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Flexible pressure sensors that have high sensitivity, high linearity, and a wide pressure-response range are highly desired in applications of robotic sensation and human health monitoring. The challenge comes from the incompressibility of soft materials and the stiffening of microstructures in the device interfaces that lead to gradually saturated response. Therefore, the signal is nonlinear and pressure-response range is limited. Here, we show an iontronic flexible pressure sensor that can achieve high sensitivity (49.1 kPa

We report a facile but general method to prepare highly water-soluble and biocompatible photoinitiators for digital light processing (DLP)-based 3D printing of high-resolution hydrogel structures. Through a simple and straightforward one-pot procedure, we can synthesize a metal-phenyl(2,4,6-trimethylbenzoyl)phosphinates (M-TMPP)-based photoinitiator with excellent water solubility (up to ∼50 g/L), which is much higher than that of previously reported water-soluble photoinitiators. The M-TMPP aqueous solutions show excellent biocompatibility, which meets the prerequisite for biomedical applications. Moreover, we used M-TMPP to prepare visible light (405 nm)-curable hydrogel precursor solutions for 3D printing hydrogel structures with a high water content (80 wt %), high resolution (∼7 μm), high deformability (more than 80% compression), and complex geometry. The printed hydrogel structures demonstrate great potential in flexible electronic sensors due to the fast mechanical response and high stability under cyclic loadings.

Three-dimensional (3D) printing technologies are advanced manufacturing technologies based on computer-aided design digital models to create personalized 3D objects automatically. They have been widely used in the industry, design, engineering, and manufacturing fields for nearly 30 years. Three-dimensional printing has many advantages in process engineering, with applications in dentistry ranging from the field of prosthodontics, oral and maxillofacial surgery, and oral implantology to orthodontics, endodontics, and periodontology. This review provides a practical and scientific overview of 3D printing technologies. First, it introduces current 3D printing technologies, including powder bed fusion, photopolymerization molding, and fused deposition modeling. Additionally, it introduces various factors affecting 3D printing metrics, such as mechanical properties and accuracy. The final section presents a summary of the clinical applications of 3D printing in dentistry, including manufacturing working models and main applications in the fields of prosthodontics, oral and maxillofacial surgery, and oral implantology. The 3D printing technologies have the advantages of high material utilization and the ability to manufacture a single complex geometry; nevertheless, they have the disadvantages of high cost and time-consuming postprocessing. The development of new materials and technologies will be the future trend of 3D printing in dentistry, and there is no denying that 3D printing will have a bright future.

Background Nanocarriers-derived antitumor therapeutics are often associated with issues of limited tumor penetration and dissatisfactory antitumor efficacies. Some multistage delivery systems have been constructed to address these issues, but they are often accompanied with complicated manufacture processes and undesirable biocompatibility, which hinder their further application in clinical practices. Herein, a novel dual-responsive multi-pocket nanoparticle was conveniently constructed through self-assembly and cross-linking of amphiphilic methoxypolyethylene glycol-lipoic acid (mPEG-LA) conjugates to enhance tumor penetration and antitumor efficacy. Results The multi-pocket nanoparticles (MPNs) had a relatively large size of ~ 170 nm at physiological pH which results in prolonged blood circulation and enhanced accumulation at the tumor site. But once extravasated into acidic tumor interstices, the increased solubility of PEG led to breakage of the supramolecular nanostructure and dissolution of MPNs to small-sized (3) bearing mice with reduced side effect. Conclusions Our facile fabrication of multi-pocket nanoparticles provided a promising way in improving solid tumor penetration and achieving a great therapeutic efficacy. Graphic Abstract

To review four types of three-dimensional imaging devices: intraoral scanners, extraoral scanners, cone-beam computed tomography (CBCT), and facial scanners, in terms of their development, technologies, advantages, disadvantages, accuracy, influencing factors, and applications in dentistry.PubMed (National Library of Medicine) and Google Scholar databases were searched. Additionally, the scanner manufacturers' websites were accessed to obtain relevant data. Four authors independently selected the articles, books, and websites. To exclude duplicates and scrutinize the data, they were uploaded to Mendeley Data. In total, 135 articles, two books, and 17 websites were included.Research and clinical practice have shown that oral and facial scanners and CBCT can be used widely in various areas of dentistry with high accuracy.Although further advancement of these devices is desirable, there is no doubt that digital technology represents the future of dentistry. Furthermore, the combined use of different devices may bring dentistry into a new era. These four devices will play a significant role in clinical utility with high accuracy. The combined use of these devices should be explored further.The four devices will play a significant role in clinical use with high accuracy. The combined use of these devices should be explored further.

