Formulation and Characterization of Triamcinolone Acetonide Acetate-Loaded Microspheres Prepared by a Static Mixing Technique.

PURPOSE: Reproducibility and scale-up production of microspheres through spray drying present significant challenges. In this study, biodegradable microspheres of Triamcinolone Acetonide Acetate (TAA) were prepared using a novel static mixing method by employing poly( lactic-co-glycolic acid) (PLGA) as the sustained-release carrier. METHODS: TAA-loaded microspheres (TAA-MSs) were prepared using a static mixing technique. The PLGA concentration, polyvinyl alcohol concentration (PVA), phase ratio of oil/water, and phase ratio of water/solidification were optimized in terms of the particle size, drug loading (DL), and encapsulation efficiency (EE) of TAA-MSs. The morphology of TAA-MSs was examined using Scanning Electron Microscopy (SEM), while the physicochemical properties were evaluated through X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC), and Fourier Transform Infrared Spectroscopy (FT-IR). The in vitro release of TAA-MSs was compared to that of the pure drug (TAA) using a water-bath vibration method in the medium of pH 7.4 at 37°C. RESULTS: The formulation composition and preparation condition for the preparation of TAA-MSs were optimized as follows: the PLGA concentration was 1%, the phase ratio of oil(dichloromethane) /water (PVA solution) was 1:3, the phase ratio of water (PVA solution)/solidification was 1:2. The optimized TAA-MSs displayed spherical particles with a size range of 30-70 µm, and DL and EE values of 27.09% and 98.67%, respectively. Moreover, the drug-loaded microspheres exhibited a significant, sustained release, with 20% of the drug released over a period of 28 days. The XRD result indicated that the crystalline form of TAA in microspheres had been partly converted into the amorphous form. DSC and FT-IR results revealed that some interactions between TAA and PLGA occurred, indicating that the drug was effectively encapsulated into PLGA microspheres. CONCLUSION: TAA-loaded PLGA microspheres have been successfully prepared via the static mixing technique with enhanced EE and sustained-release manner.

Transcriptomic Analysis of Lipid Metabolism Genes in Alzheimer's Disease: Highlighting Pathological Outcomes and Compartmentalized Immune Status.

The dysregulation of lipid metabolism has been strongly associated with Alzheimer's disease (AD) and has intricate connections with various aspects of disease progression, such as amyloidogenesis, bioenergetic deficit, oxidative stress, neuroinflammation, and myelin degeneration. Here, a comprehensive bioinformatic assessment was conducted on lipid metabolism genes in the brains and peripheral blood of AD-derived transcriptome datasets, characterizing the correlation between differentially expressed genes (DEGs) of lipid metabolism and disease pathologies, as well as immune cell preferences. Through the application of weighted gene co-expression network analysis (WGCNA), modules eigengenes related to lipid metabolism were pinpointed, and the examination of their molecular functions within biological processes, molecular pathways, and their associations with pathological phenotypes and molecular networks has been characterized. Analysis of biological networks indicates notable discrepancies in the expression patterns of the DEGs between neuronal and immune cells, as well as variations in cell type enrichments within both brain tissue and peripheral blood. Additionally, drugs targeting the DEGs from central and peripheral and a diagnostic model for hub genes from the blood were retrieved and assessed, some of which were shown to be useful for therapeutic and diagnostic. These results revealed the distinctive pattern of transcriptionally abnormal lipid metabolism in central, peripheral, and immune cell activation, providing valuable insight into lipid metabolism for diagnosing and guiding more effective treatment for AD.

Boosting the electron beam transmittance of field emission cathode using a self-charging gate.

