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•Novel α-mangostin loaded crosslinked fibroin nanopaticles using EDC/PEI are developed.•Compared to non-crosslinked particles, high drug entrapment and loading are achieved.•Particle ...charge, crystallinity, solubility, dissolution are controlled favorably.•All particles are stable for 6 months and decrease the drug hematotoxicity by 10-fold.•The particles increase drug anticancer efficacy in Caco-2 and MCF-7 cells.
Silk fibroin has been utilized extensively for biomedical purposes, especially the drug delivery systems. This study introduced and characterized three novel α-mangostin loaded crosslinked fibroin nanoparticles (FNPs), using EDC or PEI as a crosslinker, for cancer treatment. All three formulas were spherical particles with a mean size of approximately 300 nm. By varying the type and/or amount of the crosslinkers, particle surface charge was controllable from −15 to +30 mV. Crosslinked FNPs exhibited higher drug entrapment efficiency (70%) and drug loading (7%) than non-crosslinked FNP. FT-IR, XRD, and DSC analytical methods confirmed that α-mangostin was entrapped in FNPs in molecular dispersion form. Compared to the free α-mangostin, the crosslinked FNPs increased the drug’s solubility up to threefold. They also showed sustained release characteristics of more than 3 days, and reduced free α-mangostin hematotoxicity by 90%. The α-mangostin loaded FNPs were physicochemically stable for up to 24 h when dispersed in intravenous diluent and for at least 6 months when preserved as lyophilized powder at 4 °C. In terms of anticancer efficacy, on both Caco-2 colorectal and MCF-7 breast adenocarcinoma cell lines, all formulas maintain α-mangostin’s apoptotic effect while exhibit greater cytotoxicity than the free drug. In conclusion, α-mangostin loaded crosslinked FNPs show high potential for cancer chemotherapy.
Formulations for inhalation in the treatment of tuberculosis.
Dinh-Duy Pham, Elias Fattal, Nicolas Tsapis.
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•Tuberculosis remains an important health problem worldwide.•Direct drug ...delivery to the lungs seems promising. Various drug delivery systems (liposomes, microparticles etc.) have been developed but are yet to be tested in the clinics.•Inhalable dry powders should be considered in combination with conventional therapy to try to decrease the dosing frequency and the duration of TB therapy.
Tuberculosis (TB) remains a major global health problem as it is the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus (HIV). Conventional treatments fail either because of poor patient compliance to the drug regimen or due to the emergence of multidrug-resistant tuberculosis. The aim of this review is to give an update on the information available on tuberculosis, its pathogenesis and current antitubercular chemotherapies. Direct lung delivery of anti-TB drugs using pulmonary delivery systems is then reviewed since it appears as an interesting strategy to improve first and second line drugs. A particular focus is place on research performed on inhalable dry powder formulations of antitubercular drugs to target alveolar macrophages where the bacteria develop. Numerous studies show that anti-TB drugs can be incorporated into liposomes, microparticles or nanoparticles which can be delivered as dry powders to the deep lungs for instantaneous, targeted and/or controlled release. Treatments of infected animals show a significant reduction of the number of viable bacteria as well as a decrease in tissue damage. These new formulations appear as interesting alternatives to deliver directly drugs to the lungs and favor efficient TB treatment.
A rapidly developing market for portable electronic devices and hybrid electrical vehicles requires an urgent supply of mature energy‐storage systems. As a result, lithium‐ion batteries and ...electrochemical capacitors have lately attracted broad attention. Nevertheless, it is well known that both devices have their own drawbacks. With the fast development of nanoscience and nanotechnology, various structures and materials have been proposed to overcome the deficiencies of both devices to improve their electrochemical performance further. In this Review, electrochemical storage mechanisms based on carbon materials for both lithium‐ion batteries and electrochemical capacitors are introduced. Non‐faradic processes (electric double‐layer capacitance) and faradic reactions (pseudocapacitance and intercalation) are generally explained. Electrochemical performance based on different types of electrolytes is briefly reviewed. Furthermore, impedance behavior based on Nyquist plots is discussed. We demonstrate the influence of cell conductivity, electrode/electrolyte interface, and ion diffusion on impedance performance. We illustrate that relaxation time, which is closely related to ion diffusion, can be extracted from Nyquist plots and compared between lithium‐ion batteries and electrochemical capacitors. Finally, recent progress in the design of anodes for lithium‐ion batteries, electrochemical capacitors, and their hybrid devices based on carbonaceous materials are reviewed. Challenges and future perspectives are further discussed.
Mad LIBs: Electrochemical storage mechanisms based on carbon materials for both lithium‐ion batteries (LIBs) and electrochemical capacitors (ECs) are introduced. Non‐faradic processes, faradic reactions, electrochemical performance, impedance behavior, cell conductivity, electrode/electrolyte interface, and ion diffusion are explained. Finally, recent progress in the design of anodes for LIBs, ECs, and their hybrids are reviewed.
