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Fengli Huang,1,* Qun Zhang,2,* Jie Xiao,3,* Xin Zhang,1 Xingzhi Han,3 Xiao Shi,3 Jing Hu,2 Li Li,2 Xiaoping Qian1,2 1Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Department of Oncology, Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 3Department of Oncology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoping Qian, Department of Oncology, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-13951743162, Fax +86-25-68182342, Email xiaopingqian@nju.edu.cnPurpose: Recent studies have shown that traditional Chinese medicine (TCM), such as gambogic acid (GA), is involved in the regulation of tumor immune microenvironment and can be combined with other anti-tumor treatment strategies. Here, we used GA as an adjuvant to construct a nano-vaccine to improve the anti-tumor immune response of colorectal cancer (CRC).Materials and Methods: We used a previously reported two-step emulsification method to obtain poly (lactic-co-glycolic acid) /GA nanoparticles (PLGA/GA NPs), and then CT26 colon cancer cell membrane (CCM) was used to obtain CCM-PLGA/GA NPs. This novel nano-vaccine, CCM-PLGA/GA NPs, was co-synthesized with GA as an adjuvant and neoantigen provided by CT26 CCM. We further confirmed the stability, tumor targeting, and cytotoxicity of CCM-PLGA/GA NPs. The regulatory effect on the tumor immune microenvironment, the anti-tumor efficacy, and the combined anti-tumor efficacy with anti-PD-1 monoclonal Antibodies (mAbs) of this novel nano-vaccine was also detected in vivo.Results: We successfully constructed the CCM-PLGA/GA NPs. In vitro and in vivo tests showed low biological toxicity, as well as the high tumor-targeting ability of the CCM-PLGA/GA NPs. Besides, we revealed a remarkable effect of CCM-PLGA/GA NPs to activate the maturation of dendritic cells (DCs) and the formation of a positive anti-tumor immune microenvironment.Conclusion: This novel nano-vaccine constructed with GA as the adjuvant and CCM providing the tumor antigen can not only directly kill tumors by enhancing the ability of GA to target tumors, but also indirectly kill tumors by regulating tumor immune microenvironment, providing a new strategy for immunotherapy of CRC.Keywords: cancer immunotherapy, gambogic acid, nano-vaccine, tumor immune microenvironment, colorectal cancer

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) plays an important role in the initiation and development of Graves' disease (GD), especially CTLA-4 +49A/G polymorphism and genetic susceptibility to GD. However, the current conclusions are consistent. Therefore, this study adopted meta-analysis method to assess the exact correlation between this polymorphism and GD risk. Methods Literature searches were performed in PubMed, Embase, Web of Science, China National Knowledge Infrastructure, China Wanfang, and other databases for data on the correlation between polymorphisms of CTLA-4 +49A/G and GD risk. The end date for publications was May 2020. Stata 15.0 software was used for data analysis. Results A total of 33 papers were included, covering 8,555 cases and 9,533 controls. The results showed that the CTLA-4 +49 allele G compared to allele A, odds ratio (OR) = 1.62, 95% CI [1.56, 2.09]. In the dominant, recessive, homozygous, and heterozygous genetic models, comparing the GD group and the control group, the combined OR was 1.81, 95% CI [1.56, 2.09]; 1.91, 95% CI [1.66, 2.21]; 2.75, 95% CI, [2.21, 3.41]; and 1.49, 95% CI [1.29, 1.71], respectively. When it was analyzed by dividing genetic models into subgroups according to ethnicity and published year, the data the of genetic model in each subgroup were also statistically significant. Conclusion The CTLA-4 +49A/G polymorphism was strongly associated with genetic susceptibility to GD. Allele G, genotypes GG, GG + GA, and GA are correlated with an increase in the risk of GD.

Flexible pressure sensors have attracted much attention in academia owing to their wide-ranging applications in wearable electronics, medical electronics and digital health. However, practical engineering applications have been restricted because of limitations in efficiency, manufacturing costs and sensitivity. In this work, we propose an innovative method for high-efficiency printing of microstructures that replaces traditional inverted mold methods. We developed a high-sensitivity flexible piezoresistive pressure (FPP) sensor with a high manufacturing efficiency and low manufacturing cost. The sensor was encapsulated by connecting a polydimethylsiloxane film with microstructures prepared using the sandpaper-molding method, and then integrated with an interdigital electrode and spherical micro-structures fabricated via resonant printing. In this way, the manufacturing process was simplified by breaking it down into two steps. The performance of the sensor was assessed by conducting experiments under different pressure regimes. The results demonstrated ultra-high sensitivity (0.0058–0.024 kPa−1) and a wide pressure detection range (1–100 kPa), spanning the entire range of pressure monitoring typically observed for vital and health signals. The response time of the sensor was less than 72 ms. Furthermore, the performance of the fabricated sensor was highly stable after 1000 bending cycle. The potential applications of the FPP sensor are discussed in area such as the human body and mouse.