Graphene oxide (GO) is a two-dimensional atom-thick sheet generated from an oxidation of graphene. GO possesses a range of reactive oxygen functional groups on the basal planes and edges, which makes it a good candidate in the field of separation and enrichment through chemical functionalization. In this work, GO-based Fe3O4 magnetic nanoparticles were prepared, and boronic acid groups were introduced by 3-aminophenylboronic acid (APBA) at the same time to improve the enrichment efficiency. Herein, the GO-based magnetic boronate-affinity adsorbent (Fe3O4@GO@APBA) was developed focusing on the specific capture of low abundance of glycoprotein. The composites gathered excellent characters of large specific surface area and biocompatibility of GO, strong magnetic responsiveness, and enhanced affinity properties of boronic acid. The proposed system showed better specificity for glycoprotein even in the presence of non-glycoproteins. As a result, the prepared Fe3O4@GO@APBA not only exhibited high selectivity for horseradish peroxidase (HRP), and an outstanding tolerance for interference, but also showed excellent rebinding rate for an extraction application. Furthermore, this method provided a reliable way to improve conventional magnetic adsorbent, and showed great potential in analysis of low-abundant glycoprotein from even complex samples.

Rapid development of stimuli-responsive drug delivery systems (DDSs) for tumor therapy has raised increasing interest in recent decades, and many nanomedicines are prepared to achieve accurate or sustained drug release. However, the fabrication process for these nanomedicines has been far too intricate and their potential biosafety has not been fully understood, which has hampered their clinical translation. Challenges for developing DDSs remain on balancing the complexity of the fabrication process with their translational feasibility. Owing to water-solubility, biocompatibility, biodegradability and CD44-targetability, hyaluronic acid (HA) as a versatile building block has gained great popularity due to a simplified fabrication process and unique characteristics of HA for DDSs. In this review, we overviewed the biological function and multiple chemical modifications of HA, and discussed the fabrication of HA-based drug delivery systems (HA-DDSs) with specific tumor microenvironmental stimuli-responsive linkers. We systemically surveyed the applications of HA-DDSs for chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, gene delivery and combination therapy.

Interfacial solar evaporators (ISEs) for seawater desalination have garnered enormous attention in recent decades due to global water scarcity. Despite the progress in the energy conversion efficiency and production rate of ISE, the poor portability of large-area ISE during transportation as well as the clogging of water transport pathways by precipitated salts during operation remain grand challenges for its fielded applications. Here, we designed an ISE with high energy conversion efficiency and shape morphing capability by integrating carbon nanotube (CNT) fillers with a light-responsive shape memory polymer (SMP, cross-linked polycyclooctene (cPCO)). Utilizing the shape memory effect, our ISE can be folded to an origami with 1/9 of its original size to save space for transportation and allow for on-demand unfolding upon sunlight irradiation when deployed in service. In addition, the ISE is equipped with a real-time clogging monitoring function by measuring the capacitance of the electric double layer (EDL) formed at the evaporator/seawater nanointerface. Due to its good energy conversion efficiency, high portability, and clogging monitoring capability, we envisage our ISE as a promising selection in solar evaporation technologies.

