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In this paper, a novel dual-band wideband bandpass filter (BPF) based on transversal signal-interaction concepts with a wide upper stopband is proposed and investigated. The designed specification of two passbands can be managed and satisfied based on the independent controllable fractional bandwidth of the two passbands and the centered frequencies. The centered frequencies of dual-band BPF are, respectively, 0.79 GHz (ƒ1) and 1.24 GHz (ƒ2) with 3 dB fraction bandwidths of 26.54% and 11.3%. Two transmission paths consisting of coupled stub-loaded square ring resonators and anti-coupled shorted lines are used to realize signal cancellation of multiple transmission path signal transmission from Port 1 to Port 2. Eleven transmission zeros (TZs) modify harmonic suppression up to 10 ƒ1 with stopband rejection higher than 15 dB. Butterworth lumped notch network and step impedance resonator (SIR) are also utilized to improve the selectivity and harmonic suppression. A compact filter with a circuit size of 0.08λg X 0.08λg is implemented and tested. Good agreement between simulation and measured results verifies the reliability of the designing scheme.

Abstract Background Tui Na (Chinese massage) is a relatively simple, inexpensive, and non-invasive intervention, and has been used to treat stroke patients for many years in China. Tui Na acts on specific parts of the body which are called meridians and acupoints to achieve the role of treating diseases. Yet the underlying neural mechanism associated with Tui Na is not clear due to the lack of detection methods. Objective Functional near-infrared spectroscopy (fNIRS) was used to explore the changes of sensorimotor cortical neural activity in patients with upper limb motor dysfunction of stroke and healthy control groups during Tui Na Hegu Point. Methods Ten patients with unilateral upper limb motor dysfunction after stroke and eight healthy subjects received Tui Na. fNIRS was used to record the hemodynamic data in the sensorimotor cortex and the changes in blood flow were calculated based on oxygenated hemoglobin (Oxy-Hb), the task session involved repetitive Tui Na on Hegu acupoint, using a block design [six cycles: rest (20 seconds); Tui Na (20 seconds); rest (30 seconds)]. The changes in neural activity in sensorimotor cortex could be inferred according to the principle of neurovascular coupling, and the number of activated channels in the bilateral hemisphere was used to calculate the lateralization index. Result 1. For hemodynamic response induced by Hegu acupoint Tui Na, a dominant increase in the contralesional primary sensorimotor cortex during Hegu point Tui Na of the less affected arm in stroke patients was observed, as well as that in healthy controls, while this contralateral pattern was absent during Hegu point Tui Na of the affected arm in stroke patients. 2. Concerning the lateralization index in stroke patients, a significant difference was observed between lateralization index values for the affected arm and the less affected arm (P < 0.05). Wilcoxon tests showed a significant difference between lateralization index values for the affected arm in stroke patients and lateralization index values for the dominant upper limb in healthy controls (P < 0.05), and no significant difference between lateralization index values for the less affected arm in stroke patients and that in healthy controls (P = 0.36). Conclusion The combination of Tui Na and fNIRS has the potential to reflect the functional status of sensorimotor neural circuits. The changes of neuroactivity in the sensorimotor cortex when Tui Na Hegu acupoint indicate that there is a certain correlation between acupoints in traditional Chinese medicine and neural circuits.

Modified constraint-induced movement therapy (mCIMT) has shown beneficial effects on motor function improvement after brain injury, but the exact mechanism remains unclear. In this study, amplitude of low frequency fluctuation (ALFF) metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control cortical impact (CCI) rat model simulating traumatic brain injury. At 3 days after control cortical impact model establishment, we found that the mean ALFF (mALFF) signals were decreased in the left motor cortex, somatosensory cortex, insula cortex and the right motor cortex, and were increased in the right corpus callosum. After 3 weeks of an 8-hour daily mCIMT treatment, the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively. The mALFF signal values of left corpus callosum, left somatosensory cortex, right medial prefrontal cortex, right motor cortex, left postero dorsal hippocampus, left motor cortex, right corpus callosum, and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group. Finally, we identified brain regions with significantly decreased mALFF values at 3 days postoperatively. Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions. Our findings suggest that functional cortical plasticity changes after brain injury, and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric cortical remodeling. mALFF values correlate with behavioral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Multi-target neural circuit-magnetic stimulation has been clinically shown to improve rehabilitation of lower limb motor function after spinal cord injury. However, the precise underlying mechanism remains unclear. In this study, we performed double-target neural circuit-magnetic stimulation on the left motor cortex and bilateral L5 nerve root for 3 successive weeks in a rat model of incomplete spinal cord injury caused by compression at T10. Results showed that in the injured spinal cord, the expression of the astrocyte marker glial fibrillary acidic protein and inflammatory factors interleukin 1β, interleukin-6, and tumor necrosis factor-α had decreased, whereas that of neuronal survival marker microtubule-associated protein 2 and synaptic plasticity markers postsynaptic densification protein 95 and synaptophysin protein had increased. Additionally, neural signaling of the descending corticospinal tract was markedly improved and rat locomotor function recovered significantly. These findings suggest that double-target neural circuit-magnetic stimulation improves rat motor function by attenuating astrocyte activation, thus providing a theoretical basis for application of double-target neural circuit-magnetic stimulation in the clinical treatment of spinal cord injury.

Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury. We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral (right only) cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3–L4 nerve roots, five times a week. Bilateral resting motor evoked potential amplitude was increased, central motor conduction time on the side receiving cortical stimulation was significantly decreased, and lower extremity motor score, Berg balance score, spinal cord independence measure-III score, and 10 m-walking speed were all increased after treatment. Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment. These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.

Following a spinal cord injury, there are usually a number of neural pathways that remain intact in the spinal cord. These residual nerve fibers are important, as they could be used to reconstruct the neural circuits that enable motor function. Our group previously designed a novel magnetic stimulation protocol, targeting the motor cortex and the spinal nerve roots, that led to significant improvements in locomotor function in patients with a chronic incomplete spinal cord injury. Here, we investigated how nerve root magnetic stimulation contributes to improved locomotor function using a rat model of spinal cord injury. Rats underwent surgery to clamp the spinal cord at T10; three days later, the rats were treated with repetitive magnetic stimulation (5 Hz, 25 pulses/train, 20 pulse trains) targeting the nerve roots at the L5–L6 vertebrae. The treatment was repeated five times a week over a period of three weeks. We found that the nerve root magnetic stimulation improved the locomotor function and enhanced nerve conduction in the injured spinal cord. In addition, the nerve root magnetic stimulation promoted the recovery of synaptic ultrastructure in the sensorimotor cortex. Overall, the results suggest that nerve root magnetic stimulation may be an effective, noninvasive method for mobilizing the residual spinal cord pathways to promote the recovery of locomotor function.

The mouse model of multiple cerebral infarctions, established by injecting fluorescent microspheres into the common carotid artery, is a recent development in animal models of cerebral ischemia. To investigate its effectiveness, mouse models of cerebral infarction were created by injecting fluorescent microspheres, 45–53 µm in diameter, into the common carotid artery. Six hours after modeling, fluorescent microspheres were observed directly through a fluorescence stereomicroscope, both on the brain surface and in brain sections. Changes in blood vessels, neurons and glial cells associated with microinfarcts were examined using fluorescence histochemistry and immunohistochemistry. The microspheres were distributed mainly in the cerebral cortex, striatum and hippocampus ipsilateral to the side of injection. Microinfarcts were found in the brain regions where the fluorescent microspheres were present. Here the lodged microspheres induced vascular and neuronal injury and the activation of astroglia and microglia. These histopathological changes indicate that this animal model of multiple cerebral infarctions effectively simulates the changes of various cell types observed in multifocal microinfarcts. This model is an effective, additional tool to study the pathogenesis of ischemic stroke and could be used to evaluate therapeutic interventions. This study was approved by the Animal Ethics Committee of the Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences (approval No. D2021-03-16-1) on March 16, 2021.

[INLINE:1] Classic paired associative stimulation can improve synaptic plasticity, as demonstrated by animal experiments and human clinical trials in spinal cord injury patients. Paired associative magnetic stimulation (dual-target peripheral and central magnetic stimulation) has been shown to promote neurologic recovery after stroke. However, it remains unclear whether paired associative magnetic stimulation can promote recovery of lower limb motor dysfunction after spinal cord injury. We hypothesize that the current caused by central and peripheral magnetic stimulation will converge at the synapse, which will promote synapse function and improve the motor function of the relevant muscles. Therefore, this study aimed to examine the effects of paired associative magnetic stimulation on neural circuit activation by measuring changes in motor evoked and somatosensory evoked potentials, motor and sensory function of the lower limbs, functional health and activities of daily living, and depression in patients with spinal cord injury. We will recruit 110 thoracic spinal trauma patients treated in the Department of Spinal Cord Injury, China Rehabilitation Hospital and randomly assign them to experimental and control groups in a 1:1 ratio. The trial group (n = 55) will be treated with paired associative magnetic stimulation and conventional rehabilitation treatment. The control group (n = 55) will be treated with sham stimulation and conventional rehabilitation treatment. Outcomes will be measured at four time points: baseline and 4, 12, and 24 weeks after the start of intervention (active or sham paired associative magnetic stimulation). The primary outcome measure of this trial is change in lower limb American Spinal Injury Association Impairment Scale motor function score from baseline to last follow-up. Secondary outcome measures include changes in lower limb American Spinal Injury Association sensory function score, motor evoked potentials, sensory evoked potentials, modified Ashworth scale score, Maslach Burnout Inventory score, and Hamilton Depression Scale score over time. Motor evoked potential latency reflects corticospinal tract transmission time, while amplitude reflects recruitment ability; both measures can help elucidate the mechanism underlying the effect of paired associative magnetic stimulation on synaptic efficiency. Adverse events will be recorded. Findings from this trial will help to indicate whether paired associative magnetic stimulation (1) promotes recovery of lower limb sensory and motor function, reduces spasticity, and improves quality of life; (2) promotes neurologic recovery by increasing excitability of spinal cord motor neurons and stimulating synaptic plasticity; and (3) improves rehabilitation outcome in patients with spinal cord injury. Recruitment for this trial began in April 2021 and is currently ongoing. It was approved by the Ethics Committee of Yangzhi Affiliated Rehabilitation Hospital of Tongji University, China (approval No. YZ2020-018) on May 18, 2020. The study protocol was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2100044794) on March 27, 2021 (protocol version 1.0). This trial will be completed in April 2022.