Improving the conductivity of metal particle inks is a hot topic of scientific research. In this paper, a method for preparing metal-filled particles was proposed. By adding filled particles to the ink, the size distribution of particles could be changed to form a bimodal distribution structure in accordance with Horsfield’s stacking model. The filling particles had small volume and good fluidity, which could fill the gaps between the particles after printing and improve its electrical conductivity without significantly changing the metal solid content in the ink. Experimental results show that the silver content of the ink slightly increased from 15 wt% to 16.5 wt% after adding filled particles. However, the conductivity of the ink was significantly improved, and after sintering, the resistivity of the ink decreased from 70.2 μΩ∙cm to 31.2 μΩ∙cm. In addition, the filling particles prepared by this method is simple and has a high material utilization rate, which could be applied to the preparation of other kinds of metal particle inks.

A microwave-assisted two-steps method was proposed for the facile and fast preparation of silver nanoparticle conductive ink. The nanoparticles in the ink are of multi-sized, which is beneficial to getting higher packing density and better conductivity of the printed/written pattern. The effects of the reaction parameters of microwave and additives on the written pattern resistivity were studied on the basis of scanning electron microscope, X-ray diffraction and surface porosity results. Both of the microwave energy and the addition of PVP as the capping agent were found to be critical for the formation of face-centered cubic silver nanoparticles in the conductive ink. The surface porosity and the pore distribution form were also demonstrated to affect the pattern conductivity. The electrical resistivity or the pattern written with the ink prepared at microwave irradiation time of 90 s was calculated to be 364 μΩ cm. The second step of simple centrifugation process could improve the pattern conductivity effectively. After concentrated the conductive ink for two times, the electrical resistivity of the written pattern reduced from 364 to 77 μΩ cm. The proposed two-steps of microwave combined with centrifugation method is a simple and useful way for the preparation of silver nanoparticle conductive ink that can be used in printed electronics.

A facile one-step microwave approach was employed to synthesize silver nanoparticle (AgNP) conductive ink. The conductive ink contained multi-sized silver nanoparticles. Different particle size distribution can be obtained by adding different amounts of the silver source. The relationship between the conductivity of the direct written pattern using the as-prepared silver conductive ink, the particle packing morphology and the particle size distribution standard deviation was investigated. Among all the samples, conductive ink with a silver weight percentage of 10% can have an optimal electrical resistance of 98 μΩ cm after post-hot/pressure treatment at 100°C and 20 MPa for 10 min. The as-prepared conductive ink is of potential application in printed electronics because the sintering condition of low temperatures is feasible for most kinds of flexible substrate materials.

The liquid phase reduction method has a wide application prospect because of its simple equipment and low cost. However, the disadvantages, such as uneven particle size distribution and easy agglomeration of particles, make it difficult to prepare high-concentration nanoparticle ink by this method, which limits its application in the manufacture of high-resolution electronic products. This paper presents a printing and sintering process for low-concentration ink prepared by the liquid reduction method. First, the set pattern is printed by the near-field electrohydraulic printing method. At the same time as multi-layer printing, the substrate is heated by the collecting plate to accelerate the evaporation of the solvent in the printed pattern. Then, the printed multi-layer micro-conductive pattern is solidified by a hot/pressure sintering machine. This method can overcome the edge diffusion effect caused by poor ink viscosity effectively and obtain printing patterns with high thickness, high conductivity, and high resolution. The drying time of different ink layers, the pressure and temperature of hot/pressure sintering, and other parameters were studied in this paper. The electrical conductivity and reliability of the pattern with different printing layers are also analyzed, which provides a reference for the printing and sintering of low-concentration ink in the future.

In this work, we proposed a microwave method to the fast-and-direct preparation of silver nano-ink. The conductive ink is composed of multi-scaled silver nanoparticles (AgNPs) and a few of silver nanorods (AgNRs) as the conductive components. The differently sized nano-silver can provide high conductivity of the written tracks by affording high packing density. The existed one dimensional nanorods can build bridges between nanoparticles to decrease the silver content while maintaining the conductivity of the written pattern. The as-prepared conductive ink can be stored for 20 days without affecting its usability. The written tracks showed satisfying conductivity with a relatively low silver content of 0.025 mol L−1.

The effect of 0–1.0 wt% Y addition on the microstructures and mechanical properties of as-aged Mg-6Zn-1Mn-4Sn alloy was investigated. The results showed that α-Mg, α-Mn, MgZn2, Mg2Sn and MgSnY phases were found in the as-aged Y-containing alloys. The MgSnY was a high temperature phase and could promote the age-hardening response. The as-aged ZMT614-0.5Y alloy exhibited excellent mechanical properties was attributed to the high number density of β 1 ′ rods. Its yield strength (YS), ultimate tensile strength (UTS), elongation was 371 MPa, 376 MPa and 7.7%, respectively.

