Integrated nanoporous electroporation and sensing electrode array for total dynamic time-domain cardiomyocyte membrane resealing assessment

Intracellular electrophysiological research is vital for biological and medical research.Traditional planar microelectrode arrays(MEAs)have disadvantages in recording intracellular action potentials due to the loose cell-electrode interface.To investigate intracellular electrophysiological signals with high sensitivity,electroporation was used to obtain intracellular recordings.In this study,a biosensing system based on a nanoporous electrode array(NPEA)integrating electrical perforation and signal acquisition was established to dynamically and sensitively record the intracellular potential of cardiomyocytes over a long period of time.Moreover,nanoporous electrodes can induce the protrusion of cell membranes and enhance cell-electrode interfacial coupling,thereby facilitating effective electroporation.Electrophysiological signals over the entire recording process can be quantitatively and segmentally analyzed according to the signal changes,which can equivalently reflect the dynamic evolution of the electroporated cardiomyocyte membrane.We believe that the low-cost and high-performance nanoporous biosensing platform suggested in this study can dynamically record intracellular action potential,evaluate cardiomyocyte electroporation,and provide a new strategy for investigating cardiology pharmacological science.

Role of axon resealing in retrograde neuronal death and regeneration after spinal cord injury

Spinal cord injury leads to persistent behavioral deficits because mammalian central nervous system axons fail to regenerate. A neuron's response to axon injury results from a complex interplay of neuron-intrinsic and environmental factors. The contribution of axotomy to the death of neurons in spinal cord injury is controversial because very remote axotomy is unlikely to result in neuronal death, whereas death of neurons near an injury may reflect environmental factors such as ischemia and inflammation. In lampreys, axotomy due to spinal cord injury results in delayed apoptosis of spinal-projecting neurons in the brain, beyond the extent of these environmental factors. This retrograde apoptosis correlates with delayed resealing of the axon, and can be reversed by inducing rapid membrane resealing with polyethylene glycol. Studies in mammals also suggest that polyethylene glycol may be neuroprotective, although the mechanism(s) remain unclear. This review examines the early, mechanical, responses to axon injury in both mammals and lampreys, and the potential of polyethylene glycol to reduce injury-induced pathology. Identifying the mechanisms underlying a neuron's response to axotomy will potentially reveal new therapeutic targets to enhance regeneration and functional recovery in humans with spinal cord injury.

Membrane resealing as a promising strategy for early treatment of neurotrauma

Traumatic injuries to the central nervous system （CNS）, in- cluding traumatic brain injury （TBI） and spinal cord injury （SCI）, often involve an immediate mechanical damage to plas- ma membrane that surrounds neuronal sornata and axons. This initial disruption of plasma membrane following injuries has been convincingly demonstrated by increased membrane permeability to large molecules and dyes that are normally inaccessible to cellular plasma （Farkas et al., 2006; Cho and Borgens, 2012）. Further evidence comes from experiments that showed ultra-structural changes of plasma membranes, axons, and organelles, and subsequent neuronal death and axotomy （Povlishock and Pettus, 1996; Whalen et al., 2008）.

Self-sealing of fractures in indurated claystones measured by water and gas flow

Self-sealing of fractures in the indurated Callovo-Oxfordian(COX)and Opalinus(OPA)claystones,which are considered as host rocks for disposal of radioactive waste,was investigated on artificially fractured samples.The samples were extracted from four lithological facies relatively rich in clay mineral,carbonate and quartz,respectively.The self-sealing of fractures was measured by fracture closure,water permeability variation,gas penetration,and recovery of gas-induced pathways.Most of the fractured samples exhibited a dramatic reduction inwater permeability to low levels that is close to that of intact rock,depending on their mineralogical composition,fracture intensity,confining stress,and load duration.The self-sealing capacity of the clay-rich samples is higher than that of the carbonate-rich and sandy ones.Significant effects of sample size and fracture intensity were identified.The sealed fractures become gas-tight for certain in-jection pressures.However,the measured gas breakthrough pressures are still lower than the confining stresses.The gas-induced pathways can recover when contacting water.These important findings imply that fractures in such indurated claystones can effectively recover to hinder water transport but allow gas release under relatively low pressures without compromising the rock integrity.

Successful Management of Preterm Premature Rupture of Membrane in Second Trimester: A Case Report and Literature Review

The preterm premature rupture of membranes occurring in early pregnancy at less than 23 - 24 weeks (prior to fetal viability), has higher risk for early preterm delivery, and therefore, the poorer the prognosis with poor chance of neonatal survival and a high rate of severe, long-term neonatal morbidity among survivors. In such cases in absence of overt evidence of intrauterine infection at the time of diagnosis termination of pregnancy or expectant management is generally offered modality of treatment, the prior being commonly preffered. When expectant management is instituted, it is very rare that spontaneous resealing of the membranes occurs with the outcome that is equivocal to normal pregnancy. The presented case is an example of this rare happening. A 25-year-old, mangolian, primigravida at 20 weeks of pregnancy had spontaneous preterm premature rupture of membranes. After 8 days of expectant management, she had cessation of amniotic fluid leak and could continue pregnancy till term with normal feto-maternal outcome at 37 weeks of pregnancy. The risk of infection increases with prolongation of latency period but in this case, the latency period was prolonged for more than 16 weeks and there was no evidence of infection, with normal feto-maternal outcome at term. This is the first case of its kind happened in our hospital and deserves to be reported. It is expected that this article will reveal the possibility of resealing of spontaneous preterm premature rupture of membrane with proper expectant management.

Polyethylene glycol repairs membrane damage and enhances functional recovery: a tissue engineering approach to spinal cord injury

The integrity of the neuronal membrane is crucial for its function and cellular survival; thus, ineffective repair of damaged membranes may be one of the key elements underlying the neuronal degeneration and overall functional loss that occurs after spinal cord injury （SCI）. It has been shown that polyethylene glycol （PEG） can reseal axonal membranes following various injuries in multiple in vitro and in vivo injury models. In addition, PEG may also directly prevent the effects of mitochondria-derived oxidative stress on intracellular components. Thus, PEG repairs mechanically injured cells by at least two distinct pathways： resealing of the disrupted plasma membrane and direct protection of mitochondria. Besides repairing primary membrane damage, PEG treatment also results in significant attenuation of oxidative stress, likely due to its capacity to reseal the membrane, thereby breaking the cycle of cellular damage and free-radical production. Based on this, in addition to the practicality of its application, we expect that PEG may be established as an effective treatment for SCI where membrane disruption and mitochondriai damage are implicated.