Neural tract tracing is used to study neural pathways and evaluate neuronal regeneration following nerve injuries. However, it is not always clear which tracer should be used to yield optimal results. In this study, we examined the use of Alexa Fluor 488-conjugated cholera toxin subunit B (AF488-CTB). This was injected into the gastrocnemius muscle of rats, and it was found that motor, sensory, and sympathetic neurons were labeled in the spinal ventral horn, dorsal root ganglia, and sympathetic chain, respectively. Similar results were obtained when we injected AF594-CTB into the tibialis anterior muscle. The morphology and number of neurons were evaluated at different time points following the AF488-CTB injection. It was found that labeled motor and sensory neurons could be observed 12 hours post-injection. The intensity was found to increase over time, and the morphology appeared clear and complete 3–7 days post-injection, with clearly distinguishable motor neuron axons and dendrites. However, 14 days after the injection, the quality of the images decreased and the neurons appeared blurred and incomplete. Nissl and immunohistochemical staining showed that the AF488-CTB-labeled neurons retained normal neurochemical and morphological features, and the surrounding microglia were also found to be unaltered. Overall, these results imply that the cholera toxin subunit B, whether unconjugated or conjugated with Alexa Fluor, is effective for retrograde tracing in muscular tissues and that it would also be suitable for evaluating the regeneration or degeneration of injured nerves.

Upper limb motor dysfunction after stroke is a serious threat to the living quality of patients and their families. Recovery of upper limb motor function after stroke largely relies on the activation and remodeling of neural circuits. rTMS (repetitive transcranial magnetic stimulation) has been proved to promote the reconstruction of neural synapses and neural circuits. However, there are still a large number of patients who cannot fully recover and leave behind varying degrees of dysfunction. Considering the systemic pathology after stroke, in addition to focal brain injury, stroke can also cause extensive dysfunction of peripheral organs. The rehabilitation strategy for stroke should combine the treatment of primary brain lesions with the intervention of secondary systemic damage. The aim of this trial is to verify the efficacy of rTMS synergize with Tui Na (Chinese Massage) on upper limb motor function after ischemic stroke, and to explore the mechanism of activation and remodeling of sensorimotor neural circuits with functional near-infrared spectroscopy. Ninety patients will be randomly assigned to either rTMS + Tui Na + conventional rehabilitation group (the experimental group) or rTMS + conventional rehabilitation group (the control group) in 1:1 ratio. Intervention is conducted five sessions a week, with a total of twenty sessions. The primary outcome is Fugl-Meyer Assessment, and the secondary outcomes include Muscle Strength, Modified Ashworth Assessment, Modified Barthel Index Assessment, motor evoked potentials and functional near-infrared spectroscopy. There are four time points for the evaluation, including baseline, 2 weeks and 4 weeks after the start of treatment, and 4 weeks after the end of treatment. This study is a randomized controlled trial. This study was approved by Institutional Ethics Committee of Shanghai Third Rehabilitation Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (approval No. SH3RH-2021-EC-012) on December, 16th, 2021. The protocol was registered with Chinese Clinical Trial Registry (ChiCTR2200056266), on February 3th, 2022. Patient recruitment was initiated on February 10th, 2022, and the study will be continued until December 2023.

