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OBJECTIVE: To investigate the effect of honokiol on demyelination after compressed spinal cord injury (CSCI) and it's possible mechanism. DESIGN: Animal experiment study. SETTING: Institute of Neuroscience of Chongqing Medical University. INTERVENTIONS: Total of 69 Sprague–Dawley (SD) rats were randomly divided into 3 groups: sham group (n=15), honokiol group (n=27) and vehicle group (n=27). After established CSCI model by a custom-made compressor successfully, the rats of sham group were subjected to the limited laminectomy without compression; the rats of honokiol group were subjected to CSCI surgery and intraperitoneal injection of 20 mg/kg honokiol; the rats of vehicle group were subjected to CSCI surgery and intraperitoneal injection of an equivalent volume of saline. Outcome measures: The locomotor function of each group was assessed using the Basso, Beattie and Bresnahan (BBB) rating scale. The pathological changes of myelinated nerve fibers of spinal cord in 3 groups were detected by osmic acid staining and transmission electron microcopy (TME). Immunofluorescence and Western blot were used to research the experessions of active caspase-3, caspase-12, cytochrome C and myelin basic protein (MBP) respectively. RESULTS: In the vehicle group, the rats became paralyzed and spastic after injury, and the myelin sheath became swollen and broken down along with decreased number of myelinated nerve fibers. Western blot analysis manifested that active caspase-3, caspase-12 and cytochrome C began to increase 1 d after injury while the expression of MBP decreased gradually. After intervened with honokiol for 6 days, compared with the vehicle group, the locomotor function and the pathomorphological changes of myelin sheath of the CSCD rats were improved with obviously decreased expression of active caspase-3, caspase-12 and cytochrome C. CONCLUSIONS: Honokiol may improve locomotor function and protect neural myelin sheat from demyelination via prevention oligodendrocytes (OLs) apoptosis through mediate endoplasmic reticulum (ER)-mitochondria pathway after CSCI.

Vascular cognitive impairment and dementia (VCID) is defined as a progressive dementia disease related to cerebrovascular injury and often occurs in aged populations. Despite decades of research, effective treatment for VCID is still absent. The pathological processes of VCID are mediated by the molecular mechanisms that are partly modulated at the post‐transcriptional level. As small endogenous non‐coding RNAs, microRNAs (miRs) can regulate target gene expression through post‐transcriptional gene silencing. miRs have been reported to play an important role in the pathology of VCID and have recently been suggested as potential novel pharmacological targets for the development of new diagnosis and treatment strategies in VCID. In this review, we summarize the current understanding of VCID, the possible role of miRs in the regulation of VCID and attempt to envision future therapeutic strategies. Since manipulation of miR levels by either pharmacological or genetic approaches has shown therapeutic effects in experimental VCID models, we also emphasize the potential therapeutic value of miRs in clinical settings., miR regulatory mechanisms in experimental VCID.

Chondroblastoma is a rare, benign, cartilaginous-derived tumor accounting for ∼1% to 2% of all primary bone tumors and almost 9% of all benign bone tumors. In this case report, we describe a patient with chondroblastoma and a secondary aneurysmal bone cyst, with the adjacent talus being mildly affected. The initial diagnosis was giant cell tumor and was then confirmed after computed tomography-assisted biopsy. We performed a total calcanectomy via bilateral structural iliac bone autografting to relieve pain and reconstruct the loadbearing function because of the presence of extensive lesions. The patient was pain free and expressed satisfaction with postsurgical dorsiflexion and plantarflexion function at the 60-month follow-up visit. Radiographic images showed that the autografted iliac bone was completely healed, with no evidence of local recurrence.