The gate-type carbon nanotubes cathodes exhibit advantages in long-term stable emission owing to the uniformity of electrical field on the carbon nanotubes, but the gate inevitably reduces the transmittance of electron beam, posing challenges for system stabilities. In this work, we introduce electron beam focusing technique using the self-charging SiNx/Au/Si gate. The potential of SiNx is measured to be approximately -60 V quickly after the cathode turning on, the negative potential can be maintained as the emission goes on. The charged surface generates rebounding electrostatic forces on the following electrons, significantly focusing the electron beam on the center of gate hole and allowing them to pass through gate with minimal interceptions. An average transmittance of 96.17% is observed during 550 hours prototype test, the transmittance above 95% is recorded for the cathode current from 2.14 µA to 3.25 mA with the current density up to 17.54 mA cm-2.

Large-eddy simulation of vortex-excited force on a square cylinder with transverse wind fluctuations.

This study utilized 3D Large-eddy simulation to investigate the crosswind drag force on a square cylinder subjected to transverse wind fluctuation. Two distinct methods were employed to generate the fluctuation: a prescribed sine function at the inlet boundary and an upwind barrier. The frequency was normalized in the same Strouhal number form. The transverse wind fluctuation with a normalized frequency above 0.05 tends to excite the square cylinder transversely with the same frequency band. The frequency effect also exists on the square cylinder located downwind an obstacle half the square cylinder's size. However, an obstacle 2.5 times the size of the square cylinder generates a cross-wind fluctuation with the normalized frequency of 0.04, which cannot excite the square cylinder transversely. The frequency effect from the upwind barrier significantly dampens with the distance and disappears at 8-10 times the square cylinder size.

A Simple Technique to Assay Locomotor Activity in Drosophila.

Drosophila melanogaster is an ideal model organism for studying various diseases due to its abundance of advanced genetic manipulation techniques and diverse behavioral features. Identifying behavioral deficiency in animal models is a crucial measure of disease severity, for example, in neurodegenerative diseases where patients often experience impairments in motor function. However, with the availability of various systems to track and assess motor deficits in fly models, such as drug-treated or transgenic individuals, an economical and user-friendly system for precise evaluation from multiple angles is still lacking. A method based on the AnimalTracker application programming interface (API) is developed here, which is compatible with the Fiji image processing program, to systematically evaluate the movement activities of both adult and larval individuals from recorded video, thus allowing for the analysis of their tracking behavior. This method requires only a high-definition camera and a computer peripheral hardware integration to record and analyze behavior, making it an affordable and effective approach for screening fly models with transgenic or environmental behavioral deficiencies. Examples of behavioral tests using pharmacologically treated flies are given to show how the techniques can detect behavioral changes in both adult flies and larvae in a highly repeatable manner.

A low-temperature operated in situ synthesis of TiC-modified carbon nanotubes with enhanced thermal stability and electrochemical properties.

Carbon nanotubes (CNTs) with superior thermal and electrochemical properties are desirable for a large variety of applications. Herein, an in situ synthesis carried out at 1050 °C is proposed for the realization of titanium carbide (TiC) modified CNTs (TiC@CNTs) via a carbothermal treatment of the TiO2-coated CNTs deposited by a TALD technology, preserving the structural morphologies of CNT samples. Crystalline and amorphous TiC layers/nanoparticles are observed around the walls of CNTs, serving as a thermal insulation layer to enhance the thermal stability of CNTs. The TiC@CNT sample exhibits a minimal mass loss of 3.1%, which is 20.9% and 82.3% for the TiO2@CNT and pristine-CNT samples, respectively. In addition, the TiC@CNT electrode shows good energy storage performances, with a specific capacitance of 2.83 mF cm-2 at 20 µA cm-2, which is about 3.5 times higher than that of the pristine-CNT electrode, showing the potential of TiC@CNTs as next-generation electrode materials.

