近红外二区激活型小分子荧光探针研究进展

近红外二区(NIR-Ⅱ)荧光成像具有优良的组织穿透深度和空间分辨率,广泛应用于生物医学领域。与传统的常亮型荧光探针相比,激活型探针只有当特定的生物标志物存在情况下才会发生荧光信号变化,因此具有更高的信背比,会进一步提高区分病变与正常组织的准确度和可靠性。基于此,本文按照生物疾病模型进行分类,系统总结了近5年报道的近红外二区激活型小分子探针的结构、响应机理以及活体应用,并对目前激活型小分子探针面临的问题及发展方向进行简要介绍。

破裂颅内动脉瘤介入治疗的预后因素分析

目的探讨介入治疗破裂颅内动脉瘤(IA)患者预后的影响因素。方法回顾性分析2015年1月-2018年6月绍兴市人民医院113例行血管内介入治疗的破裂IA患者的临床资料。采用改良Rankin量表(mRs)评价预后,根据随访结果分为预后良好组(mRs评分0~1分)和预后不良组(mRs评分2~6分)。对可能影响预后的因素进行单因素分析和多因素Logistic回归分析。结果113例患者中,83例(73%)预后良好,30例(27%)预后不良。单因素分析结果显示,年龄、Hunt-Hess分级、Fisher分级、手术时机及脑积水对预后有影响(P<0.05)。多因素Logistic回归分析结果显示,年龄[OR^^=1.065(95%CI:1.012,1.121)]、Hunt-Hess分级[OR^^=9.497(95%CI:2.034,44.345)]、手术时机[OR^^=3.957(95%CI:1.242,12.604)]及脑积水[OR^^=8.005(95%CI:1.552,41.278)]为影响预后的独立危险因素。结论年龄、Hunt-Hess分级、手术时机及脑积水能够影响行介入治疗的破裂IA患者预后。

Influence of multiple structural parameters on interior ballistics based on orthogonal test methods

Influence of multiple structural parameters on the performance of a gun launch system driven by highpressure reactive gases is important for structural design and performance adjustment.A coupled lumped parameter model was utilized to predict the propellant combustion,and a dynamic finite element method was applied to approximate the mechanical interactions between the projectile and the barrel.The combustion and the mechanical interactions were coupled through a user subroutine interface in ABAQUS.The correctness and the capability of the finite element approximations in capturing small structural changes were validated by comparing predicted resistance with experiments.Based on the coupled model,the influence of structural parameters of a medium-caliber gun on the system performance was investigated.In order to reduce the research costs,orthogonal tests were designed to investigate the comprehensive effects of the parameters.According to statistical analysis,the important order of the structural parameters on the launching process was obtained.The results indicate that the influence of the width of the rotating band stands out among the studied parameters in the gun.The work provides a method to investigate the influence of multiple parameters on system performance and gives guidance for controlling the system performance.

Design optimization for a launching system with novel structure

A launching system with novel structure using optimization method is investigated to improve the muzzle velocity of guns in this article.This system has two tandem chambers of which the front one is ignited first and the other is ignited after a while.The launching process of this novel system is modelled and a series of different schemes are simulated,to discover the interior ballistic performance of this novel launching system.In order to obtain the optimal loading conditions,an optimization model combined with the combustion model is established.The optimal schemes can improve the muzzle velocity by 20.6%without changing the parameters of barrel.It means that this novel launch system could improve the interior ballistics performance significantly and it still has considerable potential to be ameliorated.

Numerical research on adverse effect of muzzle flow formed by muzzle brake considering secondary combustion

The simulation of the artillery interior and intermediate ballistics problem is performed to investigate the influence of a gas dynamics device,muzzle brake,on the muzzle hazard phenomena,such as flash and blast waves.The correlation of the chemical reactions with the characteristics of the muzzle flow field is analyzed by the simulation for a further understanding of the secondary combustion phenomenon of the muzzle flow.The novel structure of muzzle flow caused by the muzzle brake is presented by the simultaneous solution of the interior ballistics model and multi-species Navier-Stokes equations in order to analyze the influence of the muzzle brake structure on the chemical reactions.The secondary combustion of the muzzle flow due to the oxygen-supplement chemical reactions is obtained by the chemical reaction kinetic model.The interaction of the blast waves released from the muzzle brake is illustrated in detail and the mechanism of the formation of muzzle flash is analyzed.This research provides a reference for the studies on the suppression of the muzzle flash.

