Multiscale Anisotropic Scaffold Integrating 3D Printing and Electrospinning Techniques as a Heart-on-a-Chip Platform for Evaluating Drug-Induced Cardiotoxicity.

Cardiac safety assessments are significant in drug discovery, as drug-induced cardiotoxicity (DIC) is the primary cause of drug attrition. Despite heart-on-a-chip (HoC) technology becoming an increasingly popular tool for evaluating DIC, its development remains a challenge owing to the anisotropic cardiac structure of the native myocardium. Herein, an anisotropic multiscale cardiac scaffold is presented via a hybrid biofabrication method by combining 3D printing with electrospinning technology, where the 3D-printed micrometer-scale scaffold frames enable mimicking the interwoven myocardium anatomical structure and the branched-aligned electrospun nanofibers network is able to directionally guide cellular arrangements. The in vitro 3D bioengineered cardiac tissues are then fabricated by encapsulating three-layer multiscale scaffolds within a photocurable methacrylated gelatin hydrogel shell. It is demonstrated that such an anisotropic multiscale structure could contribute to enhancing cardiomyocyte maturation and synchronous beating behavior. More attractively, with the integration of 3D bioengineered cardiac tissues and a self-designed microfluidic perfusion system, a 3D anisotropic HoC platform is established for evaluating DIC and cardioprotective efficacy. Collectively, these results indicate that the HoC model developed by integrating the 3D bioengineered cardiac tissues could effectively recapitulate the clinical manifestations, thereby highlighting their efficacy as a valuable preclinical platform for testing drug efficacy and cardiotoxicity.

Site-selective occupation, optical spectrum regulation and photoluminescence property investigation of Eu2+-activated blue light-excited yellow-orange emitting phosphors.

We report yellow-orange emitting phosphors Sr9-xCaxMg1.5(PO4)7:0.05Eu2+ (SCxMPO:Eu2+, x = 0.5-2.5) and Sr9-yBayMg1.5(PO4)7:0.05Eu2+ (SByMPO:Eu2+, y = 0.5-3.0) with broad emission bands (450-800 nm). All these phosphors can be excited efficiently by blue light and n-UV light. Their crystal structure, photoluminescence spectra, fluorescence decay curves and thermal stability were investigated in detail. As doping concentrations of Ca2+ or Ba2+ increase, Eu2+ emitting centers will selectively occupy different Sr2+ sites, thus leading to the regulation of optical spectra of SCxMPO:Eu2+ and SByMPO:Eu2+. Accordingly, the emission colors of SCxMPO:Eu2+ and SByMPO:Eu2+ samples can gradually turn from yellow to orange when excited using 460 nm blue light. And the emission colors of a given sample can also be varied under different excitations because there are three kinds of emitting centers in SCxMPO:Eu2+ and SByMPO:Eu2+. In addition, introducing Ca2+ and Ba2+ can enhance the thermal stability of the phosphors obviously, and overall, the thermal stability of SByMPO:Eu2+ is better than that of SCxMPO:Eu2+. We chose SB2.5MPO:zEu2+ as an example to further investigate its photoluminescence properties, and found that the optimal doping concentration of Eu2+ is 0.08, and dipole-quadrupole interaction is dominated in the concentration quenching mechanism. Furthermore, high-quality warm white light can be obtained by two ways: (a) 470 nm blue LED chip + SC1.5MPO:Eu2+ [CCT = 3639 K, Ra = 82.21] and (b) 470 nm blue LED chip + SB2.5MPO:Eu2+ and YAG:Ce3+ [CCT = 4284 K, Ra = 86.69]. The excellent performances indicate that SCxMPO:Eu2+ and SByMPO:Eu2+ are attractive candidates for warm WLEDs.

Microsurgical Clipping of Complex Basilar Bifurcation Aneurysms through Different Approachs: Surgical Techniques and Results.

