Regenerative medicine strategies for chronic complete spinal cord injury

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

Advances in clinical applications of bioceramics in the new regenerative medicine era

In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and electrospinning.The new concept of regenerative medicine relies on biomaterials that can trigger in situ tissue regeneration and stem cell recruitment at the defect site.A large percentage of these biomaterials is ceramic-based as they provide the essential requirements of biomaterial principles such as tailored multisize porosity,antibacterial properties,and angiogenic properties.All these previously mentioned properties put bioceramics on top of the hierarchy of biomaterials utilized to stimulate tissue regeneration in soft and hard tissue wounds.Multiple clinical applications registered the use of these materials in triggering soft tissue regeneration in healthy and diabetic patients such as bioactive glass nanofibers.The results were promising and opened new frontiers for utilizing these materials on a larger scale.The same results were mentioned when using different forms and formulas of bioceramics in hard defect regeneration.Some bioceramics were used in combination with other polymers and biological scaffolds to improve their regenerative and mechanical properties.All this progress will enable a larger scale of patients to receive such services with ease and decrease the financial burden on the government.

Regenerative Braking Energy Recovery System of Metro Train Based on Dual-Mode Power Management

In order to fully utilize the regenerative braking energy of metro trains and stabilize the metro DC traction busbar voltage,a hybrid regenerative braking energy recovery system with a dual-mode power management strategy is proposed.Firstly,the construction of the hybrid regenerative braking energy recovery system is explained.Then,based on the power demand of low-voltage load in metro stations,a dual-mode power management strategy is proposed to allocate the reference power of each system according to the different working conditions,and the control methods of each system are set.Finally,the correctness and effectiveness of the dual-mode strategy are verified through simulation,and the proposed braking energy utilization scheme is compared with other singleform utilization schemes.The results illustrate that the hybrid system with the dual-mode strategy can effectively recycle the regenerative braking energy of metro train and inhibit the busbar voltage fluctuation;the proposed braking energy utilization scheme has certain advantages on energy recovery and DC bus voltage stabilization compared with other single-form schemes;the proposed power management strategy can correctly allocate the reference power of each system with a lower construction cost.

Modified approach of regenerative treatment for distal intrabony defect beneath non-keratinized mucosa at terminal molar:A case report

BACKGROUND Intrabony defects beneath non-keratinized mucosa are frequently observed at the distal site of terminal molars.Consequently,the application of regenerative treatment using the modified wedge-flap technique is considered impractical for these specific dental conditions.CASE SUMMARY This article proposes a modified surgical procedure aimed at exposing the distal intrabony defect by making a vertical incision in the keratinized buccal gingiva.The primary objective is to maintain gingival flap stability,thereby facilitating periodontal regeneration.The described technique was successfully employed in a case involving the left mandibular second molar,which presented with an intrabony defect without keratinized gingiva at the distal site.In this case,an incision was made on the disto-buccal gingival tissue,creating a tunnel-like separation of the distal non-keratinized soft tissue to expose the intrabony defect.Subsequently,bone grafting and guided tissue regeneration surgeries were performed,resulting in satisfactory bone fill at 9 mo postoperatively.CONCLUSION This technique offers a regenerative opportunity for the intrabony defects beneath non-keratinized mucosa and is recommended for further research.

Extracellular vesicles:Emerged as a promising strategy for regenerative medicine

Cell transplantation therapy has certain limitations including immune rejection and limited cell viability,which seriously hinder the transformation of stem cellbased tissue regeneration into clinical practice.Extracellular vesicles(EVs)not only possess the advantages of its derived cells,but also can avoid the risks of cell transplantation.EVs are intelligent and controllable biomaterials that can participate in a variety of physiological and pathological activities,tissue repair and regeneration by transmitting a variety of biological signals,showing great potential in cell-free tissue regeneration.In this review,we summarized the origins and characteristics of EVs,introduced the pivotal role of EVs in diverse tissues regeneration,discussed the underlying mechanisms,prospects,and challenges of EVs.We also pointed out the problems that need to be solved,application directions,and prospects of EVs in the future and shed new light on the novel cell-free strategy for using EVs in the field of regenerative medicine.