Post-bond heat treatment (PBHT) is an effective way to improve the bonding quality of a brazed joint. Herein, brazing of a nickel-based single crystal superalloy is carried out using a Ni-Cr-Co-B-Si-Al-Ti-W-Mo filler alloy, and the microstructure and creep property of the brazed joint are systematically investigated using scanning electron microscopy (SEM), Thermo-Calc software, an electron probe micro-analyzer (EPMA), X-ray diffractometer, confocal scanning laser microscope (CSLM), and transmission electron microscopy (TEM). The results reveal that the as-prepared joint only consists of an isothermally solidified zone (ISZ) and an athermally solidified zone (ASZ), where the cubic γ′ phase is observed in the ISZ, and skeleton-like M3B2, γ + γ′ eutectic and reticular G phases are observed in the ASZ. Furthermore, the γ + γ′ eutectic and G phases disappear and the M3B2 alters from a skeleton-like to block-like shape in the ASZ after PBHT. Meanwhile, some lath-like M3B2 phases are precipitated at the edge of the ISZ and several M3B2 phases are precipitated in the base metal, forming a new zone in the brazed joint, namely at the diffusion affected zone (DAZ). Owing to the removal of low melting point eutectics from the as-prepared joint, the creep life also increases from 188 h to 243 h after PBHT. The current work provides a method for the optimization of brazed joints based on the Ni-based single crystal superalloy.

The spread and application of computer-aided design/computer-aided manufacturing (CAD/CAM) technology have contributed to the rapid development of digitalization in dentistry. The accuracy of scan results is closely related to the devising subsequent treatment plans and outcomes. Professional standards for evaluating scanners are specified in the American National Standard/American Dental Association Standard 132 (ANSI/ADA No. 132). The aims of this study were to use the three samples mentioned in ANSI/ADA No. 132 and evaluate the accuracy and reproducibility of two extraoral scanners and an intraoral scanner based on the inspection standards recommended by ANSI/ADA No. 132. In this study, two trained operators used two extraoral scanners (E4, 3Shape, Denmark & SHINING DS100+, Shining, China) and an intraoral scanner (TRIOS SERIES3, 3Shape, Denmark) to perform 30 scans of each of the three samples at a temperature of 25 ± 2 ° C and export standard tessellation language files and used reverse engineering software to perform measurements and iterative nearest point matching experiments. The measured values obtained were compared with the reference values measured by a coordinate measuring machine (NC8107, Leader Metrology, USA). We performed a normal distribution test (Shapiro-Wilk test), the nonparametric Kruskal-Wallis test, and an independent-samples t -test to analyze the reproducibility of each scan for different models. The experimental results indicate that the trueness and precision of the two extraoral scanners and the intraoral scanner had a slight mean deviation. The trueness and precision of the three scanners on the curved surface and groove areas are poor. The accuracy and reproducibility of E4 outperformed SHINING and TRIOS. The iterative closest point matching experiment also showed good matching results. The two extraoral scanners and the intraoral scanner in this study can meet the basic clinical requirements in terms of accuracy, and we hope that digital technology will be more widely used in dentistry in the future.

Additional file 1: Fig. S1. 1H NMR spectrum (400 MHz) of mPEG-LA conjugates in CDCl3. Fig. S2. SEM image (A), size (B) and zeta potential (C) of the self-assembly of mPEG-LA conjugates (NPs, 100 g mL−1). Fig. S3. Size distribution of MPNs at different concentrations. Fig. S4. Fluorescence spectra of a mixed solution of NPs (100 μg mL−1)and MPNs (100 μg mL−1) prepared with 0.1 wt% DiO/DiI tracing the development of FRET between two dyes. Fig. S5. Critical aggregation concentration of MPNs at (A) pH 7.4 or (B) 6.5. Fig. S6. Fluorescence spectra of a mixed solution of MPNs (100 μg mL−1, pH 6.5) prepared with 0.1 wt% DiO/DiI tracing the development of FRET between two dyes over time. Fig. S7. Flow cytometric histogram profiles of 4T1 cells treated with MPNs, DOX, D-NPs and D-MPNs for 3 h (DOX concentration: 10 μg mL−1). Fig. S8. CLSM images of 4T1 cells incubated with DOX, D-NPs, D-MPNs and DOX·HCl for 1 h (DOX dosage: 2 μg mL−1). Hoechst 33342 was used to stain the cell nuclei. Scale bar: 10 μm. Fig. S9. Quantitative assessment of penetration of DOX formulations into 4T1 cells. The cells were incubated with DOX, D-NPs and D-MPNs at a DOX concentration of 5 μg mL−1 for 2 h. Fig. S10. IOD (Integrated optical density) of immunohistochemical images for saline, MPNs, DOX·HCl, D-NPs and D-MPNs groups. The apoptotic rates of tumor sections based on TUNEL images (A), tumor microvessel density based on CD31 images (B) and Ki67 positive cells (C) of tumor sections were calculated with Image-Pro Plus 6.0 software. Data were presented as mean ± SD (n = 3), *p < 0.01, **p < 0.005. Fig. S11. Body weight changes of 4T1-bearing BALB/c mice after administration with saline, MPNs, DOX·HCl, D-NPs and D-MPNs (n = 8, dosage: 5 mg DOX kg−1 mouse body weight, *p < 0.01). The arrows indicated the time points for intravenous injection. Fig. S12. Routine blood analysis results of the mice collected on the 12th day after intravenous injection of saline, MPNs, DOX·HCl, D-NPs or D-MPNs. The results show mean and standard deviation of white blood cells (WBCs), red blood cell (RBC), hemoglobin (HGB) and platelets (PLT). Fig. S13. Histological examination of major organs separated from 4T1-bearing BALB/c mice after administration with saline, MPNs, DOX·HCl, D-NPs and D-MPNs for 18 days. Scale bar: 100 μm. Fig. S14. TUNEL staining of heart (×200) of 4T1-bearing BALB/c mice after administration with saline, MPNs, DOX·HCl, D-NPs and D-MPNs for 18 days. The apoptotic cells (red arrow) and normal cells were stained brown and blue, respectively. Table S1. Pharmacokinetic parameters of DOX·HCl, D-NPs and D-MPNs after intravenous administration at an equivalent dose of 10 mg DOX/kg mouse body weight (n = 3 per group).

