Greatly enhanced corrosion/wear resistances of epoxy coating for Mg alloy through a synergistic effect between functionalized graphene and insulated blocking layer

The poor corrosion and wear resistances of Mg alloys seriously limit their potential applications in various industries.The conventional epoxy coating easily forms many intrinsic defects during the solidification process,which cannot provide sufficient protection.In the current study,we design a double-layer epoxy composite coating on Mg alloy with enhanced anti-corrosion/wear properties,via the spin-assisted assembly technique.The outer layer is functionalized graphene(FG)in waterborne epoxy resin(WEP)and the inner layer is Ce-based conversion(Ce)film.The FG sheets can be homogeneously dispersed within the epoxy matrix to fill the intrinsic defects and improve the barrier capability.The Ce film connects the outer layer with the substrate,showing the transition effect.The corrosion rate of Ce/WEP/FG composite coating is 2131 times lower than that of bare Mg alloy,and the wear rate is decreased by~90%.The improved corrosion resistance is attributed to the labyrinth effect(hindering the penetration of corrosive medium)and the obstruction of galvanic coupling behavior.The synergistic effect derived from the FG sheet and blocking layer exhibits great potential in realizing the improvement of multi-functional integration,which will open up a new avenue for the development of novel composite protection coatings of Mg alloys.

Tetraethylenepentamine-functionalized magnetic mesoporous composites as a novel adsorbent for the removal Cr(Ⅲ)-ethylenediaminetetraacetic acid in complex solution

A novel tetraethylenepentamine(TEPA) functionalized magnetic mesoporous silica adsorbent(FNMs/TEPA) was prepared for the adsorption of Cr(Ⅲ)-ethylenediaminetetraacetic acid(EDTA)from wastewater. The characterization of the prepared adsorbent certified that TEPA was modified onto the magnetic mesoporous silicon(FNMs), while FNMs/TEPA maintained the ordered mesoporous and pristine magnetic properties. The batch adsorption experiments demonstrated that TEPA significantly enhanced the removal capacity of the adsorbent for Cr(Ⅲ)-EDTA. FNMs/TEPA exhibited an excellent adsorption property(13.84 mg·g-1) at p H 4.0. Even in the presence of high concentrations of coexisting ions and organic acids, the adsorption performance of FNMs/TEPA was stable. Experimental characterization and DFT demonstrated that the adsorption of Cr(Ⅲ)-EDTA was ascribed to the electrostatic interaction, hydrogen bonding, and complexation between Cr(Ⅲ)-EDTA and amino groups on the adsorbent surface. The analysis of the independent gradient model(IGM) shows that electrostatic interaction is the main mode of action in the adsorption process. Moreover, FNMs/TEPA demonstrated remarkable reusability in three regeneration cycles. These findings indicated that FNMs/TEPA possessed excellent application prospects in the disposal of wastewater containing Cr(Ⅲ)-EDTA.

Functionalized selenium nanoparticles ameliorated acetaminophen-induced hepatotoxicity through synergistically triggering PKCδ/Nrf2 signaling pathway and inhibiting CYP 2E1

Selenium nanoparticles(SeNPs)have been demonstrated potential for use in diseases associated with oxidative stress.Functionalized SeNPs with lower toxicity and higher biocompatibility could bring better therapeutic activity and clinical application value.Herein,this work was conducted to investigate the protective effect of Pleurotus tuber-regium polysaccharide-protein complex funtionnalized SeNPs(PTR-SeNPs)against acetaminophen(APAP)-induced oxidative injure in HepG2 cells and C57BL/6J mouse liver.Further elucidation of the underlying molecular mechanism,in particular their modulation of Nrf2 signaling pathway was also performed.The results showed that PTR-SeNPs could significantly ameliorate APAP-induced oxidative injury as evidenced by a range of biochemical analysis,histopathological examination and immunoblotting study.PTR-SeNPs could hosphorylate and activate PKCδ,depress Keap1,and increase nuclear accumulation of Nrf2,resulting in upregulation of GCLC,GCLM,HO-1 and NQO-1 expression.Besides,PTR-SeNPs suppressed the biotransformation of APAP to generate intracellular ROS through CYP 2E1 inhibition,restoring the mitochondrial morphology.Furthermore,the protective effect of PTR-SeNPs against APAP induced hepatotoxicity was weakened as Nrf2 was depleted in vivo,indicating the pivotal role of Nrf2 signaling pathway in PTR-SeNPs mediated hepatoprotective efficacy.Being a potential hepatic protectant,PTR-SeNPs could serve as a new source of selenium supplement for health-promoting and biomedical applications.

