Search

Microspheres and microcapsules have been widely used in biomedical field, such as delivery systems for drugs, vaccines. Uniform particle is required for precise drug delivery and disease treatment, since the particle diameter is a key factor which controls the pharmacokinetics and efficacy of loaded drug. However, there is no universal method to prepare uniform particles either from monomer or preformed polymer raw materials. We have developed two membrane emulsification techniques (MET) to prepare uniform particles with controllable size. In this review, we introduce two MET processes and their mechanisms, and how to develop MET to different emulsion systems to obtain various uniform microspheres and microcapsules with interesting morphologies. Then, the advantages of uniform particles on biomedical application results are focused. Finally, particle design and applications as "Chassis" to form synthetic vaccine are described. What is the most favorite and original chemistry developed in your research group? We clarified the mechanism for obtaining uniform microspheres and microcapsules in O/W, W/O and double emulsion systems, which enabled us to develop the technique to a universal technique, successfully preparing various uniform particles including hydrophobic, hydrophilic and composite functional particles, and leading to the original systematic studies on biomedical applications including "Synthetic Vaccine". How do you get into this specific field? Could you please share some experiences with our readers? I started the research on preparation of nanospheres from my master course. At that time, I knew there were few universal methods to obtain uniform microspheres and microcapsules. So, after I became an assistant professor, I began to consider this scientific topic. How do you supervise your students? Our group motto is "Enjoy Science, Enjoy Work, Enjoy Life". I tried to lead the students to like their research, and tried to find interesting results with students together based on their primary experimental results. What is the most important personality for scientific research? Pure, Passion, Perseverance. How do you keep balance between research and family? Work hard, and let my family know I am enjoyable and happy with my research, getting support and encouragement from family. Who influences you mostly in your life? My father. He always read books at the desk. He always gave me encouragement no matter happy or sad. [ABSTRACT FROM AUTHOR]

The central solenoid model coil (CSMC) project was launched in the Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP). In order to develop and verify the key techniques and manufacturing process of the full-size central solenoid (CS) coil for the China Fusion Engineering Testing Reactor (CFETR). The CFETR CSMC is designed to be a superconducting magnet of 12 T maximum magnetic field when the running current is 47.65 kA, which consists of two Nb3Sn windings in the internal high field and three Niobium-Titanium (NbTi) windings in the external low field. All the windings of the CSMC are a kind of pancake coil continuously wound one-in-hand by cable-in-conduit conductor (CICC), which are electrically connected in series by ohmic joints. To minimize the heat load of the joints to the cryogenic system, the design resistance of the joint is below 5 $\text{n}\Omega $ in operating conditions. The design of the joint is based on the concept of lap joint. A NbTi-NbTi full-size joint sample has been manufactured and tested. In this article, the design and manufacturing processes of the joint sample are described in detail, and the test results show dc resistance below 5 $\text{n}\Omega $ criterion. [ABSTRACT FROM AUTHOR]

Vaccine adjuvants play an increasingly important role in the development of modern vaccines. Among of them, particle adjuvants have received wide attention due to their unique properties. In order to develop effective particle adjuvants, mimicking natural pathogens is one of the important strategies. By adopting different materials, preparation methods and design ideas, the researchers obtained various particle adjuvants that mimic the shape, surface properties and action mechanisms of natural pathogens. This mini-review outlines some selected relevant recent literatures, discusses several bionic design strategies of particle adjuvants and some important barriers to further study are described. Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract The Central Solenoid Model Coil (CSMC) project has been launched at the Institute of Plasma and Physics Chinese Academy of Sciences (ASIPP) for China Fusion Engineering Test Reactor (CFETR). Electrical joints are important aspect for CSMC, because the local heating from resistive losses can drive the superconductor into a less stable regime and result in premature quench. So part of the project is to develop joints with low DC resistance and AC loss. AC loss power and local heating of the full-size prototype conductor joint in the preliminary test scenario of CSMC are evaluated experimentally and numerically in this paper. The AC loss of the joint sample is measured in SULTAN facility with an applied harmonic field and wider frequency range. Based on the experimental results, the AC loss of the joint is characterized by Multizones Partial Shielding (MPAS) model. Then, the AC loss power of the joint is calculated in the test scenario. The temperature rise of joint is investigated numerically due to the simulated AC loss in the test scenario. The simulation results show the temperature rise in the joint is relatively higher which affects the stability greatly not only in joints, but also the coils. So the joint structure and test scenario of CSMC need to be optimized to reduce the AC loss and ensure safe operation. The way to reduce the AC loss deposit in the joint is also discussed. [ABSTRACT FROM AUTHOR]

The variation of tensile properties of A356alloy at 20 °C~−60 °C has been investigated. the distribution of dislocation slip bands near the fracture surface was studied by scanning electron microscopy SEM. Dislocation distribution was observed by transmission electron microscope TEM. The elastic stress field near the Mg 2 Si phase at low temperature was analyzed by ANSYS. When the temperature is decreased from 20 °C to −60 °C, the tensile strength and yield strength of A356 alloy increase and the elongation decreases. Under the effect of cold shrink, the elastic stress produced by the alloy matrix hinders the movement of the dislocation. In low temperature environment, the edge dislocation whose excess half atom facing toward Mg 2 Si experiences a repulsing force. On the contrary it experiences a gravitational force. [ABSTRACT FROM AUTHOR]

The effect of stress concentration on the dislocation motion, the Si particles and the crack propagation path in A356 alloy at the temperature of 20 °C to −60 °C was analyzed by scanning electron microscope and optical microscope using a series of notched tensile specimens and normal tensile specimens. The results show that the sensitivity of A356 alloy to the stress concentration increases, the tensile strength and yield strength of normal specimens and notched specimens increase, and the elongation shows a decreasing trend with the decrease of test temperature from 20 °C to −60 °C. The yield strength is not affected by the notch, and the tensile strength is sensitive to the stress concentration. Stress concentration leads to a large number of dislocation generation. Local plastic deformation occurred in the stress concentration region during the tensile process firstly. With the stress concentration in the aluminum matrix between the Si phase and the crack further increasing, the distribution of cracks along the Si phase leads to the cracking of aluminum matrix particle. [ABSTRACT FROM AUTHOR]

Particle based adjuvant showed promising signs on delivering antigen to immune cells and acting as stimulators to elicit preventive or therapeutic response. Nevertheless, the wide size distribution of available polymeric particles has so far obscured the immunostimulative effects of particle adjuvant, and compromised the progress in pharmacological researches. To conquer this hurdle, our research group has carried out a series of researches regarding the particulate vaccine, by taking advantage of the successful fabrication of polymeric particles with uniform size. In this review, we highlight the insight and practical progress focused on the effects of physiochemical property (e.g. particle size, charge, hydrophobicity, surface chemical group, and particle shape) and antigen loading mode on the resultant biological/immunological outcome. The underlying mechanisms of how the particles-based vaccine functioned in the immune system are also discussed. Based on the knowledge, particles with high antigen payload and optimized attributes could be designed for expected adjuvant purpose, leading to the development of high efficient vaccine candidates. [ABSTRACT FROM AUTHOR]

