Enhancing m^(6)A modification in the motor cortex facilitates corticospinal tract remodeling after spinal cord injury

Spinal cord injury typically causes corticospinal tract disruption. Although the disrupted corticospinal tract can self-regenerate to a certain degree, the underlying mechanism of this process is still unclear. N6-methyladenosine(m^(6)A) modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes. However, whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown. We found that expression of methyltransferase 14 protein(METTL14) in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels. Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury. Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction, we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner, thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration. Finally, we administered syringin, a stabilizer of METTL14, using molecular docking. Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14. Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.

Dysregulation of RNA modification systems in clinical populations with neurocognitive disorders

The study of modified RNA known as epitranscriptomics has become increasingly relevant in our understanding of disease-modifying mechanisms.Methylation of N6 adenosine(m^(6)A)and C5 cytosine(m^(5)C)bases occur on mRNAs,tRNA,mt-tRNA,and rRNA species as well as non-coding RNAs.With emerging knowledge of RNA binding proteins that act as writer,reader,and eraser effector proteins,comes a new understanding of physiological processes controlled by these systems.Such processes when spatiotemporally disrupted within cellular nanodomains in highly specialized tissues such as the brain,give rise to different forms of disease.In this review,we discuss accumulating evidence that changes in the m^(6)A and m^(5)C methylation systems contribute to neurocognitive disorders.Early studies first identified mutations within FMR1 to cause intellectual disability Fragile X syndromes several years before FMR1 was identified as an m^(6)A RNA reader protein.Subsequently,familial mutations within the m^(6)A writer gene METTL5,m^(5)C writer genes NSUN2,NSUN3,NSUN5,and NSUN6,as well as THOC2 and THOC6 that form a protein complex with the m^(5)C reader protein ALYREF,were recognized to cause intellectual development disorders.Similarly,differences in expression of the m^(5)C writer and reader effector proteins,NSUN6,NSUN7,and ALYREF in brain tissue are indicated in individuals with Alzheimer's disease,individuals with a high neuropathological load or have suffered traumatic brain injury.Likewise,an abundance of m^(6)A reader and anti-reader proteins are reported to change across brain regions in Lewy bodies diseases,Alzheimer's disease,and individuals with high cognitive reserve.m^(6)A-modified RNAs are also reported significantly more abundant in dementia with Lewy bodies brain tissue but significantly reduced in Parkinson's disease tissue,whilst modified RNAs are misplaced within diseased cells,particularly where synapses are located.In parahippocampal brain tissue,m^(6)A modification is enriched in transcripts associated with psychiatric disorders including conditions with clear cognitive deficits.These findings indicate a diverse set of molecular mechanisms are influenced by RNA methylation systems that can cause neuronal and synaptic dysfunction underlying neurocognitive disorders.Targeting these RNA modification systems brings new prospects for neural regenerative therapies.

Succinylation modification:a potential therapeutic target in stroke

Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology.Recently,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ischemia.However,the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood.We aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after stroke.We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke.The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases.Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes.Sirtuins,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes.Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke.Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke studies.However,their therapeutic efficacy in stroke patients should be validated.

Towards advanced zinc anodes by interfacial modification strategies for efficient aqueous zinc metal batteries

Developing sustainable and clean energy sources(e.g.,solar,wind,and tide energy)is essential to achieve the goal of carbon neutrality.Due to the discontinuous and inco nsistent nature of common clean energy sources,high-performance energy storage technologies are a critical part of achieving this target.Aqueous zinc metal batteries(AZMBs)with inherent safety,low cost,and competitive performance are regarded as one of the promising candidates for grid-scale energy storage.However,zinc metal anodes(ZMAs)with irreversible problems of dendrite growth,hydrogen evolution reaction,self-corrosio n,and other side reactions have seriously hindered the development and commercialization of AZMBs.An increasing number of researchers are focusing on the stability of ZMAs,so assessing the effectiveness of existing research strategies is critical to the development of AZMBs.This review aims to provide a comprehensive overview of the fundamentals and challenges of AZMBs.Resea rch strategies for interfacial modification of ZMAs are systematically presented.The features of artificial interfacial coating and in-situ interfacial coating of ZMAs are compared and discussed in detail,as well as the effect of modified interfacial ZMA on the full-battery performance.Finally,perspectives are provided on the problems and challenges of ZMAs.This review is expected to offer a constructive reference for the further development and commercialization of AZMBs.