Amino-functionalized UiO-66-doped mixed matrix membranes with high permeation performance and fouling resistance

For the reduction of bovine serum proteins from wastewater,a novel mixed matrix membrane was prepared by functionalizing the substrate material polyaryletherketone(PAEK),followed by carboxyl groups(C-SPAEKS),and then adding amino-functionalized UiO-66-NH_(2)(Am-UiO-66-NH_(2)).Aminofunctionalization of UiO-66 was accomplished by melamine,followed by an amidation reaction to immobilize Am-UiO-66-NH_(2),which was immobilized on the surface of the membrane as well as in the pore channels,which enhanced the hydrophilicity of the membrane surface while increasing the negative potential of the membrane surface.This nanoparticle-loaded ultrafiltration membrane has good permeation performance,with a pure water flux of up to 482.3 L·m^(-2)·h^(-1) for C-SPAEKS/AmUiO-66-NH_(2) and a retention rate of up to 98.7%for bovine serum albumin(BSA)-contaminated solutions.Meanwhile,after several hydrophilic modifications,the flux recovery of BSA contaminants by this series of membranes increased from 56.2%to 80.55%of pure membranes.The results of ultra-filtration flux time tests performed at room temperature showed that the series of ultrafiltration membranes remained relatively stable over a test time of 300 min.Thus,the newly developed mixed matrix membrane showed potential for high efficiency and stability in wastewater treatment containing bovine serum proteins.

3D printing of poly(ethyleneimine)-functionalized Mg-Al mixed metal oxide monoliths for direct air capture of CO_(2)

Direct air capture(DAC)of CO_(2)plays an indispensable role in achieving carbon-neutral goals as one of the key negative emission technologies.Since large air flows are required to capture the ultradilute CO_(2)from the air,lab-synthesized adsorbents in powder form may cause unacceptable gas pressure drops and poor heat and mass transfer efficiencies.A structured adsorbent is essential for the implementation of gas-solid contactors for cost-and energy-efficient DAC systems.In this study,efficient adsorbent poly(ethyleneimine)(PEI)-functionalized Mg-Al-CO_(3)layered double hydroxide(LDH)-derived mixed metal oxides(MMOs)are three-dimensional(3D)printed into monoliths for the first time with more than 90%adsorbent loadings.The printing process has been optimized by initially printing the LDH powder into monoliths followed by calcination into MMO monoliths.This structure exhibits a 32.7%higher specific surface area and a 46.1%higher pore volume,as compared to the direct printing of the MMO powder into a monolith.After impregnation of PEI,the monolith demonstrates a large adsorption capacity(1.82 mmol/g)and fast kinetics(0.7 mmol/g/h)using a CO_(2)feed gas at 400 ppm at 25℃,one of the highest values among the shaped DAC adsorbents.Smearing of the amino-polymers during the post-printing process affects the diffusion of CO_(2),resulting in slower adsorption kinetics of pre-impregnation monoliths compared to post-impregnation monoliths.The optimal PEI/MeOH ratio for the post-impregnation solution prevents pores clogging that would affect both adsorption capacity and kinetics.

Functionalized Hydrogel-Based Wearable Gas and Humidity Sensors

Breathing is an inherent human activity;however,the composition of the air we inhale and gas exhale remains unknown to us.To address this,wearable vapor sensors can help people monitor air composition in real time to avoid underlying risks,and for the early detection and treatment of diseases for home healthcare.Hydrogels with three-dimensional polymer networks and large amounts of water molecules are naturally flexible and stretchable.Functionalized hydrogels are intrinsically conductive,self-healing,self-adhesive,biocompatible,and room-temperature sensitive.Compared with traditional rigid vapor sensors,hydrogel-based gas and humidity sensors can directly fit human skin or clothing,and are more suitable for real-time monitoring of personal health and safety.In this review,current studies on hydrogel-based vapor sensors are investigated.The required properties and optimization methods of wearable hydrogel-based sensors are introduced.Subsequently,existing reports on the response mechanisms of hydrogel-based gas and humidity sensors are summarized.Related works on hydrogel-based vapor sensors for their application in personal health and safety monitoring are presented.Moreover,the potential of hydrogels in the field of vapor sensing is elucidated.Finally,the current research status,challenges,and future trends of hydrogel gas/humidity sensing are discussed.

