Design, Synthesis, and Biological Evaluation of Proteolysis-Targeting Chimeras as Highly Selective and Efficient Degraders of Extracellular Signal-Regulated Kinase 5.

Extracellular signal-regulated kinase 5 (ERK5) is recognized as a key member of the mitogen-activated protein kinase family and is involved in tumor growth, migration, and angiogenesis. However, the results of ERK5 inhibition in multiple studies are controversial, and a highly specific ERK5-targeting agent is required to confirm physiological functions. Using proteolysis-targeting chimera technology, we designed the selective ERK5 degrader PPM-3 and examined its biological effect on cancer cells. Interestingly, the selective degradation of ERK5 with PPM-3 did not influence tumor cell growth directly. Based on proteomics analysis, the ERK5 deletion may be associated with tumor immunity. PPM-3 influences tumor development by affecting the differentiation of macrophages. Therefore, PPM-3 is an effective small-molecule tool for studying ERK5 and a promising immunotherapy drug candidate.

Effects of Addition of Tea Polyphenol Palmitate and Process Parameters on the Preparation of High-Purity EPA Ethyl Ester.

High-purity eicosapentaenoic acid (EPA) ethyl ester (EPA-EE) can be produced from an integrated technique consisting of saponification, ethyl esterification, urea complexation, molecular distillation and column separation. In order to improve the purity and inhibit oxidation, tea polyphenol palmitate (TPP) was added before the procedure of ethyl esterification. Furthermore, through the optimization of process parameters, 2:1 (mass ratio of urea to fish oil, g/g), 6 h (crystallization time) and 4:1 (mass ratio of ethyl alcohol to urea, g/g) were found to be the optimum conditions in the procedure of urea complexation. Distillate (fraction collection), 115 °C (distillation temperature) and one stage (the number of stages) were found to be the optimum conditions for the procedure of molecular distillation. With the addition of TPP and the above optimum conditions, high-purity (96.95%) EPA-EE was finally obtained after column separation.

Hyaluronic Acid Oligosaccharide Derivatives Alleviate Lipopolysaccharide-Induced Inflammation in ATDC5 Cells by Multiple Mechanisms.

High molecular weight hyaluronic acids (HMW-HAs) have been used for the palliative treatment of osteoarthritis (OA) for decades, but the pharmacological activity of HA fragments has not been fully explored due to the limited availability of structurally defined HA fragments. In this study, we synthesized a series glycosides of oligosaccharides of HA (o-HAs), hereinafter collectively referred to as o-HA derivatives. Their effects on OA progression were examined in a chondrocyte inflammatory model established by the lipopolysaccharide (LPS)-challenged ATDC5 cells. Cell Counting Kit-8 (CCK-8) assays and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showed that o-HA derivatives (≤100 µg/mL) exhibited no cytotoxicity and pro-inflammatory effects. We found that the o-HA and o-HA derivatives alleviated LPS-induced inflammation, apoptosis, autophagy and proliferation-inhibition of ATDC5 cells, similar to the activities of HMW-HAs. Moreover, Western blot analysis showed that different HA derivatives selectively reversed the effects of LPS on the expression of extracellular matrix (ECM)-related proteins (MMP13, COL2A1 and Aggrecan) in ATDC5 cells. Our study suggested that o-HA derivatives may alleviate LPS-induced chondrocyte injury by reducing the inflammatory response, maintaining cell proliferation, inhibiting apoptosis and autophagy, and decreasing ECM degradation, supporting a potential oligosaccharides-mediated therapy for OA.

Rational Design of Tungsten Selenide @ N-Doped Carbon Nanotube for High-Stable Potassium-Ion Batteries.

