COVID-19 and healthcare system in China: challenges and progression for a sustainable future.

With the ongoing COVID-19 outbreak, healthcare systems across the world have been pushed to the brink. The approach of traditional healthcare systems to disaster preparedness and prevention has demonstrated intrinsic problems, such as failure to detect early the spread of the virus, public hospitals being overwhelmed, a dire shortage of personal protective equipment, and exhaustion of healthcare workers. Consequently, this situation resulted in manpower and resource costs, leading to the widespread and exponential rise of infected cases at the early stage of the epidemic. To limit the spread of infection, the Chinese government adopted innovative, specialized, and advanced systems, including empowered Fangcang and Internet hospitals, as well as high technologies such as 5G, big data analysis, cloud computing, and artificial intelligence. The efficient use of these new forces helped China win its fight against the virus. As the rampant spread of the virus continues outside China, these new forces need to be integrated into the global healthcare system to combat the disease. Global healthcare system integrated with new forces is essential not only for COVID-19 but also for unknown infections in the future.

Photoresponsive polyesters by incorporation of alkoxyphenacyl or coumarin chromophores along the backbone.

The synthesis and photochemical characterization of two classes of photoresponsive polyesters are described. These polyesters contain either alkoxyphenacyl or coumarin chromophores embedded along the polymer chain. The alkoxyphenacyl polyesters undergo efficient photoinduced chain scission upon irradiation at 300 nm in solution or as a nanoparticle suspension. At 254 nm the coumarin polyesters undergo polymer chain scission. Irradiation of the coumarin polyesters in solution at 350 nm results in both chain crosslinking and chain scission behavior, while irradiation of the coumarin polyesters as nanoparticles results in chain crosslinking. The properties of the alkoxyphenacyl and coumarin polyesters are influenced by the choice of diacid as seen from their thermal behavior. The use of glutamic acid enabled surface or bulk functionalization of the photoresponsive polymers. In addition, controlled release of Nile Red from coumarin polyester nanoparticles is demonstrated by modulation of the wavelength and intensity of irradiation.

MLN4924 Treatment Diminishes Excessive Lipid Storage in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) by Stimulating Hepatic Mitochondrial Fatty Acid Oxidation and Lipid Metabolites.

MLN4924 is a selective neddylation inhibitor that has shown great potential in treating several cancer and metabolic diseases, including obesity. However, it remains largely unknown whether MLN4924 has similar effect on non-alcoholic liver disease (NAFLD), which is closely associated with metabolic disorders. Here, we investigated the role of MLN4924 in NAFLD treatment and the underlying mechanism of the action using primary hepatocytes stimulated with free fatty acid, as well as high-fat diet (HFD)-induced NAFLD mouse models. We found that MLN4924 can inhibit the accumulation of lipid and reduce the expression of peroxisome proliferator-activated receptor γ (PPARγ), a key player in adipocyte differentiation and function in both in vivo and in vitro models. Moreover, we verified its important role in decreasing the synthesis and accumulation of fat in the liver, thus mitigating the development of NAFLD in the mouse model. The body weight and fat mass in MLN4924-treated animals were significantly reduced compared to the control group, while the metabolic activity, including O2 consumption, CO2 and heat production, also increased in these animals. Importantly, we demonstrated for the first time that MLN4924 can markedly boost mitochondrial fat acid oxidation (FAO) to alter liver lipid metabolism. Finally, we compared the metabolites between MLN4924-treated and untreated Huh7 cells after fatty acid induction using lipidomics methods and techniques. We found induction of several metabolites in the treated cells, including Beta-guanidinopropionic acid (b-GPA) and Fluphenazine, which was in accordance with the increase of FAO and metabolism. Together, our study provided a link between neddylation modification and energy metabolism, as well as evidence for targeting neddylation as an emerging therapeutic approach to tackle NAFLD.

Biocompatibility and in vivo tolerability of a new class of photoresponsive alkoxylphenacyl-based polycarbonates.

Potential toxicities of chromophoric or polymeric units of most photoresponsive delivery systems have impacted clinical relevance. Herein, we evaluated the biocompatibility and tolerability of alkoxylphenacyl-based polycarbonates (APPs) as a new class of photoresponsive polymers. The polymers were applied as homopolymer or copolymers of polyethylene glycol (10%, w/w) or polycaprolactone (10%, w/w). APP polymers were comparable to poly(lactic-co-glycolic acid) (PLGA) based on cytotoxicity, macrophage activation, and blood compatibility. Data from biodistribution studies in BALB/c mice showed preferential accumulation in kidney and liver. Meanwhile, potential application of APP polymers as immediate or sustained (implants) drug delivery systems indicated that liver and kidney functions were not distorted. Also, plasma levels of tumor necrosis factor-alpha and interleukin-6 were comparable to PLGA-treated mice (p > 0.05). A histological analysis of liver and kidney sections showed no detectable damage for APP polymers. The overall data strongly supported potential consideration of APP polymers as photoresponsive delivery systems especially as implantable or tissue-mimicking photopatterned biomaterials.

Photoinduced Polymer Chain Scission of Alkoxyphenacyl Based Polycarbonates.

We report the design and development of a new class of alkoxyphenacyl based photodegradable polycarbonates. These polymers incorporate the photoactive moiety in the backbone and, when irradiated at 300 nm, undergo controlled chain scission. Micropatterned thin films of these polymers were fabricated by photolithographic techniques. The use of these photodegradable polymers for controlled release applications was demonstrated by the release of Nile Red from polymeric nanoparticles. In addition, these polymers are mechanically robust, thermally stable, and hydrolytically degradable.