Synergistic anti-inflammatory effects of peimine, peiminine, and forsythoside a combination on LPS-induced acute lung injury by inhibition of the IL-17-NF-κB/MAPK pathway activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Forsythia suspensa (Thunb.) Vahl and Fritillaria thunbergii Miq are traditional Chinese medicines that exhibit the ability to clear heat and toxic material effects. In China, the combination of these two medicines is widely used to treat mucopurulent sputum and bloody phlegm, arising due to phlegm-heat obstruction in respiratory diseases. However, very limited information is available regarding the combined anti-inflammatory effect of important effective components of Forsythia suspensa (Thunb.) Vahl and Fritillaria thunbergii Miq, namely peimine, peiminine, and forsythoside A. AIM OF THIS STUDY: To investigate synergistic anti-inflammatory effects of combined administration of peimine, peiminine, and forsythoside A on LPS-induced acute lung injury compared to combined administration of two compounds or individual administration, and unravel the underlying mechanism. MATERIAL AND METHODS: In the present study, male BALB/c mice received an oral dosage of sodium carboxymethylcellulose (CMC-Na) (0.5%, 1 mL/100 g), peimine, peiminine, forsythoside A, peimine + forsythoside A, peiminine + forsythoside A, and peimine + peiminine + forsythoside A (suspended in CMC-Na; 0.5%), once daily for 7 days. Subsequently, intratracheal instillation of LPS was applied to establish acute lung injury model. After 6 h of administration, the mice were sacrificed, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. These samples were further used to determine lung W/D (wet/dry) weight ratio, total protein (TP) levels, inflammatory cytokines (IL-6, TNF-α, IL-1ß, and IL-17), and expression of proteins involved in TLR4/MAPK/NF-κB pathway and IL-17 pathway. Further, tissue sections were subjected to H&E staining to assess the pathological alterations induced by LPS. The expression of IL-6 and TNF-α proteins in lung tissues was also analyzed using immunohistochemical staining. RESULTS: A synergistic anti-inflammatory effect of peimine, peiminine, and forsythoside A was observed when administered in combination to LPS-induced acute lung injury. The combined administration of peimine, peiminine, and forsythoside A had a strongly inhibitory effects on the W/D weight ratio, total protein (TP) level and the inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-17) level in acute lung injury mice, compared to combined administration of two compounds or individual administration. The infiltration of inflammatory cells and thickened bronchoalveolar walls induced by LPS were also ameliorated through the combined administration of peimine, peiminine, and forsythoside A. More importantly, the upregulation of protein related to TLR4/MAPK/NF-κB signaling pathway and the activation of IL-17 were significantly suppressed by pretreatment with each of the three compounds alone, while the effects of individual compounds were synergistically augmented by the combined pretreatment of these three compounds. CONCLUSION: The combined administration of peimine, peiminine, and forsythoside A ameliorated inflammatory response in acute lung injury mice induced by LPS in a synergistic manner, the mechanism may be related to the dampening of the TLR4/MAPK/NF-κB signaling pathway and IL-17 activation.

Numerical Analysis of Flexural Behavior of Prestressed Steel-Concrete Continuous Composite Beams Based on BP Neural Network.

Prestressed steel-concrete continuous composite beam (PCCB) is a kind of beam, which makes reinforced concrete slab and steel beam bear load and coordinate deformation through connectors such as studs. Prestressed steel-concrete continuous composite beam is a kind of transverse load-bearing composite member formed by prestressed technology on the basis of ordinary composite beam. Aiming at the flexural behavior of prestressed steel-concrete continuous composite beams, a three-dimensional finite element numerical analysis model is established, and the whole process of the test is simulated based on BP neural network. The calculated results are in good agreement with the test. Using this model, the mechanical deformation performance of prestressed steel-concrete continuous composite beam is further analyzed, and the effects of some parameters (steel beam strength grade, concrete strength grade, concrete slab thickness, and transverse reinforcement ratio) on the flexural performance of prestressed steel-concrete continuous composite beam are discussed, which provides a reference basis for engineering design.

On-chip integration of bulk micromachined three-dimensional Si/C/CNT@TiC micro-supercapacitors for alternating current line filtering.