Atherosclerosis is the main cause of cardio-cerebrovascular diseases. Endothelial-mesenchymal transition plays an important role in atherosclerosis. Icariin has a protective effect on atherosclerosis; however, the underlying mechanism remains unclear. In this study, we explored the molecular mechanism underlying the protective function of icariin in oxidized low-density lipoprotein-stimulated human umbilical vein endothelial cells. H19, a long non-coding RNA, was identified to be downregulated in the background of the oxidized low-density lipoprotein-induced endothelial-mesenchymal transition in human umbilical vein endothelial cells. Icariin upregulated H19 expression and inhibited the transformation of endothelial cells into interstitial cells. Overexpression of H19 affected endothelial-mesenchymal transition in oxidized low-density lipoprotein-stimulated human umbilical vein endothelial cells, whereas H19 knockdown reversed endothelial protective effects of icariin and reduced human umbilical vein endothelial cell migration. Knockdown of H19 significantly downregulated oxidized low-density lipoprotein-induced E74-like factor 5 and upregulated miR-148b-3p, which was reversed by icariin. Thus, icariin may play a protective role in atherosclerosis, and H19 may be a potential therapeutic target.

Encouraging results have been reported for the use of transcranial magnetic stimulation-based nerve stimulation in studies of the mechanisms of neurological regulation, nerve injury repair, and nerve localization. However, to date, there are only a few reviews on the use of transcranial magnetic stimulation for diabetic neuropathy. Patients with diabetic neuropathy vary in disease progression and show neuropathy in the early stage of the disease with mild symptoms, making it difficult to screen and identify. In the later stage of the disease, irreversible neurological damage occurs, resulting in treatment difficulties. In this review, we summarize the current state of diabetic neuropathy research and the prospects for the application of transcranial magnetic stimulation in diabetic neuropathy. We review significant studies on the beneficial effects of transcranial magnetic stimulation in diabetic neuropathy treatment, based on the outcomes of its use to treat neurodegeneration, pain, blood flow change, autonomic nervous disorders, vascular endothelial injury, and depression. Collectively, the studies suggest that transcranial magnetic stimulation can produce excitatory/inhibitory stimulation of the cerebral cortex or local areas, promote the remodeling of the nervous system, and that it has good application prospects for the localization of the injury, neuroprotection, and the promotion of nerve regeneration. Therefore, transcranial magnetic stimulation is useful for the screening and early treatment of diabetic neuropathy. Transcranial magnetic stimulation can also alleviate pain symptoms by changing the cortical threshold and inhibiting the conduction of sensory information in the thalamo-spinal pathway, and therefore it has therapeutic potential for the treatment of pain and pain-related depressive symptoms in patients with diabetic neuropathy. Additionally, based on the effect of transcranial magnetic stimulation on local blood flow and its ability to change heart rate and urine protein content, transcranial magnetic stimulation has potential in the treatment of autonomic nerve dysfunction and vascular injury in diabetic neuropathy. Furthermore, oxidative stress and the inflammatory response are involved in the process of diabetic neuropathy, and transcranial magnetic stimulation can reduce oxidative damage. The pathological mechanisms of diabetic neuropathy should be further studied in combination with transcranial magnetic stimulation technology.

More than half of stroke patients live with different levels of motor dysfunction after receiving routine rehabilitation treatments. Therefore, new rehabilitation technologies are urgently needed as auxiliary treatments for motor rehabilitation. Based on routine rehabilitation treatments, a new intelligent rehabilitation platform has been developed for accurate evaluation of function and rehabilitation training. The emerging intelligent rehabilitation techniques can promote the development of motor function rehabilitation in terms of informatization, standardization, and intelligence. Traditional assessment methods are mostly subjective, depending on the experience and expertise of clinicians, and lack standardization and precision. It is therefore difficult to track functional changes during the rehabilitation process. Emerging intelligent rehabilitation techniques provide objective and accurate functional assessment for stroke patients that can promote improvement of clinical guidance for treatment. Artificial intelligence and neural networks play a critical role in intelligent rehabilitation. Multiple novel techniques, such as brain-computer interfaces, virtual reality, neural circuit-magnetic stimulation, and robot-assisted therapy, have been widely used in the clinic. This review summarizes the emerging intelligent rehabilitation techniques for the evaluation and treatment of motor dysfunction caused by nervous system diseases.

Abstract Background Under physiological conditions, CXCL12 modulates cell proliferation, survival, angiogenesis, and migration mainly through CXCR4. Interestingly, the newly discovered receptor CXCR7 for CXCL12 is highly expressed in many tumor cells as well as tumor-associated blood vessels, although the level of CXCR7 in normal cells is low. Recently, many studies have suggested that CXCR7 promotes cell growth and metastasis in more than 20 human malignancies, among which lung cancer is the leading cause of cancer-associated deaths worldwide. Thus, the mechanism of CXCR7 in the progression of lung cancer is urgently needed. Methods First, we explored CXCR4 and CXCR7 expression in human lung cancer specimens and cell lines by immunohistochemistry, western blot and flow cytometry. Then, we chose the human lung adenocarcinoma cell line A549 that stably overexpressed CXCR7 through the way of lentivirus-mediated transduction. Next, “wound healing” assay and transwell assay were applied to compare the cell migration and invasion ability, and stripe assay was used to evaluate the cell polarization. Last, our team established a mouse xenograft model of human lung cancer and monitored tumor proliferation and metastasis by firefly luciferase bioluminescence imaging in SCID/Beige mice. Results In clinical lung cancer samples, CXCR7 expression was almost not detected in normal tissue but upregulated in lung tumor tissue, whereas, CXCR4 was highly expressed in both normal and tumor tissues. Furthermore, overexpression of CXCR7 enhanced A549 cell migration and polarization in vitro. Besides, mouse xenograft model of human lung cancer showed that CXCR7 promoted primary lung tumor’s growth and metastasis to the second organ, such as liver or bone marrow in SCID/Beige mice in vivo. Conclusions This study describes the multiple functions of CXCR7 in lung cancer. Thus, these results suggest that CXCR7 may be a malignancy marker and may provide a novel target for anticancer therapy.