Nicotine-degrading microorganisms (NDMs) are a special microbial group which can use nicotine as the sole carbon and nitrogen source for growth. Since the 1950s, the bioconversion of nicotine by microbes has received increasing attention, and several NDMs have been identified, such as Arthrobacter nicotinovorans, Microsporum gypseum, Pellicularia filamentosa JTS-208, and Pseudomonas sp. 41. In recent years, increasing numbers of NDMs have been isolated and identified from tobacco plantation soil, leaf, and tobacco waste. Meanwhile, the metabolic pathway and degradation mechanism of nicotine have been elucidated in several NDMs, such as A. nicotinovorans, Agrobacterium tumefaciens S33, Aspergillus oryzae, and Pseudomonas putida S16. Moreover, several NDMs have been used in improving the quality of cigarettes, treating tobacco waste, and producing valuable intermediates of nicotine. Here, we summarize the diversity, phylogenetic analysis, and potential applications of NDMs. [ABSTRACT FROM AUTHOR]

Bio-degradable poly(lactide) (PLA)/poly(lactide–glycolide) (PLGA) and chitosan microspheres (or microcapsules) have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. By encapsulating protein/peptide drugs in the microspheres, the serum drug concentration can be maintained at a higher constant value for a prolonged time, or injection formulation can be changed to orally or mucosally administered formulation. PLA/PLGA and chitosan are most often used in injection formulation and oral formulation. However, in the preparation and applications of PLA/PLGA and chitosan microspheres containing protein/peptide drugs, the problems of broad size distribution and poor reproducibility of microspheres, and deactivation of protein during the preparation, storage and release, are still big challenges. In this article, the techniques for control of the diameter of microspheres and microcapsules will be introduced at first, then the strategies about how to maintain the bioactivity of protein drugs during preparation and drug release will be reviewed and developed in our research group. The membrane emulsification techniques including direct membrane emulsification and rapid membrane emulsification processes were developed to prepare uniform-sized microspheres, the diameter of microspheres can be controlled from submicron to 100 μm by these two processes, and the reproducibility of products can be guaranteed. Furthermore, compared with conventional stirring method, the big advantages of membrane emulsification process were that the uniform microspheres with much higher encapsulation efficiency can be obtained, and the release behavior can be adjusted by selecting microsphere size. Mild membrane emulsification condition also can prevent the deactivation of proteins, which frequently occurred under high shear force in mechanical stirring, sonification, and homogenization methods. The strategies for maintaining the bioactivity of protein drug were developed, such as adding additives into protein solution, using solid drug powder instead of protein solution, and employing hydrophilic poly(lactide)–poly(ethylene glycol) (PELA) as a wall material for encapsulation in PLA/PLGA microspheres/microcapsules; developing step-wise crosslinking process, self-solidification process, and adsorbing protein drug into preformed chitosan microsphere with hollow-porous morphology for encapsulation in chitosan microsphere. As a result, animal test demonstrated that PELA microcapsules with uniform size and containing recombinant human growth hormone (rhGH) can maintain higher blood drug concentration for 2 months, and increased animal weight more apparently only by single dose, compared with PLA and PLGA microcapsules; hollow-porous chitosan microsphere loading insulin decreased blood glucose level largely when it was used as a carrier for oral administration. [ABSTRACT FROM AUTHOR]

The studies on control of heterogeneous structure of porous polymer microspheres prepared for suspension polymerization system and preformed polymer system in author's research group were reviewed. Firstly, the phase-separation behavior in O/W suspension polymerization system for preparation of porous poly(divinylbenzene) microspheres was quantitatively studied by combining transmittance and gelation point measurement, from which the morphology can be manipulated. The same method can be employed to study the pore size control in W/O hydrophilic polymerization system. Because the simple porous microsphere could not satisfy new applications, we developed new methods to prepare gigaporous microsphere, which possessed much larger pores than those obtained by general diluents, for chromatographic separation media, as well as hollow-porous microsphere for construction of cell-like microreactor. Furthermore, in order to overcome the difficulty of heterogeneous structure control for preformed polymer system, we developed special methods to obtain porous, hollow-porous, and hollow chitosan microspheres. Finally, some application results by utilizing special morphologies were introduced. [ABSTRACT FROM AUTHOR]

Supporting materials, not only serve as a scaffold but also provide a unique micro-environment, which strongly affects the performance of the loaded enzyme. In this paper, particular properties of supporting materials, including surface hydrophobicity/hydrophilicity, surface curvature, spatial restriction and confined microcapsule, were reviewed. [ABSTRACT FROM AUTHOR]

Abstract: Human serum albumin (HSA) and bovine hemoglobin (Hb) conjugate is a promising candidate as a blood substitute. However, preparation of the conjugate is problematic because both proteins tend to conjugate between themselves rather than crosslink each other. In this work, a facile process for conjugation of Hb and HSA was developed through control strategy of the reaction. The reaction was carried out in a buffer containing borax-borate and mannite. The borax-borate was used for pH buffering while mannite was used as a pH switch and a reaction promoter. As a result, self-conjugation of Hb and self-conjugation of HSA were minimized. After the one-step conjugation reaction in aqueous solution, followed by the one-step purification by ion-exchange chromatography, the conjugate of HSA and Hb was obtained with the total yield about 50%. The P 50 and the Hill coefficient for the product were 16.1mmHg and 1.82, respectively. [Copyright &y& Elsevier]

Abstract: Relatively Uniform-sized biodegradable poly(lactide) (PLA) microcapsules were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and multiple emulsion-solvent evaporation method. An aqueous phase containing lysozyme was used as the internal water phase (w1), and PLA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene which was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w1/o primary emulsion. The primary emulsion was permeated through the uniform pores (5.25 μm) of an SPG membrane into the external water phase by the pressure of nitrogen gas to form the uniform w1/o/w2 droplets. Then, the solid polymer microcapsules were obtained by simply evaporating the solvent. It is necessary to avoid the phase separation of primary emulsion during the SPG membrane emulsification. It was found that when the density difference of the internal water phase and oil phase was reduced to nearly zero and Arlacel 83 was used as the oil emulsifier, the phase separation was not observed within 24 h. The w1/o/w2 emulsion with uniform diameter was obtained only when Arlaecl 83 concentration was limited below 2.5 wt.% based on oil phase. The drug encapsulation efficiency was found to be related to several factors including PLA molecular weight, additive type and its concentration in the internal water phase, the emulsifier type and concentration in the oil phase, the NaCl concentration and the pH value in the external water phase. Comparing with the stirring method, it was found that the size was more uniform and the drug encapsulation efficiency was much higher when the microcapsules were prepared by SPG membrane emulsification technique and the highest drug encapsulation efficiency of 92.20% was obtained. This is the first study to prepare PLA microcapsules by combining an SPG membrane emulsification technique and multiple emulsion-solvent evaporation method. [Copyright &y& Elsevier]