AIM: To explore the surgical approach, technique and clinical effect of treating basilar bifurcation aneurysms. MATERIAL AND METHODS: The clinical data of basilar bifurcation aneurysms treated by neuro-microsurgery are retrospectively analyzed in from September 2013 to September 2018. The aneurysms were treated via subtemporal approach and frontotemporal approach. The results were evaluated according to Glasgow Outcome Scores (GOS) and postoperative imaging results. RESULTS: There were 28 aneurysms located at the bifurcation of basilar artery in 27 patients and 1 case had multi-aneurysms. 8 cases underwent via subtemporal approach and 19 via frontotemporal approach. The operation time was 2.8-4.6 hours, the average time were 3.3 hours. The hospitalization time was 3-6 weeks, the average time was 3.8 weeks. Overall, good outcome (GOS score of 4-5) at 6 months was achieved in 77.8% of the living patients. The posterior thalamic perforator artery infarction occurred in 1 cases, and the ventriculoperitoneal shunting was performed in 2 cases due to communicating hydrocephalus. During the following-up period, 25 patients underwent head CTA examination. The CTA showed that all aneurysms were completely clipped, no aneurysm recurrence was found, the blood flow of the parent artery was unobstructed, and 2 patients were lost to follow-up. 13 patients had oculomotor nerve palsy, and all but 3 of them recovered during following-up. CONCLUSION: The satisfactory results were achieved by microsurgical clipping for basilar bifurcation aneurysms. According to the location and projection of aneurysms, personalized treatment is chosen. Trans-frontotemporal approach is the most suitable approach for the treatment of upper basilar bifurcation aneurysms, especially under subarachnoid hemorrhage causing brain swelling conditions.

Bioprinted anisotropic scaffolds with fast stress relaxation bioink for engineering 3D skeletal muscle and repairing volumetric muscle loss.

Viscoelastic hydrogels can enhance 3D cell migration and proliferation due to the faster stress relaxation promoting the arrangement of the cellular microenvironment. However, most synthetic photocurable hydrogels used as bioink materials for 3D bioprinting are typically elastic. Developing a photocurable hydrogel bioink with fast stress relaxation would be beneficial for 3D bioprinting engineered 3D skeletal muscles in vitro and repairing volumetric muscle loss (VML) in vivo; however, this remains an ongoing challenge. This study aims to develop an interpenetrating network (IPN) hydrogel with tunable stress relaxation using a combination of gelatin methacryloyl (GelMA) and fibrinogen. These IPN hydrogels with faster stress relaxation showed higher 3D cellular proliferation and better differentiation. A 3D anisotropic biomimetic scaffold was further developed via a printing gel-in-gel strategy, where the extrusion printing of cell-laden viscoelastic FG hydrogel within Carbopol supported gel. The 3D engineered skeletal muscle tissue was further developed via 3D aligned myotube formation and contraction. Furthermore, the cell-free 3D printed scaffold was implanted into a rat VML model, and both the short and long-term repair results demonstrated its ability to enhance functional skeletal muscle tissue regeneration. These data suggest that such viscoelastic hydrogel provided a suitable 3D microenvironment for enhancing 3D myogenic differentiation, and the 3D bioprinted anisotropic structure provided a 3D macroenvironment for myotube organization, which indicated the potential in skeletal muscle engineering and VML regeneration. STATEMENT OF SIGNIFICANCE: The development of a viscoelastic 3D aligned biomimetic skeletal muscle scaffold has been focused on skeletal muscle regeneration. However, a credible technique combining viscoelastic hydrogel and printing gel-in-gel strategy for fabricating skeletal muscle tissue was rarely reported. Therefore, in this study, we present an interpenetrating network (IPN) hydrogel with fast stress relaxation for 3D bioprinting engineered skeletal muscle via a printing gel-in-gel strategy. Such IPN hydrogels with tunable fast stress relaxation resulted in high 3D cellular proliferation and adequate differentiation in vitro. Besides, the 3D hydrogel-based scaffolds also enhance functional skeletal muscle regeneration in situ. We believe that this study provides several notable advances in tissue engineering that can be potentially used for skeletal muscle injury treatment in clinical.

Self-Bending Behavior and Varying Bending Stiffness of Black Phosphorus/Molybdenum Disulfide (BP/MoS2) Heterostructure.

