Star power: harnessing the reactive astrocyte response to promote remyelination in multiple sclerosis

Astrocytes are indispensable for central nervous system development and homeostasis.In response to injury and disease,astrocytes are integral to the immunological-and the,albeit limited,repair response.In this review,we will examine some of the functions reactive astrocytes play in the context of multiple sclerosis and related animal models.We will consider the heterogeneity or plasticity of astrocytes and the mechanisms by which they promote or mitigate demyelination.Finally,we will discuss a set of biomedical strategies that can stimulate astrocytes in their promyelinating response.

Self-reinforced Calcium Phosphate Cement Inspired by Sea Cucumber Dermis

A composite bone cement based onα-TCP with self-reinforcing characteristics is prepared by compounding cellulose whiskers and polyvinyl alcohol in different proportions.In this system,we are inspired by the sea cucumber,which can alter the stiffness of their inner dermis reversibly.Through the formation of hydrogen bonds between the hydroxyl groups on the cellulose whiskers and PVA,the bone cement matrix can be strengthened during the curing process of cement.In the process of bone cement blending,there is more water,the hydrogen bond connection is destroyed,so the slurry has better fluidity at this time.As the hydration of the bone cement progresses,the reduction of the water phase leads to the formation of a permeable network structure of hydrogen bond connections between the whiskers.The dual-phase action of PVA and whiskers greatly increases the mechanical strength of the bone cement system(5.5 to 23.8 MPa),while the presence of polyvinyl alcohol improves the toughness of the bone cement system.This work was supposed to explore whether the chemoresponsive materials can be adapted to biomedical materials,for example,bone repair.

Neural membrane repair at the core of regeneration

Loss of plasma membrane integrity can compromise cell functioning and viability.To countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the emergence of vital membrane processes(Cooper and McNeil,2015).This relationship between basic cellular functioning and membrane repair highlights the fundamental significance of preserving membrane integrity for cellular life.

The influence of yttrium and manganese additions on the degradation and biocompatibility of magnesium-zinc-based alloys:In vitro and in vivo studies

The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone.The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration.In this study,we prepared and modified Mg-3Zn,Mg-3Zn-1Y,and Mg-2Zn-1Mn by hot extrusion,and used Mg-2.5Y-2.5Nd was as a control.We then investigated the effect of additions of Y and Mn on alloys'properties.Our results show that Mn and Y can improve not only compression strength but also corrosion resistance.The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro,and for this reason we selected it for implantation in vivo.The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction,and the degradation products left no signs of damage to the heart,liver,kidney,or brain.Furthermore,we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.

Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.

Neuronal conversion from glia to replenish the lost neurons

Neuronal injury,aging,and cerebrovascular and neurodegenerative diseases such as cerebral infarction,Alzheimer’s disease,Parkinson’s disease,frontotemporal dementia,amyotrophic lateral sclerosis,and Huntington’s disease are characte rized by significant neuronal loss.Unfo rtunately,the neurons of most mammals including humans do not possess the ability to self-regenerate.Replenishment of lost neurons becomes an appealing therapeutic strategy to reve rse the disease phenotype.Transplantation of pluripotent neural stem cells can supplement the missing neurons in the brain,but it carries the risk of causing gene mutation,tumorigenesis,severe inflammation,and obstructive hydrocephalus induced by brain edema.Conversion of neural or non-neural lineage cells into functional neurons is a promising strategy for the diseases involving neuron loss,which may overcome the above-mentioned disadvantages of neural stem cell therapy.Thus far,many strategies to transfo rm astrocytes,fibroblasts,microglia,Muller glia,NG2 cells,and other glial cells to mature and functional neurons,or for the conversion between neuronal subtypes have been developed thro ugh the regulation of transcription factors,polypyrimidine tra ct binding protein 1(PTBP1),and small chemical molecules or are based on a combination of several factors and the location in the central nervous system.However,some recent papers did not obtain expected results,and discrepancies exist.Therefore,in this review,we discuss the history of neuronal transdifferentiation,summarize the strategies for neuronal replenishment and conversion from glia,especially astrocytes,and point out that biosafety,new strategies,and the accurate origin of the truly co nverted neurons in vivo should be focused upon in future studies.It also arises the attention of replenishing the lost neurons from glia by gene therapies such as up-regulation of some transc ription factors or downregulation of PTBP1 or drug interfe rence therapies.