Understanding Dual-Polar Group Functionalized COFs for Accelerating Li-Ion Transport and Dendrite-Free Deposition in Lithium Metal Anodes

Lithium metal batteries(LMBs)have attracted wide attentions because of their high theoretical specific capacity and low electrochemical potential.However,the growth of lithium dendrites seriously affects the practical application of LMBs.Thus,the lithium-philic carbonyl and carboxy dualgroup-modified covalent organic framework(COF-COOH)is designed to coat the polypropylene(PP)separator(COF-COOH@PP separator),realizing the regulation of ion transport and uniform lithium deposition.The plentiful and negative charge sites in the COF-COOH can suppress the diffusion of the freely movable lithium salt anion by the electrostatic interaction.Density functional theory(DFT)calculations demonstrate that the COF-COOH possesses the function of anchoring anion and desolvation.Consequently,the Li^(+)transference number(0.7),ion conductivity(0.64 mS cm^(-1)),and desolvating of Li^(+)are obviously improved by using the COF-COOH@PP separator.The modified Li-Li symmetric battery delivers stable cycle for more than 1000 h and lower voltage hysteresis(0.02 V).This dendrite-free deposition strategy holds great promise for practical application of Li metal anodes.

Restraining migration and dissolution of transition-metal-ions via functionalized separator for Li-rich Mn-based cathode with high-energy-density

Lithium-rich manganese-based materials(LRMs) are promising cathode for high-energy-density lithiumion batteries due to their high capacity,low toxicity,and low cost.However,LRMs suffer from serious voltage decay and capacity fade due to continual migration and dissolution of transition metal ions(TMs) during cycling process.Herein,a novel strategy is proposed to inhibit the TMs migration of LRMs through a modified separator by means of functionalized carbon coating layer,which depends on the chemical constraint of the abundant functional groups in the modified super P.In addition,it has been found that the dissolution of TMs can be restrained based on the Le Chatelier's principle.Moreover,the modified separator owns good wettability toward the electrolyte.As a result,the LRMs cathode with the modified separator delivers a high discharge capacity of 329.93 mA h g-1 at 0.1 C,and achieves good cyclic performance,the enhanced reaction kinetics and low voltage decay.Therefore,this work provides a new idea to promote the comprehensive electrochemical performances of Li-ion batteries with LRMs cathode through a strategy of separator modification.

Comparative study of the adsorption performance of NH_(2)-functionalized metal organic frameworks with activated carbon composites for the treatment of phenolic wastewaters

To better understand the role of the-NH_(2)group in adsorption process of phenolic wastewaters,NH_(2)-functionalized MIL-53(Al)composites with activated carbon(NH_(2)-M(Al)@(B)AC)were prepared.The results showed that the-NH_(2)group could increase the mesopore volume for composites,which promotes mass transfer and full utilization of active sites,because hierarchical mesopore structure makes the adsorbent easier to enter the internal adsorption sites.Furthermore,the introduction of the-NH_(2)group can improve the adsorption capacity,decrease the activation energy,and enhance the interaction between the adsorbent and p-nitrophenol,demonstrating that the-NH_(2)group plays a crucial role in the adsorption of p-nitrophenol.The density functional theory calculation results show that the H-bond interaction between the-NH_(2)group in the adsorbent and the-NO_(2)in the p-nitrophenol(adsorption energy of -35.5 kJ·mol^(-1)),and base-acid interaction between the primary-NH_(2)group in the adsorbent and the acidic-OH group in the p-nitrophenol(adsorption energy of -27.3 kJ·mol^(-1))are predominant mechanisms for adsorption in terms of the NH_(2)-functionalized adsorbent.Both NH_(2)-functionalized M(Al)@AC and M(Al)@BAC composites exhibited higher p-nitrophenol adsorption capacity than corresponding nonfunctionalized composites.Among the composites,the NH_(2)-M(Al)@BAC had the highest p-nitrophenol adsorption capacity of 474 mg·g^(-1).