Electrodermal devices that capture the physiological response of skin are crucial for monitoring vital signals, but they often require convoluted layered designs with either electronic or ionic active materials relying on complicated synthesis procedures, encapsulation, and packaging techniques. Here, we report that the ionic transport in living systems can provide a simple mode of iontronic sensing and bypass the need of artificial ionic materials. A simple skin-electrode mechanosensing structure (SEMS) is constructed, exhibiting high pressure-resolution and spatial-resolution, being capable of feeling touch and detecting weak physiological signals such as fingertip pulse under different skin humidity. Our mechanical analysis reveals the critical role of instability in high-aspect-ratio microstructures on sensing. We further demonstrate pressure mapping with millimeter-spatial-resolution using a fully textile SEMS-based glove. The simplicity and reliability of SEMS hold great promise of diverse healthcare applications, such as pulse detection and recovering the sensory capability in patients with tactile dysfunction., Sensing mechanical signals is an important aspect for a range of applications of E-skins. Here, the authors report on the creation of deforming iontronic sensing structures which can use ionic transport through tissues to create a simple and sensitive E-skin for sensing touch, pulse and motion demonstrating application.

The pulse is a key biomedical signal containing various human physiological and pathological information highly related to cardiovascular diseases. Pulse signals are often collected from the radial artery based on Traditional Chinese Medicine, or by using flexible pressure sensors. However, the wrist wrapped with a flexible pressure sensor exhibits unstable signals under hand motion because of the concave surface of the wrist. By contrast, fingertips have a convex surface and therefore show great promises in stable and long-term pulse monitoring. Despite the promising potential, the fingertip pulse signal is weak, calling for highly sensitive detecting devices. Here, a highly sensitive and flexible iontronic pressure sensor with a linear sensitivity of 13.5 kPa-1 , a swift response, and remarkable stability over 5000 loading/unloading cycles is developed. This sensor enables stable and high-resolution detection of pulse waveform under both static condition and finger motion. Fingertip pulse waveforms from subjects of different genders, age, and health conditions are collected and analyzed, suggesting that fingertip pulse information is highly similar to that of the radial artery. This work justifies that fingertip is an ideal platform for pulse signals monitoring, which would be a competitive alternative to existing complex health monitoring systems.

Boronate-affinity magnetic hollow molecularly imprinted polymers (B-MhMIPs) were prepared with sialic acid (SA) as the template, 3-aminophenylboronic acid (APBA) as the functional monomer and glycidilmethacrylate (GMA) as the co-monomer to chemisorb Fe3O4 nanoparticles. Furthermore, the hollow structure made the nanoparticles have more binding sites at both internal and external surfaces, which can facilitate the removal of template molecules from polymers and enhance the adsorption abilities towards SA. After optimizing, the adsorption pH was controlled at 4.0, and this was different from most cis-diol-containing compounds. Under the optimal conditions, the limit of detection for SA was 0.025 μg mL−1 (n = 3). This method was applied to analyze serum samples with different spiked levels, and the recoveries of the SA were in the range of 70.9–106.2%. These results confirmed the superiority of the B-MhMIPs for selective and efficient enrichment of trace SA from complex matrices.

