory modulation does not suppress but elicit post-inhibitory rebound(PIR)spike along with seizure to challenge the therapeutic tool.The nonlinear mechanism to avoid the PIR spike can present theoretical guidance to seizure treatment.This paper focuses on identifying credible bifurcations that underlie PIR spike by modulating multiple parameters in multiple theoretical models.The study identifies a codimension-2 bifurcation called saddle-node homoclinic orbit(SNHOB),which is an intersection between saddle node bifurcation on invariant cycle(SNIC)and other two bifurcations.PIR spike cannot be evoked for the SNIC far from the SNHOBbut induced for the SNIC close to the SNHOB,which extends the bifurcation condition for PIR spike from the well-known Hopf to SNIC.Especially,in a thalamic neuron model,increases of conductance of T-type Ca^(2+)(TC a)channel induce SNIC bifurcation approaching to the SNHOB to elicit PIR spikes,closely matching experimental results of the absence seizure or Parkinson diseases.Such results imply that,when inhibition is employed to relieve absence seizure and Parkinson diseases related to PIR spike,modulating SNIC to get far from the SNHOBto avoid PIR spike is the principle.The study also addresses the complex roles of TCacurrent and comprehensive relationships between PIR spike and nonlinear conceptions such as bifurcation types and shapes of threshold curve.

Natural variants and editing events provide insights into routes for spike architecture modification in common wheat

Spike architecture is an indicative trait of grain yield in common wheat(Triticum aestivum).A segregating population was generated for mapping genes contributing to spike morphometric traits by crossing the two common wheat cultivars'CItr 17600'with branching spikes and'Yangmai 18'with normal spikes.A major quantitative trait locus for spike length was mapped to the Q5A region of chromosome 5A.Yangmai18 carried a Q5Ab allele for short spikes,which harbored one SNP in the last intron,and a 1-bp InDel in the 720-bp fragment from the start codon,compared to Q5Aa in Chinese Spring.CItr 17600 harbored a q5Ab allele for long spikes,which has a 6-bp deletion compared to the reported q5Aa allele that was involved in the binding site of microRNA 172(miR172).This 6-bp deletion in immediately upstream of this binding site was involved in changes of four amino acids.The natural q5A allele appeared to be rare in common wheat but frequent in tetraploid T.turgidum accessions with branching spikes.The CRISPR/Cas9 technology was used to edit the upstream region involving in the miR172 binding site in Yangmai 18 and identified two independent editing events,one with a 1-bp insertion in Q5A and the other with a 2-bp deletion in Q5D,resulting in several shapes of spikes in the transgenic progeny.In addition to the effects of natural q5A allele and the edited Q5A genes,this study indicated the regeneratability and transformability of Yangmai 18 as an elite cultivar.Altogether,this study provides insight into future modification and engineering of spike architecture in common wheat.

基于预测校正算法的Spike and Slab Lasso逻辑回归模型

尽管Spike and Slab方法广泛应用于贝叶斯变量选择,但其惩罚似然估计的潜力在很大程度上被忽视了。通过在贝叶斯模态中引入惩罚化似然观点,本文提出了新的Spike and Slab Lasso逻辑回归模型,将两个拉普拉斯密度的混合先验置于单个坐标上,可以自适应地收缩系数,即弱收缩重要预测量,强收缩不相关预测量,从而可以得到准确的估计和预测。同时,我们使用了预测–校正算法来求解Spike and Slab Lasso逻辑回归模型,并将该算法扩展到不可分离惩罚的情况。该算法利用凸优化的预测校正算法,沿着整个正则化路径有效的计算解,方便了模型选择,避免了正则化参数值不同时的独立优化。最后,模拟学习和实证结果表明本文所提模型比Lasso逻辑回归模型具有更优的性能。

基于spike-and-slab先验的贝叶斯时间序列模型

贝叶斯方法通过引入先验信息并结合似然的方法进行参数估计和变量选择,使模型估计和预测结果更为精确。在贝叶斯框架下考虑时间序列之间的相关性,将偏自相关系数融合先验信息,提出基于spike-and-slab先验的贝叶斯层次时间序列模型(Spike-and-slab Prior with Partial Autocorrelation Coefficients,SS-PAC)。SS-PAC模型采用spike-and-slab先验并结合偏自相关系数,实现时间序列滞后阶数的选择、参数估计和预测。基于模拟数据和真实数据的实证研究表明,该模型相较于以往模型在变量选择和预测结果上表现更优。

Waning of Anti-Spike IgG Antibody Titer after COVID-19 Vaccination: Myth or Reality?

This observational prospective study was conducted on 25 patients who had received a full 3-dose COVID-19 vaccination scheme with a follow-up ranging from 12 to 19 months after the last injection. The aim of the study was focused on a single biological indicator the anti-spike IgG antibody titer. The age of the patients ranged from 51 to 85 years old. 15 out 25 patients (60%) presented a comorbidity. Our data showed a persistent positive anti-spike IgG antibodies titer ranging from 105 to 5680 BAU/mL (mean: 2661 BAU/mL) in all patients. In view of these results, systematic administration of a SARS-CoV-2 vaccine booster is questionable and should be individually tailored according to the patient medical condition and the anti-spike IgG antibody level.

