Core-sheath nanofibers as drug delivery system for thermoresponsive controlled release

In this work, a smart drug delivery system of core–sheath nanofiber is reported. The core-sheath nanofibers were prepared with thermoresponsive poly-(N-isopropylacrylamide) (PNIPAAm) (as core) and hydrophobic ethylcellulose (EC) (as sheath) by coaxial electrospinning. Analogous medicated fibers were prepared by loading with a model drug ketoprofen (KET). The fibers were cylindrical without phase separation and have visible core-sheath structure as shown by scanning and transmission electron microscopy. X-ray diffraction patterns demonstrated the drug with the amorphous physical form was present in the fiber matrix. Fourier transform infrared spectroscopy analysis was conducted, finding that there were significant intermolecular interactions between KET and the polymers. Water contact angle measurements proved that the core-sheath fibers from hydrophobic transformed into hydrophobic when the temperature reached the lower critical solution temperature. In vitro drug-release study of nanofibers with KET displayed that the coaxial nanofibers were able to synergistically combine the characteristics of the two polymers producing a temperature-sensitive drug delivery system with sustained release properties. In addition, they were established to be non-toxic and suitable for cell growth. These findings show that the core–sheath nanofiber is a potential candidate for controlling drug delivery system

Research on the "Agricultural and Tourism Dual Chain" Model of Leisure Agriculture from the Perspective of Circular Economy

Leisure agriculture is a growing trend in the agricultural tourism industry. Human activities negatively affect ecosystem and agricultural output, and these effects worsen as the economy grows. Therefore, most conventional agricultural firms rely on external sources for technological advancement to outsource development or only engage in a limited number of innovation chains. A novel model named the Agricultural and Tourism Dual Chain Model of Leisure Agriculture (ATDCM-LA), is proposed after a thorough examination of the circular economy and presented in this study. Improvements in modern Leisure Agriculture tourism base planning may be attained via ecological agriculture by analyzing the impacts on regional planning. Fuzzy Analytical Hierarchy Technique (FAHT) was used to generate administrators\u27 relative weights for farm leisure growth, and indicators were dynamically ranked by importance. Data Envelope Analysis (DEA) based on Circular Economy (CE) has applied to the existing state of leisure and tourism agriculture, which scales back the expansion of leisure agriculture and prioritizes growth initiatives that will have the most significant impact. This research integrates the goals of promoting rural culture with those of tourism administration and economic theory in agriculture, and it concludes with recommendations for regional growth of leisure agricultural tourist facilities. Leisure agricultural tourist base planning and administration results reveal the necessity to merge rural tradition with the sector\u27s agrarian investment. Finally, the findings indicate that a rural-culture-based Leisure Agriculture tourist basis has some potential for success in regional development

Elastic Strain Relaxation of Phase Boundary of α′ Nanoscale Phase Mediated via the Point Defects Loop under Normal Strain

Irradiation-induced point defects and applied stress affect the concentration distribution and morphology evolution of the nanophase in Fe–Cr based alloys; the aggregation of point defects and the nanoscale precipitates can intensify the hardness and embrittlement of the alloy. The influence of normal strain on the coevolution of point defects and the Cr-enriched α′ nanophase are studied in Fe-35 at.% Cr alloy by utilizing the multi-phase-field simulation. The clustering of point defects and the splitting of nanoscale particles are clearly presented under normal strain. The defects loop formed at the α/α′ phase interface relaxes the coherent strain between the α/α′ phases, reducing the elongation of the Cr-enriched α′ phase under the normal strains. Furthermore, the point defects enhance the concentration clustering of the α′ phase, and this is more obvious under the compressive strain at high temperature. The larger normal strain can induce the splitting of an α′ nanoparticle with the nonequilibrium concentration in the early precipitation stage. The clustering and migration of point defects provide the diffusion channels of Cr atoms to accelerate the phase separation. The interaction of point defect with the solution atom clusters under normal strain provides an atomic scale view on the microstructure evolution under external stress

Formation of the eclogites of the Atbashi complex, Kyrgyzstan, in a subduction zone mélange diapir

Abstract Much debate exists concerning mechanisms of crustal material transfer from subducting slab to overlying mantle. Formation of mélange rocks by physical mixing of slab components within subduction plate interface is predicted to transfer their compositional signal to source of arc magmas by ascending as diapirs from slab-top. Despite being supported conceptually and through modeling, existence of these diapirs in global subduction architecture remains inconclusive. Here we use petrological observations, thermometry and thermodynamic modeling, combined with geochemical constraints and compilation of massive existing data, to investigate eclogites from a deeply buried mélange “package” in Kyrgyz Tianshan, southern Altaids. We find that various slab components physically mixed to form eclogitic mélange rocks at threshold depth of the subarc (i.e., ≥85 km). Index mineralogical and Pressure-Temperature records indicate a thermal history with substantial heating after peak burial to condition crossing wet solidus. Such translation, toward hot corner of mantle wedge, is short-lived around several hundred thousand to few million years, serving as first tangible evidence substantiating mélange diapirs propagate and dynamically mix with overlying mantle. Contemporaneous Late Carboniferous flare-up of regional arc magmatism with mélange diapir melting signal also advocates that non-negligible process of mantle wedge hybridization by buoyant mélange materials, to transfer volatile, generate arc lavas and regulate terrestrial geochemical cycles, stands