A Facile Li_(2)TiO_(3) Surface Modification to Improve the Structure Stability and Electrochemical Performance of Full Concentration Gradient Li-Rich Oxides

Full concentration gradient lithium-rich layered oxides are catching lots of interest as the next generation cathode for lithium-ion batteries due to their high discharge voltage,reduced voltage decay and enhanced rate performance,whereas the high lithium residues on its surface impairs the structure stability and long-term cycle performance.Herein,a facile multifunctional surface modification method is implemented to eliminate surface lithium residues of full concentration gradient lithium-rich layered oxides by a wet chemistry reaction with tetrabutyl titanate and the post-annealing process.It realizes not only a stable Li_(2)TiO_(3)coating layer with 3D diffusion channels for fast Li^(+)ions transfer,but also dopes partial Ti^(4+)ions into the sub-surface region of full concentration gradient lithium-rich layered oxides to further strengthen its crystal structure.Consequently,the modified full concentration gradient lithium-rich layered oxides exhibit improved structure stability,elevated thermal stability with decomposition temperature from 289.57℃to 321.72℃,and enhanced cycle performance(205.1 mAh g^(-1)after 150 cycles)with slowed voltage drop(1.67 mV per cycle).This work proposes a facile and integrated modification method to enhance the comprehensive performance of full concentration gradient lithium-rich layered oxides,which can facilitate its practical application for developing higher energy density lithium-ion batteries.

Comprehensive analysis of the gut microbiome and posttranslational modifications elucidates the route involved in microbiota-host interactions

The gut microbiome interacts with the host to maintain body homeostasis,with gut microbial dysbiosis implicated in many diseases.However,the underlying mechanisms of gut microbe regulation of host behavior and brain functions remain unclear.This study aimed to elucidate the influence of gut microbiota on brain functions via post-translational modification mechanisms in the presence or absence of bacteria without any stimulation.We conducted succinylome analysis of hippocampal proteins in germ-free(GF)and specific pathogen-free(SPF)mice and metagenomic analysis of feces from SPF mice.These results were integrated with previously reported hippocampal acetylome and phosphorylome data from the same batch of mice.Subsequent bioinformatics analyses revealed 584 succinylation sites on 455 proteins,including 54 up-regulated succinylation sites on 91 proteins and 99 down-regulated sites on 51 proteins in the GF mice compared to the SPF mice.We constructed a panoramic map of gut microbiota-regulated succinylation,acetylation,and phosphorylation,and identified cross-talk and relative independence between the different types of post-translational modifications in modulating complicated intracellular pathways.Pearson correlation analysis indicated that 13 taxa,predominantly belonging to the Bacteroidetes phylum,were correlated with the biological functions of post-translational modifications.Positive correlations between these taxa and succinylation and negative correlations between these taxa and acetylation were identified in the modulation of intracellular pathways.This study highlights the hippocampal physiological changes induced by the absence of gut microbiota,and proteomic quantification of succinylation,phosphorylation,and acetylation,contributing to our understanding of the role of the gut microbiome in brain function and behavioral phenotypes.