Three-dimensional (3D) micro-supercapacitors (MSCs) with superior performances are desirable for miniaturized electronic devices. 3D interdigitated MSCs fabricated by bulk micromachining technologies have been demonstrated for silicon wafers. However, rational design and fabrication technologies of 3D architectures still need to be optimized within a limited footprint area to improve the electrochemical performances of MSCs. Herein, we report a 3D interdigitated MSC based on Si/C/CNT@TiC electrodes with high capacitive properties attributed to the excellent electronic/ionic conductivity of CNT@TiC core-shells with a high aspect ratio morphology. The symmetric MSC presents a maximum specific capacitance of 7.42 mF cm-2 (3.71 F g-1) at 5 mV s-1, and shows an 8 times areal capacitance increment after material coating at each step, fully exploiting the advantage of 3D interdigits with a high aspect ratio. The all-solid-state MSC delivers a high energy density of 0.45 µW h cm-2 (0.22 W h kg-1) at a power density of 10.03 µW h cm-2, and retains ∼98% capacity after 10 000 cycles. The MSC is further integrated on-chip in a low-pass filtering circuit, exhibiting a stable output voltage with a low ripple coefficient of 1.5%. It is believed that this work holds a great promise for metal-carbide-based 3D interdigitated MSCs for energy storage applications.

Combretastatin A4-loaded Poly (Lactic-co-glycolic Acid)/Soybean Lecithin Nanoparticles with Enhanced Drug Dissolution Rate and Antiproliferation Activity.

OBJECTIVE: This study aimed to prepare combretastatin A4 (CA4)-loaded nanoparticles (CA4 NPs) using poly(lactic-co-glycolic acid) (PLGA) and soybean lecithin (Lipoid S100) as carriers, and further evaluate the physicochemical properties and cytotoxicities of CA4 NPs against cancer cells. METHODS: CA4 NPs were prepared using a solvent evaporation technique. The effects of formulations on CA4 NPs were investigated in terms of particle size, zeta potential, encapsulation efficacy, and drug loading. The physicochemical properties of CA4 NPs were characterized using transmission electron microscopy, X-ray powder diffraction, differential scanning calorimetry, and Fourier transform infrared spectra. The drug release from CA4NPs was performed using a dialysis method. In addition, the cytotoxicity of CA4NPs against human alveolar basal epithelial (A549) cells was also evaluated. RESULTS: CA4 NPs prepared with a low organic/water phase ratio (1:20) and high drug/PLGA mass ratio (1:2.5) exhibited a uniform hydrodynamic particle size of 142 nm, the zeta potential of -1.66 mV, and encapsulation efficacy and drug loading of 92.1% and 28.3%, respectively. CA4 NPs showed a significantly higher release rate than pure CA4 in pH 7.4 phosphate-buffered solution with 0.5% Tween 80. It was found that the drug molecules could change from the crystal state to an amorphous form when loaded into the PLGA/Lipoid S100 matrix, and some molecular interactions could also occur between the drug and PLGA. Importantly, CA4 NPs showed a remarkably higher antiproliferation activity against A549 cancer cells compared to pure CA4. CONCLUSION: These results suggested the promising potential of PLGA/Lipoid S100 nanoparticles as the drug delivery system of CA4 for effective cancer therapy.

Synthesis and Evaluation of Bakuchiol Derivatives as Potent Anti-inflammatory Agents in Vitro and in Vivo.

Bakuchiol, a prenylated phenolic monoterpene derived from the fruit of Psoralen corylifolia L. (Buguzhi), is widely used to treat tumors, viruses, inflammation, and bacterial infections. In this study, we designed and synthesized 30 bakuchiol derivatives to identify new anti-inflammatory drugs. The anti-inflammatory activities of the derivatives were screened using lipopolysaccharide-induced RAW264.7 cells. To evaluate the anti-inflammatory activity of the compounds, we measured nitric oxide (NO), interleukin-6, and tumor necrosis factor-α production. Based on the screening results, compound 7a displayed more pronounced activity than bakuchiol and celecoxib. Furthermore, the mechanistic studies indicated that 7a inhibited pro-inflammatory cytokine release, which was correlated with activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway and blockade of the nuclear factor-κB/mitogen-activated protein kinase signaling pathway. The in vivo anti-inflammatory activity in zebrafish indicated that 7a inhibited NO and reactive oxygen species production in a dose-dependent manner. These results indicate that 7a is a potential candidate for development as an anti-inflammatory agent.