A system consisting of uniform-sized styrene monomer droplets dispersed in an aqueous phase was employed to study the compromise between dominant polymerization mechanisms in the preparation of polymer microspheres. Monomer droplets were prepared by a microporous membrane emulsification technique, with negligible size distribution. Two polymerization mechanisms were identified—polymerization in micro-sized monomer droplets and nano-sized secondary nuclei, even in the presence of a hydrophobic initiator. Factors affecting the compromise between these two dominant mechanisms were investigated. Increasing the amount of hydrophobic additive (hexadecane) and/or adding water-soluble inhibitor in the aqueous phase suppressed the polymerization in the secondary nuclei, while adding a relatively hydrophilic monomer in the styrene feed and/or increasing the amount of the initiator and the size of the monomer droplets promoted the polymerization in the secondary nuclei. Under the condition where a hydrophilic monomer was added, hollow microspheres were formed when polymerization in the secondary nuclei was dominant, while one-hole microspheres resulted when polymerization occurred only inside the larger monomer droplets, indicating that the compromise between dominant mechanisms is critical to the polymerization process. [Copyright &y& Elsevier]

The seeded emulsion polymerization, basically designed similar to the previous reports except raising the reaction temperature at the end, was conducted for preparing irregular shaped polymer particles incorporating hydrophilic polymer inside the particles as well as on the surface. A 30 wt.% solid and anionic seed latex, poly(methylmethacrylate- co-methyl acrylate), was produced by a conventional emulsion polymerization with anionic initiator and emulsifier. Then, the seeded emulsion polymerization accompanied with the controlled electrostatic coagulation process was carried out with an addition of cationic dimethylaminoethylmethacrylate (DM) and 2,2′-azobis(2-methylamidinopropane) · 2HCl. The coagulation of polymer particles progressed rapidly in the initial 2 h with decreasing the zeta potential of the particles. The polymer yield increased almost linearly until 50% of the monomer was consumed despite the significant decrease in the number of polymer particles. The mechanism of polymerization was speculated on a basis of the nucleation of hydrophilic short chains in the aqueous phase and the slow termination in a polymer particle with the desorption of radicals. The reaction temperature was raised from 333 to 353 K prior to the end of polymerization (1–5 h). The fraction of the irregular-shaped particles in the final latex increased as the duration of raising the temperature was set longer, while the irregularity developed from dumbbell to more progressive shapes. [Copyright &y& Elsevier]

A seeded emulsion polymerization was conducted in order to prepare an emulsion composed of large-sized particles, which was carried out in parallel with the controlled coagulation process induced by the formation of secondary polymers having an opposite charge to the surface charge of the seed particles. As the first part of this study, effects of agitation rate during the seed polymerization, size of the seed polymer particles and controlled pH of the reaction mixture were investigated. The lower agitation rates yielded a stable latex composed of large-sized grown particles, whereas the higher, intensive agitation rates induced undesirable coagulation between the larger particles, forcing them to separate from the latex. It was revealed that the smaller seed particles performed a well-controlled coagulation and yielded a larger particle size. The lower pH (8.0–8.5) reduced the solid content in the latex due to an uncontrollable formation of coagulums. At the higher pH (9.5–10.0), the controlled coagulation was not as effective as those obtained at the intermediate pH (8.75–9.0). [Copyright &y& Elsevier]

Customers can raise various aspects of concerns and anxieties during their participation in gamified social mobile marketing campaigns. To gain insights into how to address these anxieties, this research explores the impact of group-formation gamification mechanisms on users' emotional anxiety and their intentions to participate in such campaigns. A research model depicting group-formation gamification strategies, user anxieties and participation intentions in gamified social mobile marketing campaigns was proposed and examined through experiments involving 232 participants, which were triangulated by electroencephalogram (EEG) tests and follow-up interviews. The results of this study showed that compared with weak-tie group-formation mechanisms, strong-tie mechanisms can result in a lower level of user emotional anxiety, including reductions in user manipulation anxiety, user privacy anxiety and social image anxiety, which in turn led to higher user intentions to participate in the gamified social mobile marketing campaign. Moreover, it was found that user gender and disposable incomes had significant moderating effects on user anxiety during their interactions with the campaign. [ABSTRACT FROM AUTHOR]

Gonadotropin-releasing hormone (GnRH) agonists are peptides consisting of nine or ten amino acid residues. GnRH agonists have been applied in the therapy of sexual hormone disorders like prostate cancer, endometriosis, uterine myoma, central precious puberty, and in-vitro fertility. Treatment is achieved by continuous hormone intake and long-term agonists administration, which is usually associated with poor patient compliance. Because GnRH agonists that are administered with the parenteral route are broken down by peptidase, their half-life is short. As a result, developing sustained release for the drug delivery system is significant. Even though some drugs have been successfully delivered with long-acting release microspheres and approved by the Food and Drug Administration (FDA), some challenges remain. This review highlighted current approaches to encapsulate GnRH agonists into delivery systems and strategies encountered during the loading process. Moreover, the following sections provide strategies to improve the release profile, and animal and human studies were summarised. [ABSTRACT FROM AUTHOR]

Bio–nano interfaces are integral to all applications of nanomaterials in biomedicine. In addition to peptide‐ligand‐functionalized nanomaterials, passivation on 2D nanomaterials has emerged as a new regulatory factor for integrin activation. However, the mechanisms underlying such ligand‐independent processes are poorly understood. Here, using graphene oxide passivated with polyethylene glycol (GO‐PEG) as a test bed, a ternary simulation model is constructed that also includes a membrane and both subunits of integrin αvβ8 to characterize GO‐PEG‐mediated integrin activation on the cell membrane in a ligand‐independent manner. Combined with the experimental findings, production simulations of the ternary model show a three‐phase mechanotransduction process in the vertical interaction mode. Specifically, GO‐PEG first induces lipid aggregation‐mediated integrin proximity, followed by transmembrane domain rotation and separation, leading to the extension and activation of extracellular domains. Thus, this study presents a complete picture of the interaction between passivated 2D nanomaterials and cell membranes to mediate integrin activation, and provides insights into the potential de novo design and rational use of novel desirable nanomaterials at diverse bio–nano interfaces. [ABSTRACT FROM AUTHOR]

In this paper, the vertical arrays of ZnO nanowires (NWs) are uniformly grown on the surface of hexagonal CuGaO2 (CGO) nanoplates (NPs) through the hydrothermal method, forming the high‐density p–n heterojunction. The photoluminescence (PL) properties of these hetero‐assembled structures are characterized, and an obvious ultraviolet (UV) emission centered at 392.32 nm has been observed. Compared with the PL spectra of pure ZnO NWs, the UV peak red‐shift occurred and the spectrum broadened almost 2.5 times. A new emission located at 398 nm is attributed to the interface recombination which has been found through the Gaussian fitting. Furthermore, a red‐shift also appears in the absorption spectra of CGO NPs/ZnO NWs heterostructure, and the variation of light absorption properties results from the sub‐bandgap absorption effect in the p–n junction region. The light emission and absorption mechanisms occurring at the heterojunction have been investigated in terms of energy band theory. This work offers a new insight to realize micro/nano optoelectronic devices based on p‐CGO NPs/n‐ZnO NWs hetero‐assembled structures. The vertical arrays of ZnO nanowires are uniformly grown on the surface of hexagonal CuGaO2 nanoplates. A new emission located at 398 nm which is attributed to the interface recombination has been observed. The absorption spectra of the CuGaO2 nanoplates/ZnO nanowires heterostructure exhibited a red‐shift phenomenon which can be ascribed to the sub‐bandgap absorption effect in the p–n junction region. [ABSTRACT FROM AUTHOR]