Three-in-one LaNiO_(3) functionalized separator boosting electrochemical stability and redox kinetics for high-performance Li-S battery

The lithium-sulfur(Li-S)battery,as one of the energy storage devices,has been in the limelight due to its high theoretical energy density.However,the poor redox kinetics and the"shuttle effect"of polysulfides severely restrict the use of Li-S batteries in practical applications.Herein,a novel bimetallic LaNiO_(3) functional material with high electrical conductivity and catalytic property is prepared to act as a high-efficiency polysulfide shuttling stopper.The three LaNiO_(3) samples with different physical/chemical characteristics are obtained by controlling the calcination temperature.In conjunction with the high electrical conductivity and excellent catalytic properties of the as-prepared materials,the appropriate chemisorption toward polysulfides offers great potential to enhance electrochemical stability for highperformance Li-S batteries.Particularly,the Li-S cell with the separator modified by such functional material gives a specific capacity of 658 mA h g^(-1) after 500 cycles at a high current density of 2 C.Even with high sulfur loading of 6.05 mg cm^(-2),the Li-S battery still exhibits an areal specific capacity of 2.81 m A h cm^(-2)after 150 cycles.This work paves a new avenue for the rational design of materials for separator modification in high-performance Li-S batteries.

Minimizing Carbon Content with Three-in-One Functionalized Nano Conductive Ceramics:Toward More Practical and Safer S Cathodes of Li-S Cells

Using porous carbon hosts in cathodes of Li-S cells can disperse S actives and offset their poor electrical conductivity.However,such reservoirs would in turn absorb excess electrolyte solvents to S-unfilled regions,causing the electrolyte overconsumption,specific energy decline,and even safety hazards for battery devices.To build better cathodes,we propose to substitute carbons by In-doped SnO_(2)(ITO)nano ceramics that own three-in-one functionalities:1)using conductive ITO enables minimizing the total carbon content to an extremely low mass ratio(~3%)in cathodes,elevating the electrode tap density and averting the electrolyte overuse;2)polar ITO nanoclusters can serve as robust anchors toward Li polysulfide(LiPS)by electrostatic adsorption or chemical bond interactions;3)they offer catalysis centers for liquid–solid phase conversions of S-based actives.Also,such ceramics are intrinsically nonflammable,preventing S cathodes away from thermal runaway or explosion.These merits entail our configured cathodes with high tap density(1.54 g cm^(−3)),less electrolyte usage,good security for flame retardance,and decent Li-storage behaviors.With lean and LiNO_(3)-free electrolyte,packed full cells exhibit excellent redox kinetics,suppressed LiPS shuttling,and excellent cyclability.This may trigger great research enthusiasm in rational design of low-carbon and safer S cathodes.

Experimental Evaluation of Thermal Conductivity and Other Thermophysical Properties of Nanofluids Based on Functionalized (-OH) Mwcnt Nanoparticles Dispersed in Distilled Water

A possible way to increase thermal conductivity of working fluids, while keeping pressure drop at acceptable levels, is through nanofluids. Nanofluids are nano-sized particles dispersed in conventional working fluids. A great number of materials have potential to be used in nanoparticles production and then in nanofluids;one of them is Multi-Walled Carbon Nano Tubes (MWCNT). They have thermal conductivity around 3000 W/mK while other materials used as nanoparticles like CuO have thermal conductivity of 76.5 W/mK. Due to this fact, MWCNT nanoparticles have potential to be used in nanofluids production, aiming to increase heat transfer rate in energy systems. In this context, the main goal of this paper is to evaluate from the synthesis to the experimental measurement of thermal conductivity of nanofluid samples based on functionalized (-OH) MWCNT nanoparticles. They will be analyzed nanoparticles with different functionalization degrees (4% wt, 6% wt, and 9% wt). In addition, it will be quantified other thermophysical properties (dynamic viscosity, specific heat and specific mass) of the synthetized nanofluids. So, the present work can contribute with experimental data that will help researches in the study and development of MWCNT nanofluids. According to the results, the maximum increment obtained in thermal conductivity was 10.65% in relation to the base fluid (water).