Vertically-stacked black phosphorus/molybdenum disulfide (BP/MoS2) heterostructures have broad prospects in flexible electronics. Bending is a common and highly concerned deformation for these flexible devices. However, the discrepancy in structures and properties among the components of 2D heterostructures often induces complex bending deformations. Here, the bending behaviors of BP, MoS2 and BP/MoS2 are investigated based on a molecular dynamics simulation. Compared with the constant bending stiffness of individual BP and MoS2, that of BP/MoS2 varies with the bending angle. Notably, a self-bending configuration induced by the lattice mismatch and size difference is found in BP/MoS2. The corresponding self-bending amplitude depends on the degree of size difference of each component and the "soft/hard" competition between them. Moreover, the size difference leads to a weakened bending stiffness, which is ascribed to the reduction in interlayer interaction. A prediction formula is proposed to evaluate the bending stiffness of BP/MoS2 with the size difference. This finding reveals novel ways for regulating the bending properties of 2D heterostructures, including the bending angle, characteristic size and stacking order. It offers an effective strategy for designing flexible devices with tunable bending performance.

3D-printed high-density polyethylene scaffolds with bioactive and antibacterial layer-by-layer modification for auricle reconstruction.

High-density polyethylene (HDPE) is a promising material for the development of scaffold implants for auricle reconstruction. However, preparing a personalized HDPE auricle implant with favorable bioactive and antibacterial functions to promote skin tissue ingrowth is challenging. Herein, we present 3D-printed HDPE auricle scaffolds with satisfactory pore size and connectivity. The layer-by-layer (LBL) approach was applied to achieve the improved bioactive and antibacterial properties of these 3D printed scaffolds. The HDPE auricle scaffolds were fabricated using an extrusion 3D printing approach, and the individualized macrostructure and porous microstructure were both adjusted by the 3D printing parameters. The polydopamine (pDA) coating method was used to construct a multilayer ε-polylysine (EPL) and fibrin (FIB) modification on the surface of the 3D HDPE scaffold via the LBL self-assembly approach, which provides the bioactive and antibacterial properties. The results of the in vivo experiments using an animal model showed that LBL-coated HDPE auricular scaffolds were able to significantly enhance skin tissue ingrowth and ameliorate the inflammatory response caused by local stress. The results of this study suggest that the combination of the 3D printing technique and surface modification provides a promising strategy for developing personalized implants with biofunctional coatings, which show great potential as a scaffold implant for auricle reconstruction applications.

Characterization of the metabolism of aloin A/B and aloesin in rats using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Aloin A/B and aloesin are the major bioactive constituents in Aloe vera, with diverse pharmacological activities, including anti-bacterial, anti-tumour, anti-inflammatory and intestinal regulation. However, the in vivo metabolism of aloin A/B and aloesin is still unclear. In this study, the metabolic processes of aloin A/B and aloesin in rats were investigated using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and MetaboLynx™ software with the mass defect filter technique. Based on the proposed method, the prototype components of three compounds were all detected in rat plasma, urine and feces. Meanwhile, 25 aloin A/B metabolites (six phase I, three phase II, 16 phase I combined with phase II) and three aloesin metabolites (two phase I and one phase II) were detected in rats after oral administration of aloin A, aloin B and aloesin, and the main biotransformation reactions were hydroxylation, oxidation, methylation, acetylation and glucuronidation. In addition, aloin A and aloin B can be transformed into each other in vivo and the metabolic profiles of aloin A and aloin B are identical. These results provide essential data for further pharmaceutical research and clinical application of aloin A/B and aloesin.

[Factors affecting phenotypes in the patients with MMACHC gene c.609G>A homozygous variant cblC type methylmalonic acidemia combined with homocysteinuria].

OBJECTIVE: To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c.609G>A homologous variant. METHODS: A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164 patients of cblC type with MMACHC c.609G>A homologous variant was conducted. The patients were diagnosed by biochemical and genetic analysis from January 1998 to December 2020. RESULTS: Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated from the age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance (P<0.05). CONCLUSION: Most of the patients with MMACHC c.609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Self-reduction-induced BaMgP2O7:Eu2+/3+: a multi-stimuli-responsive phosphor for X-ray detection, anti-counterfeiting and optical thermometry.

