Prediction of the mechanisms of liver injury of Epimedii Folium by network pharmacology and validation in HepaRG Cells

Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.

Electrode-compatible fluorine-free multifunctional additive regulating solid electrolyte interphase and solvation structure for high-performance lithium-ion batteries

The rapid development and widespread application of lithium-ion batteries(LIBs) have increased demand for high-safety and high-performance LIBs. Accordingly, various additives have been used in commercial liquid electrolytes to severally adjust the solvation structure of lithium ions, control the components of solid electrolyte interphase, or reduce flammability. While it is highly desirable to develop low-cost multifunctional electrolyte additives integrally that address both safety and performance on LIBs, significant challenges remain. Herein, a novel phosphorus-containing organic small molecule, bis(2-methoxyethyl) methylphosphonate(BMOP), was rationally designed to serve as a fluorine-free and multifunctional additive in commercial electrolytes. This novel electrolyte additive is low-toxicity,high-efficiency, low-cost, and electrode-compatible, which shows the significant improvement to both electrochemical performance and fire safety for LIBs through regulating the electrolyte solvation structure, constructing the stable electrode-electrolyte interphase, and suppressing the electrolyte combustion. This work provides a new avenue for developing safer and high-performance LIBs.

Flame-retardant oligomeric electrolyte additive for self-extinguishing and highly-stable lithium-ion batteries:Beyond small molecules

Preparing both safe and high-performance lithium-ion batteries(LIBs) based on commonly used commercial electrolytes is highly desirable,yet challenging.To overcome the poor compatibility of conventional small-molecular flame-retardants as electrolyte additives for safe LIBs with graphite anodes,in this study,we propose and design a novel low-cost flame-retardant oligomer that achieves an accurate and complete reconciliation of fire safety and electrochemical performance in LIBs.Owing to the integration of phosphonate units and polyethylene glycol(PEG) chains,this oligomer,which is a phosphonatecontaining PEG-based oligomer(PPO),not only endows commercial electrolytes with excellent flame retardancy but also helps stabilize the electrodes and Li-ion migration.Specifically,adding 15 wt% of PPO can reduce 70% of the self-extinguishing time and 54% of total heat release for commercial electrolytes.Moreover,LiFePO_(4)/lithium and graphite/lithium cells as well as LiFePO_(4)/graphite pouch full cells exhibit good long-term cycling stability.

Phosphorus-silicon-integrated electrolyte additive boosts cycling performance and safety of high-voltage lithium-ion batteries

Safety and energy density are significant for lithium-ion batteries(LIBs),and the flammable organic elec-trolyte is one of the most critical causes of the safety problem of LIBs.Although LiNi0.8 Co 0.1 Mn 0.1 O 2(NCM811)cathode with high capacity can improve the energy density,the interface stability between NCM811 cathode and electrolytes needs to be improved.Herein,we report a multifunctional additive,diethyl(2-(triethoxysilyl)ethyl)phosphonate(DETSP),which can suppress the flammability of the elec-trolyte and enhance the cycling stability of NCM811 cathode with a capacity retention of 89.9%after 400 cycles at 1 C,while that of the blank electrolyte is merely 61.3%.In addition,DETSP is compati-ble well with the graphite anode without impairing the electrochemical performances.Significantly,the performance and safety of NCM811/graphite full cells are also improved.Experimental and theoretical re-sults demonstrate that DETSP can scavenge acidic byproducts and is beneficial to form a stable cathode-electrolyte interface(CEI).Accordingly,DETSP can potentially be an effective solution to ameliorating the safety of the commercial electrolyte and improving the stability of high-voltage cathodes.

Relationship between the Stratospheric Arctic Vortex and Surface Air Temperature in the Midlatitudes of the Northern Hemisphere

It is known that different relationships exist between the strength and displacement of the stratospheric polar vortex(SPV),and the surface air temperature(SAT)patterns in Eurasia and North America,but the mechanisms behind these relationships remain unclear,especially on an interannual timescale.Based on empirical orthogonal function(EOF)analysis using NCEP reanalysis data over 1958–2018,this study attempts to ascertain the relationship between the SPV intensity and displacement over the Arctic and the SATs in the midlatitudes of the Northern Hemisphere.Our results indicate that a strengthened SPV corresponds to an SAT increase in Eurasia and a decrease in eastern North America and Greenland.When the SPV is shifted towards Eurasia,however,a corresponding SAT increase occurs in both North America and Eurasia,with a larger increase in North America than in Eurasia.Specifically,a strengthened SPV tends to correspond to a positive North Atlantic Oscillation-like circulation in the troposphere with negative geopotential height(GH)anomalies in Greenland and eastern North American continent and positive GH anomalies to the north of 45°N in Eurasia,which corresponds to lower SATs in North America than in Eurasia.However,when the SPV shifted towards Eurasia,it was accompanied by a positive Pacific/North American-like pattern with a deepened Aleutian low,which corresponds to the increasing SATs in North America.These tropospheric circulation changes are related to the response of tropospheric planetary wave activity to the SPV.A strengthened SPV corresponds to the weakening of tropospheric planetary wave-1 waves,which is accompanied by a negative GH in North America but a positive GH in Eurasia.If the SPV shifted towards Eurasia,the tropospheric planetary wave-1(-2)waves strengthened(weakened),and the combined effects of the planetary wave-1 and wave-2 waves would cause positive GH anomalies in both Eurasia and North America.

Multifunctional robust aerogel separator towards high-temperature,large-rate,long-cycle lithium-ion batteries

Separators is indispensable for the normal operation of lithium-ion batteries(LIBs).However,the widely used commercial polyolefin separators have some inherent deficiencies such as poor thermotolerance,high inflammability and inferior electrolyte wettability,which restrict their further applications of the advanced and safe batteries.Herein,we design a novel thermotolerant(a shrinkage percentage of 0%at 300℃)and flame retarded aerogel separator consisting of aramid nanofibers(ANFs).Because of its high porosity(86.5%±6.1%)and excellent electrolyte uptake(695%),the ANFs aerogel separator has an ionic conductivity of 1.04 mS/cm and a high lithium-ion transference number(0.67),which can endow LIBs with outstanding rate performance and superior cycling performance.Specifically,the ANFs aerogel separator-based batteries possess a discharge specific capacity of 102 m Ah/g with a capacity retention of 90.7%and a Coulombic efficiency of 99.3%after 600 cycles at 5 C.In addition,under an operated temperature of 90℃,the battery with ANFs aerogel separator can still conduct the very steady chargedischarge,presenting a capacity retention of 90.1%and a Coulombic efficiency of 99.6%after 200 cycles at 3 C.Accordingly,the separator can probably serve as a potential candidate for application to advanced and safe LIBs.