Arginine functionalized hydroxyapatite nanoparticles and its bioactivity for gene delivery

In order to further improve the transfection efficiency of hydroxyapatite nanoparticle （HAp）, arginine functionalized hydroxyapatite （HAp/Arg） was synthesized by hydrothermal synthesis. The morphology, crystallite size and zeta potential of the HAp/Arg were characterized by transmission electron microscopy （TEM）, atomic force microscopy （AFM） and zeta potential analyzer. The loading and protecting properties of HAp/Arg to DNA were tested by electrophoresis. Its cytotoxicity was also measured in Hela cells and HAEC cells by MTT and LDH, and its transfection efficiency was examined by fluorescence microscope and flow cytometry. The results reveal that HAp/Arg is short rod-like and nano single crystal, the mean diameter is 50-90 nm and zeta potential is 35.8 mV at pH 7.4. HAp/Arg to DNA can be condensed by electrostatic effect and protect DNA against degradation in DNase I, and shows high transfection efficiency without cytotoxicity. These results suggest that HAp/Arg can be a promising alternative as a novel gene delivery system.

Selective removal of 2,4-dichlorophenoxyacetic acid from water by molecularly-imprinted amino-functionalized silica gel sorbent

A molecularly-imprinted amino-functionalized sorbent for selective removal of 2,4-dichlorophenoxyacetic acid （2,4-D） was prepared by a surface imprinting technique in combination with a sol-gel process. The 2,4-D-imprinted amino-functionalized silica sorbent was characterized by FT-IR, nitrogen adsorption and static adsorption experiments. The selectivity of the sorbent was investigated by a batch competitive binding experiment using an aqueous 2,4-D and 2,4-dichlorophenol （2,4-DCP） mixture or using an aqueous 2,4-D and 2,4- dichlorophenylacetic acid （DPAC） mixture. The largest selectivity coefficient for 2,4-D in the presence of 2,4-DCP was found to be over 18, the largest relative selectivity coefficient between 2,4-D and 2,4-DCP over 9. The static uptake capacity and selectivity coefficient of the 2,4-D-imprinted functionalized sorbent are higher than those of the non-imprinted sorbent. The imprinted functionalized silica gel sorbent offered a fast kinetics for the extraction/stripping of 2,4-D, 73% of binding capacity （200 mg/L 2,4-D onto 20 mg of imprinted sorbent） was obtained within 5 min and the adsorbed 2,4-D can be easily stripped by the mixture solution of ethanol and 6 mol/L HC1 （V：V =1：1）. In a test of five extraction/stripping cycles, the adsorption capacity of the sorbent was all above 93% of that of the fresh sorbent. Experimental result showed the potential of molecularly-imprinted amino-functionalized sorbent for selective removal of 2,4-D.

The latest development on amine functionalized solid adsorbents for post-combustion CO_(2)capture:Analysis review

Global warming and associated global climate change have led to serious efforts towards reducing CO_(2)emissions through the CO_(2)capture from the major emission sources.CO_(2)capture using the amine functionalized adsorbents is regard as a direct and effective way to reducing CO_(2)emissions due to their large CO_(2)adsorption amount,excellent CO_(2)adsorption selectivity and lower energy requirements for adsorbent regeneration.Moreover,large number of achievements on the amine functionalized solid adsorbent have been recorded for the enhanced CO_(2)capture in the past few years.In view of this,we review and analyze the recent advances in amine functionalized solid adsorbents prepared with different supporting materials including mesoporous silica,zeolite,porous carbon materials,metal organic frameworks(MOF)and other composite porous materials.In addition,amine functionalized solid adsorbents derived from waste resources are also reviewed because of the large number demand for cost-effective carbon dioxide adsorbents and the processing needs of waste resources.Considering the importance of the stability of the adsorbent in practical applications,advanced research in the capture cycle stability has also been summarized and analyzed.Finally,we summarize the review and offer the recommendations for the development of amine-based solid adsorbents for carbon dioxide capture.