Dynamic analysis of a guided projectile during engraving process

The reliability of the electronic components inside a guided projectile is highly affected by the launch dynamics of guided projectile.The engraving process plays a crucial role on determining the ballistic performance and projectile stability.This paper analyzes the dynamic response of a guided projectile during the engraving process.By considering the projectile center of gravity moving during the engraving process,a dynamics model is established with the coupling of interior ballistic equations.The results detail the stress situation of a guided projectile band during its engraving process.Meanwhile,the axial dynamic response of projectile in the several milliseconds following the engraving process is also researched.To further explore how the different performance of the engraving band can affect the dynamics of guided projectile,this paper focuses on these two aspects:(a) the effects caused by the different band geometry;and(b) the effects caused by different band materials.The time domain and frequency domain responses show that the dynamics of the projectile are quite sensitive to the engraving band width.A material with a small modulus of elasticity is more stable than one with a high modulus of elasticity.

Machine learning and numerical investigation on drag reduction of underwater serial multi-projectiles

To increase launching frequency and decrease drag force of underwater projectiles,a serial multiprojectiles structure based on the principle of supercavitation is proposed in this paper.The drag reduction and supercavitation characteristics of the underwater serial multi-projectiles are studied with computational fluid dynamics(CFD)and machine learning.Firstly,the numerical simulation model for the underwater supercavitating projectile is established and verified by experimental data.Then the evolution of the supercavitation for the serial multi-projectiles is described.In addition,the effects of different cavitation numbers and different distances between projectiles are investigated to demonstrate the supercavitation and drag reduction performance.Finally,the artificial neural network(ANN)model is established to predict the evolution of drag coefficient based on the data obtained by CFD,and the results predicted by ANN are in good agreement with the data obtained by CFD.The finding provides a useful guidance for the research of drag reduction characteristics of underwater serial projectiles.

Modeling Distortion Signals of Power Grid Based on Wiener-G Functionals

The uniform mathematical model of distortion signals in power grid has been setup with the theory of Wiener-G Functional. Firstly,the Matlab simulation models were established. Secondly,the Wiener kernel of power load was found based on the Gaussian white noise as input. And then the uniform mathematical model of the power grid signal was established according to the homogeneous of the same order of Wiener functional series. Finally,taking three typical distortion sources which are semiconductor rectifier,electric locomotive and electric arc furnace in power grid as examples,we have validated the model through the Matlab simulation and analyzed the simulation errors. The results show that the uniform mathematical model of distortion signals in power grid can approximation the actual model by growing the items of the series under the condition of the enough storage space and computing speed.

An Algorithm of Voice Activity Detection Based on EMD and Wavelet Entropy Ratio

A new method was proposed to identify speech-segment endpoints based on the empirical mode decomposition（EMD） and a new wavelet entropy ratio with improving the accuracy of voice activity detection.With the EMD, the noise signals can be decomposed into several intrinsic mode functions（IMFs）. Then the proposed wavelet energy entropy ratio can be used to extract the desired feature for each IMFs component. In view of the question that the method of voice endpoint detection based on the original wavelet entropy ratio cannot adapt to the low signal-to-noise ratio（SNR）condition, an appropriate positive constant was introduced to the basic wavelet energy entropy ratio with effectively improved discriminability between the speech and noise. After comparing the traditional wavelet energy entropy ratio with the proposed wavelet energy entropy ratio, the experiment results show that the proposed method is simple and fast. The speech endpoints can be accurately detected in low SNR environments.

Three positive charge nonapoptotic-induced photosensitizer with excellent water solubility for tumor therapy

Photodynamic therapy(PDT)has emerged as a significant cancer therapy option.Currently,cation-based organic small molecule aggregation-induced emission(AIE)photosensitizers(PSs)attract the wide atten-tion of many scientists,due to improved reactive oxygen species(ROS)production after cationization.However,such PSs tend to localize only the mitochondria,limiting the death way of tumor cells(usu-ally apoptosis)during PDT process,which may affect the therapeutic effect under some circumstances.Herein,we designed a novel water-soluble three positive charge PS,TPAN-18F,which could be distributed uniformly in cell cytoplasm and had distribution in different sub-organelles(mitochondria,endoplasmic reticulum,lysosome).The experimental results showed that TPAN-18F-based PDT process can not only disrupt mitochondrial functions(reducing ATP production and destroying mitochondrial membrane po-tential),but also elevate the intracellular lipid peroxides(LPOs)level,which evoke the non-apoptotic death manner of tumor cells.Further,in vivo studies showed that TPAN-18F-based PDT could effectively inhibit tumor growth.Accordingly,we believe that the construction of TPAN-18F is suggestive for tumor non-apoptotic therapy.