In this study, a new boronate-affinity hollow adsorbent was successfully fabricated. This adsorbent was prepared using mesoporous MCM-48 as a sacrificial support, methacrylic acid (MAA), N,N-methylenebisacrylamide (MBA) and azobisisobutyronitrile (AIBN) were applied as a functional monomer, cross-linker and initiator, respectively, and further modified with boronic acid groups (4-vinylphenylboronic acid, VPBA) to improve the enrichment efficiency. Such materials were composed of a hollow structure, a hydrophilic polymer coating of poly(MBA-MAA), and a VPBA-functionalized shell designed for capturing isoflavones. The resulting material coupled with high-performance liquid chromatography (HPLC) was applied to analyze three cis-diol isoflavones (daidzin, glycitin, and genistin) in soybean milk samples. The sorbent was characterized by transmission electron microscopy, Fourier transform infrared spectrometry and thermo-gravimetric analysis. Several parameters affecting the extraction efficiency were optimized. Owing to the hollow structure, more binding sites were located on the inner and outer surfaces of this material, which could facilitate the binding of the target molecules to the adsorbent. Adsorption selectivity studies indicated that the prepared material can selectively recognize isoflavones. Under optimized conditions, the limits of detection of the method were 3.8 to 7.3 μg L−1 for the three isoflavones based on a signal-to-noise ratio of 3 : 1. The spiked recoveries were found to be between 67.4 and 104.7% (the relative standard deviations were less than 3.8%, n = 3). This indicated the superiority of the method in selective extraction of isoflavones even from complex matrices.

The authors describe boronate-modified hollow dummy template imprinted polymers (B-hDIPs) for selective and sensitive extraction of the catecholamines norepinephrine (NE), epinephrine (E), and dopamine (DA) from urine samples prior to their detection by HPLC with UV detector. The B-hDIPs were prepared by using (a) nano-TiO2 as the sacrificial support, (b) 3-carboxyphenylboronic acid (CPBA) as the boronate-affinity functional monomer, and (c) catechol which acts as dummy template. The nano-TiO2 can be etched off by using hydrofluoric acid to form the hollow imprint. The main advantages of using such hollow polymers arise from their controllable hole structure which favors template removal and fast mass transfer. The B-hDIPs material was characterized by FT-IR, transmission electron microscope, dynamic light scattering, X-ray photoelectron spectrum, and thermal gravimetric analysis. The effects of imprinting conditions, sample pH, sample flow rate, adsorbent amount, selectivity and competitive capacities were investigated. Under optimal conditions, the limits of detection for the catecholamines are in the range from 15 to 47 ng mL−1. The method was successfully applied to their determination of NE, E, and DA in spiked urine, with recoveries ranging from 63.4 to 106.2%.

Atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) are two common arrhythmias with high similarity. Automatic electrocardiogram (ECG) detection using machine learning and neural networks has replaced manual detection, but few studies distinguishing AVNRT from AVRT have been reported. This study proposed a classification algorithm using bottleneck attention module (BAM)-based deep residual network (ResNet) through two-lead ECG records. Specifically, ResNet possessed sufficient network depth to extract abundant features, and BAM was introduced to optimize weight assignment of feature maps by fusing together channel and spatial information. Seven types of ECG signals from four public databases were used to pretrain the proposed classification model, which was then fine-tuned using the experimental dataset. The AVNRT and AVRT detection precisions were 98.95% and 87.47%, sensitivities were 87.52% and 98.58%, and the [Formula: see text]1-scores were 92.82% and 92.68%, respectively. These findings showed that our proposed classification model achieved excellent inter-patient classification performance and can assist doctors in the diagnosis of AVNRT and AVRT.