BackgroundUpper-extremity hemiplegia after stroke remains a significant clinical problem. The supplementary motor area (SMA) is vital to the motor recovery outcomes of chronic stroke patients. Therefore, rebuilding the descending motor tract from the SMA to the paralyzed limb is a potential approach to restoring arm motor function after stroke. Paired associative stimulation (PAS), which is based on Hebbian theory, is a potential method for reconstructing the connections in the impaired motor neural circuits. The study described in this protocol aims to assess the effects of cortico–peripheral Hebbian-type stimulation (HTS), involving PAS, for neural circuit reconstruction to rescue the paralyzed arm after stroke.MethodsThe study is a 4-month double-blind randomized sham-controlled clinical trial. We will recruit 90 post-stroke individuals with mild to moderate upper limb paralysis. Based on a 1:1 ratio, the participants will be randomly assigned to the HTS and sham groups. Each participant will undergo 5-week HTS or sham stimulation. Assessments will be conducted at baseline, immediately after the 5-week treatment, and at a 3-month follow-up. The primary outcome will be the Wolf Motor Function Test (WMFT). The secondary outcomes will be Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Functional Independence Measure (FIM), and functional near-infrared spectroscopy (fNIRS) parameters. The adverse events will be recorded throughout the study.DiscussionUpper-limb paralysis in stroke patients is due to neural circuit disruption, so the reconstruction of effective motor circuits is a promising treatment approach. Based on its anatomical structure and function, the SMA is thought to compensate for motor dysfunction after focal brain injury at the cortical level. Our well-designed randomized controlled trial will allow us to analyze the clinical efficacy of this novel Hebbian theory-based neuromodulation strategy regarding promoting the connection between the cortex and peripheral limb. The results may have significance for the development and implementation of effective neurorehabilitation treatments.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [ChiCTR2000039949].

Characterized by high morbidity, mortality, and disability, stroke usually causes symptoms of cerebral hypoxia due to a sudden blockage or rupture of brain vessels, and it seriously threatens human life and health. Rehabilitation is the essential treatment for post-stroke patients suffering from functional impairments, through which hemiparesis, aphasia, dysphagia, unilateral neglect, depression, and cognitive dysfunction can be restored to various degrees. Noninvasive brain stimulation (NIBS) is a popular neuromodulatory technology of rehabilitation focusing on the local cerebral cortex, which can improve clinical functions by regulating the excitability of corresponding neurons. Increasing evidence has been obtained from the clinical application of NIBS, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, without a standardized protocol, existing studies on NIBS show a wide variation in terms of stimulation site, frequency, intensity, dosage, and other parameters. Its application for neurorehabilitation in post-stroke patients is still limited. With advances in neuronavigation technologies, functional near-infrared spectroscopy, and functional MRI, specific brain regions can be precisely located for stimulation. On the basis of our further understanding on neural circuits, neuromodulation in post-stroke rehabilitation has also evolved from single-target stimulation to co-stimulation of two or more targets, even circuits and the network. The present study aims to review the findings of current research, discuss future directions of NIBS application, and finally promote the use of NIBS in post-stroke rehabilitation.

In order to better understand the particle breakage mechanics and characterization methods of calcareous sand, the particle breakage characteristics of calcareous sand in one-dimensional compression tests, isotropic compression tests, triaxial shear tests, and ring shear tests are reviewed and analyzed. The results show that the mechanism of shear crushing is essentially different from compression crushing. Compared with one-dimensional compression, it is easier to break calcareous sand under triaxial shear. In the shearing process, the particle breakage of calcareous sand will not continue indefinitely. The gradation tends to be stable and controlled by confining pressure and shear strain. The characteristic particle size measurement method for particle breakage is simple and has limitations. The description method using the particle size distribution curve is more comprehensive, but it is impossible to compare the crushing degree of particle with different particle sizes, and a suitable measurement method needs to be proposed.