Size-selective hybridization chain reaction for accurate signal amplification in living cancer cells

Accurate signal amplification in living cells is highly important in biomedical research and medical diagnostics.Benefiting from its enzyme-free,efficient isothermal signal amplification ability,hybridization chain reaction(HCR)plays an important role in intracellular signal amplification;however,HCR fails the accurate signal amplification in the situation when the properties of some biological targets and analogues are too similar.Particularly,their signal amplification accuracy for mature mi RNAs is unsatisfactory due to the signal interference of precursor micro RNAs(abbreviated as pre-mi RNAs),which also contain the sequence of mature mi RNAs.Herein,we develop the first example of size-selective hybridization chain reaction probe for accurate signal amplification,which achieved accurate and sensitive biosensing of mature mi RNAs in living cancer cells.Our probe,termed as q Tcage,consists of a DNA nanocage for size-selective responsive to mature mi RNAs,as well as a quadrivalent tetrahedral DNA structure for HCR signal amplification.Benefiting from the size-selectivity of DNA nanocage,shorter mature mi RNAs(19–23 nt)rather than longer pre-mi RNAs(60–70 nt)could enter the cavity to release triggers strand,which activates HCR reaction for fluorescence signal recovery.The probe efficiently reduces signal interference of pre-mi RNAs and improves the imaging sensitivity for intracellular mature mi RNAs,which was successfully applied for mature mi RNAs imaging during drug treatment.Overall,this strategy provides the hybridization chain reaction with the feature of size-selective ability,which holds promise for further accurate signal amplification in biological processes study and clinical diagnostics.

Engineering an asymmetric rhodamine dye suitable for developing ratiometric fluorescent probe

Fluorescent probes based on rhodamine skeleton are extensively used in biological imaging.However,the construction of ratiometric fluorescent probes based on the rhodamine skeleton without introducing additional fluorophores is still challenging.Herein,we propose an effective method to construct a rhodamine-based ratiometric fluorescent probe through the regulation of electron cloud density.A ratiometric fluorescent probe RDQF-RB-NTR was successfully constructed for the detection of nitroreductase(NTR).RDQF-RB-NTR exhibits good sensitivity,high selectivity,and ratiometric response to NTR.Cell imaging experiments showed that RDQF-RB-NTR can rapidly and accurately detect the fluctuation of NTR in cells and difference of NTR levels between normal cells and cancer cells.In addition,RDQF-RB-NTR was successfully applied to the imaging of NTR in liver tissue slices,and we found that the level of NTR was upregulated in liver cirrhosis.

Smart DNA sensors-based molecular identification for cancer subtyping

Molecular subtyping of cancer can greatly help to understand the development of disease and predict tumor behavior.Exploring detection methods for precise subtyping is appealing to prognosis and personalized therapy.During the past decades,DNA-based biosensors have exhibited great potential in cancer diagnosis due to their structural programmability and functional diversity.Despite the encouraging progress that has been made,there remains an issue in improving the accuracy and sensitivity of cancer subtyping due to the complex process of disease,especially in preclinical or clinical applications.To accelerate the development of DNA sensors in the identification of cancer subtypes,in this review,we summarized their advances in molecular subtyping by analyzing the heterogeneity in categories and levels of biomarkers between cancer subtypes.The strategies toward genomic and proteomic heterogeneity in cells or on the cell surface,as well as the cancer excretions including extracellular vesicles(EVs)and microRNA(miRNAs)in serum,are summarized.Current challenges and the opportunities of DNA-based sensors in this field are also discussed.

Nucleic acids analysis

Nucleic acids are natural biopolymers of nucleotides that store, encode, transmit and express genetic information, which play central roles in diverse cellular events and diseases in living things. The analysis of nucleic acids and nucleic acids-based analysis have been widely applied in biological studies, clinical diagnosis, environmental analysis, food safety and forensic analysis.During the past decades, the field of nucleic acids analysis has been rapidly advancing with many technological breakthroughs.In this review, we focus on the methods developed for analyzing nucleic acids, nucleic acids-based analysis, device for nucleic acids analysis, and applications of nucleic acids analysis. The representative strategies for the development of new nucleic acids analysis in this field are summarized, and key advantages and possible limitations are discussed. Finally, a brief perspective on existing challenges and further research development is provided.

HDAC inhibitors improve CRISPR-mediated HDR editing efficiency in iPSCs

Genome-edited human induced pluripotent stem cells(iPSCs)hold great promise for therapeutic applications.However,low editing efficiency has hampered the applications of CRISPR-Cas9 technology in creating knockout and homology-directed repair(HDR)-edited iPSC lines,particularly for silent genes.This is partially due to chromatin compaction,inevitably limiting Cas9 access to the target DNA.Among the six HDAC inhibitors we examined,vorinostat,or suberoylanilide hydroxamic acid(SAHA),led to the highest HDR efficiency at both open and closed loci,with acceptable toxicity.HDAC inhibitors equally increased non-homologous end joining(NHEJ)editing efficiencies(~50%)at both open and closed loci,due to the considerable HDAC inhibitor-mediated increase in Cas9 and sgRNA expression.However,we observed more substantial HDR efficiency improvement at closed loci relative to open chromatin(2.8 vs.1.7-fold change).These studies provide a new strategy for HDRediting of silent genes in iPSCs.

