肿瘤原位荧光标记技术设计和探索虚拟仿真实验

原位荧光成像技术为细胞和活体水平生化信息获取提供了强有力的手段,基于固态发光荧光探针的长时间原位标记技术能应用于精准成像与手术导航肿瘤切除。但该科研实验存在周期长、成本高、消耗大等困难,无法引入本科教学。采用U3D三维虚拟现实技术平台将该最新研究成果转化为“肿瘤原位荧光标记技术设计和探索虚拟仿真实验”,通过37步交互操作和基于重要科学问题的探究式教学,培养学生动手能力、科学思维和创新意识,实现科学素养和科研价值观的引导。

以“人才培养”为中心,全面推进一流专业建设

专业是本科教育的“四梁八柱”。专业建设是一项系统工程,涉及教师、学生以及进行教育教学活动的条件和保障等多方面内容,专业建设的水平和质量直接影响人才培养的质量。本文以湖南大学化学专业为例,分析了专业建设的现状,指明了限制专业发展的问题,同时立足“人才培养”这一中心任务,针对专业建设的短板和不足,从专业建设的软硬件方面提出了改革举措,为一流专业建设提供了借鉴和思路。

A prediction method for the performance of a low-recoil gun with front nozzle

One of the greatest challenges in the design of a gun is to balance muzzle velocity and recoil,especially for guns on aircrafts and deployable vehicles.To resolve the conflict between gun power and recoil force,a concept of rarefaction wave gun(RAVEN)was proposed to significantly reduce the weapon recoil and the heat in barrel,while minimally reducing the muzzle velocity.The main principle of RAVEN is that the rarefaction wave will not reach the projectile base until the muzzle by delaying the venting time of an expansion nozzle at the breech.Developed on the RAVEN principle,the purpose of this paper is to provide an engineering method for predicting the performance of a low-recoil gun with front nozzle.First,a two-dimensional two-phase flow model of interior ballistic during the RAVEN firing cycle was established.Numerical simulation results were compared with the published data to validate the reliability and accuracy.Next,the effects of the vent opening times and locations were investigated to determine the influence rules on the performance of the RAVEN with front nozzle.Then according to the results above,simple nonlinear fitting formulas were provided to explain how the muzzle velocity and the recoil force change with the vent opening time and location.Finally,a better vent venting opening time corresponding to the vent location was proposed.The findings should make an important contribution to the field of engineering applications of the RAVEN.

Neural Mechanisms of Mental Fatigue Revisited: New Insights from the Brain Connectome

Maintaining sustained attention during a prolonged cognitive task often comes at a cost: high levels of mental fatigue. Heuristically, mental fatigue refers to a feeling of tiredness or exhaustion, and a disengagement from the task at hand;it manifests as impaired cognitive and behavioral performance. In order to effectively reduce the undesirable yet preventable consequences of mental fatigue in many real-world workspaces, a better understanding of the underlying neural mechanisms is needed, and continuous efforts have been devoted to this topic. In comparison with conventional univariate approaches, which are widely utilized in fatigue studies, convergent evidence has shown that multivariate functional connectivity analysis may lead to richer information about mental fatigue. In fact, mental fatigue is increasingly thought to be related to the deviated reorganization of functional connectivity among brain regions in recent studies. In addition, graph theoretical analysis has shed new light on quantitatively assessing the reorganization of the brain functional networks that are modulated by mental fatigue. This review article begins with a brief introduction to neuroimaging studies on mental fatigue and the brain connectome, followed by a thorough overview of connectome studies on mental fatigue. Although only a limited number of studies have been published thus far, it is believed that the brain connectome can be a useful approach not only for the elucidation of underlying neural mechanisms in the nascent field of neuroergonomics, but also for the automatic detection and classification of mental fatigue in order to address the prevention of fatigue-related human error in the near future.

Impact of Morphology of Conductive Agent and Anode Material on Lithium Storage Properties

In this study,the impact of morphology of conductive agent and anode material(Fe3O4)on lithium storage properties was throughly investigated.Granular and belt-like Fe3O4active materials were separately blended with two kinds of conductive agents(i.e.,granular acetylene black and multi-walled carbon nanotube)as anodes in lithium-ion batteries(LIBs),respectively.It was found that the morphology of conductive agent is of utmost importance in determining LIBs storage properties.In contrast,not as the way we anticipated,the morphology of anode material merely plays a subordinate role in their electrochemical performances.Further,the morphology-matching principle of electrode materials was discussed so as to render their utilization more rational and effective in LIBs.