Spinal cord injury is linked to the interruption of neural pathways, which results in irreversible neural dysfunction. Neural repair and neuroregeneration are critical goals and issues for rehabilitation in spinal cord injury, which require neural stem cell repair and multimodal neuromodulation techniques involving personalized rehabilitation strategies. Besides the involvement of endogenous stem cells in neurogenesis and neural repair, exogenous neural stem cell transplantation is an emerging effective method for repairing and replacing damaged tissues in central nervous system diseases. However, to ensure that endogenous or exogenous neural stem cells truly participate in neural repair following spinal cord injury, appropriate interventional measures (e.g., neuromodulation) should be adopted. Neuromodulation techniques, such as noninvasive magnetic stimulation and electrical stimulation, have been safely applied in many neuropsychiatric diseases. There is increasing evidence to suggest that neuromagnetic/electrical modulation promotes neuroregeneration and neural repair by affecting signaling in the nervous system; namely, by exciting, inhibiting, or regulating neuronal and neural network activities to improve motor function and motor learning following spinal cord injury. Several studies have indicated that fine motor skill rehabilitation training makes use of residual nerve fibers for collateral growth, encourages the formation of new synaptic connections to promote neural plasticity, and improves motor function recovery in patients with spinal cord injury. With the development of biomaterial technology and biomechanical engineering, several emerging treatments have been developed, such as robots, brain-computer interfaces, and nanomaterials. These treatments have the potential to help millions of patients suffering from motor dysfunction caused by spinal cord injury. However, large-scale clinical trials need to be conducted to validate their efficacy. This review evaluated the efficacy of neural stem cells and magnetic or electrical stimulation combined with rehabilitation training and intelligent therapies for spinal cord injury according to existing evidence, to build up a multimodal treatment strategy of spinal cord injury to enhance nerve repair and regeneration.

Modified constraint-induced movement therapy is an effective treatment for neurological and motor impairments in patients with stroke by increasing the use of their affected limb and limiting the contralateral limb. However, the molecular mechanism underlying its efficacy remains unclear. In this study, a middle cerebral artery occlusion (MCAO) rat model was produced by the suture method. Rats received modified constraint-induced movement therapy 1 hour a day for 14 consecutive days, starting from the 7th day after middle cerebral artery occlusion. Day 1 of treatment lasted for 10 minutes at 2 r/min, day 2 for 20 minutes at 2 r/min, and from day 3 onward for 20 minutes at 4 r/min. CatWalk gait analysis, adhesive removal test, and Y-maze test were used to investigate motor function, sensory function as well as cognitive function in rodent animals from the 1st day before MCAO to the 21st day after MCAO. On the 21st day after MCAO, the neurotransmitter receptor-related genes from both contralateral and ipsilateral hippocampi were tested by micro-array and then verified by western blot assay. The glutamate related receptor was shown by transmission electron microscopy and the glutamate content was determined by high-performance liquid chromatography. The results of behavior tests showed that modified constraint-induced movement therapy promoted motor and sensory functional recovery in the middle cerebral artery-occluded rats, but had no effect on cognitive function. The modified constraint-induced movement therapy upregulated the expression of glutamate ionotropic receptor AMPA type subunit 3 (Gria3) in the hippocampus and downregulated the expression of the beta3-adrenergic receptor gene Adrb3 and arginine vasopressin receptor 1A, Avpr1a in the middle cerebral artery-occluded rats. In the ipsilateral hippocampus, only Adra2a was downregulated, and there was no significant change in Gria3. Transmission electron microscopy revealed a denser distribution the more distribution of postsynaptic glutamate receptor 2/3, which is an α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor, within 240 nm of the postsynaptic density in the contralateral cornu ammonis 3 region. The size and distribution of the synaptic vesicles within 100 nm of the presynaptic active zone were unchanged. Western blot analysis showed that modified constraint-induced movement therapy also increased the expression of glutamate receptor 2/3 and brain-derived neurotrophic factor in the hippocampus of rats with middle cerebral artery occlusion, but had no effect on Synapsin I levels. Besides, we also found modified constraint-induced movement therapy effectively reduced glutamate content in the contralateral hippocampus. This study demonstrated that modified constraint-induced movement therapy is an effective rehabilitation therapy in middle cerebral artery-occluded rats, and suggests that these positive effects occur via the upregulation of the postsynaptic membrane α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor expression. This study was approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.

Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model (MCAO) and paired associated magnetic stimulation (PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments—the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the foot-fault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.