Mixed-valence Eu2+/3+-activated phosphors have attracted wide attention due to their excellent luminescence tunability. Steady control of the Eu2+/Eu3+ ratio is the key to achieving reproducible Eu2+/3+ co-doped materials. In this work, BaMgP2O7:xEu2+/3+ (BMPO:Eu, x = 0.001-0.20) was successfully prepared by the traditional solid-state method in air. Eu3+ undergoes selective self-reduction at Ba2+ sites surrounded by a [P2O7] framework, leading to quantitive Eu2+/Eu3+. The phosphors exhibit a blue-violet emission band at ∼410 nm due to 5d-4f transitions of Eu2+ and a group of red emission peaks from 5D0-7FJ of Eu3+. Controllable multicolor emissions are realized by regulating the Eu content and excitations. A linear response of overall luminescence intensity to irradiation dose makes the phosphor appropriate for X-ray detection. The combination of UV-blue excitation-dependent color evolution and X-ray luminescence qualifies the phosphors with great potential for multi-level anti-counterfeiting. In addition, Eu3+ presents abnormal anti-thermal quenching, so that the fluorescence intensity ratio (FIR) of Eu2+/Eu3+ changes in the temperature range of 300-520 K, suggesting a promising application in optical thermometry. Therefore, selectively partial self-reduction in a multi-cationic host is an effective strategy to design mixed-valence co-doped materials, providing a multiplicity of applications.

Insights into the interaction of microplastic with silver nanoparticles in natural surface water.

The combined pollution induced by microplastics (MPs) and other pollutants, such as nanomaterials, has received increasing attention. The interaction between MPs and silver nanoparticles (AgNPs) may affect both their behaviors in natural environments, however, knowledge on these effects remains limited. In this study, AgNPs and three common MPs, polypropylene (PP), polyethylene (PE), and polystyrene (PS), were co-exposed to natural freshwater and brackish water to investigate the interaction between MPs and AgNPs in natural surface water. The results showed that the environmental behaviour of AgNPs in natural freshwater and brackish water is first of all affected by water chemistry and only in second instance affected by MPs. In natural freshwater, AgNPs remained stable largely dominated by dissolved organic matter (DOM), parts of which were subsequently captured by three MPs in the form of single particles without significant difference. In contrast, both ionic strength and DOM contributed to the aggregation of AgNPs in natural brackish water. PE and PP captured a small amount of AgNPs in the form of aggregates in natural brackish water, while the majority of AgNP aggregates were trapped by PS in natural brackish water. Therefore, both water chemistry and MPs types were found to play crucial roles in the interaction between MPs and AgNPs. These observations also revealed that MPs could serve as carriers for AgNP transport and advance the current understanding of combined pollution between MPs and engineered nanomaterials in natural aquatic environments.

New caffeoyl derivatives from Elephantopus scaber.

Three new caffeoyl derivatives (1-3), together with two known ones (4-5), were isolated from the whole plant of Elephantopus scaber Linn. The structures of the new compounds were elucidated using detailed spectroscopic analysis. Compound 4 was obtained and its NMR data were given for the first time. All isolates were evaluated for their anti-inflammatory activity against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production and pro-inflammatory cytokines release in RAW 264.7 cells. Compounds 2-5 showed mild inhibitory activities with IC50 values ranging from 64.78 to 87.21 µM, and 3-4 could inhibit LPS-induced tumor necrosis factor-α (TNF-α) production.

ß-Amyrin ameliorates diabetic nephropathy in mice and regulates the miR-181b-5p/HMGB2 axis in high glucose-stimulated HK-2 cells.