Effects of cultivation of Osr HSA transgenic rice on functional diversity of microbial communities in the soil rhizosphere

With the widespread cultivation of transgenic crops, there is increasing concern about unintended effects of these crops on soil environmental quality. In this study, we used the Biolog method and ELISA to evaluate the possible effects of Osr HSA transgenic rice on soil microbial utilization of carbon substrates under field conditions. There were no significant differences in average well-color development(AWCD) values, Shannon–Wiener diversity index(H), Simpson dominance indices(D) and Shannon–Wiener evenness indices(E) of microbial communities in rhizosphere soils at eight samplings between Osr HSA transgenic rice and its non-transgenic counterpart. The main carbon sources utilized by soil microbes were carbohydrates, carboxylic acids, amino acids and polymers. The types,capacities and patterns of carbon source utilization by microbial communities in rhizosphere soils were similar throughout the detection period. We detected no Osr HSA protein in the roots of Osr HSA transgenic rice. We concluded that Osr HSA transgenic rice and the r HSA protein it produced did not alter the functional diversity of microbial communities in the rhizosphere.

Numerical investigation on cooling performance of filter in a pyrotechnic gas generator

As a key part of the pyrotechnic gas generator,the filter not only removes the particulate matter but also cools the hot gas to a safe level.This paper aims to improve the understanding of the basic heat and flow phenomenon in the gas generator.The pyrotechnic gas generator is modelling by a simplified filter structure with fiber arrays.A finite-volume model of the heat and fluid flow is proposed to simulate the detailed multi-dimensional flow and energy conversion behaviors.Several verification results are in good agreement with data in different references.Simulation results demonstrate that the filter can not only absorb heat from the gas but also cause the high intensity enhancement of the heat transfer.The performance difference between inline and staggered arrays is also discussed.The findings of the study put a further prediction tool for the understanding and design of the filter system with fibers.

Finite density scaling laws of condensation phase transition in zero-range processes on scale-free networks

The dynamics of zero-range processes on complex networks is expected to be influenced by the topological structure of underlying networks.A real space complete condensation phase transition in the stationary state may occur.We study the finite density effects of the condensation transition in both the stationary and dynamical zero-range processes on scale-free networks.By means of grand canonical ensemble method,we predict analytically the scaling laws of the average occupation number with respect to the finite density for the steady state.We further explore the relaxation dynamics of the condensation phase transition.By applying the hierarchical evolution and scaling ansatz,a scaling law for the relaxation dynamics is predicted.Monte Carlo simulations are performed and the predicted density scaling laws are nicely validated.

A Consistent Time Level Implementation Preserving Second-Order Time Accuracy via a Framework of Unified Time Integrators in the Discrete Element Approach

In this work,a consistent and physically accurate implementation of the general framework of unified second-order time accurate integrators via the well-known GSSSS framework in the Discrete Element Method is presented.The improved tangential displacement evaluation in the present implementation of the discrete element method has been derived and implemented to preserve the consistency of the correct time level evaluation during the time integration process in calculating the algorithmic tangential displacement.Several numerical examples have been used to validate the proposed tangential displacement evaluation;this is in contrast to past practices which only seem to attain the first-order time accuracy due to inconsistent time level implementation with different algorithms for normal and tangential directions.The comparisons with the existing implementation and the superiority of the proposed implementation are given in terms of the convergence rate with improved numerical accuracy in time.Moreover,several schemes via the unified second-order time integrators within the framework of the GSSSS family have been carried out based on the proposed correct implementation.All the numerical results demonstrate that using the existing state-of-the-art implementation reduces the time accuracy to be first-order accurate in time,while the proposed implementation preserves the correct time accuracy to yield second-order.