Injectable hydrogel made from antler mesenchyme matrix for regenerative wound healing via creating a fetal-like niche

BACKGROUND Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing.Previous studies have indicated that antler reserve mesenchyme(RM)cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages.AIM To develop hydrogels from the antler RM matrix(HARM)and evaluate the effect on wound healing.METHODS We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin.Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application.RESULTS The results showed that HARM accelerated wound healing rate and reduced scar formation.Also,HARM stimulated the regeneration of cutaneous appendages and blood vessels,and reduced collagen fiber aggregation.Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site.The levels of fetal wound healing-related genes,including Collagen III and TGFβ3 treated with HARM were all increased,while the expression levels of Collagen I,TGFβ1,and Engrailed 1 were decreased in the healing.Moreover,the number of stem cells was increased in the fetal-like niche created by HARM,which may contribute to the regeneration of cutaneous appendages.CONCLUSION Overall,we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds.We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing,and thus pave the way for HARM to be developed for the clinic use.

基于Self-Attention-BiLSTM网络的西瓜种苗叶片氮磷钾含量高光谱检测方法

元素含量无损检测技术可以为植物生长发育的环境精准调控提供关键实时数据。以西瓜苗为例,提出了一种基于图谱特征融合的氮磷钾含量深度学习检测方法。首先,使用高光谱仪拍摄西瓜苗叶片的高光谱图像,使用连续流动化学分析仪测定叶片的3种元素含量。然后,采用基线偏移校正(BOC)叠加高斯平滑滤波(GF)的光谱预处理方法和随机森林算法(RF)建立预测模型,基于竞争性自适应重加权采样(CARS)和连续投影算法(SPA)2种算法初步筛选出特征波长,再综合考虑波长数和建模精度设计了一种最优波长评价方法,将波长数进一步减少到3~4个。最后,提取使用U-Net网络分割的彩色图像颜色和纹理特征,和光谱反射率特征一起作为输入,基于自注意力机制-双向长短时记忆(Self-Attention-BiLSTM)网络构建了3种元素含量的预测模型。实验结果表明,氮磷钾含量预测的R2分别为0.961、0.954、0.958,RMSE分别为0.294%、0.262%、0.196%,实现了很好的建模效果。使用该模型对另2个品种西瓜进行测试,R2超过0.899、RMSE小于0.498%,表明该模型具有很好的泛化性。该高光谱建模方法使用少量波长光谱即实现了高精度检测,在精度和效率上达成了很好的平衡,为后续便携式高光谱检测装备开发奠定了理论基础。

Pitfalls and promises of bile duct alternatives:There is plenty of room in the regenerative surgery

Current abdominal surgery has several approaches for biliary reconstruction.However,the creation of functional and clinically applicable bile duct substitutes still represents an unmet need.In the paper by Miyazawa and colleagues,approaches to the creation of bile duct alternatives were summarized,and the reasons for the lack of development in this area were explained.The history of bile duct surgery since the nineteenth century was also traced,leading to the conclusion that the use of bioabsorbable materials holds promise for the creation of bile duct substitutes in the future.We suggest three ideas that may stimulate progress in the field of bile duct substitute creation.First,a systematic analysis of the causative factors leading to failure or success in the creation of bile duct substitutes may help to develop more effective approaches.Second,the regeneration of a bile duct is delicately balanced between epithelialization and subsequent submucosal maturation within limited time frames,which may be more apparent when using quantitative models to estimate outcomes.Third,the utilization of the organism’s endogenous regeneration abilities may enhance the creation of bile duct substitutes.We are convinced that an interdisciplinary approach,including quantitative methods,machine learning,and deep retrospective analysis of the causes that led to success and failure in studies on the creation of bile duct substitutes,holds great value.Additionally,more attention should be directed towards the balance of epithelialization and submucosal maturation rates,as well as induced angiogenesis.These ideas deserve further investigation to pave the way for bile duct restoration with physiologically relevant outcomes.