Transmissible gastroenteritis coronavirus (TGEV) is a member of the genus Coronavirus, family Coronaviridae, order Nidovirales. TGEV is an enteropathogenic coronavirus that causes highly fatal acute diarrhoea in newborn pigs. An oral Lactobacillus casei (L. casei) vaccine against anti-transmissible gastroenteritis virus developed in our laboratory was used to study mucosal immune responses. In this L. casei vaccine, repetitive peptides expressed by L. casei (specifically the MDP and tuftsin fusion protein (MT)) were repeated 20 times and the D antigenic site of the TGEV spike (S) protein was repeated 6 times. Immunization with recombinant Lactobacillus is crucial for investigations of the effect of immunization, such as the first immunization time and dose. The first immunization is more important than the last immunization in the series. The recombinant Lactobacillus elicited specific systemic and mucosal immune responses. Recombinant L. casei had a strong potentiating effect on the cellular immunity induced by the oral L. casei vaccine. However, during TGEV infection, the systemic and local immune responses switched from Th1 to Th2-based immune responses. The systemic humoral immune response was stronger than the cellular immune response after TGEV infection. We found that the recombinant Lactobacillus stimulated IL-17 expression in both the systemic and mucosal immune responses against TGEV infection. Furthermore, the Lactobacillus vaccine stimulated an anti-TGEV infection Th17 pathway. The histopathological examination showed tremendous potential for recombinant Lactobacillus to enable rapid and effective treatment for TGEV with an intestinal tropism in piglets. The TGEV immune protection was primarily dependent on mucosal immunity.

Hollow structured l -lysine modified polydopamine coating shells (h-PDA@L-lys) were prepared using polystyrene (PS) as sacrificial support, the dopamine was used to coat PS by self-polymerization, L-lys as adsorpt ligand. The PS can be etched to form hollow structure, where more binding sites locate on the inner and outer surfaces can be utilized maximum. The h-PDA@L-lys were used as adsorbent for the specific bilirubin (BR) enrichment from animal livers. The adsorbent was characterized in details and its selectivity and binding capacity were evaluated. The experimental conditions (sample pH, adsorbent amounts, eluent types, eluent pH and volume) were optimized. The results indicate that h-PDA@L-lys exhibite good selective adsorption ability and higher adsorption amount. According to the adsorption experiments, the adsorption kinetics obey pseudo-second-order adsorption kinetics and the equilibrium data are best described by Langmuir isotherm model. The saturated adsorption capacity is 12.0 mg g−1, which is not only higher than the adsorption capacities of non-hollow adsorbents, but also superior to those of many reported adsorbents for enrich of BR. Moreover, this method was successfully applied in the selective recognition of BR in animal livers. Thus, this work provide potential possibility and practical platform for detection of BR in complex matrices.

D-Glucose was used as a dummy template in a strategy to fabricate boronate-based hollow molecularly imprinted polymers (h-MIPs) for the recognition of glycosides. 3-Aminophenylboronic acid (APBA) was selected as the functional monomer to impart glycoside binding capability. A polystyrene core was synthesized via an emulsifier-free emulsion polymerization. It was then be corroded to form a hollow structure where the binding sites on the inner surface can be fully utilized. Adsorption studies indicate that the resulting h-MIPs can specifically recognize glycosides. The h-MIPs were applied as a sorbent for solid phase extraction of the glycosides (daidzin, glycitin, rutin, and genistin) in soy products. Following desorption with 1% TFA in acetonitrile-water (3:7, v/v), the glycosides were quantified by HPLC with UV detection. The detection limits for the glycosides range from 3.5 to 10.8 ng·mL−1.

In this work, the boronate-affinity hollow stannic oxide based fragment template molecularly imprinted polymers (Bh@SnO2-FMIPs) were fabricated successfully. Polystyrene was used as sacrificial support, SnO2 was selected as inorganic matrix, surface imprinting using catechol as fragment template and 4-vinylphenylboronic acid as boronate-affinity functional monomer. A thin layer of poly 2-anilinoethanol (2-AE) was formed to coat the boronate-affinity hollow SnO2 surface through self-polymerization, it has strong hydrophilicity and limited residual boric acid content, avoiding non-specific binding. The hollow structure could bind to target molecules effectively and facilitate the removal of template molecules. The Bh@SnO2-FMIPs were used to extract three cis-diol polyphenols containing catechin, chlorogenic acid, and caffeic acid in tea and juice samples. Combination with seven characterizations of the material confirmed the successful preparation. Effecting the imprinting conditions and extraction efficiency parameters were optimized separately. Selective and competitive adsorption experiments indicated that the materials could specific recognition polyphenols. Using solid phase extraction and high performance liquid chromatography method, the detection limits were 0.005–0.046 μg mL−1 and the recoveries were between 82.3–104.3%. The improved adsorption performance may be assigned to the synergistic effects among boronate-affinity, hollow SnO2, and 2-AE self-polymerization. It may enhance binding cavities, hydrophilicity, biocompatibility of adsorbent material, and prevent the aggregation of Sn during the preparation processes.