In this study, top-down synthesis of sulfur-doped graphene nanosheets (SDGNs) by simple electrochemical exfoliation was explored as a means of producing metal-free electrocatalysts for oxygen ...reduction and oxygen evolution reactions (ORR and OER, respectively). In a typical procedure, graphite foils were used to obtain bulk quantities of SDGN catalysts in the presence of thiosulfate as a sulfur source. Highly stable colloidal dispersions of SDGNs were obtained by applying a voltage of 15 V at an optimized Na2S2O3:H2SO4 molar ratio of 5 : 1 (denoted SDGN(5)). Physicochemical characterizations by Raman spectroscopy, transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy confirmed the existence of sulfur and its electronic/structural properties in graphene nanosheets. In alkaline media, SDGN(5)-modified electrodes were comparable or superior to pristine graphene and a benchmark commercial platinum-based electrodes in terms of stability, methanol tolerance, n values, and onset potential for ORR and OER. The specific capacitance (149.9 F g−1) of SDGN(5) supported its excellent ORR/OER performance and enhanced surface area.
This article proposes neural network (NN) based observer schemes and a sensorless robust optimal control scheme for partially unknown permanent magnet synchronous motors with disturbances and ...saturating voltages. First, an NN-observer scheme is designed to estimate back-electromotive force (EMF), for which the mathematical model in rotary or stationary reference frames is relaxed. The NN weight tuning law is designed via Lyapunov theory to guarantee that EMF is ultimately uniformly bounded. Second, to compensate the inexact extraction of the estimated back-EMF at any speed conditions, disturbances, and NN approximation errors, another NN-observer scheme is designed to estimate the tracking errors of rotor position and speed, for which low-pass filters and/or phase-locked loops are not needed. Third, a sensorless saturated robust optimal control scheme dealing with general disturbances and saturating voltages is designed. The scheme includes the augmented feedforward controller to transform the speed and current tracking problem into an optimal control problem. Finally, the feedback control law and worst disturbance law are obtained without estimating unknown internal dynamics. The effectiveness of the proposed schemes is tested through simulations and comparative experiments on a load drive application with a DSP board TMS320F28379D.
Flash flood is one of the most common natural hazards affecting many mountainous areas. Previous studies explored flash flood susceptibility models; however, there is still a lack of case studies in ...the transport sector. This paper aimed to develop advanced hybrid machine learning (ML) algorithms for flash flood susceptibility modeling and mapping using data from the road network National Highway 6 in Hoa Binh province, Vietnam. A single ML model of reduced error pruning trees (REPT) and four hybrid ML models of Decorate-REPT, AdaBoostM1-REPT, Bagging-REPT, and MultiBoostAB-REPT were applied to develop flash flood susceptibility maps. Field surveys were conducted about the flash flood locations on the 115-km route length of the National Highway 6 in 2017, 2018, and 2019 flood events. This study used 88 flash flood locations and 14 flood conditioning factors to construct and validate the proposed models. Statistical metrics, including sensitivity, specificity, accuracy, root mean square error, and area under the receiver operating characteristic curve, were applied to evaluate the models’ performance and accuracy. The DCREPT model showed the best performance (AUC = 0.988) among the training models and had the highest prediction accuracy (AUC = 0.991) among the testing models. We found that 12,572 ha (Decorate-REPT), 9564 ha (AdaBoostM1-REPT), 11,954 ha (Bagging-REPT), 14,432 ha (MultiBoostAB-REPT), and 17,660 ha (REPT) of the 3-km buffer area of the highway are in the high- and very high-flash-flood-susceptibility areas. The proposed methodology could be potentially generalized to other transportation routes in mountainous areas to generate flash flood susceptibility prediction maps.
In response to the mixed views about the appointment-based connectedness between CEO and subordinate C-level executives, we systematically analyze the net effect of top management team (TMT) ...connectedness in the context of real corporate investment activities. We document a robust negative association between TMT connectedness and corporate investments, driven by the reduction in corporate R&D spending and acquisitions. Further tests show investment inefficiency in firms with closely connected managers, suggesting an average weak governance effect of TMT connectedness. To explain such an effect, we find that connected executives tend to avoid risky investments and shirk investment responsibilities when facing little career concerns. Interestingly, the agency cost and coordination benefit of interconnected TMT are not mutually exclusive. The adverse investment effect of TMT connectedness tempers in firms facing financial constraints and even reverses during the Global Financial Crisis when financial constraints are most likely binding.
In response to infection, naïve CD4
T cells differentiate into two subpopulations: T follicular helper (T
) cells, which support B cell antibody production, and non-T
cells, which enhance innate ...immune cell functions. Interleukin-2 (IL-2), the major cytokine produced by naïve T cells, plays an important role in the developmental divergence of these populations. However, the relationship between IL-2 production and fate determination remains unclear. Using reporter mice, we found that differential production of IL-2 by naïve CD4
T cells defined precursors fated for different immune functions. IL-2 producers, which were fated to become T
cells, delivered IL-2 to nonproducers destined to become non-T
cells. Because IL-2 production was limited to cells receiving the strongest T cell receptor (TCR) signals, a direct link between TCR-signal strength, IL-2 production, and T cell fate determination has been established.
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