A New Heptamethine Cyanine-Based Near-Infrared Fluorescent Probe for Divalent Copper Ions with High Selectivity

A new near-infrared fluorophore 2-(2-Aminoethyl) pyridine-tricarbocyanine (1) was rationally designed and synthe-sized as a fluorescent probe for detection of Cu2+ with high selectivity. The response of Probe 1 is based on the fluorescence quenching upon binding to Cu2+. The sensing performance of the proposed Cu2+-sensitive Probe 1 was then investigated. The probe can be applied to the quantification detection of Cu2+ with a linear concentration range covering from 4.8 × 10-7 to 1.6 × 10-4 mol/L and a detection limit of 9.3 × 10-8 mol/L. The experimental results showed that the response of 1 to Cu2+ was independent of pH in medium condition (pH 6.0-8.0), and exhibited excellent selectivity towards Cu2+ over other common metal cations.

Preparation of Fe–Co based MOF-74 and its effective adsorption of arsenic from aqueous solution

To obtain a cost-effective adsorbent for the removal of arsenic in water,a novel nanostructured Fe–Co based metal organic framework(MOF-74)adsorbent was successfully prepared via a simple solvothermal method.The adsorption experiments showed that the optimal molar ratio of Fe/Co in the adsorbent was 2:1.The Fe_2Co_1MOF-74 was characterized by various techniques and the results showed that the nanoparticle diameter ranged from60 to 80 nm and the specific surface area was 147.82 m^2/g.The isotherm and kinetic parameters of arsenic removal on Fe_2Co_1MOF-74 were well-fitted by the Langmuir and pseudo-second-order models.The maximum adsorption capacities toward As(III)and As(V)were 266.52 and 292.29 mg/g,respectively.The presence of sulfate,carbonate and humic acid had no obvious effect on arsenic adsorption.However,coexisting phosphate significantly hindered the removal of arsenic,especially at high concentrations(10 mmol/L).Electrostatic interaction and hydroxyl and metal–oxygen groups played important roles in the adsorption of arsenic.Furthermore,the prepared adsorbent had stable adsorption ability after regeneration and when used in a real-water matrix.The excellent adsorption performance of Fe_2Co_1MOF-74 material makes it a potentially promising adsorbent for the removal of arsenic.

Self-assembled multifunctional DNA nanoflowers for the circumvention of multidrug resistance in targeted anticancer drug delivery

Cancer chemotherapy has been limited by its side effects and multidrug resistance （MDR）, the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circumvent MDR are needed. Here, we report multifunctional DNA nanoflowers （NFs） for targeted drug delivery to both chemosensitive and MDR cancer cells that circumvented MDR in both leukemia and breast cancer cell models. NFs are self-assembled via potential co-precipitation of DNA and magnesium pyrophosphate generated by rolling circle replication, during which NFs are incorporated using aptamers for specific cancer cell recognition, fluorophores for bioimaging, and doxorubicin （Dox）- binding DNA for drug delivery. NF sizes are tunable （down to N200 nm in diameter）, and the densely packed drug-binding motifs and porous intrastructures endow NFs with a high drug-loading capacity （71.4%, wt/wt）. Although the Dox- loaded NFs （NF-Dox） are stable at physiological pH, drug release is facilitated under acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not in nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising tools for circumventing MDR in targeted cancer therapy.

Gold nanorod-photosensitizer conjugate with extracellular pH-driven tumor targeting ability for photothermal/photodynamic therapy

Chlorin e6-pHLIPss-AuNRs, a gold nanorod-photosensitizer conjugate containing a pH （low） insertion peptide （pHLIP） with a disulfide bond which imparts extracellular pH （pHe）-driven tumor targeting ability, has been successfully developed for bimodal photodynamic and photothermal therapy. In this bimodal therapy, chlorin e6 （Ce6）, a second-generation photosensitizer （PS）, is used for photodynamic therapy （PDT）. Gold nanorods （AuNRs） are used as a hyperthermia agent for photothermal therapy （PTT） and also as a nanocarrier and quencher of Ce6. pHLIPss is designed as a pile-driven targeting probe to enhance accumulation of Ce6 and AuNRs in cancer cells at low pH. In Ce6- pHLIPss-AuNRs, Ce6 is close to and quenched by AuNRs, causing little PDT effect. When exposed to normal physiological pH 7.4, Ce6-pHLIPs^-AuNRs loosely associate with the cell membrane. However, once exposed to acidic pH 6.2, pHLIP actively inserts into the cell membrane, and the conjugates are translocated into cells. When this occurs, Ce6 separates from the AuNRs as a result of disulfide bond cleavage caused by intracellular glutathione （GSH）, and singlet oxygen is produced for PDT upon light irradiation. In addition, as individual PTT agent, AuNRs can enhance the accumulation of PSs in the tumor by the enhanced permeation and retention （EPR） effect. Therefore, as indicated by our data, when exposed to acidic pH, Ce6-pHLIPss-AuNRs can achieve synergistic PTT/PDT bimodality for cancer treatment.

