Regulating the Chiroptical Expression of Aggregated Solvophobic Core by Solvophilic Segments.

The investigation of chiral supramolecular stacking is of essential significance for the understanding of the origin of homochirality in nature. Unlike structurally well-defined amphiphilic liposomes, it remains unclear whether the solvophilic segments of the amphiphilic block copolymer play a decisive role in the construction of asymmetric superstructures. Herein, insights are presented into the stacking patterns and morphological regulation in azobenzene-containing block copolymer assemblies solely by modulating the solvophilic chain length. The solvophilic poly(methacrylic acid) (PMAA) segments of different molecular weights could cause multi-mode chirality inversions involving stacking transitions between intra-chain π-π stacking, inter-chain H- and J-aggregation. Furthermore, the length of the solvophilic PMAA also affects the morphology of the chiral supramolecular assemblies; rice grain-like micelles, worms, nanofibers, floccules, and lamellae can be prepared at different solvophilic-solvophobic balance. The comprehensive mechanism is collectively revealed by utilizing various measurement methods, such as including circular dichroism (CD), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD). This study highlights the critical importance of fully dissolved solvophilic segments for the chiroptical regulation of the aggregated core, providing new insights into the arrangement of chiral supramolecular structures in polymer systems.

Unveiling the Impact of Light-Induced Acceptor-Generated ROS on Device Stability in Organic Photovoltaics.

The intrinsic stability of the acceptor is a crucial component of the photovoltaic device stability. In this study, we investigated the efficiency and stability of the nonfused-ring acceptors LC8 and BC8 under indoor light conditions. Interestingly, we found that devices based on BC8 with terminal side chains exhibited a higher indoor efficiency and stability. Through accelerated aging experiments, we discovered that the acceptors generate singlet oxygen under light exposure with BC8 demonstrating lower levels of ROS compared to LC8. We attribute this difference to the modulation of the acceptor aggregation orientation. Furthermore, the generated reactive oxygen species (ROS) further deteriorate the acceptor structure, and this phenomenon is also observed in high-efficiency acceptor structures, such as Y6. Our research reveals important mechanisms of acceptor photo-oxidation processes, providing a theoretical basis for enhancing the intrinsic stability of acceptors.

A biomimetic renal fibrosis progression model on-chip evaluates anti-fibrotic effects longitudinally in a dynamic fibrogenic niche.

Although renal fibrosis can advance chronic kidney disease and progressively lead to end-stage renal failure, no effective anti-fibrotic drugs have been clinically approved. To aid drug development, we developed a biomimetic renal fibrosis progression model on-chip to evaluate anti-fibrotic effects of natural killer cell-derived extracellular vesicles and pirfenidone (PFD) across different fibrotic stages. First, the dynamic interplay between fibroblasts and kidney-derived extracellular matrix (ECM) resembling the fibrogenic niche on-chip demonstrated that myofibroblasts induced by stiff ECM in 3 days were reversed to fibroblasts by switching to soft ECM, which was within 2, but not 7 days. Second, PFD significantly down-regulated the expression of α-SMA in NRK-49F in medium ECM, as opposed to stiff ECM. Third, a study in rats showed that early administration of PFD significantly inhibited renal fibrosis in terms of the expression levels of α-SMA and YAP. Taken together, both on-chip and animal models indicate the importance of early anti-fibrotic intervention for checking the progression of renal fibrosis. Therefore, this renal fibrosis progression on-chip with a feature of recapitulating dynamic biochemical and biophysical cues can be readily used to assess anti-fibrotic candidates and to explore the tipping point when the fibrotic fate can be rescued for better medical intervention.

Scale-out production of extracellular vesicles derived from natural killer cells via mechanical stimulation in a seesaw-motion bioreactor for cancer therapy.