A concise review on surface and structural modification of porous zeolite scaffold for enhanced hydrogen storage

Investigating zeolites as hydrogen storage scaffolds is imperative due to their porous nature and favorable physicochemical properties.Nevertheless,the storage capacity of the unmodified zeolites has been rather unsatisfactory(0.224%-1.082%(mass))compared to its modified counterpart.Thus,the contemporary focus on enhancing hydrogen storage capacities has led to significant attention towards the utilization of modified zeolites,with studies exploring surface modifications through physical and chemical treatments,as well as the integration of various active metals.The enhanced hydrogen storage properties of zeolites are attributed to the presence of aluminosilicates from alkaline and alkaline-earth metals,resulting in increased storage capacity through interactions with the charge density of these aluminosilicates.Therefore,there is a great demand to critically review their role such as well-defined topology,pore structure,good thermal stability,and tunable hydrophilicity in enhanced hydrogen storage.This article aimed to critically review the recent research findings based on modified zeolite performance for enhanced hydrogen storage.Some of the factors affecting the hydrogen storage capacities of zeolites that can affect the rate of reaction and the stability of the adsorbent,like pressure,structure,and morphology were studied,and examined.Then,future perspectives,recommendations,and directions for modified zeolites were discussed.

Influence of laser parameters on the microstructures and surface properties in laser surface modification of biomedical magnesium alloys

Biodegradable implants from magnesium(Mg)alloys have emerged in the biomedical field especially in the orthopedic and cardiovascular stent applications owing to their low density,high specific strength,excellent machinability,good biocompatibility,and biodegradability.The primary shortcoming of Mg-based implants is their low corrosion resistance in the physiological environment,which results in premature mechanical integrity loss before adequate healing and the production of excessive hydrogen gas,which is harmful to the body tissues and negatively affects the biocompatibility of the implant.Laser surface modification has recently received attention because it can improve the surface properties such as surface chemistry,roughness,topography,corrosion resistance,wear resistance,hydrophilicity,and thus cell response to the surface of the material.The composition and microstructures including textures and phases of laser-treated surfaces depend largely on the laser processing parameters(input laser power,laser scan velocity,frequency,pulse duration,pressure,gas circulation,working time,spot size,beam focal position,and laser track overlap)and the thermophysical properties of the substrate(solubility,melting point,and boiling point).This review investigates the impacts of various laser surface modification techniques including laser surface melting,laser surface alloying,laser cladding,laser surface texturing,and laser shock peening,and highlights their significance in improving the surface properties of biodegradable Mg alloys for implant applications.Additionally,we explore how different laser process parameters affect its composition,microstructure,and surface properties in each laser surface modification technique.

Emerging perovskite materials for supercapacitors:Structure,synthesis,modification,advanced characterization,theoretical calculation and electrochemical performance

As a new generation electrode materials for energy storage,perovskites have attracted wide attention because of their unique crystal structure,reversible active sites,rich oxygen vacancies,and good stability.In this review,the design and engineering progress of perovskite materials for supercapacitors(SCs)in recent years is summarized.Specifically,the review will focus on four types of perovskites,perovskite oxides,halide perovskites,fluoride perovskites,and multi-perovskites,within the context of their intrinsic structure and corresponding electrochemical performance.A series of experimental variables,such as synthesis,crystal structure,and electrochemical reaction mechanism,will be carefully analyzed by combining various advanced characterization techniques and theoretical calculations.The applications of these materials as electrodes are then featured for various SCs.Finally,we look forward to the prospects and challenges of perovskite-type SCs electrodes,as well as the future research direction.

Mechanism, modification and stability of tungsten oxide-based electrocatalysts for water splitting: A review

Electrocatalysis plays a crucial role in the field of clean energy conversion and provides essential support for the development of eco-friendly technology. There is a pressing need for electrocatalysts in renewable energy systems that exhibit exceptional activity, selectivity, stability, and economic viability. The utilization of metal oxides as electrocatalysts for the process of water splitting has made substantial progress in both theoretical and practical aspects and has emerged as a widely explored field of research. Tungsten oxides(WO_(x)) have attracted much attention and are regarded as a highly promising electrocatalytic material due to their exceptional electrocatalytic activity, cost-effectiveness, and ability to withstand extreme conditions. This review introduces the fundamental mechanism of WOx-based electrocatalysts for the hydrogen evolution reaction and the oxygen evolution reaction, providing a comprehensive overview of recent research advancements in their modification. Factors contributing to the catalytic activity and stability of WOxare explored, highlighting their potential for industrial applications. The aim herein is to provide guidelines for the design and fabrication of WOx-based electrocatalysts, thereby facilitating further research on their mechanistic properties and stability improvements in water splitting.