Super large proteinaceous particles (SLPPs) such as virus, virus like particles, and extracellular vesicles have successful and promising applications in vaccination, gene therapy, and cancer treatment. The unstable nature, the complex particulate structure and composition are challenges for their manufacturing and applications. Rational design of the processing should be built on the basis of fully understanding the characteristics of these bio‐particles. This review highlights useful analytical techniques for characterization and stabilization of SLPPs in the process development and product formulations, including high performance size exclusion chromatography, multi‐angle laser light scattering, asymmetrical flow field‐flow fractionation, nanoparticle tracking analysis, CZE, differential scanning calorimetry, differential scanning fluorescence, isothermal titration calorimetry , and dual polarization interferometry. These advanced analytical techniques will be helpful in obtaining deep insight into the mechanism related to denaturation of SLPPs, and more importantly, in seeking solutions to preserve their biological functions against deactivation or denaturation. Combination of different physicochemical techniques, and correlation with in vitro or in vivo biological activity analyses, are considered to be the future trend of development in order to guarantee a high quality, safety, and efficacy of SLPPs. [ABSTRACT FROM AUTHOR]

Effective treatment of wound injuries can prevent infections and promote healing. In this work, a sprayed Pickering emulsion composed of chitosan nanoparticles, tea tree oil and curcumin was formulated. The shear thinning behaviour allowed this Pickering emulsion to spray even with a high viscosity provided by the aqueous phase containing chitosan nanoparticles. Moreover, the Pickering emulsion could recover to the high viscosity after spraying onto the wounds, leading to the long residence time and intimate contact. In addition, the Pickering emulsion provided a carrier to encapsulate the tea tree oil, which caused sustained-release effects and further strengthened tea tree oil's antibacterial activity towards the Gram-negative Escherichia coli (E. coli), Gram-positive Staphylococcus aureus (S. aureus) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Besides, this multi-phase system offered a platform to load with hydrophobic curcumin, leading to better synergistic healing effects. Meanwhile, the Pickering emulsion avoided the irritation and toxicity related to surfactants, which was far safer than the classical emulsion especially when used in the defective skin. All these excellent properties endowed this sprayed Pickering emulsion with promising prospects for wound healing. • Shear thinning behaviour allowed Pickering emulsion to spray while having high viscosity. • Pickering emulsion provided a platform to encapsulate tea tree oil and hydrophobic drug. • Pickering emulsion avoided the irritation and toxicity related to surfactants. [ABSTRACT FROM AUTHOR]

Pulmonary lobe segmentation is an important prerequisite for accurately quantifying pulmonary damage in many pulmonary diseases and planning treatment. However, due to the incomplete lobar structures and morphological changes caused by diseases, the lobe segmentation still encounters great challenges. In this study, a Learnable Interpolation and Extrapolation Network (LIE‐Net) is proposed to form complete and consecutive fissure surfaces by learning to extract information of the fissures from existing fissure points and absent points (unsegmented points belonging to fissures) to predict the z coordinate of the absent fissure points. The completed pulmonary fissures are further used for accurate pulmonary lobe segmentation. Specifically, LIE‐Net takes the coordinate information of existing fissure points (their (x, y, z) coordinates) and absent fissure points (their (x, y) coordinates) as two independent inputs, and predicts the z coordinates of absent points. The proposed LIE‐Net makes voxel‐wise predictions based on the spatial structure characteristics of the lung fissure, and is able to provide a consecutive fissure surface in space. According to the evaluation of radiologists, the lobe segmentation performance was remarkably enhanced in approximately 76% of patients in our additional dataset after the application of LIE‐Net, especially for those cases with large‐scale missing fissures. [ABSTRACT FROM AUTHOR]

Regeneration and reutilization of cofactors remain as the biggest challenge facing the industrial application of cofactor-dependent redox, while efficient communication and synergism between enzymes and cofactors are the major requirements for implementation of such processed. Inspired by swinging arms facilitating multistep catalytic transformations in nature, polyelectrolytes-based artificial swinging arms were introduced to a multienzyme system by coaxial electrospinning technology. The poly(allylamine hydrochloride) (PAH), pre-dissolved in the core-phase solution, would penetrate across the shell of hollow nanofibers, thus act as artificial swinging arms and enable effective tethering and retention of the enzymes and cofactors on the outer surface of nanofibers via the ion-exchange interactions. With further intercalary insertion of another negatively charged polyelectrolyte poly(styrene sulfonate) (PSS), a sandwich-like structure was formed on the outer surface of the hollow nanofiber. It was found that PSS layer not only effectively prevented the leaking of enzymes and cofactors, the double-polyelectrolytes also imposed crowding and confinement effects on the sandwiched multienzymes, thus the communication of the dehydrogenases and the shared cofactors were further facilitated. The methanol yield obtained with the sandwiched multienzymes system reached to 98.27%, which was 2.72-fold higher than that of the free system, and even 1.52-fold higher than that without PSS layer. [ABSTRACT FROM AUTHOR]

Presenting exogenous antigens on virus-like particles (VLPs) through "plug-and-display" decoration strategies based on SpyTag/SpyCatcher isopeptide bonding have emerged as attractive technology for vaccine synthesis. However, whether the position of ligation site in VLPs will impose effects on immunogenicity and physiochemical properties of the synthetic vaccine remains rarely investigated. Here in the present work, the well-established hepatitis B core (HBc) protein was used as chassis to construct dual-antigen influenza nanovaccines, with the conserved epitope peptides derived from extracellular domain of matrix protein M2 (M2e) and hemagglutinin (HA) as target antigens. The M2e antigen was genetically fused to the HBc in the MIR region, together with the SpyTag peptide, which was fused either in the MIR region or at the N-terminal of the protein, so that a recombinant HA antigen (rHA) linked to SpyCatcher can be displayed on it, at two different localizations. Both synthetic nanovaccines showed ability in inducing strong M2e and rHA-specific antibodies and cellular immunogenicity; nevertheless, the one in which rHA was conjugated by N-terminal Tag ligation, was superior to another one synthesized by linking the rHA to MIR region SpyTagged-HBc in all aspects, including higher antigen-specific immunogenicity responses, lower anti-HBc carrier antibody, as well as better dispersion stability. Surface charge and hydrophobicity properties of the two synthetic nanovaccines were analyzed, results revealed that linking the rHA to MIR region SpyTagged-HBc lead to more significant and disadvantageous alteration in physiochemical properties of the HBc chassis. This study will expand our knowledge on "plug-and-display" decoration strategies and provide helpful guidance for the rational design of HBc-VLPs based modular vaccines by using SpyTag/Catcher synthesis. [ABSTRACT FROM AUTHOR]

