Reconstruction of Postinfarcted Cardiac Functions Through Injection of Tanshinone ⅡA@Reactive Oxygen Species-Sensitive Microspheres Encapsulated in a Thermoreversible Hydrogel

Myocardial damage resulting from acute myocardial infarction often leads to progressive heart failure and sudden death,highlighting the urgent clinical need for effective therapies.Recently,tanshinoneⅡA has been identified as a promising therapeutic agent for myocardial infarction.However,efficient delivery remains a major issue that limits clinical translation.To address this problem,an injectable thermosensitive poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(lactic acid-co-glycolic acid)gel(PLGA-PEG-PLGA)system encapsulating tanshinoneⅡA-loaded reactive oxygen species-sensitive microspheres(Gel-MS/tanshinoneⅡA)has been designed and synthesized in this study.The thermosensitive hydrogel exhibits good mechanical properties after reaching body temperature.Microspheres initially immobilized by the gel exhibit excellent reactive oxygen species-triggered release properties in a high-reactive oxygen species environment after myocardial infarction onset.As a result,encapsulated tanshinoneⅡA is effectively released into the infarcted myocardium,where it exerts local anti-pyroptotic and anti-inflammatory effects.Importantly,the combined advantages of this technique contribute to the mitigation of left ventricular remodeling and the restoration of cardiac function following tanshinoneⅡA.Therefore,this novel,precision-guided intra-tissue therapeutic system allows for customized local release of tanshinoneⅡA,presenting a promising alternative treatment strategy aimed at inducing beneficial ventricular remodeling in the post-infarct heart.

Effects of Perceived Teacher Support on Student Behavioral Engagement in the Blended Learning Environment:Learning Experience as a Mediator

Blended learning(BL)has been widely adopted to improve students’academic achievements in higher education.However,its success relies mainly on student engagement,which plays an essential role in active learning and provides a rich understanding of students’experiences.The study utilized three self-designed scales-the Teacher Support Scale,Student Engagement Scale,and Student Learning Experience Scale-to gauge and examine the impact and relationship between perceived teacher support,student behavioral engagement,and the intermediary role of learning experiences.A cohort of 899 college students undertaking the obligatory College English course through BL modes across five Chinese universities actively participated by completing a comprehensive questionnaire.The results showed significant correlations between perceived teacher support,learning experience,and behavioral engagement.Perceived teacher support significantly predicted students’behavioral engagement,with socio-affective support exerting the most substantial predictive effects.All predictive effects were partially mediated by learning experience(learning mode,online resources,overall LMS-based learning,interaction with their instructor and peers,and learning outcome).The influence of perceived teacher support on behavioral engagement differed between students who reported the most positive(vs.negative)learning experiences.Suggestions for further research are offered for consideration.

Assessment of outcomes of hearing and speech rehabilitation in children with cochlear implantation

Objectives:This study aimed to assess the effect of hearing and speech rehabilitation in patients with Nurotron■cochlear implants.Design:Ninety-eight paediatric patients with bilateral severe-to-profound sensorineural deafness who received cochlear implantation were divided into three groups according to age:group A(≤3 years),group B(4-7 years),and group C(8-16 years).All patients were followed up for one year for hearing and speech performance after the surgery.The comprehensive Auditory Perception Assessment,MAIS,CAP and SIR hearing and speech assessments and rating materials were used for assessment before the surgery and at 3,6,and 12 months after implant activation.Results:The scores of patients in the open-set speech assessment,Chinese Auditory Perception Assessment,MAIS,CAP and SIR significantly improved after cochlear implantation in all age groups.The younger the age at implantation,the better the results.Moreover,the hearing and speech performance of cochlear implant recipients gradually improved with the extension of rehabilitation time.Conclusions:Nurotron■Venus^TM cochlear implantation can improve the hearing and speech performance of patients with bilateral severe-to-profound sensorineural deafness.