Unleashing the healing potential:Exploring next-generation regenerative protein nanoscaffolds for burn wound recovery

Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management.In this study,a greater efficacy in burn wound healing and the associated mechanisms ofα-lactalbumin(ALA)based electrospun nanofibrous scaffolds(ENs)as compared to other regenerative protein scaffolds were established.Bovine serum albumin(BSA),collagen type I(COL),lysozyme(LZM)and ALA were separately blended with poly(ε-caprolactone)(PCL)to fabricate four different composite ENs(LZM/PCL,BSA/PCL,COL/PCL and ALA/PCL ENs).The hydrophilic composite scaffolds exhibited an enhancedwettability and variablemechanical properties.The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs.As compared to PCL ENs and other composite scaffolds,the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen sponge^(■)on third-degree burn model.The enhanced wound healing activity of ALA/PCL ENs compared to other ENs could be attributed to their ability to promote serotonin production at wound sites.Collectively,this investigation demonstrated that ALA is a unique protein with a greater potential for burn wound healing as compared to other regenerative proteins when loaded in the nanofibrous scaffolds.

A Review of Electromagnetic Energy Regenerative Suspension System&Key Technologies

The active suspension has undoubtedly improved the performance of the vehicle,however,the trend of“lowcarbonization,intelligence,and informationization”in the automotive industry has put forward higher and more urgent requirements for the suspension system.The automotive industry and researchers favor active energy regeneration suspension technology with safety,comfort,and high energy regenerative efficiency.In this paper,we review the research progress of the structure form,optimization method,and control strategy of electromagnetic energy regenerative suspension.Specifically,comparing the pros and cons of the existing technology in solving the contradiction between dynamic performance and energy regeneration.In addition,the development trend of electromagnetic energy regenerative suspension in the field of structure form,optimization method,and control technology prospects.

Regenerative Medicine: A Review of Solutions in the Treatment of Skin Defects

The issue of skin defects is a major concern of almost every trauma surgeon after surgery. Despite numerous conventional methods and introduction of the reconstruction ladder, managing skin defects is still a challenge for the trauma surgeons. In recent years, parallel to the advances in the more conventional methods of skin repair, regenerative medicine has offered new and novel treatments. This article aims to explore these contemporary regenerative solutions as well as to review the conventional methods of treating skin defects.

Regenerative Medicine in Orthopaedics: Microsurgery Achievements for Translational Animal Model

Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of such primary findings. Method: By searching the papers related to the history of Regenerative Medicine (RM) and the news of Tissue Engineering (TE) in orthopedics in Pubmed, Scopus, and Google Scholar databases, we accessed a complete archive of various topics related to this field. Result: We first assessed the history and achievements of regenerative medicine, then we realized the importance of translational medical sciences and the role of animal models in this incipient phenomenon. Finally, after mastering the capabilities of microsurgery and the useful contribution of this technique to the advancement of clinical applications of regenerative medicine in various branches such as skin, skeletal system, nerves, and blood vessels, we decided to express the gist of our studies through this article. Conclusion: Considering the widespread use of small animals in regenerative medicine projects and the inevitable role of microsurgery in performing the best intervention on these animal models, the significant progress of regenerative medicine clinical application requires special attention to microsurgery in associated research.

Regenerative peripheral nerve interface prevents neuroma formation after peripheral nerve transection

Neuroma formation after peripheral nerve transection often leads to severe neuropathic pain.Regenerative peripheral nerve interface has been shown to reduce painful neuroma in the clinic.However,no reports have investigated the underlying mechanisms,and no comparative animal studies on regenerative peripheral nerve interface and other means of neuroma prevention have been conducted to date.In this study,we established a rat model of left sciatic nerve transfection,and subsequently interfered with the model using the regenerative peripheral nerve interface or proximal nerve stump implantation inside a fully innervated muscle.Results showed that,compared with rats subjected to nerve stump implantation inside the muscle,rats subjected to regenerative peripheral nerve interface intervention showed greater inhibition of the proliferation of collagenous fibers and irregular regenerated axons,lower expressions of the fibrosis markerα-smooth muscle actin and the inflammatory marker sigma-1 receptor in the proximal nerve stump,lower autophagy behaviors,lower expressions of c-fos and substance P,higher expression of glial cell line-derived neurotrophic factor in the ipsilateral dorsal root ganglia.These findings suggested that regenerative peripheral nerve interface inhibits peripheral nerve injury-induced neuroma formation and neuropathic pain possibly via the upregulation of the expression of glial cell line-derived neurotrophic factor in the dorsal root ganglia and reducing neuroinflammation in the nerve stump.