[Display omitted] Essential oils (EOs) are common additives in daily products by virtue of their olfactory, physicochemical, and biological characteristics. However, EOs are physicochemically unstable and susceptible to degradation or loss, leading to limited shelf life and inadequate efficacy. Herein we propose a new bi-layered encapsulation structure in combination with complex coacervation and self-coating of polydopamine (PDA) on membrane emulsified mono-dispersion of EOs droplets. A mono-dispersed EOs emulsion stabilized by nonionic surfactants was produced by membrane emulsification, wherein the EOs droplets were applied as soft templates to deposit a superficial PDA layer. Under alkaline conditions, gelatin (GE) was bound to the PDA layer and further applied as in situ coacervation sites for gum Arabic (GA). Structural identification and morphological observation proved the successful preparation of bi-layered EOs capsules. Compared with traditional complex coacervation strategies, current novel bi-layered capsules showed significantly improved structural stability, thermal stability, providing better protection of EOs with sustained release properties. Moreover, the encapsulation efficiency and loading content were both proved higher for the bi-layered system. The first report on PDA-coating onto surfactants-absorbed macroemulsion droplets also provides an in-depth insight into applying PDA as versatile intermediate functional biomaterials. [ABSTRACT FROM AUTHOR]

In polydopamine (PDA)-supported in situ complex coacervation, PDA is pre-coated onto emulsion droplets, and further applied as an interlayer to support the interfacial immobilization of coacervates biopolymers. In the current research, the stepwise immobilization of gelatin (GE) and gum Arabic (GA) onto PDA layer is monitored to in-depth investigate the mechanism of PDA layer as coating material and functional substrates. GE and GA were applied as adsorbates, with different forms of PDA (spherical shell, planar solid, and nanoparticles) as substrates. Real-time observations of the binding steps were performed using quartz crystal monitor with dissipation (QCM-D) and isothermal titration calorimetry (ITC). Meanwhile, using PDA-supported coacervates as encapsulating material, sustained release of essential oil volatiles was also evaluated, either dispersed in detergent solution or freeze dried in open air. The anti-oxidation performance was determined by measuring the absorbance of lipid hydroperoxide using UV spectrophotometer. The results revealed that PDA enabled synergistic immobilization of biopolymers through chemical bonding and adhesive force during the processing of in situ complex coacervation, thus enhanced protection of core compounds with two-stage releasing kinetics and prevented hyperoxidation. Also, PDA-based colloids and substrates also exhibit controllable conformation characteristic, provide a promising prospect as versatile intermediate functional biomaterials for encapsulation. [Display omitted] • Constructing in situ complex coacervation supported by Polydopamine interlayer. • PDA provides synergistic immobilization of biopolymers through chemical bonding and adhesive force. • Two-stage releasing profile proves enhanced protection over core actives from PDA interlayer. [ABSTRACT FROM AUTHOR]

Macroporous agarose microspheres for bioseparation of giant biomolecules were prepared by a surfactant micellar swelling method, and the effects of preparation conditions on both particle size and its distribution and pore structure were systematically studied. Under the optimal condition with a surfactant amount of 20% (v/v), Triton X-100 to sodium dodecyl sulfate ratio (SDS) of 5:1 (w/w), an oil-absorbing-swelling time of 2.5 h, and a stirring speed of 250 rpm, macroporous agarose microspheres were successfully prepared, characterized by inverse size exclusion chromatography. Distribution coefficient (Kd) of dextran probes for agarose microspheres after being cross-linked was almost the same as that for agarose microspheres before being cross-linked. Inverse size exclusion chromatography results showed that macroporous agarose microspheres had a pore size distribution of more than 40 nm or even close to 60 nm, while that of conventional microspheres was no more than 40 nm. Macroporous agarose microspheres functionalized with diethylaminoethyl groups had a higher adsorption capacity and faster adsorption rate for hepatitis B surface antigen (HBsAg) compared with both commercial DEAE-agarose chromatographic media and conventional DEAE-agarose microspheres which were both based on agarose microspheres prepared using a traditional method. Confocal laser scanning microscopy results showed that macroporous agarose microspheres had a good binding ability to HBsAg, and this antigen completely entered the inside of the microspheres. Compared with conventional agarose chromatographic media, the macroporous agarose media combined macromolecular proteins more quickly and fully, having wider applications in the field of purification of giant biomolecules. [ABSTRACT FROM AUTHOR]

Effective antigen delivery and immune stimulation in nasal mucosa determine the success of mucosal immunity. Here, an oil-in-ionic liquid (o/IL) nanoemulsion formulated with choline and niacin IL ([Cho][Nic]), squalene, and Tween 80 surfactant is explored as a vaccine delivery system for intranasal mucosal immunization. Compared to the o/w emulsion counterpart without the ILs, the o/IL manoemulsion showed a reduced and more uniform size of approximately 168 nm and significantly improved stability. Studies in mice model showed that when was used as an intranasal vaccine delivery system for influenza split-virus antigens, the antigens in the o/IL nanoemulsion induced strong mucosal immune responses with secretory IgA titers 25- and 5.8-fold higher than those of naked and commercial MF59-adjuvanted antigens, respectively. The o/IL nanoemulsion system also induced stronger systemic humoral responses. The excellent mucosal adjuvant effects of the o/IL nanoemulsion mainly benefited from the prolonged retention of antigens in the nasal cavity, enhanced antigen permeation into the submucosa, and the consequently promoted proliferation of CD11b cells and CD4+ T cells in nasal mucosa-associated lymphoid tissue. Moreover, when used as an injection adjuvant, the o/IL nanoemulsion also induced stronger humoral immune responses than MF59. Thus, the [Cho][Nic]-based o/IL nanoemulsion vaccine delivery system can serve as a promising adjuvant platform. [Display omitted] [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the image classification and case characteristics of pigmented nevus (PN) diagnosed by dermoscopy under deep learning. 268 patients were included as the research objects and they were randomly divided into observation group (n = 134) and control group (n = 134). Image recognition algorithm was used for feature extraction, segmentation, and classification of dermoscopic images, and the image recognition and classification algorithm were studied as the performance and accuracy of fusion classifier were compared. The results showed that the classifier was optimized, and the linear kernel accuracy was 85.82%. The PN studied mainly included mixed nevus, junctional nevus, intradermal nevus, and acral nevus. The sensitivity under collaborative training was higher than that under feature training and fusion feature training, and the differences among three trainings were significant (P < 0.05). The sensitivity of the observation group was 88.65%, and the specificity was 90.26%, while the sensitivity and the specificity of the control group were 85.65% and 84.03%, respectively; there were significant differences between the two groups (P < 0.05). In conclusion, dermoscopy under deep learning could be applied as a diagnostic way of PN, which helped improve the accuracy of diagnosis. The dermoscopic manifestations of PN showed a certain corresponding relationship with the type of cases and could provide auxiliary diagnosis in clinical practice. It could be applied clinically. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal. Results: Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route. Conclusions: This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy. [ABSTRACT FROM AUTHOR]