Co-location of QTL for Sclerotinia stem rot resistance and flowering time in Brassica napus

Sclerotinia stem rot(SSR) caused by Sclerotinia sclerotiorum(Lib.) de Bary is one of the most devastating diseases of Brassica napus worldwide. Both SSR resistance and flowering time(FT) adaptation are major breeding goals in B. napus. However, early maturing rapeseed varieties, which are important for rice-rapeseed rotation in China, are often highly susceptible to SSR. Here, we found that SSR resistance was significantly negatively correlated with FT in a natural population containing 521 rapeseed inbred lines and a double haploid(DH) population with 150 individual lines, both of which had great variation in FT. Four chromosomal regions on A2, A6, C2, and C8 affecting both SSR resistance and FT were identified using quantitative trait loci(QTL) mapping after constructing a high-density genetic map based on single nucleotide polymorphism markers in the DH population.Furthermore, we aligned QTL for the two traits identified in the present and previous studies to the B. napus reference genome, and identified four colocalized QTL hotspots of SSR resistance and FT on A2(0–7.7 Mb), A3(0.8–7.5 Mb), C2(0–15.2 Mb), and C6(20.2–36.6 Mb). Our results revealed a genetic link between SSR resistance and FT in B.napus, which should facilitate the development of effective strategies in both early maturing and SSR resistance breeding and in map-based cloning of SSR resistance QTL.

Host-induced gene silencing of multiple pathogenic factors of Sclerotinia sclerotiorum confers resistance to Sclerotinia rot in Brassica napus

Sclerotinia sclerotiorum is generally considered one of the most economically damaging pathogens in oilseed rape(Brassica napus).Breeding for Sclerotinia resistance is challenging,as no immune germplasm available in B.napus.It is desirable to develop new breeding strategies.In the present study,hostinduced gene silencing(HIGS),developed based on RNA interference(RNAi),was applied to protect B.napus from S.sclerotiorum infection.Three pathogenicity genes,the endo-polygalacturonase gene(Ss PG1),cellobiohydrolase gene(Ss CBH),and oxaloacetate acetylhydrolase gene(Ss OAH1),were chosen as HIGS targets.Co-incubation of synthesized double-stranded RNAs(ds RNAs)with S.sclerotiorum in liquid medium significantly reduced the transcript levels of the target genes.Application to plant surfaces of ds RNA targeting the three genes conferred effective protection against S.sclerotiorum.Stable transgenic B.napus plants expressing small interfering RNAs with sequence identity to Ss PG1,Ss CBH,and Ss OAH1 were generated.HIGS transgenic B.napus prevented the expression of S.sclerotiorum target genes,slowed pathogenicity-factor accumulation,impeded fungal growth,and suppressed appressorium formation,thereby conferring resistance to S.sclerotiorum.Simultaneous silencing of Ss PG1,Ss CBH,and Ss OAH1 by stable expression of a chimeric hairpin RNAi construct in B.napus led to enhanced protection phenotypes(with disease lesion size reduced by 36.8%–43.7%).We conclude that HIGS of pathogenic-factor genes of S.sclerotiorum is a promising strategy for controlling Sclerotinia rot in oilseed rape.

MECOM promotes supporting cell proliferation and differentiation in cochlea

Permanent damage to hair cells(HCs)is the leading cause of sensory deafness.Supporting cells(SCs)are essential in the restoration of hearing in mammals because they can proliferate and differentiate to HCs.MDS1 and EVI1 complex locus(MECOM)is vital in early development and cell differentiation and regulates the TGF-βsignaling pathway to adapt to pathophysiological events,such as hematopoietic proliferation,differentiation and cells death.In addition,MECOM plays an essential role in neurogenesis and craniofacial development.However,the role of MECOM in the development of cochlea and its way to regulate related signaling are not fully understood.To address this problem,this study examined the expression of MECOM during the development of cochlea and observed a significant increase of MECOM at the key point of auditory epithelial morphogenesis,indicating that MECOM may have a vital function in the formation of cochlea and regeneration of HCs.Meanwhile,we tried to explore the possible effect and potential mechanism of MECOM in SC proliferation and HC regeneration.Findings from this study indicate that overexpression of MECOM markedly increases the proliferation of SCs in the inner ear,and the expression of Smad3 and Cdkn2b related to TGF signaling is significantly down-regulated,corresponding to the overexpression of MECOM.Collectively,these data may provide an explanation of the vital function of MECOM in SC proliferation and trans-differentiation into HCs,as well as its regulation.The interaction between MECOM,Wnt,Notch and the TGF-βsignaling may provide a feasible approach to induce the regeneration of HCs.