Investigating the soil-water characteristics of calcareous soil has a great significance for preventing geological disasters on island-reefs as well as maintaining the foundation stability of hydraulic-filled island-reefs. In this study, calcareous silty sands with different fines contents and dry densities were studied to reveal their effects on the soil-water characteristics of calcareous soil on hydraulic-filled island-reefs. The soil-water characteristic curve (SWCC) of the calcareous silty sand was measured using a pressure plate apparatus. Taking into account the porous meso-structure, the effects of fines content and dry density on the SWCC of calcareous silty sand were analyzed, and the applicability of existing SWCC models to calcareous silty sand was verified. A SWCC model suitable for assessing soil-water characteristic of calcareous silty sand was proposed. Results of this study provide some reference for quantifying the water-holding capacity of calcareous silty sand.

The settlement and deformation monitoring for existing tunnels would encounter the difficulties in sensor installation and health evaluation in real time. Thus, it is necessary to develop effective methods for settlement and deformation measurements in the existing tunnels. This study proposed a more practical tunnel deformation monitoring theory and developed remote wireless tunnel deformation real-time monitoring and early warning system based on infrared laser ranging technology and cable sensing technology. The system could monitor the settlement and deformation of the tunnel in real time from a long distance and transmit the deformation data wirelessly in real time; then, three-dimensional space model of tunnel deformation was established, which intuitively and comprehensively reflected the actual deformation of the tunnel and intelligently identified the deformation. Finally, based on the practice of deformation control during tunnel excavation at Xiaohongshu Station of Wuhan Metro Line 8 of China, the measurement results of this new method were compared with the measurement results of particle image velocimetry technology (PIV), the reliability of the new tunnel deformation monitoring method was proved, the settlement error of each monitoring point was found to be less than 1 mm, and the deformation trend was consistent with the actual deformation. The results of this research could provide useful guidance for tunnel deformation monitoring.

Long-term hypertension can lead to both structural and functional impairments of the myocardium. Reversing left ventricular (LV) myocardial fibrosis has been considered as a key goal for curing chronic hypertension and has been a hot field of research in recent years. The aim of the present work is to investigate the effect of electroacupuncture (EA) at PC6 on hypertension-induced myocardial fibrosis in spontaneously hypertensive rats (SHRs). Thirty SHRs were randomized into model, SHR + EA, and SHR + Sham EA groups with WKY rats as a normal control. EA was applied once a day for 8 consecutive weeks. The cardiac fibrosis as well as the underlying mechanisms were investigated. After 8 weeks of EA treatment at PC6, the enhanced myocardial fibrosis in SHRs was characterized by an increased ratio of left ventricular mass index (LVMI), collagen volume fraction (CVF), and elevated content of hydroxyproline (Hyp) as well as the upregulated expression of collagen I and collagen III in myocardium tissue of SHRs. All these abnormal alterations in the SHR + EA group were significantly lower compared to the model group. In addition, EA at PC6 significantly improved the pathological changes of myocardial morphology. Meanwhile, the increased levels of angiotensin II (Ang II) and tumor necrosis factor-α (TNFα) and expression of transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF), matrix metalloproteinase (MMP)-2, and MMP-9 in the serum or heart tissue of SHRs were also markedly diminished by EA. These results suggest that EA at bilateral PC6 could ameliorate cardiac fibrosis in SHRs, which might be mediated by the regulation of the Ang II – TGF-β1 pathway.

Slope failure and debris flow cause lots of casualties and property loss. An early-warning system for slope collapse and debris flow is essential to ensure safety of human beings and assets. Based on fiber optic sensing technology and Internet of Things, a new sensing transducer for internal earth pressure measurement in a soil slope is proposed, fabricated, and tested in this paper. The working principles, theoretical analysis, laboratory calibrations, and discussions of the proposed pressure transducers are elaborated. Extensive evaluations of the resolutions, physical properties, and response to the applied pressures have been performed through modeling and experimentations. The results show that the sensitivity of the designed pressure sensor is 0.1287 kPa/με across a pressure range of 140 kPa. Finally, a field soil slope was instrumented with the developed fiber optic sensors and other sensors. Through internet and cloud computing platform, the stability of the soil slope was analyzed. In the cloud computing platform, the numerical simulation is carried out by considering the slope internal deformations, rainfall infiltration, and limit force equilibrium. The factor of safety of the soil slope was calculated, which could be used to determine health condition of the instrumented slope. The performance was evaluated and classified into three categories. It proves that the proposed early-warning system has potential to monitor the health condition of the soil slopes.

A novel fiber-optic based earth pressure sensor (FPS) with an adjustable measurement range and high sensitivity is developed to measure earth pressures for civil infrastructures. The new FPS combines a cantilever beam with fiber Bragg grating (FBG) sensors and a flexible membrane. Compared with a traditional pressure transducer with a dual diaphragm design, the proposed FPS has a larger measurement range and shows high accuracy. The working principles, parameter design, fabrication methods, and laboratory calibration tests are explained in this paper. A theoretical solution is derived to obtain the relationship between the applied pressure and strain of the FBG sensors. In addition, a finite element model is established to analyze the mechanical behavior of the membrane and the cantilever beam and thereby obtain optimal parameters. The cantilever beam is 40 mm long, 15 mm wide, and 1 mm thick. The whole FPS has a diameter of 100 mm and a thickness of 30 mm. The sensitivity of the FPS is 0.104 kPa/με. In addition, automatic temperature compensation can be achieved. The FPS’s sensitivity, physical properties, and response to applied pressure are extensively examined through modeling and experiments. The results show that the proposed FPS has numerous potential applications in soil pressure measurement.