There are several attractive opportunities for using magnetic nanomaterials for anticancer applications. Herein, a magnetic nanomaterial platform is successfully developed based on natural Fe3O4 magnetosomes extracted from the bacterium Magnetospirillum magneticum AMB‐1 for anticancer therapy. The authors initially functionalize the magnetosome membranes in situ with gold nanoparticles to construct an attractive core‐satellite structure. Subsequently, the physical properties and application potentials of these structures are characterized as contrast agents for photoacoustic imaging and magnetic resonance imaging and as therapeutic agents with selective magnetic field guidance for diverse antitumor modalities, including starving, chemodynamic, and photothermal therapies. Owing to the high‐performance imaging‐guided synergistic effect, only a single injection and single laser irradiation result in excellent therapeutic efficacy against tumor growth in multiple cell‐derived xenograft tumor models and, most notably, patient‐derived organoid and patient‐derived xenograft tumor models. The demonstrations of the use of natural magnetic nanomaterials to achieve strong and synergistic antitumor performances highlight the promising application potential of this flexible and easy‐to‐prepare platform for developing innovative treatments for diseases in humans. [ABSTRACT FROM AUTHOR]

The low percentage of pores at which droplets are formed results in lower production efficiency, which is one of the main issues hampering the application of microporous membrane emulsification on a large scale. The effect of microporous membrane pore activation on the droplet's formation and emulsion performance was systemically investigated by changing both transmembrane pressures and membrane wettability during membrane emulsification. It indicated that the high transmembrane pressure increased the pore activation ratio (the percentage of pores at which droplets are formed) by the growing flux. These induced the enhancements of emulsification efficiency and the degradation of emulsion performance. Different wettability of membrane inflow and outflow influenced the pore activation speed (the speed which droplets are formed at pores). It indicated that the wettability of membrane outflow had a key effect on droplet formation and the high pore activation speed avoided splashing for high emulsion performance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Particle-in-oil-in-water multiple emulsion adjuvant is a promising vaccine adjuvant. • The adjuvant with chitosan nanoparticles as the internal water phase had good cellular and humoral immune effects. • The increase in the content of the internal aqueous phase helps to reduce antigen concentration and reduce the cost of antigen purification. Particle-in-oil-in-water (P/O/W) multiple emulsion adjuvants introduce particles into the internal water phase of a water-in-oil-in-water emulsion, combining the advantages of both particle and emulsion adjuvants to enhance humoral and cellular immune responses. In this study, we optimized P/O/W multiple emulsion adjuvants. Chitosan, poly (lactic-co-glycolic acid), and aluminum gel were used to prepare the particles, which were introduced into a water-in-oil-in-water emulsion to obtain three P/O/W multiple emulsion adjuvants. The immune enhancement effects and safety of the three adjuvants were compared, and it was proven that the adjuvant with chitosan nanoparticles in the internal water phase had good cellular and humoral immune effects. Simultaneously, the proportion of the internal water phase increased from 13% to 20%, reducing the antigen concentration required for embedding to one-third of the original concentration and expanding the application range of the composite adjuvant. [ABSTRACT FROM AUTHOR]

Adsorption isotherm type is a key factor in simulating chromatographic profiles. In this study, the adsorption isotherm type of pure bovine serum albumin (BSA) and immunoglobulin G (IgG) on hydrophobic interaction chromatography (HIC) media was found to shift from Freundlich to Langmuir with the increase of salt concentration. For BSA on butyl-, phenyl- and octyl-sepharose, the isotherm type shift occurred when the salt concentrations were higher than 1.8, 1.5 and 1.4 mol/L, respectively. For IgG, the turning points were 1.0 mol/L on phenyl-sepharose and 0.9 mol/L on octyl-sepharose. Circular dichroism spectra and high-performance size-exclusion chromatography found no obvious conformational change or oligomer formation for the proteins in the solutions with different salt concentrations. HIC profiles of BSA and IgG revealed that the isotherm type shift greatly affected the chromatographic behavior, because the original single peak was coincidentally split into two peaks at the salt concentrations over which the isotherm type shift occurred. Combining both the isotherm type shift and peak-splitting phenomena, it was possible that the change of protein–protein repulsion among adsorbed protein molecules under different salt concentrations caused the abnormal behavior of adsorption isotherm and chromatographic profiles. [ABSTRACT FROM AUTHOR]

Abstract: Cofactor-dependent multi-step enzymatic reactions generally require dynamic interactions among cofactor, enzyme and substrate molecules. Maintaining such molecular interactions can be quite challenging especially when the catalysts are tethered to solid state supports for heterogeneous catalysis for either biosynthesis or biosensing. The current work examines the effects of the pattern of immobilization, which presumably impacts molecular interactions on the surface of solid supports, on the reaction kinetics of a multienzymic system including glutamate dehydrogenase, glucose dehydrogenase and cofactor NAD(H). Interestingly, particle collision due to Brownian motion of nanoparticles successfully enabled the coupled reactions involving a regeneration cycle of NAD(H) even when the enzymes and cofactor were immobilized separately onto superparamagnetic nanoparticles (124nm). The impact of particle motion and collision was evident in that the overall reaction rate was increased by over 100% by applying a moderate alternating magnetic field (500Hz, 17Gs), or using additional spacers, both of which could improve the mobility of the immobilized catalysts. We further observed that integrated immobilization, which allowed the cofactor to be placed in the molecular vicinity of enzymes on the same nanoparticles, could enhance the reaction rate by 1.8 fold. These results demonstrated the feasibility in manipulating molecular interactions among immobilized catalyst components by using nanoscale fabrication for efficient multienzymic biosynthesis. [Copyright &y& Elsevier]

Diverse delivery vectors for personalized cancer vaccines. [Display omitted] In recent years, personalized cancer vaccines have gained increasing attention as emerging immunotherapies with the capability to overcome interindividual differences and show great benefits for individual patients in the clinic due to the highly tailored vaccine formulations. A large number of materials have been studied as delivery vectors to enhance the therapeutic performance of personalized cancer vaccines, including artificial materials, engineered microorganisms, cells and cell derivatives. These delivery vectors with distinct features are employed to change antigen biodistributions and to facilitate antigen uptake, processing and presentation, improving the strength, velocity, and duration of the immune response when delivered by different strategies. Here, we provide an overview of personalized cancer vaccine delivery vectors, describing their materials, physicochemical properties, delivery strategies and challenges for clinical transformation. [ABSTRACT FROM AUTHOR]

Direct conjugation of bovine hemoglobin (Hb) and human serum albumin (HSA) with glutaraldehyde would result in a complex mixture of dimers Hb-Hb, Hb-HSA, HSA-HSA and other oligomers. To obtain a high yield of target Hb-HSA, modulation of the reaction environment was carried out. It was found that polyethylene glycol (PEG), a hydrophilic polymer, could improve the yield of Hb-HSA conjugate. The degree of improvement depended on the molecular weight and concentration of PEG. Under optimum condition of 9% (w/v) of PEG 4000, the reaction proceeded in a controlled mode with conversion yield of starting proteins to Hb-HSA increasing from 6% to 30%. The purity was about 88% of the total conjugates. Furthermore, the impurities were mainly tetrameric molecules of two Hb-HSA conjugates. The improvement could be attributed to the "micro-compartment" created by addition of polyethylene glycol, which brings HSA and Hb close together, thus increasing the chance of conjugation between the two molecules. [ABSTRACT FROM AUTHOR]