Role of the periotic mesenchyme in the development of sensory cells in early mouse cochlea

Objective:To investigate the role of the periotic mesenchyme(POM)in the development of sensory cells of developing auditory epithelium.Methods:Developing auditory epithelium with or without periotic mesenchyme was isolated from mice at embryonic days 11.5(E11.5),E12.5 and E13.5,respectively,and cultured in vitro to an equivalent of E18.5’s epithelium in vivo.Then,the explants were co-stained with antibodies targeting myosin VIIA,Sox2 and BrdU.Results:More hair cells in E11.5 t 7 DIV,E12.5 t 6 DIV and E13.5 t 5 DIV auditory epithelia were found upon culture with POM(225.90±62.44,476.94±100.81,and 1386.60±202.38,respectively)compared with the non-POM group(68.17±23.74,205.00±44.23,and 1266.80±38.84,respectively).Moreover,regardless of developmental stage,the mesenchymal tissue increased the amount of cochlear sensory cells as well as the ratio of differentiated hair cells to total sensory cells.Conclusions:The periotic mesenchyme promotes the development of cochlear sensory cells,and its effect depends on the developmental stage of the auditory epithelium.

Differential expression of exosomal circRNAs and regulatory framework genes in myocardial infarction patients with cardiac remodeling in response to Tongguan Capsules

Objective:Cardiac remodeling when myocardial infarction(MI)is achieved is an established prognostic factor for function-related damage and failure of hear that happen progressively.Tongguan Capsules(TGC),i.e.,a Chinese herbal treatment with patent has been previously demonstrated its potential benefits in cardiac function,but little is known about related mechanisms.This study sought to isolate and characterize exosomal circRNA profiles from post-MI cardiac remodeling patients in response to TGC,and further explore the possible molecular mechanisms.Methods:Exosomes were isolated from the plasma and analyzed by the detection of protein marker expression and transmission electron microscopy.This study employed DESeq2 package within Bioconductor for exploring circRNAs and determining the circRNA with differential expressions.Co-expression investigation was performed with the use of a weighted correlation framework.An investigation was conducted on the molecular framework and channels of different circRNA based on the investigation system of the and Kyoto Encyclopedia of Genes and Genomes(KEGG)Gene Ontology(GO)channels.The prediction was conducted for circRNA-miRNA interactions on the basis of frequently employed target prediction software,and the framework was built with the use of Cytoscape software.Results:In total,33084 circRNAs were detected in all chromosomes and 10065 circRNAs were identified with the use of circBase.Of them,40,207 and 258 differentially expressed circRNAs were detected between the MI group and control,MI and TGC groups,and the control and TGC groups.The differentially expressed circRNAs between the MI group and control,MI group and TGC group,and control and TGC group were significantly enriched in microtubule nucleation(BP,GO:0007020),protein binding(MF,GO:0005515),regulation of natural killer cell mediated cytotoxicity(BP,GO:0042269)corresponding to the cell cycle(hsa04110),lysine degradation(hsa00310)and lysine degradation(hsa00310)in KEGG channel investigation.Module_darkorange2 indicated the most differentiation with other modules by WGCNA investigation.This study employed a total of 14 circRNAs and 8 miRNAs which have significant interactions with each other for building the circRNA-miRNA frameworks,which indicated that has-miR-619-5p,has-miR-1268a and hasmiR-1285‐3p were under the regulation of a higher amount of circRNAs as compared with other miRNAs.Conclusion:In conclusion,different mechanisms and channels participated in the pathological processes associated with cardiac remodeling following MI.The altered circRNAs are likely to be critical to the cardioprotection of TGC through the circRNA-miRNA frameworks.