Role of transforming growth factor-βin peripheral nerve regeneration

Injuries caused by trauma and neurodegenerative diseases can damage the peripheral nervous system and cause functional deficits.Unlike in the central nervous system,damaged axons in peripheral nerves can be induced to regenerate in response to intrinsic cues after reprogramming or in a growth-promoting microenvironment created by Schwann cells.However,axon regeneration and repair do not automatically result in the restoration of function,which is the ultimate therapeutic goal but also a major clinical challenge.Transforming growth factor(TGF)is a multifunctional cytokine that regulates various biological processes including tissue repair,embryo development,and cell growth and differentiation.There is accumulating evidence that TGF-βfamily proteins participate in peripheral nerve repair through various factors and signaling pathways by regulating the growth and transformation of Schwann cells;recruiting specific immune cells;controlling the permeability of the blood-nerve barrier,thereby stimulating axon growth;and inhibiting remyelination of regenerated axons.TGF-βhas been applied to the treatment of peripheral nerve injury in animal models.In this context,we review the functions of TGF-βin peripheral nerve regeneration and potential clinical applications.

Spent graphite regeneration:Exploring diverse repairing manners with impurities-catalyzing effect towards high performance and low energy consumption

Spent battery recycling has received considerable attention because of its economic and environmental potential.A large amount of retired graphite has been produced as the main electrode material,accompanied by a detailed exploration of the repair mechanism.However,they still suffer from unclear repair mechanisms and physicochemical evolution.In this study,spent graphite was repaired employing three methodologies:pickling-sintering,pyrogenic-recovery,and high-temperature sintering.Owing to the catalytic effect of the metal-based impurities and temperature control,the as-obtained samples displayed an ordered transformation,including the interlayer distance,crystalline degree,and grain size.As anodes of lithium ions batteries,the capacity of repaired samples reached up to 310 mA h g^(-1)above after 300loops at 1.0 C,similar to that of commercial graphite.Meanwhile,benefitting from the effective assembly of carbon atoms in internal structure of graphite at>1400℃,their initial coulombic efficiency were>87%.Even at 2.0 C,the capacity of samples remained approximately 244 mA h g^(-1)after 500 cycles.Detailed electrochemical and kinetic analyses revealed that a low temperature enhanced the isotropy,thereby enhancing the rate properties.Further,economic and environmental analyses revealed that the revenue obtained through suitable pyrogenic-recovering manners was approximately the largest value(5500$t^(-1)).Thus,this study is expected to clarify the in-depth effect of different repair methods on the traits of graphite,while offering all-round evaluations of repaired graphite.

Experimental and Finite Element Analysis of Corroded High-Pressure Pipeline Repaired by Laminated Composite

Repairs of corroded high-pressure pipelines are essential for fluids transportation under high pressure.One of the methods used in their repairs is the use of layered composites.The composite used must have the necessary strength.Therefore,the experiments and analytical solutions presented in this paper are performed according to the relevant standards and codes,including ASME PCC-2,ASME B31.8S,ASME B31.4,ISO 24817 and ASME B31.G.In addition,the experimental tests are replicated numerically using the finite element method.Setting the strain gauges at different distances from the defect location,can reduce the nonlinear effects,deformation,and fluctuations due to the high pressure.The direct relationship between the depth of an axial defect and the stress concentration is observed at the inner side edges of the defect.Composite reparation reduces the non-linearities related to the sharp variation of the geometry and a more reliable numerical simulation could be performed.

Preheating-assisted solid-state friction stir repair of Al-Mg-Si alloy plate at different rotational speeds

Additive friction stir deposition(AFSD)is a novel structural repair and manufacturing technology has become a research hotspot at home and abroad in the past five years.In this work,the microstructural evolution and mechanical performance of the Al-Mg-Si alloy plate repaired by the preheating-assisted AFSD process were investigated.To evaluate the tool rotation speed and substrate preheating for repair quality,the AFSD technique was used to additively repair 5 mm depth blind holes on 6061 aluminum alloy substrates.The results showed that preheat-assisted AFSD repair significantly improved joint bonding and joint strength compared to the control non-preheat substrate condition.Moreover,increasing rotation speed was also beneficial to improve the metallurgical bonding of the interface and avoid volume defects.Under preheating conditions,the UTS and elongation were positively correlated with rotation speed.Under the process parameters of preheated substrate and tool rotation speed of 1000 r/min,defect-free specimens could be obtained accompanied by tensile fracture occurring in the substrate rather than the repaired zone.The UTS and elongation reached the maximum values of 164.2MPa and 13.4%,which are equivalent to 99.4%and 140%of the heated substrate,respectively.

