Application of Organ-on-Chip in Drug Discovery

Nowadays the pharmaceutical industry is facing long and expensive drug discovery processes. Current preclinical drug evaluation strategies that utilize oversimplified cell cultures and animal models cannot satisfy the growing demand for new and effective drugs. The microengineered biomimetic system, namely organ-on-chip (OOC), simulating both the biology and physiology of human organs, has shown greater advantages than traditional models in drug efficacy and safety evaluation. The microengineered co-culture models recapitulate the complex interactions between different types of cells in vivo. Organ-on-chip system has also avoided the substantial interspecies differences in key disease pathways and disease-induced changes in gene expression profiles between human and other animal models. Biomimetic microsystems representing different organs have been integrated into a single microdevice and linked by a microfluidic circulatory system in a physiologically relevant manner. In this review, I outline the current development of organ-on-chip, and their applications in drug discovery. This human-on-chip system can model the complex, dynamic process of drug absorption, distribution, metabolism and excretion, and more reliably evaluate drug efficacy and toxicity. I also discuss, for the next generation of organ-on-chip, more research is required to identify suitable materials that can be used to mass produce organs-on-chips at low cost, and to scale up the system to be suitable for high-throughput analysis and commercial applications. There are more aspects that need to be further studied, thereby bring a much better tool to patients, drug developers, and clinicians.

Techno-economic analysis of MJ class high temperature Superconducting Magnetic Energy Storage(SMES) systems applied to renewable power grids

High temperature Superconducting Magnetic Energy Storage(SMES) systems can exchange energy with substantial renewable power grids in a small period of time with very high efficiency. Because of this distinctive feature, they store the abundant wind power when the power network is congested and release the energy back to the system when there is no congestion. However, considering the cost and lifespan of SMES systems, there is an urgent demand to conduct a cost-benefit analysis to justify its role in smart grid development. This study explores the application and performs economic analysis of a 5 MJ SMES in a practical renewable power system in China based on the PSCAD/EMTDC software. An optimal location of SMES in Zhangbei wind farm is presented using real power transmission parameters. The stabilities of the renewable power grid with and without SMES are discussed. In addition, a financial feasibility study is conducted by comparing the cost and the savings from wind power curtailment of deploying SMES and battery. The economic analysis tries to find the balance between SMES investment cost and wind farm operation cost by using real data over a calendar year. The technical analysis can help guide the optimal allocation of SMES for compensating power system instability with substantial wind power. Further, the economic analysis provides a useful indication of its practical application feasibility to fight the balance between cost and benefit.

Study on polyurethane-based porous materials and their adsorption properties

The flexible superhydrophobic thermoplastic polyurethane(TPU)porous material was prepared by heat-induced phase separation method with two cooling steps.The influence of the preparation process on the microstructure of the material was discussed in depth.The microstructure,hydrophobicity and specific surface area of porous TPU materials were analyzed in detail.The surface wettability,separation selectivity,saturated adsorption capacity and adsorption rate,mechanical properties,environmental adaptability and cyclic properties of porous TPU materials were studied.The results show that the TPU-8%porous monolithic material prepared by heat-induced phase separation method shows good performance when the polymer concentration is 8%,the phase separation temperature is 0℃,the phase separation time is 30min,and the mixing solvent ratio is 9:1.

Macroscopic electromagnetic synergy network-enhanced N-doped Ni/C gigahertz microwave absorber with regulable microtopography

To achieve excellent electromagnetic wave(EMW)absorption properties,the microstructure design of the absorber is critical.In this work,six kinds of N-Ni/C nanostructures with different morphologies were prepared by one-step hydrothermal method and high temperature carbonization by adjusting the types of nickel salts and reaction solvents.The EMW absorption performance of six different morphologies of N-Ni/C nanostructures was compared and analyzed.Among them,it is found that the nanoflowerlike N-Ni/C composite has excellent dielectric loss and magnetic loss synergistic effect due to its polycrystalline structure,and can obtain excellent EMW absorption performance.The minimum reflection loss value at a thickness of 1.9 mm is-59.56 dB at 16.88 GHz,and the effective absorption bandwidth value reaches 6.0 GHz at a thickness of 2.2 mm.Our research shows that different morphologies and multiple lattice structures of nanostructures with the same composition have a significant influence on EMW absorption performance,which provides new research ideas for developing high-performance EMW absorbing materials.