Formulation Optimization and In Vitro Characterization of Granisetronloaded Polylactic-co-glycolic Acid Microspheres Prepared by a Dropping-in-liquid Emulsification Technique.

PURPOSE: Traditional dosage forms of granisetron (GRN) decrease patient compliance associated with repeated drug administration because of the short half-life of the drug. METHODS: In this study, novel GRN-loaded Polylactic-co-glycolic Acid (PLGA) sustained-release microspheres were prepared for the first time via a dropping-in-liquid emulsification technique. The effects of various factors, such as pH of the outer phase, Tween 80, Polyvinyl Alcohol (PVA) concentrations, and hardening process, on the Encapsulation Efficiency (EE), Drug Loading (DL), and particle size of microspheres were extensively studied. The physicochemical properties, including drug release, surface morphology, crystallinity, thermal changes, and molecular interactions, were also studied. RESULTS: GRN has a pH-dependent solubility and it exhibits a remarkably high solubility under acidic condition. The EE of the alkaline medium (pH 8) was higher than that of the acidic medium (pH 4.0). EE and DL decreased in the presence of Tween 80 in the outer phase, whereas EE significantly increased during hardening. The particle size of microspheres was not affected by PVA and Tween 80 concentrations, but it was influenced by PVA volume and hardening. X-ray diffraction and differential scanning calorimetry results showed that the physical state of the drug changed from a crystalline form to an amorphous form, thereby confirming that the drug was encapsulated into the PLGA matrix. Fourier transform-infrared spectroscopy confirmed that some molecular interactions occurred between the drug and the polymer. GRN-loaded PLGA microspheres showed sustained release profiles of over 90% on week 3. CONCLUSION: GRN-loaded PLGA microspheres with sustained-release were successfully prepared, and they exhibited a relatively high EE without Tween 80 as an emulsifier and with the hardening process.

Protective effect of pteryxin on LPS-induced acute lung injury via modulating MAPK/NF-κB pathway and NLRP3 inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: Peucedanum praeruptorum seed root is a common medicinal herb with antipyretic, expectorant, antitussive, and therapeutic effects against bronchitis and furuncle. The roots of this herb contain many coumarin compounds, including pteryxin. AIM OF THIS STUDY: To investigate whether pteryxin can alleviate the LPS-induced lung injury and the mechanism involved. MATERIAL AND METHODS: Male BALB/C mice were orally given sodium carboxymethylcellulose (CMC-Na) (0.5%, 1mL/100g) and pteryxin (suspended in CMC-Na; 0.5%) at 5, 10, 25 mg/kg once daily for 7 days. Subsequently, the mice received a single intratracheal instillation of 5 mg/kg LPS or saline as the control. After 8 hours, the mice were sacrificed to collect bronchoalveolar lavage fluid (BALF) and lung tissues. These samples were used to determine the lung W/D (wet/dry) weight ratio, total protein (TP) levels, inflammatory cytokines (IL-6, TNF-α, and IL-1ß) and expression of protein involved in MAPK/NF-κB pathway and NLRP3 inflammasome. H&E staining was carried out on tissue sections to explore the pathological alterations induced by LPS. The protein expression of F4/80 and NLRP3 in lung tissues was analyzed using immunohistochemical staining. The binding of pteryxin to target proteins (MAPK, NF-κB and NLRP3) was determined based on molecular docking tests. RESULTS: Treatment with pteryxin reduced the lung W/D weight ratio, total protein (TP) level and levels of inflammatory cytokines (TNFα, IL-6 and IL-1 ß) significantly. Therefore, it ameliorated LPS-induced inflammatory response in BALB/C mice. Moreover, pteryxin suppressed LPS-induced upregulation of proteins involved in MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. The expression level of F4/80 and NLRP3 was also downregulated by pteryxin pretreatment in lung tissues. Docking analysis revealed that pteryxin bound to target proteins (MAPK, NF- κB and NLRP3) with a fit-well pattern . CONCLUSION: Pteryxin may attenuate LPS-induced acute lung injury by dampening MAPK/NF-κB signaling and NLRP 3 inflammasome activation.