Coupling effect of cement-stabilization and biopolymer-modification on the mechanical behavior of dredged sediment

Nowadays,biopolymer stabilization as a promising eco-friendly approach in soft ground improvement has attracted wide attentions.However,the feasibility of using biopolymer as a green additive of cementstabilized dredged sediment(CDS)with high water content is still unknown.In this study,guar gum(GG)and xanthan gum(XG)were adopted as typical biopolymers,and a series of unconfined compressive strength(UCS),splitting tensile strength(STS)and scanning electron microscopy(SEM)tests were performed to evaluate the mechanical and microstructural properties of XG-and GG-modified CDSs considering several factors including biopolymer modification,binderesoil ratio and wateresolid ratio.Furthermore,the micro-mechanisms revealing the evolutions of mechanical properties of biopolymermodified CDS were analyzed.The results indicate that the addition of XG can effectively improve the strength of CDS,while the GG has a side effect.The XG content of 9%was recommended,which can improve the 7 d-and 28 d-UCSs by 196%and 51.8%,together with the 7 d-and 28 d-STSs by 118.3%and 42.2%,respectively.Increasing the binderesoil ratio or decreasing the wateresolid ratio significantly improved the strength gaining but aggravated the brittleness characteristics of CDS.Adding XG to CDS contributed to the formation of microstructure with more compactness and higher cementation degrees of ordinary Portland cement(OPC)-XG-stabilized DS(CXDS).The micro-mechanism models revealing the interactions of multiple media including OPC cementation,biopolymer film bonding and bridging effects inside CXDS were proposed.The key findings confirm the feasibility of XG modification as a green and high-efficiency mean for improving the mechanical properties of CDS.

Recent Advances in Interface Modification of Cu/graphite Composites and Layered Ternary Carbides of Modified Layer Candidate

We review the fundamental properties and significant issues related to Cu/graphite composites.In particular,recent research on the interfacial modification of Cu/graphite composites is addressed,including the metal-modified layer,carbide-modified layer,and combined modified layer.Additionally,we propose the use of ternary layered carbide as an interface modification layer for Cu/graphite composites.

Effect of Modification Treatment on Chloride Ions Permeability and Microstructure of Recycled Brick-mixed Aggregate Concrete

The modification methods of pozzolan slurry combined with sodium silicate and silicon-based additive were respectively adopted to treat recycled coarse brick-mixed aggregate(RCBA)in this study.The compressive strength and chloride permeability resistance of recycled aggregate concrete(RAC)before and after modification treatment were tested,and the microstructure of RAC was analyzed by mercury intrusion porosimetry(MIP)and scanning electron microscopy(SEM).The results show that the physical properties of RCBA strengthened by modification treatment are improved,and the compressive strength and chloride permeability resistance of treated RAC are also significantly improved.The modification treatment optimizes the pore size distribution of RAC,which increases the number of gel pores and transition pores,and decreases the number of capillary pores and macro pores.The surface fractal dimension shows a significant correlation with chloride diffusion coefficient,indicating that the variation of chloride permeability of treated RAC is consistent with the microstructure evolution.