Degradable magnesium alloy suture promotes fibrocartilaginous interface regeneration in a rat rotator cuff transosseous repair model

Despite transosseous rotator cuff tear repair using sutures is widely accepted for tendon-bone fixation,the fibrocartilaginous enthesis regeneration is still hardly achieved with the traditional sutures.In the present work,degradable magnesium(Mg)alloy wire was applied to suture supraspinatus tendon in a rat acute rotator cuff tear model with Vicryl Plus 4±0 absorbable suture as control.The shoulder joint humerus-supraspinatus tendon complex specimens were retrieved at 4,8,and 12 weeks after operation.The Mg alloy suture groups showed better biomechanical properties in terms of ultimate load to failure.Gross observation showed that hyperplastic response of the scar tissue at the tendon-bone interface is progressively alleviated over time in the both Mg alloy suture and Vicryl suture groups.In the histological analysis,for Mg alloy suture groups,chondrocytes appear to proliferate at 4 weeks postoperatively,and the tendon-bone interface showed an orderly structural transition zone at 8 weeks postoperatively.The collagenous fiber tended to be aligned and the tendon-bone interlocking structures apparently formed,where transitional structure from unmineralized fibrocartilage to mineralized fibrocartilage was closer to the native fibrocartilaginous enthesis.In vivo degradation of the magnesium alloy wire was completed within 12 weeks.The results indicated that Mg alloy wire was promising as degradable suture with the potential to promotes fibrocartilaginous interface regeneration in rotator cuff repair.

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

Bicuspidization Using the Open-Sleeve Technique for Congenital Aortic Stenosisduring Infancy

Congenital aortic stenosis(cAS)frequently requires intervention during the neonatal or infantile period.However,surgical repair is challenging because of the narrow surgical space.We performed bicuspidization using the open-sleeve technique for cAS with a unicuspid aortic valve in two patients.Postoperatively,the patients were doing well without reintervention for the aortic valve for 8 and 6 years,respectively.Their aortic annular diameter increased along with somatic growth.Bicuspidization for neonates or infancy can be performed safely using the open-sleeve technique as its midterm results have been satisfactory.

Reliability-based life-cycle cost seismic design optimization of coastal bridge piers with nonuniform corrosion using different materials

Reinforcement corrosion is the main cause of performance deterioration of reinforced concrete(RC)structures.Limited research has been performed to investigate the life-cycle cost(LCC)of coastal bridge piers with nonuniform corrosion using different materials.In this study,a reliability-based design optimization(RBDO)procedure is improved for the design of coastal bridge piers using six groups of commonly used materials,i.e.,normal performance concrete(NPC)with black steel(BS)rebar,high strength steel(HSS)rebar,epoxy coated(EC)rebar,and stainless steel(SS)rebar(named NPC-BS,NPC-HSS,NPC-EC,and NPC-SS,respectively),NPC with BS with silane soakage on the pier surface(named NPC-Silane),and high-performance concrete(HPC)with BS rebar(named HPC-BS).First,the RBDO procedure is improved for the design optimization of coastal bridge piers,and a bridge is selected to illustrate the procedure.Then,reliability analysis of the pier designed with each group of materials is carried out to obtain the time-dependent reliability in terms of the ultimate and serviceability performances.Next,the repair time of the pier is predicted based on the time-dependent reliability indices.Finally,the time-dependent LCCs for the pier are obtained for the selection of the optimal design.

Association between Helicobacter pylori infection,mismatch repair,HER2 and tumor-infiltrating lymphocytes in gastric cancer

BACKGROUND The influence of Helicobacter-pylori(H.pylori)infection and the characteristics of gastric cancer(GC)on tumor-infiltrating lymphocyte(TIL)levels has not been extensively studied.Analysis of infiltrating-immune-cell subtypes as well as survival is necessary to obtain comprehensive information.AIM To determine the rates of deficient mismatch-repair(dMMR),HER2-status and H.pylori infection and their association with TIL levels in GC.METHODS Samples from 503 resected GC tumors were included and TIL levels were evaluated following the international-TILs-working-group recommendations with assessment of the intratumoral(IT),stromal(ST)and invasive-border(IB)compartments.The density of CD3,CD8 and CD163 immune cells,and dMMR and HER2-status were determined by immunohistochemistry(IHC).H.pylori infection was evaluated by routine histology and quantitative PCR(qPCR)in a subset of samples.RESULTS dMMR was found in 34.4%,HER2+in 5%and H.pylori-positive in 55.7%of samples.High IT-TIL was associated with grade-3(P=0.038),while ST-TIL with grade-1(P<0.001),intestinal-histology(P<0.001)and no-recurrence(P=0.003).dMMR was associated with high TIL levels in the ST(P=0.019)and IB(P=0.01)compartments,and STCD3(P=0.049)and ST-CD8(P=0.05)densities.HER2-was associated with high IT-CD8(P=0.009).H.pylorinegative was associated with high IT-TIL levels(P=0.009)when assessed by routine-histology,and with high TIL levels in the 3 compartments(P=0.002-0.047)and CD8 density in the IT and ST compartments(P=0.001)when assessed by qPCR.A longer overall survival was associated with low IT-CD163(P=0.003)and CD8/CD3(P=0.001 in IT and P=0.002 in ST)and high IT-CD3(P=0.021),ST-CD3(P=0.003)and CD3/CD163(P=0.002).CONCLUSION TIL levels were related to dMMR and H.pylori-negativity.Low CD8/CD3 and high CD163/CD3 were associated with lower recurrence and longer survival.