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review.

Inflammation and disease are closely related. Inflammation can induce various diseases, and diseases can promote inflammatory response, and two possibly induces each other in a bidirectional loop. Inflammation is usually treated using synthetic anti-inflammatory drugs which are associated with several adverse effects hence are not safe for long-term use. Therefore, there is need for anti-inflammatory drugs which are not only effective but also safe. Several researchers have devoted to the research and development of effective anti-inflammatory drugs with little or no side effects. In this review, we studied some small molecules with reported anti-inflammatory activities and hence potential sources of anti-inflammatory agents. The information was retrieved from relevant studies published between January 2019 and May, 2021 for review. This review study was aimed to provide relevant information towards the design and development of effective and safe anti-inflammation agents.

Design, Synthesis, and In Vitro and In Vivo Biological Evaluation of Limonin Derivatives for Anti-Inflammation Therapy.

In this study, limonin derivatives were used to design new anti-inflammatory compounds with high pharmacological activity and low toxicity. A total of 23 new limonin derivatives were discovered, synthesized, and screened for their anti-inflammatory activity against lipopolysaccharide (LPS)-treated RAW 264.7 cells. Of them, compound f4 was found to be the most active, with a higher efficiency compared with limonin and celecoxib. Subsequently, we studied the mechanism underlying the activity of f4 and found that it inhibited proinflammatory cytokines by blocking the NF-κB/MAPK signaling pathway in LPS-treated RAW 264.7 cells as well as mice. In conclusion, f4 may be a promising anti-inflammatory lead compound.

Structurally modified glycyrrhetinic acid derivatives as anti-inflammatory agents.

With the aim of finding new anti-inflammatory drugs, a series of new Glycyrrhetinic acid derivatives (1-34) have been designed and synthesized by structural modification, and their anti-inflammatory activities in vitro have been evaluated. The anti-inflammatory activities assay demonstrated that compound 5b suppressed the expression of pro-inflammatory cytokines including IL-6, TNF-α and NO, it also suppressed the expression of iNOS and COX-2 in LPS-induced RAW264.7 cells in a dose-dependent manner. Additionally, western blot results indicated that the suppressing effect of compound 5b on pro-inflammatory cytokines were correlated with the suppression of NF-κB and MAPK signaling pathways. The results attained in this study indicated that compound 5b had the potential to be developed into an anti-inflammation agent and it may be applied to the prevention and treatment of inflammatory diseases.

Collagenase IV and clusterin-modified polycaprolactone-polyethylene glycol nanoparticles for penetrating dense tumor tissues.