An electric field ( $E$ -field) detector with the features of precise time base, full-waveform storage, and wireless data transmission has been developed, which can be used in combination with location algorithm for accurate location of the transient electromagnetic radiation source over a large-scale area. The maximum sampling rate is 2 GS/s, and the memory depth is up to 128 kB and can be adjustable. The measurement range can be adjusted from hundreds of V/m to tens of kV/m with different lengths of antennas. With the help of the global positioning system (GPS), both the clock and the position of the detector can be synchronized. In particular, the time instant triggered by the signal could be recorded with the time resolution of tens of nanoseconds. Therefore, the precise time base alignment among multiple detectors could be achieved, which is crucial for location accuracy. Then, all data including the signal, the position, and the time instant could be sent to a remote server by the fourth-generation mobile (4G) communication technology. The calibration results show that the bandwidth of the detector could vary from 10 kHz to 500 MHz, while the time base alignment error between any two detectors is less than 50 ns. An experiment was performed by means of electromagnetic time reversal (EMTR) method to prove the applicability of the detector and its location accuracy. The detector could be used to measure and locate lightning, partial discharge, or fault.

BackgroundA retrospective study was conducted to evaluate and compare the clinical and radiological outcomes of one-stage fibular impaction allografting and vascularized greater trochanter flap autografting for the treatment of bilateral osteonecrosis of the femoral head (ONFH).MethodsPatients who underwent one-stage aforementioned hip-preserving surgeries due to bilateral ONFH were retrospectively reviewed from January 2008 to December 2013. Sixty-nine patients (138 hips) with a mean age of 31.5 years and mean follow-up of 7.0 years were included. Hips that underwent fibular impaction allografting and vascularized greater trochanter flap autografting were assigned as group A and group B, respectively. Harris Hip Score (HHS) and Visual Analogue Scale (VAS) were used for clinical evaluation, and a series of X-ray images were used for radiological assessment. For inter-group analysis, the pairedttest was used for continuous data, and the Wilcoxon rank sum test was used for non-parametric data, while the Mann-WhitneyUtest was used for intra-group analysis.ResultsThe HHS and VAS in both groups A and B had a substantial advancement when compared with the preoperative level (p p p = 0.04). It was discovered that the appropriate indication for each procedure was patients with Association for Research on Osseous Circulation (ARCO) stages II and III, respectively.ConclusionOne-stage hip-preserving surgeries for the management of bilateral ONFH could obtain good medium and long-term outcomes. It was recommended that fibular impaction allografting is more suitable for patients in ARCO stage II, while for patients in ARCO stage III, vascularized greater trochanter flap autografting is a better preference.Trial registrationRetrospectively registered.

Nitro-oleic acid (OA-NO2), a nitroalkene formed in nitric oxide-dependent oxidative reactions, has been found in human plasma and is thought to regulate pathophysiological functions. Recently, accumulating evidence suggests that OA-NO2 may function as an anti-inflammatory mediator, and ameliorate the progression of diabetes and cardiovascular diseases. However, the role of OA-NO2 in ischemic brain injury remains unexplored. In this study, C57BL/6 mice were subjected to 1 h transient middle cerebral artery occlusion (MCAO) and followed by 1– 7 days of reperfusion. These mice were treated with vehicle, OA, or OA-NO2 (10 mg/kg) via tail vein injection at 2 h after the onset of MCAO. Our results show that intravenous administration of OA-NO2 led to reduced BBB leakage in ischemic brains, reduced brain infarct, and improved sensorimotor functions in response to ischemic insults when compared to OA and vehicle controls. Also, OA-NO2 significantly reduced BBB leakage-triggered infiltration of neutrophils and macrophages in the ischemic brains. Moreover, OA-NO2 treatment reduced the M1-type microglia and increased M2-type microglia. Mechanistically, OA-NO2 alleviated the decline of mRNA and protein level of major endothelial TJs including ZO-1 in stroke mice. Treatment of OA-NO2 also significantly inhibited stroke-induced inflammatory mediators, iNOS, E-selectin, P-selectin, and ICAM1, in mouse brains. In conclusion, OA-NO2 preserves BBB integrity and confers neurovascular protection in ischemic brain damage. OA-NO2-mediated brain protection may help us to develop a novel therapeutic strategy for the treatment of ischemic stroke.