不同季秸秆还田对冬小麦不同穗粒位结实粒数和粒重的影响

为探讨安徽淮北平原砂姜黑土区长期秸秆连续全量还田对冬小麦穗部结实特性的影响,2021-2022年基于农业农村部华东地区作物栽培科学观测站13年的长期定位试验,比较分析了小麦单季秸秆全量粉碎覆盖还田(T1)、小麦玉米秸秆全量粉碎还田(T2)、玉米秸秆全量粉碎翻埋还田(T3)、小麦玉米秸秆全年不还田(CK)4个不同还田模式下小麦不同小穗位结实粒数及粒重的差异。结果表明,T1、T2、T3处理的主茎穗小穗结实总粒数较CK分别提高了21.21%、7.50%和12.55%;第2粒位(G2)结实粒数分别提高了7.71%、7.71%和5.79%;上部小穗结实粒数分别提高了51.41%、22.79%和31.36%,其G2结实粒数分别提高了30.95%、30.95%和23.09%,其中T1处理对小麦粒数的提升效果最好。不同季秸秆还田处理下小麦主茎穗及其G2粒重、分蘖穗及其第三粒位(G3)粒重均高于CK,T1、T2和T3处理的主茎穗粒重增幅分别为16.06%、4.14%和16.06%,分蘖穗增幅分别为9.86%、0.71%和8.87%;T1、T2和T3处理下主茎穗G2粒重增幅分别为20.69%、10.34%和17.24%,分蘖穗G3粒重4.55%、2.27%和6.82%,其中T1处理对粒重提升效果最好,其次是T3。综合来看,在安徽淮北平原砂姜黑土区长期秸秆还田能够提高小麦穗粒数和粒重,进而促进产量提升,其中T1处理对小麦结实粒数和粒重的提升效果最好,是适宜在该地区推广的秸秆还田模式。

房角切开术围手术期前房出血及术后一过性眼压升高管理方案专家推荐意见

房角切开术(GT)是一种安全、有效的微创青光眼手术(MIGS),在我国已得到广泛应用,适用于治疗原发性开角型青光眼和中晚期原发性闭角型青光眼。尽管GT手术的安全性较高,但前房出血和一过性眼压升高仍然是GT术后常见的并发症。然而,在处理这类问题时,临床医生缺乏统一的标准化规范。这种情况不仅可能影响临床医生对手术效果的判断,还可能对手术预后产生不利影响。因此,有必要制定详细、完整的围手术期前房出血及术后一过性眼压升高管理方案,指导临床医生合理、规范地处理并发症,推动MIGS的进一步发展和完善。为此国内部分青光眼治疗专家及广东省医学会眼科学分会青光眼学组相关专家共同回顾既往文献,通过反复讨论,对GT围手术期前房出血和术后一过性眼压升高的管理方案达成一致性推荐意见,包括围手术期前房出血的定义、高危因素、转归,术前预防出血的方法、术中减少出血的方法、术后前房出血的管理,及一过性眼压升高的定义、发生原因、影响因素、处理及转归等方面,以供临床医生参考使用。

气动杆与喷流组合模型高超声速减阻机理研究

采用数值方法研究了由气动杆、逆向喷流和侧向喷流构成的组合模型的高超声速减阻机理,该方法基于有限体积法,且采用了AUSM+空间离散格式和Menter's SST k-ω湍流模型。结果表明:气动杆对流场进行了有利控制,削弱了原始激波,逆向喷流增强了气动杆前方弓形激波的强度,实现了高超声速来流的首次减速,而侧向喷流形成的桶状激波实现了气流的二次减速,三者的联合作用减弱了钝头体的再附激波,实现了高超声速钝头体的减阻。此外,增加气动杆长度和两个喷流总压均可提高系统减阻性能,但阻力系数降低的速率逐渐减小。

天气雷达三体散射长钉回波特征分析

利用2016—2020年中国中东部地区47个强对流个例中50部S波段多普勒天气雷达的基本反射率因子产品资料,在筛选出2626个样本的基础上,分析三体散射长钉(TBSS)特征。结果表明:TBSS在1.5 km和5 km高度附近出现频次最高;在2.4°仰角出现频次最高。TBSS主要出现在雷达静锥区边缘至雷达径向距离210 km范围,在距离雷达115 km附近达到峰值;TBSS在雷达极坐标系中呈现南多北少、西多东少的形势;当对流风暴移动方向与雷达径向方向的夹角大于30°时有利于观测到TBSS。TBSS回波强度在起始端径向向外0~15 km范围内迅速降低至5 dBz,15 km之后在-5~10 dBz波动,TBSS区域中70%以上为低于25 dBz的弱回波;99%的TBSS长度小于40 km,不同长度的TBSS形态符合正态分布。TBSS出现频次和长度与强回波的中心最高值和区域面积没有显著相关关系。