Extracellular vesicles (EVs) derived from immune cells have shown great anti-cancer therapeutic potential. However, inefficiency in EV generation has considerably impeded the development of EV-based basic research and clinical translation. Here, we developed a seesaw-motion bioreactor (SMB) system by leveraging mechanical stimuli such as shear stress and turbulence for generating EVs with high quality and quantity from natural killer (NK) cells. Compared to EV production in traditional static culture (229 ± 74 particles per cell per day), SMB produced NK-92MI-derived EVs at a higher rate of 438 ± 50 particles per cell per day and yielded a total number of 2 × 1011EVs over two weeks via continuous dynamic fluidic culture. In addition, the EVs generated from NK-92MI cells in SMB shared a similar morphology, size distribution, and protein profile to EVs generated from traditional static culture. Most importantly, the NK-92MI-derived EVs in SMB were functionally active in killing melanoma and liver cancer cells in both 2D and 3D culture conditionsin vitro, as well as in suppressing melanoma growthin vivo. We believe that SMB is an attractive approach to producing EVs with high quality and quantity; it can additionally enhance EV production from NK92-MI cells and promote both the basic and translational research of EVs.

A Component Content Measurement Method Modified Using Indirect Hard Modeling for Polymer Blends Based on Raman Spectroscopy.

Raman spectroscopy has been proven to be useful for the component content measurement of polymer blends. However, the soft modeling methods commonly used in quantitative analysis of Raman spectroscopy require a large number of training samples, resulting in a waste of materials and time. This work adopted a modified indirect hard modeling (IHM) method to measure the component content of polymer blends based on Raman spectroscopy. The Raman spectra of polypropylene (PP)/polystyrene (PS) blends with different component content were collected and resolved into the sum of multiple Voigt peak functions. For a large number of peak parameters, the two-dimensional correlation spectroscopy was used to screen out the characteristic Voigt peaks highly correlated with component content to reduce the parameter dimensions and build the parameterized spectral models. The spectral model of the blend was expressed as the weighted sum of the pure component spectral models, during which the parameters of the pure component models were adjusted within a range. According to the relationship between the weight and content of the pure component, a linear regression model for component content prediction was established. The coefficient of determination (R2)/root mean squared error of the IHM component content prediction model was 0.9931/0.4367 wt%. Besides, two popular soft modeling methods, partial least squares and artificial neural network, were compared with the IHM method, which showed that the IHM model had higher prediction accuracy with fewer training samples.

An electrochemical immunosensor based on reduced graphene oxide/multiwalled carbon nanotubes/thionine/gold nanoparticle nanocomposites for the sensitive testing of follicle-stimulating hormone.

Follicle-Stimulating Hormone (FSH) is a kind of gonadotropin which can promote human reproduction and development. Abnormal FSH levels may lead to endocrine disorders and infertility. Sensitive determination of FSH is very significant for the clinical diagnosis of these diseases. Here, an electrochemical immunosensor based on a screen-printed electrode (SPE) was developed for the detection of FSH. Nanocomposites, compounded with reduced graphene oxide (rGO), multiwalled carbon nanotubes (MWCNTs), thionine (Thi) and gold nanoparticles (AuNPs), were used for increasing the specific surface area to adsorb molecules and amplify signals. The rGO/MWCNTs/Thi/AuNP nanocomposites, anti-FSH and BSA were successively assembled onto a SPE to fabricate the immunosensor. Electrochemical performance of the modified immunosensor was studied by differential pulse voltammetry (DPV), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). FSH testing was based on the principle that the insulating FSH antigen-antibody immunocomplex could retard the electron transfer of Thi which led to the decrease of the DPV current response. Under optimum conditions, the rGO/MWCNTs/Thi/AuNP modified immunosensor exhibited high sensitivity and accuracy for the determination of FSH in a linear range from 1 mIU mL-1 to 250 mIU mL-1, and the detection limit was 0.05 mIU mL-1 at a signal-to-noise ratio of 3. The immunosensor was successfully applied for the determination of quality serum samples with a recovery of 94.0-109.8%. The electrochemical immunosensor could be utilized for testing other gonadotropins.

Cell membrane-encapsulated magnetic nanoparticles for enhancing natural killer cell-mediated cancer immunotherapy.