Background To compare the mid-long-term clinical and radiological outcomes between a combination of cortico-cancellous iliac bone graft with vascularized greater trochanter flap (Group A) and isolate iliac bone graft (Group B) in the treatment of Osteonecrosis of the Femoral Head (ONFH). Methods From January 2006 to December 2012, 123 patients (135 hips) who underwent abovementioned hip-preserving surgeries were included for analysis. Clinical outcomes were assessed based on Harris Hip Score (HHS) System and The Western Ontario and McMaster University Index (WOMAC) scores between the preoperative and the last follow-up. A series of postoperative X-rays were compared to preoperative images for radiological evaluation. Results The HHS in Group A and B were enhanced from 50.57 ± 3.39 to 87.60 ± 4.15 and from 50.24 ± 3.30 to 85.18 ± 6.45, respectively, which both showed significance between preoperative and postoperative latest follow-up (p 0.05). Conclusions A combination of cortico-cancellous iliac bone graft and concurrent vascularized greater trochanter flap with the lateral femoral circumflex transverse branch has been proved can obtain better functional and radiological results than isolate iliac bone grafting, which is attributed to blood reconstruction of the femoral head.

BACKGROUND High-mobility group box 1 (HMGB1) is an essential contributor towards initiation and progression of many kinds of cancers. Nevertheless, our understanding of the molecular etiology of HMGB1-modulated vasculogenesis, as well as invasion, of breast cancer is poor. This study explored HMGB1 expression in breast cancer and its role in the development and spread of malignancy. MATERIAL AND METHODS We enrolled 15 patients with breast cancer who received primary surgery at the Department of Thyroid and Breast Surgery in our hospital. HMGB1 was recorded and analyzed. RESULTS Our investigation successfully proves that HMGB1 is upregulated in breast cancer tissues in comparison to the surrounding non-malignant tissues. HMGB1 enhanced vessel formation in breast cancer tissues by regulating hypoxia-inducible factor 1 (HIF-1alpha), which in turn upregulates the expression of VEGF. Furthermore, HMGB1-mediated upregulation of HIF-1alpha relies on its ability to stimulate the phosphatidylinositol 3-kinase (PI3K) pathway to reinforce AKT subunit phosphorylation. HMGB1 overexpression reinforces the vasculogenesis in malignancies not only in vivo but also in vitro. Additionally, shRNA knockdown of HMGB1 prohibited the vessel-forming and invasive capabilities, downregulated VEGF and HIF-1alpha, and suppressed AKT phosphorylation in breast cancer cells. Most importantly, PI3K/AKT axis suppression eliminated the effect of HMGB1-modulated vascularization and invasion in breast cancer cells. CONCLUSIONS Our research indicates that HMGB1 serves as a crucial regulator of malignant cell-modulated vessel formation and is involved in the development of malignancy. Our findings indicate that HMGB1 is a promising target for breast cancer treatment.

Background Osteonecrosis of the femoral head (ONFH) is a disabling disease, which often involves young patients. Recently, various hip-preserving surgeries were recommended to delay total hip arthroplasty (THA). Questions/purposes This study aimed to compare clinical outcomes and survival rate in the long-term follow-up between core decompression combined with a non-vascularized autologous fibular graft (group A) and an allogeneic fibular graft (group B) for the treatment of ONFH. Patients and methods We retrospectively evaluated 117 patients (153 hips) with ONFH (Association Research Circulation Osseous [ARCO] stages IIa to IIIc) who underwent the abovementioned hip-preserving surgeries between January 2003 and June 2012. The mean (range) follow-up times (years) were 12.9 (7–16) and 9.3 (6–16) in groups A and B, respectively. Clinical outcomes were assessed using the Harris Hip Score (HHS), visual analog scale (VAS) score, and forgotten joint score (FJS). A survival analysis was performed using the Kaplan-Meier method. The end point was THA. Results Groups A and B showed postoperative improvements, respectively, in HHS from 65 ± 7.2 to 80.3 ± 14.5 and from 66 ± 5.9 to 82.4 ± 13.6 (p p p > 0.05) and 15-year survival rate (84.1% and 86%, respectively, p > 0.05) were found between groups A and B. Conclusions Autologous and allogeneic fibular grafts can attain equally good clinical outcomes and high survival rates in long-term follow-up, and thus can greatly delay THA owing to good bone osseointegration and sufficient mechanical support. Notably, the ratio of failure will increase when patients were more than 37 years old. Level of evidence Level III, therapeutic study