Abstract: Rigid porous poly(glycidyl methacrylate–divinylbenzene) (P(GMA–DVB)) microspheres were synthesized through suspension polymerization with a mixture of isooctane and 4-methyl-2-pentonal as the porogen. The microspheres were intended to use as column packing materials for protein separation. However, irreversible adsorption of protein was found on the polymer microsphere. To circumvent the problem, polyethylene glycol (PEG) was coupled to the microspheres. The coupling reaction took place between the hydroxyl group of PEG and the epoxy group of the P(GMA–DVB) solid medium in the presence of boron trifluoride. The density of PEG immobilized onto the P(GMA–DVB) can be determined easily by saponification of modified microsphere firstly and then titration of glycerol–PEG. The effect of the cross-linker content of microsphere on the density of PEG immobilization was investigated. Molecular weight of PEG was found to influence the PEG-immobilization density, which subsequently affects the hydrophilicity of the modified P(GMA–DVB). Bovine serum albumin (BSA) and trypsin were used as model proteins to examine the adsorption and desorption properties of the modified P(GMA–DVB) microspheres. The results demonstrated that P(GMA–DVB) porous microsphere with 20% DVB and modified with PEG4000 showed excellent adsorption and desorption properties. Adsorption capacity of BSA on the modified microsphere attained to 51.6mg/g microsphere, and BSA mass recovery and trypsin activity recovery was up to 97.6% and 98.7%, respectively. The modified microsphere was demonstrated to be a promising hydrophobic interaction chromatography material for purification of protein. [Copyright &y& Elsevier]

A facile, preparative low-pressure chromatographic process was developed for purification of paclitaxel from crude extract of Taxus spp. The process consisted of normal-phase and a reversed-phase chromatography without utilization of any liquid-liquid partition step. The normal phase chromatography was designed lo separate paclitaxel from a majority of unwanted compounds to obtain an initial purification. Silica gel and Al2O3, were compared as packing materials for this step. The result demonstrated that basic Al2O3 was better than silica gel to give a higher throughput. A further advantage of the Al2O3 was its ability of removing l0-deacetyl-7-epipaclitaxel. a compound difficult to be separated from the paclitaxel in subsequent purification. The chromatographic fraction of A2O3 was purified by a subsequent reversed-phase column chromatography, employing a novel uniform porous microsphere, named PST, as the packing material. Combination of the two steps of column chromatography and one step of crystallization was able to purify paclitaxel, from 0.46% to more than 98% with the total recovery- of 71%. This integrated chromatographic procedure was reproducible, efficient, and simple to use. [ABSTRACT FROM AUTHOR]

Abstract: Flow-through chromatography was a method for purification of hemoglobin (Hb) from red cell lysate. The presence of 0–5% polyethylene glycol (PEG) increased the retention time of Hb peak from 15min to 20min in flow-through ion-exchange chromatography (IEC) but decreased the retention time from 88min to 62min in the hydrophobic interaction chromatography (HIC). However, the purification and the recovery were both increased. For IEC the recovery of hemoglobin increased from 75% to more than 90%, and the purified Hb showed single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and one peak in size-exclusion HPLC. For HIC, the recovery of hemoglobin was improved significantly from 20% to 85% and the removal of lipids was 100%. The bioactivity of hemoglobin was well preserved in these two chromatographic processes. The mechanism for the effect of PEG in these two flow-through chromatographic processes was discussed. [Copyright &y& Elsevier]

A novel nanodisc‐based immobilization method was developed for high‐efficient purification and reconstitution of cytochrome P450 in one step. Using membrane scaffold protein containing a histidine tag, charged‐nanodiscs were prepared in the form of self‐assembly of lipid‐protein nanoparticles. Their properties including the particle diameter and its distribution and Zeta potential were controlled well by adjusting molar ratios of phospholipids to membrane scaffold protein. At an optimum lipid‐to‐membrane scaffold protein molar ratio of 60:1, uniformly regular‐shaped and discoidal nanodiscs with an average particle diameter of 10 nm and Zeta potential of –19 mV were obtained. They can be well fractionated by size exclusion chromatography. Charged‐nanodiscs were successfully immobilized onto Ni‐chelating microspheres via histidine tags with a density of 6.6 mg membrane scaffold protein/mL gel. After being packed in a column, chromatography studies demonstrated that this nanodisc‐immobilized chromatographic medium had a specific binding to cytochrome P450 in rat liver microsome. Nanodiscs containing cytochrome P450 can be furthermore eluted from the column with a diameter of about 87.0 nm and height of about 8.0 nm, respectively. The purity of cytochrome P450 after purification increased 25 folds strikingly. This nanodisc‐immobilized chromatography method is promising for the one‐step purification and reconstitution of membrane protein. [ABSTRACT FROM AUTHOR]

Here, we reported particles with approximately 80-μm diameter with phase-separated morphology of ternary polymer blends containing poly(4-butyltriphenylamine) (PBTPA), poly(methyl methacrylate) (PMMA), and PBTPA-b-PMMA fabricated via a microfluidic emulsification technique with a Y-shaped microreactor followed by a solvent evaporation. Addition of block copolymer changed the macroscopic structure from core-shell to Janus and more complicated sea-island type with the increase of the block copolymer content. The Janus structure with a PMMA hemisphere containing small PBTPA domain was observed at 10 wt% of the block copolymer. Meanwhile, the rapid evaporation changed the morphology macroscopically from the Janus to the undeveloped one where PMMA-rich phase mainly located at center sandwiched with outside PBTPA phases, suggesting that morphologies are governed by the kinetical factors together with the conventionally accepted thermodynamic ones. After the solvent annealing with toluene, distinct and enlarged PMMA phase appeared radiately, of which size gradiently decreased from the surface to the center (200–500 nm) in each particle. [ABSTRACT FROM AUTHOR]

As membrane‐bound extracellular vesicles, exosomes have targeting ability for specific cell types, and the cellular environment strongly impacts their content and uptake efficiency. Inspired by these natural properties, the impacts of various cellular stress conditions on the uptake efficiency of tumor iterated exosomes are evaluated, and low‐pH treatment caused increased uptake efficiency and retained cell‐type specificity is found. Lipidomics analyses and molecular dynamics simulations reveal a glycerolipid self‐aggregation‐based mechanism for the enhanced homologous uptake. Furthermore, these low‐pH reprogrammed exosomes are developed into a smart drug delivery platform, which is capable of specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the exosome rupture by the near‐infrared irradiance‐triggered burst of reactive oxygen species. This platform exerts safe and enhanced antitumor effects demonstrated by multiple model mice experiments. These results open a new avenue to reprogram exosomes for smart drug delivery and potentially personalized therapy against their homologous tumor. [ABSTRACT FROM AUTHOR]