Natural killer (NK) cells have exhibited therapeutic potential for various malignant tumors. However, the cytotoxic effect of NK cells is relatively weak and less specific compared to other immunotherapy approaches such as chimeric antigen receptor T-Cell (CART) therapy, constituting a great challenge for adoptive immunotherapy. Here, we report cell membrane-encapsulated magnetic nanoparticles for activating NK cells and enhancing anti-tumor effects. Magnetic nanoparticles were coated with silicon dioxide (SiO2), and cancer cell membranes were mixed with Fe3O4@SiO2 to construct cancer cell membrane coated Fe3O4@SiO2 magnetic nanoparticles (CMNPs). The functionalized nanoparticles bearing cancer-specific antigens on the surface effectively stimulated NK cells by enhancing expression of surface activating receptors and boosting anti-tumor function through the secretion of soluble cytotoxic effectors. To conclude, the biomimetic magnetic nanoparticles offer a versatile and powerful tool to present tumor-specific antigens, priming anti-tumor capability, which is promising to enhance NK cell-based adoptive cancer immunotherapy.

High-Fidelity End-Functionalization of Poly(ethylene glycol) Using Stable and Potent Carbamate Linkages.

Commercial PEG-amine is of unreliable quality, and conventional PEG functionalization relies on esterification and etherification steps, suffering from incomplete conversion, harsh reaction conditions, and functional-group incompatibility. To solve these challenges, we propose an efficient strategy for PEG functionalization with carbamate linkages. By fine-tuning terminal amine basicity, stable and high-fidelity PEG-amine with carbamate linkage was obtained, as seen from the clean MALDI-TOF MS pattern. The carbamate strategy was further applied to the synthesis of high-fidelity multi-functionalized PEG with varying reactive groups. Compared to with an ester linkage, amphiphilic PEG-PS block copolymers bearing carbamate junction linkage exhibits preferential self-assembly tendency into vesicles. Moreover, nanoparticles of the latter demonstrate higher drug loading efficiency, encapsulation stability against enzymatic hydrolysis, and improved in vivo retention at the tumor region.

[68Ga]Ga-HBED-CC-DiAsp: A new renal function imaging agent.

INTRODUCTION: [68Ga]Ga-EDTA ([68Ga]Ga-ethylenediaminetetraacetic acid) was previously reported as a renal imaging agent for measuring GFR (glomerular filtration rate). In an effort to provide new agents with better in vivo characteristics for renal imaging, [68Ga]Ga-HBED-CC-DiAsp (Di-Aspartic acid derivative of N,N'-bis [2-hydroxy-5-(carboxyethyl)benzyl]-ethylenediamine-N,N'-diacetic acid) was prepared and tested. METHOD: HBED-CC-DiAsp was synthesized and labeled with [68Ga]GaCl4- at room temperature. Plasma protein and red blood cells (RBC) binding were also evaluated. Biodistribution and dynamic PET imaging studies were performed in mice and rats, respectively. RESULTS: [68Ga]Ga-HBED-CC-DiAsp was radiolabeled at room temperature by a one-step kit formulation in high purity without any purification (radiochemical purity >98%). Previous reports suggested that Ga-HBED-CC exhibited a higher stability constant and rapid chelating formation rate than that of Ga-EDTA (logKGaL = 38.5 vs 22.1, respectively). In vitro stability studies indicated that it was stable up to 120 min. The log DOW value, partition coefficient between n-octanol and water, was found to be -2.52 ± 0.08. Plasma protein and RBC binding was similar to that observed for [68Ga]Ga-EDTA. Biodistribution and dynamic PET/CT imaging studies in rats revealed a rapid clearance primarily through the renal-urinary pathway. The PET-derived [68Ga]Ga-HBED-CC-DiAsp renograms in rats showed an average time-to-peak of 3.6 ± 0.7 min which was similar to that observed for [68Ga]Ga-EDTA (3.1 ± 0.5 min). The time-to-half-maximal activity was also comparable to that of [68Ga]Ga-EDTA (8.8 vs 8.2 min, respectively). Pretreatment of probenecid, a renal tubular excretion inhibitor, showed no significant effect on renal excretion. CONCLUSIONS: [68Ga]Ga-HBED-CC-DiAsp could be prepared quickly at room temperature in high yield and purity. Results of in vitro studies and in vivo biodistribution in mice and rats suggested that [68Ga]Ga-HBED-CC-DiAsp might be useful as a PET imaging agent for measurement of GFR.