Diabetic nephropathy (DN) is a diabetic complication that can cause renal failure. ß-amyrin has been identified to possess anti-diabetic property. This study was designed to evaluate the potential role of ß-amyrin in DN and its underlying mechanism. Streptozotocin-induced diabetic mice were used as the in vivo model, and high glucose (HG)-stimulated human proximal tubular HK-2 cells were utilized as the in vitro model. Renal histological changes in mice were assessed by hematoxylin-eosin and periodic acid-Schiff staining. HK-2 cell viability and apoptosis were detected by Cell Counting Kit-8 assay and flow cytometry analysis, respectively. ß-amyrin was found to ameliorate kidney injury in DN mice and suppressed inflammatory response as well as apoptosis of HG-stimulated HK-2 cells. miR-181-5p expression in murine renal tissues and HK-2 cells was detected by in situ hybridization (ISH) and fluorescence in situ hybridization (FISH). MiR-181b-5p, a previously identified target for diabetic kidney disease, was downregulated in renal tissues and HG stimulated HK-2 cells, and ß-amyrin induced the upregulation of miR-181b-5p. Binding relationship between miR-181b-5p and high mobility group box 2 (HMGB2) was confirmed by luciferase reporter assay. MiR-181b-5p bound to 3' untranslated region of HMGB2 to suppress its expression. As shown by immunohistochemical staining and immunofluorescence staining, HMGB2 was upregulated in the in vivo and in vitro models of DN, and ß-amyrin induced the downregulation of HMGB2. Moreover, HMGB2 overexpression neutralized the suppressive effects of miR-181b-5p elevation on the inflammatory response and apoptosis of HG-treated HK-2 cells. Overall, ß-amyrin ameliorates DN in mice and suppresses inflammatory response and apoptosis of HG-stimulated HK-2 cells via the miR-181b-5p/HMGB2 axis.

Influence of Mo Segregation at Grain Boundaries on the High Temperature Creep Behavior of Ni-Mo Alloys: An Atomistic Study.

Based on molecular dynamics simulations, the creep behaviors of nanocrystalline Ni before and after the segregation of Mo atoms at grain boundaries are comparatively investigated with the influences of external stress, grain size, temperature, and the concentration of Mo atoms taken into consideration. The results show that the creep strain rate of nanocrystalline Ni decreases significantly after the segregation of Mo atoms at grain boundaries due to the increase of the activation energy. The creep mechanisms corresponding to low, medium, and high stress states are respectively diffusion, grain boundary slip and dislocation activities based on the analysis of stress exponent and grain size exponent for both pure Ni and segregated Ni-Mo samples. Importantly, the influence of external stress and grain size on the creep strain rate of segregated Ni-Mo samples agrees well with the classical Bird-Dorn-Mukherjee model. The results also show that segregation has little effect on the creep process dominated by lattice diffusion. However, it can effectively reduce the strain rate of the creep deformation dominated by grain boundary behaviors and dislocation activities, where the creep rate decreases when increasing the concentration of Mo atoms at grain boundaries within a certain range.

Salvia miltiorrhiza and Pueraria lobata, two eminent herbs in Xin-Ke-Shu, ameliorate myocardial ischemia partially by modulating the accumulation of free fatty acids in rats.

BACKGROUND: Xin-Ke-Shu (XKS), a commonly used traditional Chinese medicine, has been clinically proven to be effective for treatment of acute myocardial ischemia (AMI). Numerous studies underscore the important role of fatty acid metabolism in the pathogenesis of AMI. PURPOSE: This study examined the relationship between free fatty acids (FFAs) and AMI and the contributions of individual herbs found in XKS to provide a basis for the study of the compatible principle of XKS. METHODS: UFLC-MS/MS-based targeted metabolomics was performed to analyze the levels of 15 FFAs in the plasma and myocardium of isoproterenol (ISO)-induced AMI rats treated with XKS and the subtracted prescriptions of XKS. Electrocardiogram data, H&E staining, biochemical analysis and western blotting were assayed to illustrate the cardioprotection of XKS and its subtracted prescription in AMI. Correlation analysis was used to reveal the relationship between the levels of FFAs and overexpressed proteins/biochemical enzymes. RESULTS: We found aberrant fatty acid metabolism in AMI rats. In both plasma and myocardium, the concentrations of most of quantified FFAs were significantly altered, whereas the concentrations of stearic acid and behenic acid were similar between the control and AMI groups. Correlation analysis revealed that palmitic acid, oleic acid, linoleic acid and arachidonic acid were potentially the most relevant FFAs to inflammatory and apoptotic proteins and CK-MB. Moreover, XKS effectively alleviated pathological alterations, FFA metabolism abnormity, inflammation and apoptosis found in the myocardium of AMI rats. Notably, the removal of Salvia miltiorrhiza and Pueraria lobata from XKS resulted in markedly regulation loss of cardioprotection during AMI, especially mediation loss of FFA metabolism. The other three herbs of XKS also played a role in improving AMI. CONCLUSION: Fatty acid metabolism aberrance occurred during AMI. S. miltiorrhiza and P. lobata play vital roles in the anti-inflammatory and anti-apoptotic action partially by regulating FFA levels. Our findings revealed potential novel clinical FFAs for predicting AMI and extended the insights into the compatible principle of XKS in which S. miltiorrhiza and P. lobata can potently modulate FFA metabolism.