Recently, the TODIM has been used to solve multiple attribute decision making (MADM) problems. The single-valued neutrosophic sets (SVNSs) are useful tools to depict the uncertainty of the MADM. In this paper, we will extend the TODIM method to the MADM with the single-valued neutrosophic numbers (SVNNs). Firstly, the definition, comparison, and distance of SVNNs are briefly presented, and the steps of the classical TODIM method for MADM problems are introduced. Then, the extended classical TODIM method is proposed to deal with MADM problems with the SVNNs, and its significant characteristic is that it can fully consider the decision makers’ bounded rationality which is a real action in decision making. Furthermore, we extend the proposed model to interval neutrosophic sets (INSs). Finally, a numerical example is proposed.

With the rapid construction of metro tunnels in many metropolises, a fast and convenient solution to capture tunnel deformation is desired by civil engineers. This contribution reports an automatic and wireless tunnel deformation monitoring system using ultrasonic transducers. A processing algorithm of the redundant ultrasonic information (RUI) approach is proposed to improve measurement accuracy. The feasibility of this tunnel deformation monitoring method is carefully examined with various probe angles, distances, and surrounding temperature variations. The results indicate that high accuracy can be achieved with different coefficients for various probe angles and sensor distances, as well as temperatures. In addition, a physical tunnel model was fabricated to verify the new processing algorithm of the RUI approach for a wireless tunnel deformation sensing system. The test results reveal that average measurement errors decreased from 7% to 3.75% using the RUI approach. Therefore, it can be concluded that the proposed approach is well suited to the automatic detection of critical conditions such as large deformation events in metro tunnels.

A measurement approach for small deformations of soil specimens has been proposed in this study. The proposed approach consists of a small deformation transducer (SDT) based on fiber Bragg grating sensors which could provide an alternative tool to measure local small deformations of a soil specimen with high accuracy. The working principle, design procedures, calibrations and applications of the SDT are presented. An analytical solution is derived to obtain the relationship between the small deformation of the transducer and the wavelength shift of the FBG sensor, which was further evident in the laboratory calibration tests. The measurement range and resolution of the SDT can be adjusted by choosing different length and thickness of the material. The SDT can achieve a strain resolution of 4.45 micro-strains for a soil specimen with 80 mm in height. Measurement errors and stability were also examined and the results show that the maximum measurement error was around 0.01 mm. The designed SDT was further installed in a modified triaxial apparatus. Three shearing tests under different confining pressures were conducted. Results measured by the newly developed SDT are analyzed with comparisons to the results using external linear variable differential transformer (LVDT) transducers. The results provide evidence that this measurement approach is suitable for measuring the local deformations of soil specimens with high accuracy and stability.

Background: The study aimed to find predictive biomarkers to evaluate donor kidney function to predict graft dysfunction as well as to assess an early signs of acute graft rejection. Method: Twenty-seven deceased donors and 54 recipients who underwent a successful kidney transplantation were enrolled in the study. An assessment was made in sentm and urine from donors and recipients to measure the following biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (K1M-1), tissue inhibitor of metalloproteinase 2 (TIMP-2) and urinary N-acetyl-b-D-glucosaminidase (uNAG). These biomarkers were used to establish a model for predicting a reduced graft function (RGF) classified as either a delayed or slow graft function. Result. Our analysis suggest that out of four tested biomarkers, the serum TIMP-2 and uNAG levels of the donors had a predictive value for RGF; the area under the receiver operating characteristic curves (AUROC) of serum TIMP-2 and uNAG were 0.714 and 0.779, respectively. The combined best fitting prediction model of serum TIMP-2, uNAG, and creatinine levels was better in predicting RGF than the serum creatinine level alone. In addition, the recipient serum TIMP-2 level on the third day post-transplantation (D3) was associated with the estimated glomerular filtration rate (eGFR) on the seventh day post-transplantation (07; OR 1.119, 95% CI 1.016-1.233, p - 0.022). Furthermore, the ROC curve value revealed that the AUROC of TIMP-2 on D3 was 0.99 (95% CI 0.97-1, p < 0.001), and this was the best predictive value of the renal function on D7. Conclusions: Donor serum TIMP-2 and uNAG levels are useful predictive biomarkers because they can provide the donor-based prediction for RGF. [ABSTRACT FROM AUTHOR]