Few-shot learning (FSL) inspired by deep neural network and its practice on electromagnetic susceptibility evaluation are reported. By the assistance of model, metric or optimization, FSL can not only make use of the prior information, but also gain the ability of learning the pattern for distinguishing and classifying input vectors from only a few samples. For transient electromagnetic disturbances, the recurrent neural network (RNN) is involved to help with the memory of the input signal with the style of 1-D time sequence. In order to learn the proper feature of transient disturbances, a Siamese neural network containing two RNNs is built and trained, and the distance of two outputs can be measured by a preselected distance function. This makes the proposed model capable to learn the difference between normal cases and failure cases. In order to demonstrate this method, a pulse current injection testing on a certain electronic system is conducted and evaluated with the metric-based FSL. The result confirms the practicability of the proposed model, for the correct classification rate can be 83.3% with only 36 samples.

BACKGROUND: Small cell lung cancer (SCLC) is the most deadly and aggressive type of primary lung cancer, with the 5-year survival rate lower than 5%. The FDA has approved arsenic trioxide (As(2)O(3)) for acute promyelocytic leukemia (APL) treatment. However, its role in SCLC-derived cancer stem cells (CSCs) remains largely unknown. METHODS: CSCs were enriched from SCLC cell lines by culturing them as spheres in conditioned serum-free medium. Then, qPCR, western blot, serial passage, limiting dilution, Transwell, and tumorigenesis assay were performed to verify the cells’ stem phenotypic characteristics. Anticancer efficiency of As(2)O(3) was assessed in these cells using CCK8, colony formation, sphere formation, flow cytometry, qPCR, western blot analysis in vitro, and tumor growth curve, immunofluorescence, and TUNEL staining analyses in vivo. RESULTS: The fifth-passage SCLC spheres showed a potent self-renewal capacity, higher clonal formation efficiency (CFE), SOX2, c-Myc, NANOG, and OCT4 levels, and invasion ability, and stronger tumorigenesis capacity than the parental SCLC cells, indicating that the SCLC sphere cells displayed CSC features. As(2)O(3) inhibited the proliferation, clonality and sphere forming ability of SCLC-derived CSCs and suppressed the tumor growth of CSCs-derived xenograft tumors. As(2)O(3) induced apoptosis and downregulation of SOX2 and c-Myc in vitro and in xenografts. Besides, SOX2 knockdown suppressed SCLC-derived CSCs to self-renew and induced apoptosis. Mechanistically, expression of GLI1 (a key transcription factor of Hedgehog pathway) and its downstream genes increased in SCLC-derived CSCs, compared to the parental cells. As(2)O(3) dramatically downregulated GLI1 and its downstream genes in vitro and in vivo. The GLI inhibitor (GANT-61) recapitulated and enhanced the effects of As(2)O(3) on SCLC-derived CSCs, including growth suppression, apoptosis induction, and GLI1, SOX2 and c-Myc downregulation. CONCLUSIONS: Altogether, As(2)O(3) effectively suppressed SCLC-derived CSCs growth by downregulating stem cell-maintenance factors and inducing apoptosis. These effects are mediated at least partly via the Hedgehog signaling blockade.

Output power of a transistorized pulser is usually limited by the power capacity of avalanche transistors. To improve the total output power, the power synthesis method is widely used, in which a single pulser with high output power and high time base stability is required. However, the time base stability tends to deteriorate as the output power increases. To improve the output power under the premise of high time base stability, from the perspective of carrier movement, the mechanisms of pulse jitter and pulse drift are investigated. It is found that the pulse jitter is caused by time dispersion of the ionization process in the collector depletion region, while the pulse drift is due to the decrement of the diffusion coefficient Dn and the electron mobility μn, which are both temperature-dependent. Based on the microscopic theoretical study, some macroscopic improvements on the time base stability are made. Some parameters of the trigger pulse and the circuit (e.g., charging capacitance) are optimized experimentally. Consequently, we achieved a pulser with an amplitude of 1.8 kV, pulse jitter of 25 ps, pulse drift of 100 ps/min at a pulse repetition frequency (PRF) of 100 kHz. Additionally, a new parameter k, the product of the highest PRF f and the peak power Ep, is defined to evaluate the output power. With almost the same time base stability, the proposed pulser has a k of 6.48 GHz W, which is improved significantly. Finally, a synthesized pulser with an amplitude of 2.5 kV and highest PRF of 100 kHz is achieved.