Using molecular dynamics simulations based on explicit-solvent model, we study migration of polymer-modified nanoparticles through nanochannels coated with polymers. The polymers densely grafted on the spherical nanoparticle and the channel surface form spherical polymer brush (SPB) and planar polymer brush (PPB), respectively. The migration of the neutral polymer-modified nanoparticle is driven by electroosmotic flow (EOF). The effects of the electric field strength and the SPB–PPB interaction on polymer conformations and transport dynamics of the SPB are explored. The migration velocity of the SPB reduces as the interaction between the SPB and the PPB increases. For strong SPB–PPB interaction, the directional migration of the SPB can be triggered only after the electric field strength exceeds a critical value. The high EOF velocity forces the center of mass of the spherical nanoparticle to keep near the central region of the channel due to high shear rate close to the brush–fluid interface. Unlike electrophoresis of charged polymer-grafted spherical particles, the SPB adopts a more extended conformation in the plane perpendicular to the EOF direction.

The thermodynamic characteristics and solidification sequence of Mg–6Zn–1Mn–4Sn–xNd (x = 0.5, 1.0, 1.0, wt-%, ZMT614-xNd) alloys were investigated using CALPHAD, Miedema model, differential scannin...

Non particle nano Ag conductive ink is a promising material for the patterning of flexible circuits by using the electrohydrodynamic micro printing technology. The pulse voltage control mold has been mainly used in the on demand droplet control in the patterning process. In this paper, the effect of pulse voltage amplitude on cone jetting behavior of this ink in one pulse period has been investigated by using the sequential images technology. Results indicated that under the same base direct current voltage applied on the nozzle, the pulse voltage applied on the substrate induced pulsant cone jetting rather than stable cone jetting in a pulse period if the value is under a critical value. When the voltage amplitude above this critical value was used, the stable cone jetting was obtained for each ejection. The increasing voltage amplitude resulted in the shortening of jetting starting time and also the ending time, and the jetting duration was decreased with the increasing of pulse voltage amplitude. There...

We study the number and distribution of limit cycles of some planarZ4-equivariant quintic near-Hamiltonian systems. By the theories of Hopf and heteroclinic bifurcation, it is proved that the perturbed system can have 24 limit cycles with some new distributions. The configurations of limit cycles obtained in this paper are new.

We report an all-atom molecular dynamics study of the structures and dynamics of salty water droplets on a silicon surface under the influence of applied electric field. Our simulation results support ion-specific effects on the elongation dynamics of salty nanodroplets, induced by the field. This feature has not been explored up to now in monovalent salts. Nevertheless, the importance of ion-specific effects is widely confirmed in biological and colloidal systems. In particular, the increase of salt concentration enhances the effect of the nature of ions on the wetting properties of droplets. In the presence of electric field (0.05 V A-1), a complete spreading is implemented in a short time for different droplets at a concentration of 1 M, and the droplet morphology is stable, observed at long time scales. However, a higher salt concentration of 4 M considerably suppresses the spreading process owing to the increase of surface tension. It was found that the NaCl droplet shows deformation oscillations along the external field, but cannot fully wet the substrate surface. By contrast, the CsCl droplet reaches complete elongation rapidly and adopts a steady strip shape. The KCl droplet undergoes frequent transitions between breakup and connection. Additionally, the droplets can be elongated only when the electric field strength exceeds a threshold value. The dipole orientation of interfacial water and the ionic diffusion exhibit ion-specific dependences, but the hydrogen bond network is scarcely disturbed, excluding a concentration-dependent effect.

At present, the feature machining is recognized automatically for the typical CAM software, but there are some shortcomings in the technological rule base which support feature machining scheme. First, the classification and data model and the identification method of manufacturing feature are given. Then, the mapping of parts feature model to the processing schemes is given; the main variables are defined as follows: blank material, size tolerance, surface roughness and shape characteristics. The processing scheme of the non-hole class characteristics and hole class characteristics are defined according to the difference of shape feature. Based on above, association method of the recognition feature machining scheme is proposed based on extension comprehensive correlation functions. At last, the application instance shows the better operability of this method, and the automatic generation of feature machining scheme has come true.

The excitation selection sort method of manufacturing feature was proposed based on the characteristics oriented to manufacturing feature of STEP-NC to realize the process route planning of STEP-NC. First, match the recognizing manufacturing feature, the manufacturing feature with multi machining operation was disintegrated in order that every manufacturing feature has only a processing operation. Then, the rationality constraint problems of machining operation was translated into the processing order problem of manufacturing feature, and the optimal constraint problem of machining operation was translated into the corresponding manufacture feature set. The process route was generated by the operations of excitation, selection, deletion and transfer for the feature of different manufacture feature set. The last, the feasibility and effectiveness of the process route excitation generation method was verified by an example, and show that this method was better solved the problems of process rules and the representation of knowledge.

