Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein thrombosis.Surgery is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury patients.Development of effective therapies fo r chronic spinal co rd injury patients is needed.We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive rehabilitation.This clinical trial was registered at ClinicalTrials.gov(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord compression.We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training alone.Overall,the surgical procedures and intensive rehabilitation were safe.American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries.Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Analytical Model and Topology Optimization of Doubly-fed Induction Generator

As the core component of energy conversion for large wind turbines,the output performance of doubly-fed induction generators (DFIGs) plays a decisive role in the power quality of wind turbines.To realize the fast and accurate design optimization of DFIGs,this paper proposes a novel hybriddriven surrogate-assisted optimization method.It firstly establishes an accurate subdomain model of DFIGs to analytically predict performance indexes.Furthermore,taking the inexpensive analytical dataset produced by the subdomain model as the source domain and the expensive finite element analysis dataset as the target domain,a high-precision surrogate model is trained in a transfer learning way and used for the subsequent multi-objective optimization process.Based on this model,taking the total harmonic distortion of electromotive force,cogging torque,and iron loss as objectives,and the slot and inner/outer diameters as parameters for optimizing the topology,achieve a rapid and accurate electromagnetic design for DFIGs.Finally,experiments are carried out on a 3MW DFIG to validate the effectiveness of the proposed method.

Motor neuron-specific RhoA knockout delays degeneration and promotes regeneration of dendrites in spinal ventral horn after brachial plexus injury

Dendrites play irreplaceable roles in the nerve conduction pathway and are vulnerable to various insults.Peripheral axotomy of motor neurons results in the retraction of dendritic arbors,and the dendritic arbor can be re-expanded when reinnervation is allowed.RhoA is a target that regulates the cytoskeleton and promotes neuronal survival and axon regeneration.However,the role of RhoA in dendrite degeneration and regeneration is unknown.In this study,we explored the potential role of RhoA in dendrites.A line of motor neuronal conditional knockout mice was developed by crossbreeding HB9~(Cre+)mice with RhoA~(flox/flox)mice.We established two models for assaying dendrite degeneration and regeneration,in which the brachial plexus was transection or crush injured,respectively.We found that at 28 days after brachial plexus transection,the density,complexity,and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice were slightly decreased compared with that in Cre mice.Dendrites underwent degeneration at 7 and 14 days after brachial plexus transection and recovered at 28–56 days.The density,complexity,and structural integrity of dendrites in the ventral horn of the spinal cord of RhoA conditional knockout mice recovered compared with results in Cre mice.These findings suggest that RhoA knockout in motor neurons attenuates dendrite degeneration and promotes dendrite regeneration after peripheral nerve injury.

Inhibitor of DNA binding 2 accelerates nerve regeneration after sciatic nerve injury in mice

Inhibitor of DNA binding 2(Id2)can promote axonal regeneration after injury of the central nervous system.However,whether Id2 can promote axonal regeneration and functional recovery after peripheral nerve injury is currently unknown.In this study,we established a mouse model of bilateral sciatic nerve crush injury.Two weeks before injury,AAV9-Id2-3×Flag-GFP was injected stereotaxically into the bilateral ventral horn of lumbar spinal cord.Our results showed that Id2 was successfully delivered into spinal cord motor neurons projecting to the sciatic nerve,and the number of regenerated motor axons in the sciatic nerve distal to the crush site was increased at 2 weeks after injury,arriving at the tibial nerve and reinnervating a few endplates in the gastrocnemius muscle.By 1 month after injury,extensive neuromuscular reinnervation occurred.In addition,the amplitude of compound muscle action potentials of the gastrocnemius muscle was markedly recovered,and their latency was shortened.These findings suggest that Id2 can accelerate axonal regeneration,promote neuromuscular reinnervation,and enhance functional improvement following sciatic nerve injury.Therefore,elevating the level of Id2 in adult neurons may present a promising strategy for peripheral nerve repair following injury.The study was approved by the Experimental Animal Ethics Committee of Jinan University(approval No.20160302003)on March 2,2016.

Effect of chondroitin sulfate proteoglycans on neuronal cell adhesion, spreading and neurite growth in culture

As one major component of extracellular matrix （ECM） in the central nervous system, chondroitin sul- fate proteoglycans （CSPGs） have long been known as inhibitors enriched in the glial scar that prevent axon regeneration after injury. Although many studies have shown that CSPGs inhibited neurite out- growth in vitro using different types of neurons, the mechanism by which CSPGs inhibit axonal growth remains poorly understood. Using cerebellar granule neuron （CGN） culture, in this study, we evaluated the effects of different concentrations of both immobilized and soluble CSPGs on neuronal growth, in- cluding cell adhesion, spreading and neurite growth. Neurite length decreased while CSPGs concentration arised, meanwhile, a decrease in cell density accompanied by an increase in cell aggregates formation was observed. Soluble CSPGs also showed an inhibition on neurite outgrowth, but it required a higher concen- tration to induce cell aggregates formation than coated CSPGs. We also found that growth cone size was significantly reduced on CSPGs and neuronal cell spreading was restrained by CSPGs, attributing to an inhibition on lamellipodial extension. The effect of CSPGs on neuron adhesion was further evidenced by interference reflection microscopy （IRM） which directly demonstrated that both CGNs and cerebral cortical neurons were more loosely adherent to a CSPG substrate. These data demonstrate that CSPGs have an effect on cell adhesion and spreading in addition to neurite outgrowth.