Potassium-ion batteries (PIBs) are deemed as one of the most promising energy storage systems due to their high energy density and low cost. However, their commercial application is far away from satisfactory because of limited suitable electrode materials. Herein, core-shell structured WSe2 @N-doped C nanotubes are rationally designed and synthesized via selenizing WO3 @ polypyrrole for the first time. The large interlayer spacing of WSe2 can facilitate the intercalation/deintercalation of K+ . Meanwhile, the core-shell structured nanotube provides favorable interior void space to accommodate the volume expansion of WSe2 during cycling. Thus, the obtained electrode exhibits superb electrochemical performance with a high capacity of 301.7 mAh g-1 at 100 mA g-1 over 120 cycles, and 122.1 mAh g-1 can remain at 500 mA g-1 even after 1300 cycles. Ex-situ X-ray diffraction analysis reveals the K-ion storage mechanism of WSe2 @N-doped C includes intercalation and conversion reaction. Density function theory (DFT) calculation demonstrates the reasonable diffusion pathway of K+ . In addition, the obtained WSe2 @N-doped C nanotubes have been used as anode material for lithium-ion batteries, which also show good rate performance and high cycle stability. Therefore, this work offers a new methodology for the ration design of new structure electrode materials with long cycle stability.

Effects of gallic acid alkyl esters and their combinations with other antioxidants on oxidative stability of DHA algae oil.

The most effective composite antioxidants for DHA algae oil were optimized by combining the selected gallic acid (GA) alkyl ester with other commonly used antioxidants. Results of Rancimat induction time, peroxide value, thiobarbituric acid-reactive substances, and free radical generation indicated that octyl gallate (OG) was the best one in DHA algae oil among GA alkyl esters with various chain lengths. Therefore, OG was used to combine other antioxidants (antioxidant of bamboo leaves, rosemary extract, tea polyphenols, tea polyphenol palmitate (TPP), ascorbyl palmitate, vitamin E, phytic acid and phospholipid) for further improving the oxidative stability of DHA algae oil. The combination of OG + TPP showed the best antioxidant effect among the composite antioxidants of two and three components. Through optimization of mixture ratio, the combination of 53.20 mg/kg OG + 360 mg/kg TPP demonstrated the best antioxidant capacity, which prolonged the shelf life of DHA algae oil by 4.24 folds.

Hydrogen-Bond-Mediated Aglycone Delivery: Synthesis of ß-d-Fructofuranosides.

The construction of ß-d-fructofuranosidic linkages is one of the major challenges in carbohydrate chemistry. In this work, we developed an efficient method for the synthesis of ß-d-fructofuranosides by using a 6-picoloyl-protected fructofuranosyl thioglycoside as the glycosyl donor. Subsequently, we applied the approach to a wide variety of donors and acceptors. Furthermore, the successful synthesis of levantetrose confirmed its applicability in the multistep synthesis of oligosaccharides.

A multi-shelled CoP nanosphere modified separator for highly efficient Li-S batteries.

Lithium-sulfur batteries are considered to be one of the most promising energy-storage systems because of their high theoretical energy density, as well as low cost, nontoxicity and natural abundance of sulfur. However, their poor cycling stability mostly originates from the shuttling of polysulfides which hinders their future practical applications. Here, multi-shelled CoP nanospheres are designed as a coated separator material for Li-S batteries for the first time. Conductive CoP can efficiently anchor polysulfides not only owing to its polar character but also its partial natural surface oxidation feature as evidenced by XPS results, which further activates Co sites for chemically trapping polysulfides via strong Co-S bonding. Furthermore, the unique multi-shelled structure can capture polysulfides to alleviate the "shuttle effect". Consequently, the battery using a CoP coated separator exhibits outstanding cycling stability with a capacity degradation of 0.078% per cycle over 500 cycles at a current density of 1 C and excellent rate performance (725 mA h g-1 at 5 C). It is also worth noting that a high areal capacity of 3.2 mA h cm-2 can be achieved even with a sulfur loading of 3.24 mg cm-2. Our approach demonstrates the convenient fabrication and application potential for a multi-shelled CoP nanosphere modified separator for highly efficient Li-S batteries.