Energy Management of Networked Smart Railway Stations Considering Regenerative Braking, Energy Storage System, and Photovoltaic Units

The networking of microgrids has received significant attention in the form of a smart grid.In this paper,a set of smart railway stations,which is assumed as microgrids,is connected together.It has been tried to manage the energy exchanged between the networked microgrids to reduce received energy from the utility grid.Also,the operational costs of stations under various conditions decrease by applying the proposed method.The smart railway stations are studied in the presence of photovoltaic(PV)units,energy storage systems(ESSs),and regenerative braking strategies.Studying regenerative braking is one of the essential contributions.Moreover,the stochastic behaviors of the ESS’s initial state of energy and the uncertainty of PV power generation are taken into account through a scenario-based method.The networked microgrid scheme of railway stations(based on coordinated operation and scheduling)and independent operation of railway stations are studied.The proposed method is applied to realistic case studies,including three stations of Line 3 of Tehran Urban and Suburban Railway Operation Company(TUSROC).The rolling stock is simulated in the MATLAB environment.Thus,the coordinated operation of networked microgrids and independent operation of railway stations are optimized in the GAMS environment utilizing mixed-integer linear programming(MILP).

Self-Healable and Stretchable PAAc/XG/Bi_(2)Se_(0.3)Te_(2.7) Hybrid Hydrogel Thermoelectric Materials

Thermoelectric power generators have attracted increasing interest in recent years owing to their great potential in wearable electronics power supply.It is noted that thermoelectric power generators are easy to damage in the dynamic service process,resulting in the formation of microcracks and performance degradation.Herein,we prepare a new hybrid hydrogel thermoelectric material PAAc/XG/Bi_(2)Se_(0.3)Te_(2.7)by an in situ polymerization method,which shows a high stretchable and self-healable performance,as well as a good thermoelectric performance.For the sample with Bi_(2)Se_(0.3)Te_(2.7)content of 1.5 wt%(i.e.,PAAc/XG/Bi2Se0.3Te27(1.5 wt%)),which has a room temperature Seebeck coefficient of-0.45 mV K^(-1),and exhibits an open-circuit voltage of-17.91 mV and output power of 38.1 nW at a temperature difference of 40 K.After being completely cut off,the hybrid thermoelectric hydrogel automatically recovers its electrical characteristics within a response time of 2.0 s,and the healed hydrogel remains more than 99%of its initial power output.Such stretchable and self-healable hybrid hydrogel thermoelectric materials show promising potential for application in dynamic service conditions,such as wearable electronics.

RepBoTNet-CESA:An Alzheimer’s Disease Computer Aided Diagnosis Method Using Structural Reparameterization BoTNet and Cubic Embedding Self Attention

Various deep learning models have been proposed for the accurate assisted diagnosis of early-stage Alzheimer’s disease(AD).Most studies predominantly employ Convolutional Neural Networks(CNNs),which focus solely on local features,thus encountering difficulties in handling global features.In contrast to natural images,Structural Magnetic Resonance Imaging(sMRI)images exhibit a higher number of channel dimensions.However,during the Position Embedding stage ofMulti Head Self Attention(MHSA),the coded information related to the channel dimension is disregarded.To tackle these issues,we propose theRepBoTNet-CESA network,an advanced AD-aided diagnostic model that is capable of learning local and global features simultaneously.It combines the advantages of CNN networks in capturing local information and Transformer networks in integrating global information,reducing computational costs while achieving excellent classification performance.Moreover,it uses the Cubic Embedding Self Attention(CESA)proposed in this paper to incorporate the channel code information,enhancing the classification performance within the Transformer structure.Finally,the RepBoTNet-CESA performs well in various AD-aided diagnosis tasks,with an accuracy of 96.58%,precision of 97.26%,and recall of 96.23%in the AD/NC task;an accuracy of 92.75%,precision of 92.84%,and recall of 93.18%in the EMCI/NC task;and an accuracy of 80.97%,precision of 83.86%,and recall of 80.91%in the AD/EMCI/LMCI/NC task.This demonstrates that RepBoTNet-CESA delivers outstanding outcomes in various AD-aided diagnostic tasks.Furthermore,our study has shown that MHSA exhibits superior performance compared to conventional attention mechanisms in enhancing ResNet performance.Besides,the Deeper RepBoTNet-CESA network fails to make further progress in AD-aided diagnostic tasks.

Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury:A comparative analysis with mesenchymal stem cells

BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferation.CONCLUSION Our study demonstrated the potential of USCs for the treatment of AKI,representing a new clinical therapeutic strategy.

