The prevalence of obesity has reached alarming levels, which is considered a major risk factor for several metabolic diseases, including type 2 diabetes (T2D), non-alcoholic fatty liver, ...atherosclerosis, and ischemic cardiovascular disease. Obesity-induced chronic, low-grade inflammation may lead to insulin resistance, and it is well-recognized that macrophages play a major role in such inflammation. In the current review, the molecular mechanisms underlying macrophages, low-grade tissue inflammation, insulin resistance, and T2D are described. Also, the role of macrophages in obesity-induced insulin resistance is presented, and therapeutic drugs and recent advances targeting macrophages for the treatment of T2D are introduced.
Liver fibrosis is a key pathological process shared by the progression of various chronic liver diseases. Treatment of liver fibrosis can effectively block the occurrence and development of hepatic ...cirrhosis or even carcinoma. Currently, there is no effective drug delivery vehicle for curing liver fibrosis. In this study, we designed matrine (MT)-loaded mannose 6-phosphate (M6P) modified human serum albumin (HSA) conjugated solid lipid nanoparticles (SLN), named M6P-HSA-MT-SLN for treatment of hepatic fibrosis. We demonstrated that M6P-HSA-MT-SLN exhibited controlled and sustained release properties and good stability over 7 days. The drug release experiments showed that M6P-HSA-MT-SLN exhibited slow and controlled drug release characteristics. In addition, M6P-HSA-MT-SLN showed a significant targeted ability to fibrotic liver. Importantly, in vivo studies indicated that M6P-HSA-MT-SLN could significantly improve histopathological morphology and inhibit the fibrotic phenotype. In addition, in vivo experiments demonstrate that M6P-HSA-MT-SLN could reduce the expression of fibrosis markers and alleviate the damage of liver structure. Hence, the M6P-HSA-MT-SLN provide a promising strategy to deliver therapeutic agents to fibrotic liver to prevent liver fibrosis.
Gout is a kind of joint disease characterized by the accumulation of monosodium urate (MSU) crystals in the joint and its surrounding tissue, causing persistent hyperuricemia. Colchicine is the first ...choice of treatment for acute gout attacks. Due to strong toxicity of colchicines oral tablets, there are high fluctuations of blood drug concentration and serious irritation of gastrointestinal tract, and hence a transdermal preparation can help to slow down the blood drug concentration, reduce the frequency of drug taking, and improve the patients' compliance of the drug. The ethosome is a lipid carrier with high concentration of ethanol and has been proved to promote the penetration of drugs into the skin. Borneol (BO) is an excellent penetration enhancer in Chinese medicine, which can promote the entry of drugs into the skin. This paper prepared the borneol-physically-modified colchicine ethosome (COL-bpES) and used the prepared borneol-dioleoyl phosphoethanloamine (BO-DOPE) to prepare borneol-chemically-modified colchicine ethosome (COL-bcES). Compared to the free colchicine aqueous solution (free COL) and normal colchicine ethosome (COL-ES), the borneol-modified colchicine ethosome (COL-bES) demonstrated better drug penetration effect, while the particle size of the COL-bcES was lower than that of the COL-bpES. Toxicity, in vitro diffusion, pharmacokinetics and pharmacodynamics are superior to those of COL-bpES, providing a better delivery system for the treatment of small molecule inflammatory drugs.
The explosive development of emerging telecommunication services has stimulated a huge growth in bandwidth demand as people seek universal access to telecommunication networks. In addition, the kinds ...of services of an existing optical access network are becoming more flexible. In order to provide higher capacity and meet higher transmission performance requirements, it is necessary to further explore the application of the beyond-100G passive optical network (PON). This paper offers a comprehensive review and outline of the prospects of technologies for bringing a beyond-100G PON to practical applications in the future. We review the current existing technologies, mainly in terms of the physical layer and higher media access control layer. These key technologies for the beyond-100G PON, which plays an increasingly significant role, include the advanced multiplexing technology, physical layer digital signal processing technology, infrastructure-sharing technology, security protection technology, and intelligent control management key technologies. Finally, open issues and new challenges for the next-generation PON are focused upon.
Dantrolene sodium (DS) is the only drug specifically used for the treatment of malignant hyperthermia. Nevertheless, its clinical application is significantly restricted due to its aqueous ...insolubility and the limited formulations available in clinical practice. In order to solve these problems, a novel mixed micelle composed of phospholipid and Cremophor EL was designed and evaluated. The mixed micelle was prepared using a stirring- ultrasonic method. The Dynamic Light Scattering (DLS) results showed that the micelle was small in size (12.14 nm) and narrowly distributed (PdI = 0.073). Transmission Electron Microscopy (TEM) images showed that the micelle was homogeneous and spherical. The stability study indicated that the system was stable for storage and dilution with distilled water, while the safety testing showed that the micelle was safe for intravenous administration with low hemolysis rates and low allergic reaction rates. In the pharmaceutics study, the C
and AUC
of the DS-loaded micelle were 4- and 4.5- folds higher than that of the DS. Therefore, the constructed phospholipid-Cremophor EL mixed micelle is a promising drug delivery system for DS.