γ-Al2O3 nanoparticle-bonded graphene oxide (γ-Al2O3-GO) was prepared for use as a solid phase extraction absorbent and for preconcentration of four nucleosides in human urine samples for investigation by high-performance liquid chromatography (HPLC). Transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FT-IR) were employed to characterize the absorbent. Several parameters (eluent species, absorbent amount, sample volume, and sample pH) were optimized, and the absorption efficiency was determined based on equilibrium absorbent amounts. Under optimal conditions, the γ-Al2O3-GO absorbent displayed enhanced absorbent ability for nucleosides. The calibration curve showed good linearities in the range of 0.10-10 mg/L for cytidine, inosine, and guanosine, and 0.05-10 mg/L for uridine; the correlation coefficient was observed to be in the range of 0.9967-0.9973. The limits of detection for the four nucleosides were in the range of 0.010-0.021 mg/L. Intra-day and inter-day relative standard deviations were 0.1%-0.8% and 1.0%-3.1%, respectively. The recoveries of the four nucleosides in urine samples ranged from 71.3% to 107.4%, and the relative standard deviations (n=3) were less than 4.8%. The results demonstrated that the proposed method is faster, more sensitive, and more efficient. Therefore, solid phase extraction (SPE)-based γ-Al2O3-GO can be considered more suitable for the determination and enrichment of nucleosides in urine samples.

Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We previously developed a fluorescence-activated cell sorting (FACS)-based method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. However, this method requires pooling samples from many rats. We now describe a modified FACS-based method to characterize molecular alterations in Fos-expressing dorsal striatal neurons from a single rat using a multiplex pre-amplification strategy. Fos and NeuN (a neuronal marker) immunohistochemistry indicate that 5-6% of dorsal striatum neurons were activated 90 min after acute methamphetamine injections (5 mg/kg, i.p.) while less than 0.5% of neurons were activated by saline injections. We used FACS to separate NeuN-labeled neurons into Fos-positive and Fos-negative neurons and assessed mRNA expression using RT-qPCR from as little as five Fos-positive neurons. Methamphetamine induced 3-20-fold increases of immediate early genes arc, homer-2, c-fos, fosB, and its isoforms (ΔfosB and a novel isoform ΔfosB-2) in Fos-positive but not Fos-negative neurons. Immediate early gene mRNA induction was 10-fold lower or absent when assessed in unsorted samples from single dorsal striatum homogenates. Our modified method makes it feasible to study unique molecular alterations in neurons activated by drugs or drug-associated cues in complex addiction models. Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We here report an improved method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. We used FACS along with targeted PCR pre-amplification to assess acute methamphetamine-induced gene expression from as few as 5 Fos-expressing neurons from a single rat dorsal striatum. Methamphetamine induced 3-20-fold increases of immediate early genes (IEGs) in Fos-positive but not Fos-negative neurons. Targeted PCR pre-amplification makes it feasible to study unique molecular alterations in neurons activated by drugs or drug-associated cues in complex addiction models. Methamphetamine and other drugs activate a small proportion of all neurons in the brain. We here report an improved method to characterize molecular alterations induced selectively in activated neurons that express the neural activity marker Fos. We used FACS along with targeted PCR pre-amplification to assess acute methamphetamine- induced gene expression from as few as 5 Fos-expressing neurons from a single rat dorsal striatum. Methamphetamine induced 3-20-fold increases of immediate early genes (IEGs) in Fos-positive but not Fos-negative neurons. Targeted PCR pre-amplification makes it feasible to study unique molecular alterations in neurons activated by drugs or drug-associated cues in complex addiction models.