Antidepressant-like effect and phytochemical profile of supercritical CO2 extract from Citri reticulatae pericarpium.

Citri reticulatae pericarpium is a condiment, adding much flavor in Chinese food. Also it can be used to treat depression as a Traditional Chinese Medicine (TCM). The study here aimed to evaluate the antidepressant effect between the supercritical CO2 extract (SC-E) from Citri reticulatae pericarpium and the essential oil extracted by steam distillation (SD-E). And chemical compositions of SC-E were qualitatively analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS). Compared with SD-E, SC-E showed a stronger antidepressant-like effect in FST and TST mice. And it also decreased the content of monoamine oxidase (MAO) in the cerebral cortex of stressed mice. A total of 60 compounds were identified in SC-E. Among them, 28 compounds were characterized in UPLC-Q-TOF/MS analysis and all are polymethoxyflavones (PMFs). Three main compounds, 3,5,6,7,8,3',4'-heptamethoxyflavone, nobiletin and tangeretin, together account for 66.09% of the total relative peak area. 33 terpenes were identified by GC-MS analysis, such as D-limonene (12.34%), ß-elemene (8.86%), germacrene D (5.59%) and (Z, E)-α-farnesene (5.44%). Polymethoflavones and terpenes are the main constituents of SC-E responsible for its antidepressant-like effect. The study could stimulate further investigations into the antidepressant effects and mechanism of Citri reticulatae pericarpium.

Machine learning for reparameterization of four-site water models: TIP4P-BG and TIP4P-BGT.

Parameterizing an effective water model is a challenging issue because of the difficulty in maintaining a comprehensive balance among the diverse physical properties of water with a limited number of parameters. The advancement in machine learning provides a promising path to search for a reliable set of parameters. Based on the TIP4P water model, hence, about 6000 molecular dynamics (MD) simulations for pure water at 1 atm and in the range of 273-373 K are conducted here as the training data. The back-propagation (BP) neural network is then utilized to construct an efficient mapping between the model parameters and four crucial physical properties of water, including the density, vaporization enthalpy, self-diffusion coefficient and viscosity. Without additional time-consuming MD simulations, this mapping operation could result in sufficient and accurate data for high-population genetic algorithm (GA) to optimize the model parameters as much as possible. Based on the proposed parameterizing strategy, TIP4P-BG (a conventional four-site water model) and TIP4P-BGT (an advanced model with temperature-dependent parameters) are established. Both the water models exhibit excellent performance with a reasonable balance among the four crucial physical properties. The relevant mean absolute percentage errors are 3.53% and 3.08%, respectively. Further calculations on the temperature of maximum density, isothermal compressibility, thermal expansion coefficient, radial distribution function and surface tension are also performed and the resulting values are in good agreement with the experimental values. Through this water modeling example, the potential of the proposed data-driven machine learning procedure has been demonstrated for parameterizing a MD-based material model.

Electrochemical dual signal sensing platform for the simultaneous determination of dopamine, uric acid and glucose based on copper and cerium bimetallic carbon nanocomposites.

A highly sensitive electrochemical sensor for the simultaneous dual signal determination of dopamine (DA), uric acid (UA) and glucose (Glu) has been obtained using nanocomposites based on the copper and cerium bimetallic nanoparticles and carbon nanomaterials of graphene and single-walled carbon nanotubes in the presence of Tween 20 (GR-SWCNT-Ce-Cu-Tween 20) modified glassy carbon electrode. The surface morphology of the nanocomposites was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), and the electrochemical behavior of the sensor was investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) with potassium ferricyanide as probe. In the coexistence system of DA, UA and Glu, three clear and well-isolated voltammetric peaks were obtained by CV and differential pulse voltammetry (DPV), and oxidation peak currents of DA and UA are positively correlated with their concentrations respectively, while the peak current of Glu is negatively correlated with its concentration. Linearity was obtained in the ranges of 0.1-100 µM for dopamine, 0.08-100 µM for uric acid and 1-1000 µM for glucose with DPV, and the detection limits (S/N = 3) of 0.0072 µM, 0.0063 µM, and 0.095 µM for DA, UA and Glu, respectively. The method was successfully applied to the determination of DA, UA and Glu in blood serum samples, which provided a reference for further sensor research.