As membrane‐bound extracellular vesicles, exosomes have targeting ability for specific cell types, and the cellular environment strongly impacts their content and uptake efficiency. Inspired by these natural properties, the impacts of various cellular stress conditions on the uptake efficiency of tumor iterated exosomes are evaluated, and low‐pH treatment caused increased uptake efficiency and retained cell‐type specificity is found. Lipidomics analyses and molecular dynamics simulations reveal a glycerolipid self‐aggregation‐based mechanism for the enhanced homologous uptake. Furthermore, these low‐pH reprogrammed exosomes are developed into a smart drug delivery platform, which is capable of specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the exosome rupture by the near‐infrared irradiance‐triggered burst of reactive oxygen species. This platform exerts safe and enhanced antitumor effects demonstrated by multiple model mice experiments. These results open a new avenue to reprogram exosomes for smart drug delivery and potentially personalized therapy against their homologous tumor. [ABSTRACT FROM AUTHOR]

• Performances of media as function of pore-to-adsorbate size ratio were studied • Proteins with large span of radius ranges from 2.9 nm to 14.1 nm were studied • The best ratio of pore-to-adsorbate size was dependent on the protein size • Large protein needs greater pore-to-adsorbate size ratio • The study provides guidance to select suitable adsorbent for a given protein Two commercially available agarose ion exchange media, DEAE-Capto and DEAE-Sepharose FF (DEAE-FF), and two gigaporous media DEAE -AP-120 nm and DEAE-AP-280 nm were evaluated for their applicability in adsorption of five proteins with large span of radius ranges from 2.9 nm to 14.1 nm, which include ovalbumin, bovine serum albumin (BSA), haptoglobin, thyroglobulin and hepatitis B surface antigen (HBsAg) virus like particle. The average pore radius of the four media was determined to be 6.9 nm, 18.5 nm, 59.4 nm and 139.3 nm, respectively, which was obtained by log normal distribution for DEAE-Capto and DEAE-FF and by bimodal Gaussian distribution for the two DEAE-AP media. The performance of these four media including phase ratio, static and dynamic binding capacity, and transport properties for the adsorption of these five model proteins as function of pore-to-adsorbate size ratio were investigated and compared. The best ratio of pore-to-adsorbate size was found dependent on the protein size. For protein with radius from 2.9 nm (ovalbumin) to 5.4 nm (BSA), the agarose media was superior to gigaporous media. Both the static and dynamic adsorption capacities reduced with the increase of pore size, and the highest values were obtained at the smallest pore-to-adsorbate size of about 2 times in this study, although the highest accessible surface area was obtained at pore-to-adsorbate size ratio about 16 to 20. For proteins with radius of 5.4 nm or larger than that, their adsorption capacities decreased firstly and then increased with the increase of ratio of pore-to-adsorbate size, and the highest values were obtained on the gigaporous media DEAE-AP-280 nm, which could provide faster diffusivity and larger accessible surface area. However, protein with radius of 14.1 nm (HBsAg) had much lower capacities compared to other proteins at the same pore-to-adsorbate size ratio, implying large protein needs greater pore-to-adsorbate size ratio to achieve a satisfactory capacity. For all the five tested proteins, the DEAE-Capto media having the smallest pore radius and branched dextran chains, was found superior to DEAE-FF in terms of both higher adsorption capacities and uptake kinetics, which suggested that the "chain delivery effect" took place on proteins over large size span from ovalbumin to HBsAg, though the effect on the larger proteins was much less significant than that on the smaller ones. Results from the present work provided more information on how do the relationships of pore size of chromatography media and adsorbate size interactively affect the chromatography behaviors, thus will provide general guidance for selection of suitable adsorbent for biologics of a given size. [ABSTRACT FROM AUTHOR]

• The significant influences of terminal groups on properties of microsphere were attributed to specific intermolecular interaction on microcosmic level. • The reaction activation centers were verified by density functional simulation calculation and frontier molecular orbital theory at the molecular level. • Sustained release ability in vivo , duration and intensity of the anesthetic effect as well as safety and toxicity were evaluated by PK and PD study. Currently, the influences of free terminal groups (hydroxyl, carboxyl and ester) of PLGA on encapsulating active pharmaceutical ingredient are relatively ambiguous even though PLGA types were defined as critical quality attributes in vast majority of design of experiment process. In this study, emulsion method combined with premix membrane emulsification technique has been used to encapsulate ropivacaine (RVC), a small molecule local anesthetic in clinical. Based on the narrow particle size distribution, the influences and mechanisms of the terminal groups on properties of ropivacaine loaded microspheres have been investigated in detail. It was found that microspheres prepared by PLGA with hydroxyl or ester groups exhibited lower encapsulation efficiency but faster in vitro release rate than that of carboxyl groups. In the meanwhile, on microcosmic level analysis by quartz crystal microbalance with dissipation, atomic force microscope and confocal laser scanning microscopy, we attributed this distinction to the specific interaction between ropivacaine and different terminal groups. Subsequently, the reaction activation centers were verified by density functional simulation calculation and frontier molecular orbital theory at molecular level. Additionally, pharmacokinetics and pharmacodynamic research of infiltration anesthesia model were performed to compare sustained release ability, duration and intensity of the anesthetic effect in vivo. Finally, potential safety and toxicity were evaluated by the biochemical analysis. This study not only provides a novel mechanism of drug encapsulation process but also potential flexible selections in terms of various anesthesia indications in clinical. [ABSTRACT FROM AUTHOR]

3D cell carriers with porous structures have the potential to promote cellular interactions and extracellular matrix remolding, making it a promising strategy to investigate the complex mechanisms behind drug treatments for tumors. Nevertheless, the applicability of currently reported porous microcarriers is still limited by the relatively small size and poor pore interconnectivity. Herein, a well-defined gigantic highly-porous poly(lactic-co-glycolic acid) (PLGA) microsphere (named LPMs) fabrication platform is reported. Utilizing this "LPMs" platform, arrays of well-uniform particles with sizes up to approximately 1000 µm are prepared in an orderly and controlled manner. The preparation matrix and crucial parameters affecting the particle size and pore size were established through extensive single-factor screening. It was also found that the loading of human gastric cancer cells MGC-803 to the LPMs cell carriers was facilitated not only by the increased pore size, but the particle size should also be enlarged along with the increased pore size. Through surface modification of gelatin on LPMs, cell loading could be dramatically enhanced, and microtissue-like structures were formed through cross-linking LPMs under extended 3D culture time. Under the guidance of these findings, we successfully constructed massive tumor cell carriers with 1000 µm LPMs, a preliminary prototype of a massive tumor tissue mimic. Together, the fabrication of these gigantic highly-porous microcarriers possibly allows for the high-efficiency 3D cell culture and represents the attractive potential of the construction of artificial tumor tissue models with massive and multiple-type cells. [Display omitted] [ABSTRACT FROM AUTHOR]