Effect of surface modification on the radiation stability of diamond ohmic contacts

The ohmic contact interface between diamond and metal is essential for the application of diamond detectors.Surface modification can significantly affect the contact performance and eliminate the interface polarization effect.However,the radiation stability of a diamond detector is also sensitive to surface modification.In this work,the influence of surface modification technology on a diamond ohmic contact under high-energy radiation was investigated.Before radiation,the specific contact resistivities(ρc)between Ti/Pt/Au-hydrogen-terminated diamond(H-diamond)and Ti/Pt/Au-oxygenterminated diamond(O-diamond)were 2.0×10^(-4)W·cm^(2) and 4.3×10^(-3)Wcm^(2),respectively.After 10 MeV electron radiation,the ρc of Ti/Pt/Au H-diamond and Ti/Pt/Au O-diamond were 5.3×10^(-3)W·cm^(2)and 9.1×10^(-3)W·cm^(2),respectively.The rates of change of ρc of H-diamond and O-diamond after radiation were 2550%and 112%,respectively.The electron radiation promotes bond reconstruction of the diamond surface,resulting in an increase in ρc.

Modification of a ReaxFF potential at short range for energetic materials OA

The ReaxFF can describe the properties of energetic materials(EMs)at equilibrium state,but does not work properly in simulating high-energy particle irradiation process because of its weak short-range interaction.In this paper,a modification was made for such a potential by connecting ZieglerBiersack-Littmark(ZBL)potential to ReaxFF-lg through comparing to Density Functional Theory(DFT)results to accurately describe short-range interactions.After modification,the newly fitted ReaxFF-lg/ZBL potential predicts better the equation of state for EMs In displacement cascade simulations,comparing to results from ab initio molecular dynamics(AIMD),ReaxFF-lg/ZBL presented the similar transferred energy from a primary knock-on atom to surrounding atoms,better than the original ReaxFF-lg potential.Further large-scale displacement cascade simulations indicated ReaxFF-lg/ZBL could be applied for cascade simulations with PKA energy from less than 1 keV to high energy(e.g.35 keV)cases,which is suitable for effectively simulating high-energy displacement cascades in EMs using molecular dynamics method.

Synergy of Polydopamine‑Assisted Additive Modification and Hierarchical‑Morphology Poly(Vinylidene Fluoride)Nanofiber Mat for Ferroelectric‑Assisted Triboelectric Nanogenerator

In the last decade,numerous physical modification methods have been introduced to enhance triboelectric nanogenerator(TENG)performance although they generally require complex and multiple fabrication processes.This study proposes a facile fabrication process for Poly(vinylidene fluoride)(PVDF)nanofiber(NF)mats incorporating additive and nonadditive physical modifications.Patterned PVDF NF mats are prepared by electrospinning using a metal mesh as the NF collector.As a negative triboelectric material,the TENG with the patterned PVDF NF mat exhibits superior performance owing to the engineered morphology of the contact layer.PVDF is crucial in TENGs owing to its superior ferroelectric properties and surface charge density when combined with specific electroceramics.Hence,the synergy of the physical modification methods is achieved by incorporating BaTiO3(BTO)nanoparticles(NPs)into the PVDF.By functionalizing BTO NPs with polydopamine,the TENG performance is further improved owing to the enhanced dispersion of NPs and improved crystallinity of the PVDF chains.Utilizing large NPs produces a nanopatterning effect on the NF surface,thereby resulting in the hierarchical structure of the NF mats.The source of the voltage signals from the TENG is analyzed using fast Fourier transform.

Implications of electrode modifications in aqueous organic redox flow batteries

Aqueous organic redox flow batteries(RFBs)exhibit favorable characteristics,such as tunability,multielectron transfer capability,and stability of the redox active molecules utilized as anolytes and catholytes,making them very viable contenders for large-scale grid storage applications.Considerable attention has been paid on the development of efficient redox-active molecules and their performance optimization through chemical substitutions at various places on the backbone as part of the pursuit for high-performance RFBs.Despite the fact that electrodes are vital to optimal performance,they have not garnered significant attention.Limited research has been conducted on the effects of electrode modifications to improve the performance of RFBs.The primary emphasis has been given on the impact of electrode engineering to augment the efficiency of aqueous organic RFBs.An overview of electron transfer at the electrode-electrolyte interface is provided.The implications of electrode modification on the performance of redox flow batteries,with a particular focus on the anodic and cathodic half-cells separately,are then discussed.In each section,significant discrepancies surrounding the effects of electrode engineering are thoroughly examined and discussed.Finally,we have presented a comprehensive assessment along with our perspectives on the future trajectory.