Rational design of hollow mesoporous titania nanoparticles loaded with curcumin for UV-controlled release and targeted drug delivery.

Curcumin (Cur), appeared to provide huge potential in biomedical application. However, its therapeutic efficacy was greatly limited as the result of poor solubility and instability. To address these limitations, we create a new type of hollow mesoporous titania nanoparticle (HMTN) to encapsulate Cur. HMTN was decorated with a layer of hydrophilic polyethylenimine (PEI), which controlled the release rate of Cur inside the pore due to its dendritic structure. Combined with the folic acid (FA) mediated targeting effect, the potential multifunctional Cur loaded titania nanoparticle (Cur-FA-PEI-HMTN) showed excellent biocompatibility and bioavailability, as well as the UV-responsive drug release properties. The operating parameters to prepare hollow structure were studied and the Cur-FA-PEI-HMTN nanosystem had been fully characterized by Brunauer-Emmet-Teller, Fourier transform infrared spectroscopy, transmission electron microscope, thermal gravity analysis, differential thermal analysis, x-ray diffraction, dynamic light scattering and zeta potential. In addition, the hemolytic test, as well as CCK8, flow cytometry, Hoechst 33342 staining experiment, were carried out to confirm the low cytotoxity and high biocompatibility. The confocal microscopy analysis results also revealed the increasing uptake of Cur@FA-PEI-HMTN by MCF-7 cells. The synthesized nanoparticles displayed great potential as drug nanovehicles with high biocompatibility.

Anti-inflammatory constituents in the root and rhizome of Polygonum cuspidatum by UPLC-PDA-QTOF/MS and lipopolysaccharide-activated RAW264.7 macrophages.

The root and rhizome of Polygonum cuspidatum (Hu-Zhang) has been used for treatment of various inflammatory disorders in China. In our pervious study, we found that three fractions (HZE-30, HZE-60 and HZE-95) from the ethanol extract of Hu-Zhang (HZE) all could inhibit NO production, and HZE-60 shows the most potent anti-inflammatory activity. In order to understand the major contribution constituents of Hu-Zhang responsible for its anti-inflammatory effect, quantitative composition-activity relationship method was performed. Firstly, the constituents in HZE-60 were characterized using an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) approach. Second, quantitative analyzed five major constituents identified in HZE-60 and compare the difference of five major constituents in HZE and three anti-inflammatory activity fractions. Finally, evaluated the anti-inflammatory effects of major constituents in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. The results showed that a total of 31 compounds were identified from HZE-60, including 12 anthraquinones, 7 diphenylethenes, 9 phenols and 3 others. The contents of five major constituents (polydatin (6), resveratrol (7), emodin-1-O-ß-d-glucoside (15), emodin-8-O-ß-d-glucoside (21) and emodin (31)) were simultaneously determined by UPLC-PDA with good linearity (correlation coefficients > 0.9990) and satisfactory repeatability (RSD < 0.99 %), precision (RSD < 0.01 %), stability (RSD < 0.67 %) and recoveries (99.52 %-101.23 %, RSD < 0.91 %). All five major constituents could be detected in HZE and HZE-60 fraction, but only 6 was detected in HZE-30, and 31 in HZE-95. Moreover, 7, 15 and 21 exhibited significant anti-inflammatory activity via suppressing supernatant pro-inflammatory mediators, such as NO, tumor Necrosis Factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1). Therefore, we conclude that the bioactivity of HZE is the syngeneic effect of its constituents, and 7, 15 and 21 should make great contributions for the anti-inflammatory effect of Hu-Zhang. The findings define the anti-inflammatory chemical constituents of Hu-Zhang, which will benefit further investigation on its quality control and the mechanism of action.