Nanovoid-confinement and click-activated nanoreactor for synchronous delivery of prodrug pairs and precise photodynamic therapy

Bioorthogonal cleavage reaction-triggered prodrug activation by the pretargeted methods can achieve accurate cancer therapy.However,the click and release efficiency of these methods in vivo is limited by the space-time dislocation of bioorthogonal prodrug-trigger pairs within the tumor area,caused by their asynchronous administration and inconsistent accumulation for most delivery systems.We herein created a nanovoid-confinement and click-activated(NCCA)core–shell nanoreactor by incorporating prodrugs within zeolitic imidazolate framework-90(ZIF-90)as core and coating tetrazine-based covalent organic framework(COF)as shell.After surface modification of aptamer polymer,the NCCA nanoreactor enabled the sufficient delivery of photodynamic prodrugs within tumor.Notably,the core of ZIF-90 was decomposed by tumor acidic environment,inducing the high-efficiency activation of photodynamic prodrugs via nanoconfined bioorthogonal reaction with tetrazine-based COF shell.As a result,such photodynamic agents are efficiently and safely accumulated into tumor and specifically activated for precise photodynamic therapy of cancer cells and tumor bearing mice with minimizing toxic side effect.Taken together,such NCCA nanoreactor clearly demonstrates the critical feasibility to realize the synchronous delivery of both prodrugs and triggers for precise treatment,which most of delivery systems are not able to afford.

A NON-LINEAR MODEL FOR ESTIMATING THE COST OF ACHIEVING EMISSION REDUCTION TARGETS:THE CASE OF THE U.S.,CHINA AND INDIA

With the world talking about climate change, the United States （U.S.）, China and India have announced their carbon emission reduction targets. For these three countries to achieve their targets, significant questions arise, shch as what will be the annual emission reduction efforts to achieve those targets, how much it would cost and what would be the economic effects. This paper puts the carbon intensity reduction targets of China and India together with the absolute emission reduction target of the U.S. into the same non-linear model to quantitatively study the optimal emission control strategies and associated total cost for achieving those targets by the year 2020, and estimate and compare the minimized total costs of the three countries to reach their targets. Our results show that the total cost for the U.S. to achieve its emission reduction target is greater than those of China and India in terms of absolute amount. However, in terms of proportion of total cost to GDP, China and India＇s ratios are significantly greater than that of the U.S., indicating that for the developing countries such as China and India, the achievement of emission reduction targets needs relatively greater effort.

Cellular Reprogramming of Human Peripheral Blood Cells

Breakthroughs in cell fate conversion have made it possible to generate large quantities of patient-specific cells for regenerative medicine. Due to multiple advantages of peripheral blood cells over fibroblasts from skin biopsy, the use of blood mononuclear cells （MNCs） instead of skin fibroblasts will expedite reprogramming research and broaden the application of reprogramming technology. This review discusses current progress and challenges of generating induced pluripotent stem cells （iPSCs） from peripheral blood MNCs and of in vitro and in vivo conversion of blood cells into cells of therapeutic value, such as mesenchymal stem cells, neural cells and hepatocytes. An optimized design of lentiviral vectors is necessary to achieve high reprogramming efficiency of peripheral blood cells. More recently, non-integrating vectors such as Sendai virus and episomal vectors have been successfully employed in generating integration-free iPSCs and somatic stem cells.

A new fluorescent probe with ultralow background fluorescence for imaging of endogenous cellular selenol under oxidative stress

A new fluorescent probe（Rhod-Sec） for selenol detection with ultralow background fluorescence have been developed in this paper, which showed a 380-fold off-on fluorescence response, and the nontoxic Rhod-Sec is well suitable for detecting and imaging both exogenous and endogenous selenol in living cells. It also can be applied to visualize the fluctuation of selenol in HepG2 cells through LPS-induced cells oxidation resistance.

Dynamics of a stochastic heroin epidemic model with bilinear incidence and varying population size

We investigate a stochastic heroin epidemic model with bilinear incidence and varying population size.Sufficient criteria for the extinction of the drug abusers and the existence of ergodic stationary distribution for the model are established by constructing suitable stochastic Lyapunov functions.By analyzing the sensitivity of the threshold of spread,we obtain that prevention is better than cure.Numerical simulations are carried out to confirm the analytical results.