Solvent-free nanocasting toward universal synthesis of ordered mesoporous transition metal sulfide@N-doped carbon composites for electrochemical applications

Transition metal sulfides (TMSs) have a wide range of applications owing to their intriguing properties.Significant efforts have been devoted to nanostructuring TMSs to enhance their properties and performance,still there is a high need in general synthesis of TMS nanostructures.Herein,for the first time,a simple solvent free reactive nanocasting approach that integrates solid precursor loading,in-situ sulfuration and carbonization into a single heating step is developed for the universal synthesis of ordered mesoporous TMS@N-doped carbon composites (denoted as OM-TMS@NCs) with methionine (Met) and metal chlorides as the precursors and the mesoporous silica (SBA-15) as the hard template.A series of OM-TMS@NCs with a hexagonal mesostructure,ultra-high surface areas (430-754 m2·g-1),large pore volumes (0.85-1.32 cm3·g-1),and unique TMS stoichiometries,including MoS2,Fe7S8,Co9S8,NiS,Cu7S4 and ZnS,are obtained.Two distinct structure configurations,namely,highly dispersed ultrathin TMS nanosheets within NCs and TMS@NC co-nanowire arrays,can be obtained depending on different metals.The structure evolution of the OM-TMS@NCs over the solvent-free nanocasting process is studied in detail for a deep understanding of the synthesis.As demonstrations,these materials are promising for electrocatalytic hydrogen evolution reaction and lithium ion storage with high performances.

Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease

Metabolic-associated fatty liver disease(MAFLD),which is previously known as non-alcoholic fatty liver disease(NAFLD),represents a major health concern worldwide with limited therapy.Here,we provide evidence that ferroptosis,a novel form of regulated cell death characterized by iron-driven lipid peroxidation,was comprehensively activated in liver tissues from MAFLD patients.The canonical-GPX4(cGPX4),which is the most important negative controller of ferroptosis,is downregulated at protein but not mRNA level.Interestingly,a non-canonical GPX4 transcript-variant is induced(inducible-GPX4,iGPX4)in MAFLD condition.The high fat-fructose/sucrose diet(HFFD)and methionine/choline-deficient diet(MCD)-induced MAFLD pathologies,including hepatocellular ballooning,steatohepatitis andfibrosis,were attenuated and aggravated,respectively,in cGPX4-and iGPX4-knockin mice.cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes.Knockdown of iGPX4 by siRNA alleviated lipid stress,ferroptosis and cell injury.Mechanistically,the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress,and thus promotes ferroptosis.Co-immunoprecipitation and nano LC–MS/MS analyses confirmed the interaction between iGPX4 and cGPX4.Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis,and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Large deviation principle for a class of SPDE with locally monotone coefficients

This work aims to prove the large deviation principle for a class of stochastic partial differential equations with locally monotone coefficients under the extended variational framework, which generalizes many previous works. Using stochastic control and the weak convergence approach, we prove the Laplace principle,which is equivalent to the large deviation principle in our framework. Instead of assuming compactness of the embedding in the corresponding Gelfand triple or finite dimensional approximation of the diffusion coefficient in some existing works, we only assume some temporal regularity in the diffusion coefficient.

Assessment of Marginal Emissions Factor in Power Systems Under Ramp-Rate Constraints

Reducing carbon emissions in the power sector is critical for transitioning to a sustainable and low-carbon future.Estimating carbon efficiency of demand side response(DSR)in the power system is an important step towards realizing potential environmental benefits.Marginal emission factor(MEF)is an effective tool for estimating incremental changes in carbon emissions as a result of a change in demand.However,estimation methods currently used for evaluating MEF can be improved upon,specifically,by factoring in the ramp-rate constraint of generators in the fuel cost based merit order dispatch.In this paper is described a new method for MEF assessment under ramp-rate constraints;the method is then compared with two conventional estimations in a British power system.Three fuel price scenarios are used to conduct a sensitivity analysis of MEFs to fuel prices.Conclusions are drawn that can pave the way for future improvements in estimating MEF in power systems.

Diastereodivergent synthesis of fully disubstituted spiro[indoline-3,2’-pyrrolidin]-2-ones via tuneable Lewis base/Brønsted base-promoted(3+2)cycloadditions

Herein we report a diastereodivergent synthesis of fully disubstituted spiro[indoline-3,2’-pyrrolidin]-2-ones through base-promoted(3+2)cycloadditions.Importantly,the catalysts are found to have full control over the configuration of the stereocenters.When a Lewis base(PCy3)is used as a catalyst,good yields and excellent diastereoselectivities are obtained,regardless of the properties of the substituents,whereas spiro[indoline-3,2’-pyrrolidin]-2-ones of a different diastereoisomer are produced in good yields when a Brønsted base(K_(2)CO_(3))is used.ESI-MS experiments proved the existence of key zwitterionic intermediates.