Background Pinin (PNN), a desmosome associated protein, was demonstrated to be over-expressed and act as a tumor-promoting factor in ovarian cancer, hepatocellular carcinoma and colorectal cancer. However, the precise role of PNN in prostate cancer is still unknown. Methods The expression levels of PNN were assessed in prostate cancer by qRT-PCR, western blotting and immunohistochemical staining. The other proteins were quantified by western blotting. PNN-depleted cells were produced by infecting with lentivirus bearing short hairpin RNAs against PNN. PNN over-expression was performed by transfecting PNN expression vector. The proliferation of each cell line was assessed by MTS and colony formation assays. Tumors were induced on nude mice by injecting tumor cells subcutaneously. Apoptosis and cell cycle were evaluated by flow cytometry. Transwell and wound healing assay were performed to determined the ability of cell invasion and migration. The TCGA data were analyzed with GEPIA (Gene Expression Profiling Interactive Analysis) and GraphPad Prism. Results Here, we reported that PNN was upregulated in prostate cancer tissues and PNN expression was positively associated with Gleason score, tumor stage and tumor metastasis. PNN promoted cell growth and tumorigenicity in vitro and in vivo, and might modulate cell growth through driving G1/S transition via CDK6, CDK2, and Cyclin D1 in prostate cancer cells. Furthermore, PNN accelerated cell invasion, migration and EMT processes of prostate cancer cells accompanied with the up-regulation of MMP-2, MMP-9, N-cadherin, Vimentin and down-regulation of E-cadherin. Mechanism study demonstrated that the proliferation- and motility-promoting effects of PNN on prostate cancer cells dependent on the activation of PI3K/AKT/CREB signaling, which was reversed by AKT and CREB inhibitors. Conclusions Collectively, these findings indicated that PNN plays important roles in prostate cancer tumorigenesis and progression and it may be a potential therapeutic target for prostate cancer treatment.

To enhance food safety, environmental sustainability, and corporate governance, the Financial Supervisory Commission of Taiwan have required four types of listed companies to produce and file corporate social responsibility (CSR) reports since 2014: companies in the food, finance, and chemical industries and those with more than NT$40 billion in capital. This policy aims to enforce companies’ commitment to social responsibility. However, does this policy boost companies’ operating performance and help them achieve sustainable operations? This study employed data from the Taiwan Economic Journal and CSR reports from 2010 to 2017 for analysis. The operating performance of companies covered by this policy after it was implemented was not significantly better than that before policy implementation. For companies that voluntarily produced CSR reports before the policy, their return on assets was superior to that of companies that did not voluntarily produce CSR reports. The hypotheses were only partially supported by the results. The conclusions may provide a reference for companies reviewing their performance when complying with the policy to make improvements and adjustments accordingly and for the Financial Supervisory Commission in reviewing their policies.

In order to solve the current situation of low management efficiency in university laboratories and the inconvenience to use it, this paper proposes and designs an intelligent experiment management system based on Internet of things technology. This system puts forward a feasible and detailed design scheme, which adopts the Internet of things technology to design the intelligent experiment management system and uses Java to realize the intelligent experiment management platform. Finally, the function of the management system is tested and verified. The test shows that the intelligent experiment management system has basically achieved the expected functions and meets the needs of the intelligent experiment management platform of universities.