We conducted coarse-grained molecular dynamics simulations to study the responsive behaviors of polyampholyte brushes (PABs) under external electric fields. The effects of charge sequence, chain rigidity and electric field strength on the conformational transition and local structures of grafted chains were addressed systematically. Without electric field, the calculations indicate that the thickness of the PABs is smaller compared to polyelectrolyte brushes (PEBs). The presence of electric field leads to inconsistency of densities between negatively and positively charged monomers except for the alternating brush. Counterions from the PABs can diffuse inside or outside the brush. Unlike the PABs, to separate the polyelectrolytes and their counterions the electric field needs to overcome the osmotic pressure of counterions. The critical field which induces the extension of the flexible PABs is much larger than the PEBs. Meanwhile, it was also found that the critical field which induces the collapse of the PABs decreases as the block length increases. In the limit of strong field studied, the chains with longer blocks are in a local extended state. For diblock brushes, once oppositely charged blocks in a single chain are separated, the chain will become straighter due to strong electrostatic repulsion in intrablock.

Aiming at two quality factors (warpage quantity and shrinkage rate) of the plastic injection process, the optimum method on craft parameters of plastic injection based on synthesis relation degree, Kriging model and adaptive genetic-ant colonies algorithm is provided. The definition and calculation method of synthesis relation degree are given at first, and the approximate model based on Kriging model and genetic-ant colonies algorithm are given also. In the case study of plastic injection of fruit plate, the range of craft parameters and the deciding method of design variables based on orthogonal experiment are given, then the approximate model is gotten by Hyper-Latin square experiment and Kriging method, the optimum result is gotten by genetic-ant algorithm. According to the CAE and actual experiment of plastic injection, it shows that the optimum result of plastic injection is reliability, and has good practical meaning.

Aiming at the two principal; quality factors (warpage quantity and shrinkage rate) in injection molding process, the optimum method on injection molding condition based on RBF network and ant colony algorithm is provided. The definition and calculation method of excellent degree are given first and then the optimum method of the approximate model based on radial basis neural network is given. In the case study of plastic injection of fruit plate, the range of molding condition and the design method of design variables based on excellent degree are given, then the approximate model is gotten by Hyper-Latin square experiment and RBF network, the optimum result is gotten by improved ant colony algorithm of continuous field. It shows that the optimum result of plastic injection parameters based on radial basis neural network response surface and ant colony algorithm is reliable, and has good practical meaning.

The system reliability which applies redundant style of reservoir is studied aiming at the fuzziness of reliability parameter. Firstly, fuzzy chance constrained model of redundant system reliability optimization is given. Then the solution strategy of ant colonies algorithm with fuzzy simulated is studied, and the detailed steps of hybrid intelligent algorithm is given. At last, an instance is given, a reservoir system which has four parts (stages) is solved by ant colonies algorithm with fuzzy simulated, the feasibility of ant colonies hybrid intelligence algorithm with fuzzy simulated is verified by the result of calculation.

The problem of maximum multi-reliabilities is studied aiming to the network structures. Firstly, the optimum model of network structures based on random and fuzzy chances constrained is given. The solution strategy of genetic-ant colonies algorithm with stochastic simulation and fuzzy simulated is studied, and the detailed steps of hybrid intelligence are given based on stochastic simulation and fuzzy simulation. At last, an instance is given, multi-objects model with chance constrained programming is provided, the model is solved by genetic-anti colonies algorithm. The feasibility of hybrid intelligence of genetic algorithm and ant colonies with stochastic simulation and fuzzy simulated is verified by the result of calculation.

For the parameters of product reliability design are uncertain, based on the Liu's fuzzy chance constrained theory, provides a fuzzy chance constrained programming module of product reliability design that has N sub-systems and several designs can be chosen in every sub-system. The detailed processes of genetic algorithm and ant colonies algorithm are given respectively, checking fuzzy simulation for the fuzzy chance constrains are improved. The detailed method of solution based on genetic-ant colonies with fuzzy simulated is given. At the end of the paper, an instance is given to test that the algorithm and the improvement are reliable, and the searching speed can be improved.

The problem of minimum cost is studied aiming to the network structures. Firstly, the chance constrained model of optimum network structures is given. Then the solution strategy of ant colonies algorithm with random simulated and mutation operator is studied, and the detailed steps of hybrid intelligence is given. At last, an instance is given, optimum network structures of minimum cost which have 10 terminal nodes are solved by hybrid intelligence of ant colonies algorithm, and the result of calculation is analyzed.