A ＂green pathway＂ different from simple diffusion in soft matter： Fast molecular transport within micro/nanoscale multiphase porous systems

Soft matter has attracted extensive attention due to its special physical/chemical properties and holds great promise in many applications. However, obtaining a detailed understanding of both complex fluid and mass transport in soft matter, especially in hierarchical porous media of biological tissues, still remains a huge challenge. Herein, inspired by fast tracer transport in loose connective tissues of living systems, we observed an interesting phenomenon of fast molecular transport in situ in an artificial hierarchical multiphase porous medium （a micrometer scale hydrophobic fiber network filled with nanometer scale hydrophilic porous medium）, which was simply fabricated through electro- spinning technology and polymerization. The transportation speed of molecules in the micrometer fiber network is larger than simple diffusion in nanometer media, which is better described by Fick＇s law. We further proved that the phenomenon is based on the nanoconfined air/water/solid interface around the micrometer hydrophobic fibers. We focus on the key factors, referring to SA, （the confined multiphase area around the microfibers） and Nc （the connectivity node degree of the skeletal portion in the nanometer hydrogel medium）. Next, a quantitative parameter, VTCM （transport chance mean-value）, was introduced to describe the molecular transport capability of the fiber network within hierarchical multiphase porous systems. These fundamental advances can be applied de novo to understand the process of so-called simple diffusion in biological systems, and even to re-describe many molecular events in biologically nanoconfined spaces.

快速纯化重组腺联病毒的受体结合捕捉方法

【目的】建立用于重组腺联病毒(AAV)纯化的受体结合捕捉方法。【方法】将AAV受体的多囊肾病(PKD)结构域1和2与类弹性蛋白多肽(ELP)在重组大肠杆菌中进行融合表达,利用相变循环(ITC)纯化ELP-PKD融合蛋白;分别用昆虫和AAV-293细胞制备rAAV-GFP,与ELP-PKD融合蛋白共孵育后进行ITC,从沉淀复合物提取病毒DNA进行PCR检测;在优化条件下利用ELP-PKD蛋白结合捕捉rAAV-GFP,利用电子显微镜观察、免疫转印和细胞感染试验进行rAAV鉴定。【结果】ELP-PKD融合蛋白获得正确、可溶性表达,ITC纯化的蛋白纯度大于90%;ELP-PKD蛋白能特异结合rAAV-GFP,结合具有p H、温度和时间依赖性,受体结合捕捉方法可在1h内完成,从两种细胞纯化rAAV-GFP的回收率分别为58%和56%;rAAV-GFP洗脱具有p H和温度依赖性,洗脱rAAV-GFP的回收率分别为46%和44%;纯化rAAV-GFP具有AAV的典型形态和结构蛋白。【结论】建立的ELP-PKD结合捕捉法可用于不同细胞源rAAV的快速纯化。

Day-ahead scheduling of large numbers of thermostatically controlled loads based on equivalent energy storage model

Due to their heat/cool storage characteristics, thermostatically controlled loads(TCLs) play an important role in demand response programmers. However, the modeling of the heat/cool storage characteristic of large numbers of TCLs is not simple. In this paper, the heat exchange power is adopted to calculate the power instead of the average power, and the relationship between the heat exchange power and energy storage is considered to develop an equivalent storage model, based on which the time-varying power constraints and the energy storage constraints are developed to establish the overall day-ahead schedulingmodel. Finally, the proposed scheduling method is verified using the simulation results of a six-bus system.

Identification of Gesture Based on Combination of Raw sEMG and sEMG Envelope Using Supervised Learning and Univariate Feature Selection

In this paper,we propose a novel study for gesture identification using surface electromyography(sEMG)signal,and the raw sEMG signal and the sEMG envelope signal are collected by the sensor at the same time.An efficient method of gesture identification based on the combination of two signals using supervised learning and univariate feature selection is implemented.In previous research techniques,researchers tend to use the raw sEMG signal and extract several constant features for classification,which inevitably causes a result of ignoring individual differences.Our experiment shows that both the optimal feature set and redundant feature set are not same for different subjects.In order to address this problem,we extract all the common features from two signals,up to 76 features,most of which has been established as the common EMG-based gesture index.In addition,extracting too many features in an application can reduce operational efficiency,so we apply for feature selection to get the optimal feature set and decrease the number of extracting feature.As a result,the combination of two signals is better than using a single signal.The feature selection can be used to select optimal feature set from all features to achieve the best classification performance for each subject.The experimental results demonstrate that the proposed method achieves the performance with the highest accuracy of 95%for identifying up to nine gestures only using two sensors.Finally,we develop a real-time intelligent sEMG-driven bionic hand system by using the proposed method.