Preparation of organically functionalized silica gel as adsorbent for copper ion adsorption

A novel adsorbent （AMPS-silica） was synthesized by bounding AMPS （2-acrylamido-2-methylpropanesulfonic acid） onto silica surface, which functioned with γ-methacryloxypropyltrimethoxysilane reagent. The adsorbent was characterized by nitrogen adsorption/desorption measurement, thermogravimetric analysis （TGA） and potentiometric titration analysis. The TGA result indicated that the surface modification reactions introduced some organic functional groups onto the surface of silica. The surface area of AMPSsilica was 389.7 m2/g. The adsorbent was examined for copper ion removal in series of batch adsorption experiments. Results showed that the adsorption of Cu2＋ onto AMPS-silica was pH dependent, and the adsorption capacity increased with increasing pH from 2 to 6. The adsorption kinetics showed that Cu^2＋ adsorption was fast and the data fitted well with a pseudo secondorder kinetic model. The adsorption of Cu^2＋ onto AMPS-silica obeyed both Freundlich and Langmuir isotherms, with r^2 = 0.993 and r^2 = 0.984, respectively. The maximum Cu^2＋ adsorption capacity was 19.9 mg/g. The involved mechanism might be the adsorption through metal binding with organic functional groups such as carboxyl, amino and sulfonic groups. Cu^2＋ loaded on AMPS-silica could be desorbed in HNO3 solution, and the adsorption properties remain stable after three adsorption-desorption cycles.

Synthesis of Fischer indole derivatives using carboxyl-functionalized ionic liquid as an efficient and recyclable catalyst

Fischer indole cyclization of phenylhydrazine and various ketones using carboxyl-functionalized ionic liquid, 1-carboxymethyl- 3-methylimidazolium tetrafluoroborate （abbreviated as [crnmim] [BF4]） as catalyst was successfully performed. The yields of the target compounds were 80-92%, the purities were 96-98%. The catalyst could be recovered and reused for at least six times without significant loss in activity.

The investigation and optimization of drag reduction in turbulent flow of Newtonian fluid passing through horizontal pipelines using functionalized magnetic nanophotocatalysts and lecithin

The nanophotocatalysts were synthesized in four stages and evaluated by FTIR, FESEM and VSM analysis. The influence of nanofluids containing functionalized magnetic Ti O2 nanophotocatalyst and dipalmitoylphosphatidylcholine lecithin in drag reduction of turbulent flow in four horizontal pipelines was studied. The effective parameters on drag reduction(nanoparticle concentration, surfactant concentration, p H and Re number) were investigated and optimized in each pipeline using response surface method. The drag reduction in 1/2 " galvanized, 3/4" galvanized, 1/2 "five-layer and 1/2" cuprous pipelines was found 99.1%, 92.5%, 87.6% and 85.2%, respectively. The model adequacy was measured using ANOVA. Based on the high determination coefficient, more than 95% of variance of experimental data in all pipelines was described by quadratic model.

Platinum catalysts supported on Nafion functionalized carbon black for fuel cell application

We report a high performance supported Pt catalyst, in which a perfluorosulfonic acid （Nation） functionalized carbon black is used as support. The catalyst is characterized by infrared spectroscopy （IR）, transmission electron microscopy （TEM） and X-ray diffraction （XRD）. The TEM image shows that the active Pt component is in nanoparticles and highly dispersed on the carbon black with an average particle size of 1.9 nm. The catalyst shows improved activity towards the methanol anodic oxidation and oxygen reduction reaction （ORR）, resulting from the high dispersion of active Pt component. It leads to increases in electrochemically accessible surface areas and ion channels, as well as easier charge- transfer at polymer/electrolyte interfaces. The high platinum utilization and high performance of Pt/Nafion-C catalyst make it a promising electrocatalyst for fuel cell application.

Functionalized Hydrogels for Articular Cartilage Tissue Engineering

Articular cartilage(AC)is an avascular and flexible connective tissue located on the bone surface in the diarthrodial joints.AC defects are common in the knees of young and physically active individuals.Because of the lack of suitable tissue-engineered artificial matrices,current therapies for AC defects,espe-cially full-thickness AC defects and osteochondral interfaces,fail to replace or regenerate damaged carti-lage adequately.With rapid research and development advancements in AC tissue engineering(ACTE),functionalized hydrogels have emerged as promising cartilage matrix substitutes because of their favor-able biomechanical properties,water content,swelling ability,cytocompatibility,biodegradability,and lubricating behaviors.They can be rationally designed and conveniently tuned to simulate the extracel-lular matrix of cartilage.This article briefly introduces the composition,structure,and function of AC and its defects,followed by a comprehensive review of the exquisite(bio)design and(bio)fabrication of func-tionalized hydrogels for AC repair.Finally,we summarize the challenges encountered in functionalized hydrogel-based strategies for ACTE both in vivo and in vitro and the future directions for clinical translation.