From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

Spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoration of the injured spinal cord.

Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients

BACKGROUND RAS,BRAF,and mismatch repair(MMR)/microsatellite instability(MSI)are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer(CRC).However,their characteristics and influencing factors in Chinese patients have not been thoroughly described.AIM To analyze the clinicopathological features of KRAS,NRAS,BRAF,and PIK3CA mutations and the DNA MMR status in CRC.METHODS We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital.MMR proteins were tested using immunohistochemical analysis,and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction.Microsatellite status was determined using an MSI detection kit.Statistical analyses were conducted using SPSS software and logistic regression.RESULTS The KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 44.6%,3.4%,3.7%,and 3.9% of CRC patients,respectively.KRAS mutations were more likely to occur in patients with moderate-to-high differentiation.BRAF mutations were more likely to occur in patients with right-sided CRC,poorly differentiated,or no perineural invasion.Deficient MMR(dMMR)was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas.KRAS,NRAS,BRAF,and PIK3CA mutations were detected in 29.6%,1.1%,8.1%,and 22.3% of patients with dMMR,respectively.The dMMR was more likely to occur in patients with a family history of CRC,aged<50 years,right-sided CRC,poorly differentiated histology,no perineural invasion,and with carcinoma in situ,stage I,or stage II tumors.CONCLUSION This study analyzed the molecular profiles of KRAS,NRAS,BRAF,PIK3CA,and MMR/MSI in CRC,identifying key influencing factors,with implications for clinical management of CRC.

Study of damage behavior and repair effectiveness of patch repaired carbon fiber laminate under quasi-static indentation loading

Damage caused due to low-velocity impacts in composites leads to substantial deterioration in their residual strength and eventually provokes structural failure.This work presents an experimental investigation on the effects of different patch and parent laminate stacking sequences on the enhancement of impact strength of Carbon Fiber Reinforced Polymers(CFRP)composites by utilising the adhesively bonded external patch repair technique.Damage evolution study is also performed with the aid of Acoustic Emission(AE).Two different quasi-isotropic configurations were selected for the parent laminate,viz.,[45°/45°/0°/0°]s and[45°/0°/45°/0°]s.Quasi Static Indentation(QSI)test was performed on both the pristine laminates,and damage areas were detected by using the C-scan inspection technique.Damaged laminates were repaired by using a single-sided patch of two different configurations,viz.,[45°/45°/45°/45°]and[45°/0°/0°/45°],and employing a circular plug to fill the damaged hole.Four different combinations of repaired laminates with two configurations of each parent and patch laminate were produced,which were further subjected to the QSI test.The results reveal the effectiveness of the repair method,as all the repaired laminates show higher impact resistance compared to the respective pristine laminates.Patches of[45°/0°/0°/45°]configuration when repaired by taking[45°/45°/0°/0°]s and[45°/0°/45°/0°]s as parents exhibited 68%and 73%higher peak loads,respectively,than the respective pristine laminates.Furthermore,parent and patch of configuration[45°/0°/45°/0°]s and[45°/0°/0°/45°],respectively,attain the highest peak load,whereas[45°/45°/0°/0°]s and[45°/45°/45°/45°]combinations possess the most gradual decrease in the load.

High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

Resilience-Oriented Load Restoration Method and Repair Strategies for Regional Integrated Electricity-Natural Gas System

The rising frequency of extreme disaster events seriously threatens the safe and secure operation of the regional integrated electricity-natural gas system(RIENGS).With the growing level of coupling between electric and natural gas systems,it is critical to enhance the load restoration capability of both systems.This paper proposes a coordinated optimization strategy for resilience-enhanced RIENGS load restoration and repair scheduling and transforms it into a mixed integer second-order cone programming(MISOCP)model.The proposed model considers the distribution network reconfiguration and the coordinated repair strategy between the two systems,minimizing the total system load loss cost and repair time.In addition,a bi-directional gas flow model is used to describe the natural gas system,which can provide the RIENGS with more flexibility for load restoration during natural gas system failure.Finally,the effectiveness of the proposed approach is verified by conducting case studies on the test systems RIENGS E13-G7 and RIENGS E123-G20.