Synthesis of novel technetium-99m tricarbonyl-HBED-CC complexes and structural prediction in solution by density functional theory calculation.

HBED-CC (N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylene diamine-N,N'-diacetic acid, L1 ) is a common bifunctional chelating agent in preparation of 68Ga-radiopharmaceuticals. Due to its high stability constant for the Ga3+ complex (logKGaL = 38.5) and its acyclic structure, it is well known for a rapid and efficient radiolabelling at ambient temperature with Gallium-68 and its high in vivo stability. [99mTc][Tc(CO)3(H2O)3]+ is an excellent precursor for radiolabelling of biomolecules. The aim of this study was to develop a novel preparation method of 99mTc-HBED-CC complexes. In this study, HBED-CC-NI (2,2'-(ethane-1,2-diylbis((2-hydroxy-5-(3-((2-(2-nitro-1H-imidazol-1-yl)ethyl)amino)-3-oxopropyl)benzyl)-azanediyl))-diacetic acid, L2 ), a derivative of HBED-CC, was designed and synthesized. Both L1 and L2 were radiolabelled by [99mTc][Tc(CO)3(H2O)3]+ successfully for the first time. In order to explore the coordination mode of metal and chelates, non-radioactive Re(CO)3 L1 and Re(CO)3 L2 were synthesized and characterized spectroscopically. Tc(CO)3 L1 and Tc(CO)3 L2 in solution were calculated by density functional theory and were analysed with radio-HPLC chromatograms. It showed that [99mTc]Tc(CO)3 L2 forms two stable diastereomers in solution, which is similar to those of [68Ga]Ga-HBED-CC complexes. Natural bond orbital analysis through the natural population charges revealed a charge transfer between [99mTc][Tc(CO)3]+ and L1 or L2 . The experimental results showed that tricarbonyl technetium might form stable complex with HBED-CC derivatives, which is useful for the future application of using HBED-CC as a bifunctional chelating agent in developing new 99mTc-radiopharmaceuticals as diagnostic imaging agents.

Selective Localization of Carbon Black in Bio-Based Poly (Lactic Acid)/Recycled High-Density Polyethylene Co-Continuous Blends to Design Electrical Conductive Composites with a Low Percolation Threshold.

The electrically conductive poly (lactic acid) (PLA)/recycled high-density polyethylene (HDPE)/carbon black (CB) composites with a fine co-continuous micro structure and selective localization of CB in the HDPE component were fabricated by one-step melt processing via a twin-screw extruder. Micromorphology analysis, electrical conductivity, thermal properties, thermal stability, and mechanical properties were investigated. Scanning electron microscope (SEM) images indicate that a co-continuous morphology is formed, and CB is selectively distributed in the HDPE component. With the introduction of CB, the phase size of the PLA component and the HDPE component in PLA/HDPE blends is reduced. In addition, differential scanning calorimetry (DSC) and thermos gravimetric analysis (TGA) results show that the introduction of CB promotes the crystallization behavior of the PLA and HDPE components, respectively, and improves the thermal stability of PLA70/30HDPE/CB composites. The electrically conductive percolation threshold of the PLA70/30HDPE/CB composites is around 5.0 wt %, and the electrical conductivity of PLA70/30HDPE/CB composites reaches 1.0 s/cm and 15 s/cm just at the 10 wt % and 15 wt % CB loading, respectively. Further, the tensile and impact tests show that the PLA70/30HDPE/CB composites have good mechanical properties. The excellent electrical conductivity and good mechanical properties offer the potential to broaden the application of PLA/HDPE/CB composites.

Fusion of Near-Infrared and Raman Spectroscopy for In-Line Measurement of Component Content of Molten Polymer Blends.