Improved Efficiency and Stability of Organic Solar Cells by Interface Modification Using Atomic Layer Deposition of Ultrathin Aluminum Oxide

The interfacial contacts between the electron transporting layers(ETLs)and the photoactive layers are crucial to device performance and stability for OSCs with inverted architecture.Herein,atomic layer deposition(ALD)fabricated ultrathin Al_(2)O_(3)layers are applied to modify the ETLs/active blends(PM6:BTP-BO-4F)interfaces of OSCs,thus improving device performance.The ALD-Al_(2)O_(3)thin layers on ZnO significantly improved its surface morphology,which led to the decreased work function of ZnO and reduced recombination losses in devices.The simultaneous increase in open-circuit voltage(V_(OC)),short-circuit current density(J_(SC))and fill factor(FF)were achieved for the OSCs incorporated with ALD-Al_(2)O_(3)interlayers of a certain thickness,which produced a maximum PCE of 16.61%.Moreover,the ALD-Al_(2)O_(3)interlayers had significantly enhanced device stability by suppressing degradation of the photoactive layers induced by the photocatalytic activity of ZnO and passivating surface defects of ZnO that may play the role of active sites for the adsorption of oxygen and moisture.

Modification of Li_(3)PO_(4) layer effectively boosting lithium storage and thermal safety performance for LiCoO_(2) batteries

To meet the demand for high-performance LiCoO_(2) batteries,it is necessary to overcome challenges such as interface degradation and rapid capacity degradation caused by changes in bulk structure,especially under deep delithiation and high temperature conditions.The ion conductive coating layer of Li_(3)PO_(4) has been directly modified on the surface of LiCoO_(2) particles using magnetron sputtering method,significantly improving the lithium storage performance of LiCoO_(2)@Li_(3)PO_(4) composites.Compared to pure LiCoO_(2),the modified LiCoO_(2) sample exhibits obviously better cycle life and high-temperature performance.Especially,under the conditions of 2 and 1 C,the LiCoO_(2)@Li_(3)PO_(4) electrode delivers excellent cycling performance at high voltage of 4.5 V,with capacity retention rates of 89.7%and 75.7%at room temperature and high temperature of 45℃,being far greater than those of 12.3%and 29.1%for bare LiCoO_(2) electrodes.It is discovered that the Li_(3)PO_(4) coating layer not only effectively enhances interface compatibility and suppresses the irreversible phase transition of LiCoO_(2),but also further improves the Li^(+)transport kinetics and significantly reduces battery polarization,ultimately enabling the modified LiCoO_(2) electrode to exhibit excellent lithium storage performance and thermal safety characteristics under high voltage conditions.Thus,such effective modified strategy can undoubtedly provide an important academic inspiration for LiCoO_(2) implication.

Stem cell-based ischemic stroke therapy:Novel modifications and clinical challenges

Ischemic stroke(IS)causes severe disability and high mortality worldwide.Stem cell(SC)therapy exhibits unique therapeutic potential for IS that differs from current treatments.SC’s cell homing,differentiation and paracrine abilities give hope for neuroprotection.Recent studies on SC modification have enhanced therapeutic effects for IS,including gene transfection,nanoparticle modification,biomaterial modification and pretreatment.Thesemethods improve survival rate,homing,neural differentiation,and paracrine abilities in ischemic areas.However,many problems must be resolved before SC therapy can be clinically applied.These issues include production quality and quantity,stability during transportation and storage,as well as usage regulations.Herein,we reviewed the brief pathogenesis of IS,the“multi-mechanism”advantages of SCs for treating IS,various SC modification methods,and SC therapy challenges.We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.