Purpose: Novel collagenase IV (ColIV) and clusterin (CLU)-modified polycaprolactone-polyethylene glycol (PCL-PEG) nanoparticles that load doxorubicin (DOX) were designed and fully evaluated in vitro and in vivo. Methods: PCL-PEG-ColIV was synthesized by linking PCL-PEG and ColIV through a carbodiimide method. DOX-loaded nanoparticles (DOX-PCL-PEG-ColIV) were self-assembly prepared, followed by noncovalently adsorbing CLU on the DOX-PCL-PEG-ColIV surface to obtain DOX-PCL-PEG-ColIV /CLU nanoparticles, which can penetrate through the tumor extracellular matrix (ECM) and inhibit phagocytosis by macrophage. The physicochemical properties of nanoparticles were characterized. The cellular uptake and antiphagocytosis ability of nanoparticles in MCF-7 tumor cells and RAW264.7 cells were investigated. The penetration ability of nanoparticles was individually evaluated in the two-dimensional (2D) and three-dimensional (3D) ECM models. The tissue distribution and antitumor effect of nanoparticles were evaluated in MCF-7 cell-bearing nude mice. Results: Compared with DOX-PCL-PEG-COOH nanoparticles, DOX-PCL-PEG-ColIV/CLU nanoparticles could effectively overcome the phagocytosis by RAW264.7 and showed excellent cellular uptake in MCF-7 cells. In addition, they showed remarkable penetration ability through the 2D and 3D ECM models. DOX-PCL-PEG-ColIV/CLU nanoparticles significantly reduced the drug distribution in the liver and spleen and enhanced the drug accumulation in tumor tissue compared with DOX-PCL-PEG-COOH or DOX-PCL-PEG-ColIV nanoparticles. DOX-PCL-PEG-ColIV/CLU nanoparticles showed remarkable antitumor effect but did not cause severe pathological damages in the main tissues, including the heart, liver, spleen, lung, and kidney. Conclusion: Novel ColIV and CLU-modified PCL-PEG nanoparticles showed excellent cellular uptake, ECM penetration, antiphagocytosis, and antitumor effects both in vitro and in vivo.

Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on ß-Amyloid-Induced PC12 Cells.

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a-5v) exerted neuroprotective effects on ß-amyloid (Aß)-induced PC12 cells as a potential approach for the treatment of Alzheimer's disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aß25-35-induced PC12 cells at 5 µg/mL. We found that compound 5c was non-neurotoxic at 30 µg/mL and significantly increased the viability of Aß25-35-induced PC12 cells at 1.25, 2.5 and 5 µg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3ß) and decreased the expression of nuclear factor-κB (NF-κB) in Aß25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aß25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), ß-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3ß/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.

Silicon-Based 3D All-Solid-State Micro-Supercapacitor with Superior Performance.

The large-scale fabrication of high-performance on-chip micro-supercapacitors (MSCs) is the footstone for the development of next-generation miniaturized electronic devices. In practical applications, however, MSCs may suffer from a low areal energy density as well as a complicated fabrication strategy that is incompatible with semiconductor processing technology. Herein, we propose a scalable fabrication strategy for the realization of a silicon-based three-dimensional (3D) all-solid-state MSC via the combination of semiconductor-based electrode processing, chemical vapor deposition, and hydrothermal growth. The individual Si/C/MnO2 electrode shows a maximum specific capacitance of 223.74 mF cm-2, while the symmetric electrodes present a maximum areal energy density of 5.01 µWh cm-2 at the scan rate of 1 mV s-1. The full 3D Si/C/MnO2 MSC delivers a high energy density of 2.62 µWh cm-2, at a power density of 117.82 µW cm-2, as well as a long cycle life with capacitance retention >92% after 4000 cycles. Our proposed method enables the fabrication of 3D MSCs based on a thick silicon interdigitated electrode array, holding a great promise for the development of 3D on-chip microscale energy storage devices.

A GSH Fluorescent Probe with a Large Stokes Shift and Its Application in Living Cells.

Intracellular GSH is the most abundant non-protein biothiol and acts as a central antioxidant to defend against aging toxins and radicals. Meanwhile abnormal level of intracellular GSH concentration is directly related to some diseases. In this case, detecting intracellular GSH rapidly and sensitively is of great significance. We synthesize a simple fluorescent probe (named GP) which can discriminate GSH from Cys (cysteine) or Hcy (homocysteine) and presents a 50-fold fluorescence increasing. The response time of GP to GSH was only 5 min and the product GO (the product of GP after reacting with GSH) after reacting with GSH possesses a larger Stokes shift for 135 nm than that in reported work. Probe GP can detect intracellular effectively and shows obvious yellow fluorescence. Briefly, probe GP can detect intracellular GSH rapidly and effectively both in vitro and in living cells.