With the explosion of traffic demand in recent years, the integration of satellite optical networks and terrestrial networks (ISTN) creates a promising networking solution for future low-latency, ...high-rate, and high-capacity communications. Owing to the high cost of deploying and maintaining a satellite optical network, it is critical to carefully design and plan the network to ensure the performance of the network. Thus, a semi-physical simulation platform based on software-defined networks (SDNs) is developed to simulate a satellite optical network and evaluate the performance of the proposed label-based advanced orbiting system (AOS) frame switching method that adheres to the Consultative Committee for Space Data Systems’ recommended standard (CCSDS). The semi-physical simulation platform has two major innovations: (1) adapting and integrating network protocols between the CCSDS and open system interconnect (OSI) reference models, particularly at the data link layer, and (2) the foundation for an SDN-based satellite optical network. In the control plane, real-time VxWorks Simulators serve as controllers to establish and manage various network protocols and the link manager protocol (LMP). Here, network protocols include open shortest path first (OSPF) for routing managing and controlling messages, constraint shortest path first–traffic engineering (CSPF-TE), and constraint-label distribution protocol (CR-LDP) for routing data services. LMP is used to assign and reserve satellite optical link resources. The performance of the architecture and protocols is evaluated via a semi-physical simulation platform.
With the rapid increase in vehicle ownership, exhaust pollution has become one of the important sources of air pollution in China. In this study, a MAHA METDH 6.3 exhaust gas test experimental ...platform was developed, and an emission model suitable for coupling with real-time road conditions was established based on large-scale vehicle emission test data. Based on traffic big data such as traffic volume, average vehicle speed, and vehicle model distribution, ArcGIS was used to select the road network information in the study area and combined with the emission model to realize the spatial distribution of line sources of vehicle emissions. Finally, based on the road network simulation model built by VISSIM, the emission changes caused by the two measures of trunk line optimization and new energy vehicle development were simulated and analyzed. The results show that the spatial distribution characteristics of vehicle exhaust pollutants in Zhangdian District are closely related to road type. Taking trunk line optimization measures and developing new energy vehicles have a certain reduction effect on vehicle emissions in Zhangdian District. This study lays a foundation for proposing targeted measures to reduce motor vehicle emissions based on big traffic operation data.
Ziconotide (ZIC) is an N-type calcium channel antagonist for treating severe chronic pain that is intolerable, or responds poorly to the administration of other drugs, such as intrathecal morphine ...and systemic analgesics. As it can only work in the brain and cerebrospinal fluid, intrathecal injection is the only administration route for ZIC. In this study, borneol (BOR)-modified liposomes (LIPs) were fused with exosomes from mesenchymal stem cells (MSCs) and loaded with ZIC to prepare microneedles (MNs) to improve the efficiency of ZIC across the blood-brain barrier. To evaluate local analgesic effects of MNs, the sensitivity of behavioral pain to thermal and mechanical stimuli was tested in animal models of peripheral nerve injury, diabetes-induced neuropathy pain, chemotherapy-induced pain, and ultraviolet-B (UV-B) radiation-induced neurogenic inflammatory pain. BOR-modified LIPs loaded with ZIC were spherical or nearly spherical, with a particle size of about 95 nm and a Zeta potential of −7.8 mV. After fusion with MSC exosomes, the particle sizes of LIPs increased to 175 nm, and their Zeta potential increased to −3.8 mV. The nano-MNs constructed based on BOR-modified LIPs had good mechanical properties and could effectively penetrate the skin to release drugs. The results of analgesic experiments showed that ZIC had a significant analgesic effect in different pain models. In conclusion, the BOR-modified LIP membrane-fused exosome MNs constructed in this study for delivering ZIC provide a safe and effective administration for chronic pain treatment, as well as great potential for clinical application of ZIC.
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•To provide a transdermal delivery system for the delivery of ziconotide.•ZIC@MSCEXO/LIP-BOR can improve the ability of crossing the BBB effectively.•ZIC@MSCEXO/LIP-BOR have the characteristics of liposomes and exosomes.•Various pain models were established to evaluate the analgesic effect.•MN#ZIC@MSCEXO/LIP-BOR has high biocompatibility and analgesic effect.
To evaluate the future passenger car market related environmental impact, first, a competitive prediction model was introduced based on Lotka-Volterra model. Further, the limit of passenger car life ...cycle system is extended to analyze the scale of future energy consumption and pollutant emission. The proportion of new energy passenger cars, average rate of change in the quality of passenger cars, and the share of renewable energy power generation were used as evaluation indicators to conduct scenario simulations for assessing the environmental benefits under the following policy scenarios: lightweight, electrification, and end-use energy cleaning of automobile. The results show that market share of new energy passenger cars will surpass traditional passenger cars around 2040. The energy consumption per unit mileage of the four types of passenger cars throughout the life cycle is 3.88, 3.51, 3.23, and 3.72 MJ/km. Compared with traditional passenger cars, new energy passenger cars will decrease by 17%, but less than expected. The total amount of VOC, CO, and CHG emissions from passenger cars will reach the peak in 2030 and then rapidly decrease. The amount of NOx emission will slowly decrease after reaching a peak of 11.6 ten-kilo-tons around 2040. The total emission of SO2 and PH2.5 will increase as the number of passenger cars increases. However, the growth rate will decrease to 4–6%. Finally, with the continuous advancement of three policies, the energy and emission factor will decrease by 10.0–13.5%. Among these factors, the impact of end-use cleaning energy in the mid-end terminal is the highest due to the sensitivity to fuel cycle. However, traditional single policy may not be effective since they do not consider the structure of vehicle cycle.
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•Market share is compared for four types passenger cars from 2020 to 2050.•The modelling framework contributes to update life cycle environmental inventories.•Potentials of different policies in improving environment are investigated.•New energy passenger vehicles cannot achieve the expected mitigation potentials.•Not all the simplification environmental policy measures have positive benefits.
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