Rafting and redissolution of γʹ phase in Ni–Al alloy under external stress

The volume fraction and rafting degree of the γʹ-Ni3Al phase under stress and high temperature are the key characteristics of mechanical properties in Ni-based superalloys, the rafting and redissolution of γʹ phase caused by the creep at high temperature damage the morphology and properties of Ni-based superalloys. The phase-field simulation is performed to study the rafting accompany with the redissolution of γʹ phase under high temperature and loading stress in Ni–Al alloy, the driving force and kinetics evolution of the γʹ rafting were revealed. During the rafting under continuous heating, the elastic energy in the vertical γ channel is different to that of the horizontal γ channel, this difference in elastic energy drives the elements diffusion directionally to form the γʹ rafts morphology. With the increased tensile stress, the decrease of specific surface of the γʹ phase slows down the redissolution, a higher volume fraction is reserved for the rafted γʹ phase. With temperature increases, the interface of γ/γʹ phase becomes more diffusional and wider under stress. The results give an insight on the rafting mechanism of γʹ phase and the kinetics evolution in Ni-based superalloys under excess temperature

Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results.

Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.0+ antisense drug that targets apoC3 mRNA in patients with hypertriglyceridemia, including familial chylomicronemia syndrome (n = 3), volanesorsen monotherapy (n = 51), and as add-on to fibrate (n = 26), treated for 85 days and followed for 176 days. Compared with placebo, volanesorsen was associated with an 82.3 ± 11.7%, 81.3 ± 15.7%, and 80.8 ± 13.6% reduction in apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoA-I, respectively (300 mg dose;P< 0.001 for all), at day 92. Strong correlations in all assay measures were noted with total plasma apoC-III, chylomicron-apoC-III, and VLDL-apoC-III. In conclusion, novel high-throughput ELISAs were developed to detect lipoprotein-associated apoC-III, including for the first time on Lp(a). Volanesorsen uniformly lowers apoC-III on apoB-100, Lp(a), and apoA-I lipoproteins, and may be a potent agent to reduce triglycerides and cardiovascular risk mediated by apoC-III

Nanosized TiO2-induced reproductive system dysfunction and its mechanism in female mice.

Recent studies have demonstrated nanosized titanium dioxide (nano-TiO2)-induced fertility reduction and ovary injury in animals. To better understand how nano-TiO2 act in mice, female mice were exposed to 2.5, 5, and 10 mg/kg nano-TiO2 by intragastric administration for 90 consecutive days; the ovary injuries, fertility, hormone levels, and inflammation-related or follicular atresia-related cytokine expression were investigated. The results showed that nano-TiO2 was deposited in the ovary, resulting in significant reduction of body weight, relative weight of ovary and fertility, alterations of hematological and serum parameters and sex hormone levels, atretic follicle increases, inflammation, and necrosis. Furthermore, nano-TiO2 exposure resulted in marked increases of insulin-like growth factor-binding protein 2, epidermal growth factor, tumor necrosis factor-α, tissue plasminogen activator, interleukin-1β, interleukin -6, Fas, and FasL expression, and significant decreases of insulin-like growth factor-1, luteinizing hormone receptor, inhibin α, and growth differentiation factor 9 expression in mouse ovary. These findings implied that fertility reduction and ovary injury of mice following exposure to nano-TiO2 may be associated with alteration of inflammation-related or follicular atresia-related cytokine expressions, and humans should take great caution when handling nano-TiO2

Identification of ARGLU1 as a potential therapeutic target for gastric cancer based on genome-wide functional screening data

Background: Due to the molecular mechanism complexity and heterogeneity of gastric cancer (GC), mechanistically interpretable biomarkers were required for predicting prognosis and discovering therapeutic targets for GC patients. Methods: Based on a total of 824 GC-specific fitness genes from the Project Score database, LASSOCox regression was performed in TCGA-STAD cohort to construct a GC Prognostic (GCP) model which was then evaluated on 7 independent GC datasets. Targets prioritization was performed in GC organoids. ARGLU1 was selected to further explore the biological function and molecular mechanism. We evaluated the potential of ARGLU1 serving as a promising therapeutic target for GC using patients derived xenograft (PDX) model. Findings: The 9-gene GCP model showed a statistically significant prognostic performance for GC patients in 7 validation cohorts. Perturbation of SSX4, DDX24, ARGLU1 and TTF2 inhibited GC organoids tumor growth. The results of tissue microarray indicated lower expression of ARGLU1 was correlated with advanced TNM stage and worse overall survival. Over-expression ARGLU1 significantly inhibited GC cells viability in vitro and in vivo. ARGLU1 could enhance the transcriptional level of mismatch repair genes including MLH3, MSH2, MSH3 and MSH6 by potentiating the recruitment of SP1 and YY1 on their promoters. Moreover, inducing ARGLU1 by LNP-formulated saRNA significantly inhibited tumor growth in PDX model. Interpretation: Based on genome-wide functional screening data, we constructed a 9-gene GCP model with satisfactory predictive accuracy and mechanistic interpretability. Out of nine prognostic genes, ARGLU1 was verified to be a potential therapeutic target for GC. Funding: National Natural Science Foundation of China