The blood-brain barrier (BBB) maintains a stable brain microenvironment. Breakdown of BBB integrity during cerebral ischemia initiates a devastating cascade of events that eventually leads to neuronal loss. MicroRNAs are small noncoding RNAs that suppress protein expression, and we previously showed that the miR-15a/16-1 cluster is involved in the pathogenesis of ischemic brain injury. Here, we demonstrated that when subjected to experimentally induced stroke, mice with an endothelial cell (EC)-selective deletion of miR-15a/16-1 had smaller brain infarcts, reduced BBB leakage, and decreased infiltration of peripheral immune cells. These mice also showed reduced infiltration of proinflammatory M1-type microglia/macrophage in the peri-infarct area without changes in the number of resolving M2-type cells. Stroke decreases claudin-5 abundance, and we found that EC-selective miR-15a/16-1 deletion enhanced claudin-5 mRNA and protein abundance in ischemic mouse brains. In cultured mouse brain microvascular endothelial cells (mBMECs), the miR-15a/16-1 cluster directly bound to the 3’ untranslated region (3’-UTR) of Claudin-5 and lentivirus-mediated ablation of miR-15a/16-1 diminished oxygen-glucose deprivation (OGD)-induced downregulation of claudin-5 mRNA and protein abundance and endothelial barrier dysfunction. These findings suggest that genetic deletion of endothelial miR-15a/16-1 suppresses BBB pathologies after ischemic stroke. Elucidating the molecular mechanisms of miR-15a/16-1-mediated BBB dysfunction may enable the discovery of new therapies for ischemic stroke.

Gorham-Stout syndrome (GSS) is a rare disease characterized by spontaneous and progressive osteolysis caused by benign proliferation of lymphatic vessels or capillaries. It most commonly occurs in children or young individuals without any inherited predisposition. GSS most commonly affects the shoulder girdle, pelvis, ribs and skull. Its diagnosis is mainly based on radiological and pathological findings. The present study reports on the case of a 22-year-old male patient diagnosed with GSS involving the C1-T1 vertebrae accompanied by bilateral pleural effusion. Resection of the occipital and cervical vertebral lesions and spinal reconstruction using an internal fixator were successfully performed via the posterior approach. After the surgery, the patient received bisphosphonate treatment and vitamin D supplementation. The pleural effusion gradually decreased. At the 18-month follow-up visit, no evidence of new bone obstruction was present and the patient had no neurological sequelae.

Rationale: Angiogenesis promotes neurological recovery after stroke and is associated with longer survival of stroke patients. Cerebral angiogenesis is tightly controlled by certain microRNAs (miRs), such as the miR-15a/16-1 cluster, among others. However, the function of the miR-15a/16-1 cluster in endothelium on postischemic cerebral angiogenesis is not known. Objective: To investigate the functional significance and molecular mechanism of endothelial miR-15a/16-1 cluster on angiogenesis in the ischemic brain. Methods and Results: Endothelial cell-selective miR-15a/16-1 conditional knockout (EC-miR-15a/16-1 cKO) mice and wild-type littermate controls were subjected to 1 hour middle cerebral artery occlusion followed by 28-day reperfusion. Deletion of miR-15a/16-1 cluster in endothelium attenuates post-stroke brain infarction and atrophy and improves the long-term sensorimotor and cognitive recovery against ischemic stroke. Endothelium-targeted deletion of the miR-15a/16-1 cluster also enhances post-stroke angiogenesis by promoting vascular remodeling and stimulating the generation of newly formed functional vessels, and increases the ipsilateral cerebral blood flow. Endothelial cell-selective deletion of the miR-15a/16-1 cluster up-regulated the protein expression of pro-angiogenic factors VEGFA (vascular endothelial growth factor), FGF2 (fibroblast growth factor 2), and their receptors VEGFR2 (vascular endothelial growth factor receptor 2) and FGFR1 (fibroblast growth factor receptor 1) after ischemic stroke. Consistently, lentiviral knockdown of the miR-15a/16-1 cluster in primary mouse or human brain microvascular endothelial cell cultures enhanced in vitro angiogenesis and up-regulated pro-angiogenic proteins expression after oxygen-glucose deprivation, whereas lentiviral overexpression of the miR-15a/16-1 cluster suppressed in vitro angiogenesis and down-regulated pro-angiogenic proteins expression. Mechanistically, miR-15a/16-1 translationally represses pro-angiogenic factors VEGFA, FGF2, and their receptors VEGFR2 and FGFR1, respectively, by directly binding to the complementary sequences within 3′-untranslated regions of those messenger RNAs. Conclusions: Endothelial miR-15a/16-1 cluster is a negative regulator for postischemic cerebral angiogenesis and long-term neurological recovery. Inhibition of miR-15a/16-1 function in cerebrovascular endothelium may be a legitimate therapeutic approach for stroke recovery.