Unified Description of the Three Stable Particles in Self-Action Allows Determination of Their Relative Masses

The Dirac equation γμ(δμ-eAμ)Ψ=mc2Ψ describes the bound states of the electron under the action of external potentials, Aμ. We assumed that the fundamental form of the Dirac equation γμ(δμ-Sμ)Ψ=0 should describe the stable particles (the electron, the proton and the dark-matter-particle (dmp)) bound to themselves under the action of their own potentials Sμ. The new equation reveals that self energy is consequence of self action, it also reveals that the spin angular momentum is consequence of the dynamic structure of the stable particles. The quantitative results are the determination of their relative masses as well as the determination of the electromagnetic coupling constant.

Safety and efficacy of Kaffes intraductal self-expanding metal stents in the management of post-liver transplant anastomotic strictures

BACKGROUND Endoscopic management is the first-line therapy for post-liver-transplant anas-tomotic strictures.Although the optimal duration of treatment with plastic stents has been reported to be 8-12 months,data on safety and duration for metal stents in this setting is scarce.Due to limited access to endoscopic retrograde cholan-giopancreatography(ERCP)during the coronavirus disease 2019 pandemic in our centre,there was a change in practice towards increased usage and length-of-stay of the Kaffes biliary intraductal self-expanding stent in patients with suitable anatomy.This was mainly due to the theoretical benefit of Kaffes stents allowing for longer indwelling periods compared to the traditional plastic stents.METHODS Adult liver transplant recipients aged 18 years and above who underwent ERCP were retrospectively identified during a 10-year period through a database query.Unplanned admissions post-Kaffes stent insertion were identified manually through electronic and scanned medical records.The main outcome was the incidence of complications when stents were left indwelling for 3 months vs 6 months.Stent efficacy was calculated via rates of stricture recurrence between patients that had stenting courses for≤120 d or>120 d.RESULTS During the study period,a total of 66 ERCPs with Kaffes insertion were performed in 54 patients throughout their stenting course.In 33 ERCPs,the stent was removed or exchanged on a 3-month interval.No pancreatitis,perfor-ations or deaths occurred.Minor post-ERCP complications were similar between the 3-month(abdominal pain and intraductal migration)and 6-month(abdominal pain,septic shower and embedded stent)groups-6.1%vs 9.1%respectively,P=0.40.All strictures resolved at the end of the stenting course,but the stenting course was variable from 3 to 22 months.The recurrence rate for stenting courses lasting for up to 120 d was 71.4%and 21.4%for stenting courses of 121 d or over(P=0.03).There were 28 patients that were treated with a single ERCP with Kaffes,21 with removal after 120 d and 7 within 120 d.There was a significant improvement in stricture recurrence when the Kaffes was removed after 120 d when a single ERCP was used for the entire stenting course(71.0%vs 10.0%,P=0.01).CONCLUSION Utilising a single Kaffes intraductal fully-covered metal stent for at least 4 months is safe and efficacious for the management of post-transplant anastomotic strictures.

Blended Regenerative Anti-Lock Braking System and Electronic Wedge Brake Coordinate Control Ensuring Maximal Energy Recovery and Stability of All-Wheel-Motor-Drive Electric Vehicles

ABS is an active safety system which showed a valuable contribution to vehicle safety and stability since it was first introduced. Recently, EVs with in-wheel-motors have drawn increasing attention owing to their greatest advantages. Wheels torques are precisely and swiftly controlled thanks to electric motors and their advanced driving techniques. In this paper, a regenerative-ABS control RABS is proposed for all-in-wheel-motors-drive EVs. The RABS is realized as a pure electronic braking system called brake-by-wire. A coordination strategy is suggested to control RABS compromising three layers. First, wheels slip control takes place, and braking torque is calculated in the higher layer. In the coordinate interlayer, torque is allocated between actuators ensuring maximal energy recovery and vehicle stability. While in the lower layer, actuator control is performed. The RABS effectiveness is validated on a 3-DOF EVSimulink model through two straight-line braking manoeuvres with low and high initial speeds of 50 km/h and 150 km/h, respectively. Both regular and emergency braking manoeuvres are considered with ABS enabled and disabled for comparison. Simulation results showed the high performance of the proposed RABS control in terms of vehicle stability, brake response, stopping distance, and battery re-charging.