Spectral measurement techniques, such as the near-infrared (NIR) and Raman spectroscopy, have been intensively researched. Nevertheless, even today, these techniques are still sparsely applied in industry due to their unpredictable and unstable measurements. This paper put forward two data fusion strategies (low-level and mid-level fusion) for combining the NIR and Raman spectra to generate fusion spectra or fusion characteristics in order to improve the in-line measurement precision of component content of molten polymer blends. Subsequently, the fusion value was applied to modeling. For evaluating the response of different models to data fusion strategy, partial least squares (PLS) regression, artificial neural network (ANN), and extreme learning machine (ELM) were applied to the modeling of four kinds of spectral data (NIR, Raman, low-level fused data, and mid-level fused data). A system simultaneously acquiring in-line NIR and Raman spectra was built, and the polypropylene/polystyrene (PP/PS) blends, which had different grades and covered different compounding percentages of PP, were prepared for use as a case study. The results show that data fusion strategies improve the ANN and ELM model. In particular, mid-level fusion enables the in-line measurement of component content of molten polymer blends to become more accurate and robust.

A paper-based electrochemical immunosensor with reduced graphene oxide/thionine/gold nanoparticles nanocomposites modification for the detection of cancer antigen 125.

A paper-based electrochemical immunosensor was developed for the detection of cancer antigen 125 (CA125) by screen-printing technique. The reduced graphene oxide/thionine/gold nanoparticles (rGO/Thi/AuNPs) nanocomposites were compounded and coated onto the working electrode of immunosensor for CA125 antibody (anti-CA125) immobilization and detection signal amplification. The detection principle was based on the fact that the immunocomplex formed by specify binding of CA125 antibody and antigen could reduce the current response of thionine, which was proportional to the corresponding concentration of CA125 antigen. The immunoassay results showed that the linear range of CA125 was from 0.1 U mL-1 to 200 U mL-1 with the limit of detection (LOD) of 0.01 U mL-1 at signal to noise of 3. Quality control serum samples measured by our proposed immunosensor showed acceptable agreement with traditional ELISA method with the relative error less than 8.05%. The immunosensor exhibited good electrochemical performance with high reproducibility, reliability, stability and accuracy. The proposed immunosensor could be used for the determination of CA125 and had the potential for point-of-care testing (POCT) of other tumor marker.

Versatile pH-response Micelles with High Cell-Penetrating Helical Diblock Copolymers for Photoacoustic Imaging Guided Synergistic Chemo-Photothermal Therapy.

With high optical absorption efficiency, near infrared (NIR) dyes have been proposed as theranostic agents for fluorescence imaging, photoacoustic imaging (PAI), and photothermal therapy (PTT). However, inherent hydrophobicity and short circulation time of small molecule hinder the further biomedical application. Herein smart amphiphilic copolymer was synthesized containing IR780/camptothecin@poly(ε-caprolactone) (IR780/CPT@PCL) as core, helical poly(phenyl isocyanide) (PPI) blocks as shell with the pH-responsive rhodamine B (RhB) moieties in the core-shell interface. With hydrophilic helical PPI coronas, these micelles present significantly enhanced cell-penetrating capacity that plays a key role in facilitating intracellular delivery of various cargos. By encapsulating CPT and IR780 molecules, the multifunctional self-assemble probe has huge potential to realize functional cooperativity and adaptability for cancer diagnosis and therapy. The in vitro and in vivo experimental results demonstrate that the pH-triggered fluorescent responsiveness and strong acoustic generation permit them efficient fluorescent and PA signal sensing for cancer diagnosis. Moreover, with 808 nm laser irradiation, the generated heat significantly improves the drug release from PCL core, leading to synergetic chemo-photothermal therapy and decreases tumor recurrence rates in mice. Overall, the biocompatible multifunctional micelles with these combined advantages can potentially be utilized for PAI guided disease diagnosis and tumor ablation.

Polypeptide-b-Poly(Phenyl Isocyanide) Hybrid Rod-Rod Copolymers: One-Pot Synthesis, Self-Assembly, and Cell Imaging.