Ultra-low-loss on-chip zero-index materials

Light travels in a zero-index medium without accumulating a spatial phase,resulting in perfect spatial coherence.Such coherence brings several potential applications,including arbitrarily shaped waveguides,phase-mismatch-free nonlinear propagation,large-area single-mode lasers,and extended superradiance.A promising platform to achieve these applications is an integrated Dirac-cone material that features an impedance-matched zero index.Although an integrated Dirac-cone material eliminates ohmic losses via its purely dielectric structure,it still entails out-of-plane radiation loss,limiting its applications to a small scale.We design an ultra-low-loss integrated Dirac cone material by achieving destructive interference above and below the material.The material consists of a square array of low-aspectratio silicon pillars embedded in silicon dioxide,featuring easy fabrication using a standard planar process.This design paves the way for leveraging the perfect spatial coherence of large-area zero-index materials in linear,nonlinear,and quantum optics.

Control Parameter Optimization of Thermostatically Controlled Loads Using a Modified State-queuing Model

Thermostatically controlled loads(TCLs)are one of the best candidates to participate in direct load control(DLC).However,little attention is given to the parameter optimization of the TCLs control system due to the complexity of the TCLs’dynamics.In this paper,the parameters of the feedback control system based on the direct compressor control mechanism(DCCM)are optimized using the modified state-queuing(SQ)model,which can provide good characterizaton and greatly simplifies the dynamics of the TCLs.The simulation results verify the effectiveness of the proposed method.

Demand response for frequency control of multi-area power system

Over the last few years, lots of attentions have been given to the demand response(DR) for the frequency control. DR can be incorporated with traditional frequency control method and enhance the stability of the system. In this paper, the frequency control strategy of DR for a multiarea power system is specially designed. In order to quickly stabilize the frequency of different areas, the tie-line power is adopted as the additional input signal of DR. To get the optimal parameters of the control system, the frequency control problem is formulated as a multi-objective optimization problem, and the parameters such as the integral gains of secondary frequency control, the frequency bias parameters, and coefficients of DR are optimized. Numerical results verify the effectiveness of the proposed method.

Transport of antibiotic resistance plasmids in porous media and the influence of surfactants

Transport of engineered antibiotic resistance plasmids in porous media has been reported to potentially cause significant spreading of antibiotic resistance in the environment. In this work, transport of an indigenous resistance plasmid pK5 in porous media was investigated through packed column experiments. At identical ionic strengths in CaC12 solutions, the breakthroughs of pK5 from soil columns were very close to those from quartz sand columns, indicating that transport ofpK5 in quartz sand and soil was similar. A similarity in transport behavior was also tbund between pK5 and an engineered plasmid pBR322 that has approximately the same number of base pairs as pK5. The influence of surfactants, a major group of constituents in soil solutions, was examined using an engineered plasmid pcDNA3.1（＋）/myc-His A. The impact of an anionic surfactant, sodium dodecyl sulfate （SDS）, was negligible at concentrations up to 200 rag. L I. Cetyltrimethyl ammonium bromide （CTAB）, a cationic surfactant, was fbund to significantly enhance plasmid adsorption at high concentrations. However~ at environmentally relevant concentrations （ 〈 I mg. L I）, the effect of this surfactant was also minimal. The negligible impact of surfactants and the similarity between the transport of engineered and indigenous plasmids indicate that under environmentally relevant conditions, indigenous plasmids in soil also have the potential to transport over long distances and lead to the spreading of antibiotic resistance.