Recent advances in DNAzyme-based gene silencing

DNAzymes, generated through in vitro selection processes, are single-stranded DNA catalysts that can catalyze a wide variety of reactions, such as RNA or DNA cleavage and ligation or DNA phosphorylation. Based on specific cofactor dependence and potent catalytic ability, DNAzymes have been extensively used to develop highly sensitive and specific sensing platforms for metal ions,small molecules, and biomacromolecules. However, in spite of their multiple strong enzymatic turnover properties, few reports have addressed the potential application of RNA-cleaving DNAzymes as therapeutic gene-silencing agents. The main challenges are being met with low efficiency of cellular uptake, instability and the lack of sufficient cofactors for cellular or in vivo study, which have limited the development of DNAzymes for clinical application. In recent years, substantial progress has been made to enhance the delivery efficiency and stability of DNAzymes by developing variety of methods. Smart metal oxide nanomaterials have also been used to meet the requirement of cofactors in situ. This review focuses on the gene silencing application of DNAzymes as well as their physicochemical properties. Methods of increasing the efficacy of DNAzymes in gene therapy are also discussed: delivery systems to enhance the cellular uptake, modifications to enhance the stability and smart systems to generate sufficient cofactors in situ. Finally, some future trends and perspectives in these research areas are outlined.

3D brain glioma segmentation in MRI through integrating multiple densely connected 2D convolutional neural networks

To overcome the computational burden of processing three-dimensional(3 D)medical scans and the lack of spatial information in two-dimensional(2 D)medical scans,a novel segmentation method was proposed that integrates the segmentation results of three densely connected 2 D convolutional neural networks(2 D-CNNs).In order to combine the lowlevel features and high-level features,we added densely connected blocks in the network structure design so that the low-level features will not be missed as the network layer increases during the learning process.Further,in order to resolve the problems of the blurred boundary of the glioma edema area,we superimposed and fused the T2-weighted fluid-attenuated inversion recovery(FLAIR)modal image and the T2-weighted(T2)modal image to enhance the edema section.For the loss function of network training,we improved the cross-entropy loss function to effectively avoid network over-fitting.On the Multimodal Brain Tumor Image Segmentation Challenge(BraTS)datasets,our method achieves dice similarity coefficient values of 0.84,0.82,and 0.83 on the BraTS2018 training;0.82,0.85,and 0.83 on the BraTS2018 validation;and 0.81,0.78,and 0.83 on the BraTS2013 testing in terms of whole tumors,tumor cores,and enhancing cores,respectively.Experimental results showed that the proposed method achieved promising accuracy and fast processing,demonstrating good potential for clinical medicine.

Recent advances in molecular fluorescent probes for organic phosphate biomolecules recognition

Organic phosphate biomolecules(OPBs) are indispensable components of eukaryotes and prokaryotes,such as acting as the fundamental components of cell membranes and important substrates for nucleic acids. They play pivotal roles in various biological processes, such as energy conservation, metabolism,and signal modulation. Due to the difficulty of detection caused by variety OPBs, investigation of their respective physiological effects in organisms has been restrained by the lack of efficient tools. Many small fluorescent probes have been employed for selective detection and monitoring of OPBs in vitro or in vivo due to the advantages of tailored properties, biodegradability and in situ high temporal and spatial resolution imaging. In this review, we summarize the recent advances in fluorescent probes for OPBs,such as nucleotides, NAD(P)H, FAD/FMN and PS. Importantly, we describe their identification mechanisms in detail and discuss the general strategies for these OPBs probe designs, which provide new insights and ideas for the future probe designs.