Hybrid rod-rod diblock copolymers, poly(γ-benzyl L-glutamate)-poly(4-cyano-benzoic acid 2-isopropyl-5-methyl-cyclohexyl ester) (PBLG-PPI), with determined chirality are facilely synthesized through sequential copolymerization of γ-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) and phenyl isocyanide monomers bearing chiral menthyl pendants using a Ni(cod)(bpy) complex as the catalyst in one-pot. Circular dichroism and absorption spectra reveal that each block of the block copolymers possesses a stable helical conformation with controlled helicity in solution due to the induction of chiral pendants. The two diastereomeric polymers self-assemble into helical nanofibrils with opposite handedness due to the different chiral induction of the L- and D-menthyl pendants, confirmed by transmission electron microscopy (TEM). Deprotection of the benzyl groups of the PBLG segment affords biocompatible amphiphilic diblock copolymers, poly(L-glutamic acid)-poly(4-cyano-benzoic acid 2-isopropyl-5-methyl-cyclohexyl ester) (PLGA-PPI), that can self-assemble into well-defined micelles by cosolvent induced aggregation. Very interestingly, a chiral rhodamine chromophores RhB(D) can be selectively encapsulated into the chiral polymeric micelles, which is efficiently internalized into living cells when directly monitored with a confocal microscope. This contribution will be useful for developing novel rod-rod biocompatible hybrid block copolymers with a controlled helicity, and may also provide unique chiral materials for potential bio-medical applications.

Construction of polyelectrolyte-responsive microgels, and polyelectrolyte concentration and chain length-dependent adsorption kinetics.

We report on the construction of a polyelectrolyte-responsive system evolved from sterically stabilized protonated poly(2-vinylpyridine) (P2VPH(+)) microgels. Negatively charged sodium dodecylbenzenesulfonate (SDBS) surfactants could be readily internalized into the cationic microgels by means of electrostatic interactions, resulting in microgel collapse and concomitant formation of surfactant micellar domains (P2VPH(+)/SDBS)-contained electrostatic complexes. These internal hydrophobic domains conferred the opportunity of fluorescent dyes to be loaded. The obtained fluorescent microgel complexes could be further disintegrated in the presence of anionic polyelectrolyte, poly(sodium 4-styrenesulfonate) (PNaStS). The stronger electrostatic attraction between multivalent P2VPH(+) microgels and PNaStS polyelectrolyte than single-charged surfactant led to triggered release of the encapsulated pyrene dyes from the hydrophobic interiors into microgel dispersion. The process was confirmed by laser light scattering (LLS) and fluorescence measurements. Furthermore, the entire dynamic process of PNaStS adsorption into P2VPH(+) microgel interior was further studied by stopped-flow equipment as a function of polyelectrolyte concentration and degree of polymerization. The whole adsorption process could be well fitted with a double-exponential function, suggesting a fast (τ1) and a slow (τ2) relaxation time, respectively. The fast process (τ1) was correlated well with the approaching of PNaStS with P2VPH(+) microgel to form a nonequilibrium complex within the microgel shell, while the slow process (τ2) was consistent with the formation of equilibrium complexes in the microgel deeper inside. This simple yet feasible design augurs well for the promising applications in controlled release fields.

A wavelet bicoherence-based quadratic nonlinearity feature for translational axis condition monitoring.

The translational axis is one of the most important subsystems in modern machine tools, as its degradation may result in the loss of the product qualification and lower the control precision. Condition-based maintenance (CBM) has been considered as one of the advanced maintenance schemes to achieve effective, reliable and cost-effective operation of machine systems, however, current vibration-based maintenance schemes cannot be employed directly in the translational axis system, due to its complex structure and the inefficiency of commonly used condition monitoring features. In this paper, a wavelet bicoherence-based quadratic nonlinearity feature is proposed for translational axis condition monitoring by using the torque signature of the drive servomotor. Firstly, the quadratic nonlinearity of the servomotor torque signature is discussed, and then, a biphase randomization wavelet bicoherence is introduced for its quadratic nonlinear detection. On this basis, a quadratic nonlinearity feature is proposed for condition monitoring of the translational axis. The properties of the proposed quadratic nonlinearity feature are investigated by simulations. Subsequently, this feature is applied to the real-world servomotor torque data collected from the X-axis on a high precision vertical machining centre. All the results show that the performance of the proposed feature is much better than that of original condition monitoring features.