A brief review of recent advances in stem cell biology

Stem cells have the remarkable potential to develop into many different cell types, essentially with- out limit to replenish other cells as long as the person or animal is still alive, offering immense hope of curing Alzheimer＇s disease, repairing damaged spinal cords, treating kidney, liver and lung diseases and making damaged hearts whole. Until recently, scientists primarily worked with two kinds of stem cells from animals and humans： embryonic stem cells and non-embryonic ＂somatic＂ or ＂adult＂ stem cells. Recent breakthrough make it possible to convert or ＂reprogram＂ specialized adult cells to assume a stem stem-like cells with different technologies. The review will briefly dis- cuss the recent progresses in this area.

Accelerating hybrid and compact neural networks targeting perception and control domains with coarse-grained dataflow reconfiguration

Driven by continuous scaling of nanoscale semiconductor technologies,the past years have witnessed the progressive advancement of machine learning techniques and applications.Recently,dedicated machine learning accelerators,especially for neural networks,have attracted the research interests of computer architects and VLSI designers.State-of-the-art accelerators increase performance by deploying a huge amount of processing elements,however still face the issue of degraded resource utilization across hybrid and non-standard algorithmic kernels.In this work,we exploit the properties of important neural network kernels for both perception and control to propose a reconfigurable dataflow processor,which adjusts the patterns of data flowing,functionalities of processing elements and on-chip storages according to network kernels.In contrast to stateof-the-art fine-grained data flowing techniques,the proposed coarse-grained dataflow reconfiguration approach enables extensive sharing of computing and storage resources.Three hybrid networks for MobileNet,deep reinforcement learning and sequence classification are constructed and analyzed with customized instruction sets and toolchain.A test chip has been designed and fabricated under UMC 65 nm CMOS technology,with the measured power consumption of 7.51 mW under 100 MHz frequency on a die size of 1.8×1.8 mm^2.

Dimericbiscognienynes B and C: New diisoprenyl-cyclohexene-type meroterpenoid dimers from Biscogniauxia sp.

Dimericbiscognienynes B and C(1 and 2), two new diisoprenyl-cyclohexene-type meroterpenoid dimers,were isolated from Biscogniauxia sp. 71-10-1-1. Their structures, including the absolute configurations,were determined by spectroscopic analyses and ECD experiments. Meroterpenoids are special natural products that originate from mixed terpenoid-nonterpenoid pathway. As a member of meroterpenoid family, diisoprenyl-cyclohexene/ane-type meroterpenoids composed of two isoprenyl chains(C5 unit)and a cyclohexene/ane moiety(C6 unit), featuring diverse skeleton structures with wide range of bioactivities. In these reported diisoprenyl-cyclohexene/ane-type meroterpenoids, only three dimers were identified. The discovery of the two new dimers added members of this rare class of meroterpenoids.

Inhibition of MALT1 paracaspase activity improves lesion recovery following spinal cord injury

Spinal cord injury(SCI) is a devastating traumatic injury that causes persistent, severe motor and sensory dysfunction. Immune responses are involved in functional recovery after SCI. Mucosa-associated lymphoid tissue lymphoma translocation 1(MALT1) has been shown to regulate the survival and differentiation of immune cells and to play a critical role in many diseases, but its function in lesion recovery after SCI remains unclear. In this paper, we generated KI(knock in) mice with a point mutation(C472 G) in the active center of MALT1 and found that the KI mice exhibited improved functional recovery after SCI.Fewer macrophages were recruited to the injury site in KI mice and these macrophages differentiated into anti-inflammatory macrophages. Moreover, macrophages from KI mice exhibited reduced phosphorylation of p65, which in turn resulted in decreased SOCS3 expression and increased pSTAT6 levels.Similar results were obtained upon inhibition of MALT1 paracaspase with the small molecule inhibitor‘‘MI-2' or the more specific inhibitor ‘‘MLT-827'. In patients with SCI, peripheral blood mononuclear cells(PBMC) displayed increased MALT1 paracaspase. Human macrophages showed reduced proinflammatory and increased anti-inflammatory characteristics following the inhibition of MALT1 paracaspase. These findings suggest that inhibition of MALT1 paracaspase activity in the clinic may improve lesion recovery in subjects with SCI.

Planar cell polarity genes, Celsr1-3, in neural development

flamingo is among the ＇core＇ planar cell-polarity genes, protein of which belongs to a unique cadherin subfamily. In contrast to the classic cadherins, composed of several extracellular cadherin repeats, one transmembrane domain and one cytoplasmic segment linked to catenin binding, Drosophila Flamingo has seven transmembrane segments and a cytoplasmic tail with no catenin-binding sequence. In Drosophila, Flamingo has pleotropic roles in controlling epithelial polarity and neuronal morphogenesis. Three mammalian orthologs of flamingo, Celsrl-3, are widely expressed in the nervous system. Recent work has shown that Celsrl-3 play important roles in neural development, such as in axon guidance, neuronal migration, and cilium polarity. CeIsrl-3 single-gene knockout mice exhibit different phenotypes, but there are cooperative interactions among these genes.