Nanocarrier based on the assembly of protein and antisense oligonucleotide to combat multidrug resistance in tumor cells

Chemotherapy-induced multi-drug resistance(MDR) in tumors poses a huge challenge for clinical treatment of tumors. The downregulation of the multi-drug resistance relative protein, represented by P-glycoprotein(P-gp), can reverse MDR of cancer cells. In this study, we developed doxorubicin-loading nanocarrier based on the assembly of protein and antisense oligonucleotide(ASO) to combat MDR of cancer cells. The data demonstrate that the nanocarrier can efficiently deliver ASO to cytoplasm and downregulate the P-glycoprotein expression, subsequently improving the therapeutic effects of Dox in doxorubicin-resistant MCF-7/ADR cancer cells. The preparation is simple and effective, providing a powerful tool for gene delivery. Therefore, our nanocarrier shows high promise in cancer treatment.

Copper-thioguanine metallodrug with self-reinforcing circular catalysis for activatable MRI imaging and amplifying specificity of cancer therapy

For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species(ROS) based cancer therapeutic strategy(e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug(6-thioguanine) as ligand copper ions, we achieve a high drug loading rate(60.1%) and 100% of utilization of metal-drug coordination nanoplatform(Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione(GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging(MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo.

A rapid chemometrics model for antioxidant substance mining of Chinese dwarf cherry[Cerasus humilis(Bge.)Sok.]based on polyphenol profile and antioxidant capacity of 30 germplasms

Chinese dwarf cherry(Ouli)is a native shrub in northwest China with high ecological value,but the nutritive potential remains to be explored.In this study,the total content of polyphenols,flavonoids,proanthocyanidins,and anthocyanins of Ouli from 30 germplasms were measured,and the antioxidant activities were evaluated by FRAP and ABTS assays.The polyphenol profile was determined by ultra-high-performance liquid chromatography-high resolution mass spectrometry.Grey relational analysis and partial least squares were utilized to build chemometrics models for selecting antioxidant compounds.The contents of total flavonoids,proanthocyanidins,phenols and total anthocyanidins of 30 germplasms of Ouli were 119.92-668.76 mg/100 g fresh weight(FW),90.81-555.44 mg/100 g FW,148.42-390.43 mg/100 g FW,0.02-17.26 mg/100 g FW,respectively.A total of 61 compounds were identified,including 40 flavonoids(26 flavonols,4 anthocyanins,6 dihydroflavonols,2 dihydrochalcones,and 2 flavones),12 proanthocyanidins,6 phenolic acids,and 3 types of other class compounds(one stilbene and two phenols).The proanthocyanidin compounds in Ouli contributes most to the total antioxidant capacity with the antioxidant rank that procyanidin trimer>tetramer>dimer≈monomer.Catechin and procyanidin B1 were the most abundant compounds and were 18.45-162.50μg/g FW and 30.52-149.42μg/g FW,respectively.Shanxi(SX)2 and SX10 could be considered as potential germplasms,and proanthocyanidins could be chosen as a characteristic nutrient evaluation index of Ouli.This study not only takes a key step to lay the groundwork for further research of Ouli but also provides a reference for the discovery of the functional ingredients of other foods.

Engineering a customized nanodrug delivery system at the cellular level for targeted cancer therapy

Drug administration customized to individual cells could intrinsically address cancer heterogeneity and provide a safe and effective method for delivering personalized treatment. To accomplish this, we developed a smart nanodrug delivery system characterized by cancer cell-targeted drug delivery and intracellular biomarker-responsive drug activation. This system was composed of a long-nicked DNA duplex formed by tandem hybridization of two extended antisense oligonucleotides whose ends were separately blocked with a cancer cell-specific aptamer, AS1411,and a replaceable anti-biomarker probe(ABP). We demonstrated that this DNA nanodrug was directed to cancer cells with the guidance power of AS 1411 and then activated by the presence of a given intracellular biomarker. By using such a belt-and-braces strategy, this DNA nanodrug system could safely and efficiently accelerate apoptosis of target cancer cells. Moreover, since the expression level of biomarkers tends to indicate the specific physiological state of individual cells, biomarker-responsive activation of the nanodrug is expected to enable customized drug administration at the cellular level.