Objectives To investigate the value of a post-operative gait training program to improve pelvic obliquity (PO) and decrease leg length discrepancy (LLD) for patients with Crowe type I developmental dysplasia of the hip (DDH) undergoing unilateral total hip arthroplasty (THA). Methods The prospective group consisted of 35 patients who underwent one-stage unilateral THA. Pre- and post-training PO and LLD were measured for the radiological assessment and Harris Hip Score (HHS) was used for the functional assessment. Results The HHS improved from 55.54 ± 10.61 pre-operatively to 84.97 ± 7.63 after surgery. The mean post-training PO angle for grade 0, grade 1, and grade 2 were 2.66 ± 1.42, 2.94 ± 1.42, and 5.60 ± 1.90, respectively, compared with pre-training values of 1.42 ± 0.58, 4.17 ± 0.90, and 6.96 ± 0.46. The mean post-training LLD for grade 0, grade 1, and grade 2 were 0.83 ± 0.91, 0.56 ± 0.48, and 0.36 ± 0.30, respectively, compared with pre-training values of 0.70 ± 0.23, 1.25 ± 0.90, and 1.46 ± 1.60. Conclusion Gait training following unilateral THA can improve PO and decrease functional LLD in grade I DDH patients. This method may have moderate success for grade 0 DDH patients and provide limited benefit for grade II patients. Appropriate release of the soft tissues may be required for grade II DDH patients to obtain a better walking gait.

Introduction: Cerebral angiogenesis is tightly controlled by certain microRNAs (miRs), such as the miR-15a/16-1 cluster, among others. Recently, we demonstrated that endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis and improves long-term neurological recovery by increasing protein levels of VEGFA, FGF2, and their receptors VEGFR2 and FGFR1. Here, we further investigated the downstream signaling pathways of these pro-angiogenic factors by using a potent Src family inhibitor, saracatinib (AZD0530), in endothelial cell-selective miR-15a/16-1 conditional knockout (EC-miR-15a/16-1 cKO) mice after ischemic stroke. Hypothesis: Pharmacological inhibition of Src signaling cascade using AZD0530 diminishes enhanced post-stroke angiogenesis and long-term neurological recovery induced by the genetic deletion of miR-15a/16-1 in the endothelium. Methods: EC-miR-15a/16-1 cKO and WT littermate controls were subjected to 1h MCAO and 28d reperfusion. AZD0530 (20 mg/kg) was administered daily to both genotypes at 3-21d after MCAO by oral gavage. Cognitive outcomes were determined by Morris water maze tests. Brain atrophy was measured by MAP2 immunostaining. Cerebral blood flow (CBF) was monitored by laser speckle imaging. Brain capillary density and functional vessels were examined by CD31/BrdU and tomato lectin/BrdU double-immunostaining, respectively. Src signaling pathway-related molecules were analyzed by western blotting. Results: Treatment with AZD0530 exacerbates cognitive impairments and brain atrophy in EC-miR-15a/16-1 cKO mice following MCAO. AZD0530 also attenuates the long-term CBF recovery, correlated with inhibiting the generation of newly formed microvessels and functional vessels in the peri-infarct brain regions in EC-miR-15a/16-1 cKO mice after cerebral ischemia. Moreover, EC-targeted deletion of miR-15a/16-1 upregulates the Src signaling pathway, while AZD0530 blocks the Src signaling pathway by downregulating p-Src and its downstream mediators (p-Stat3, p-Akt, p-FAK, p-p38 MAPK) in ischemic brains. Conclusions: Endothelium-targeted deletion of miR-15a/16-1 promotes post-stroke angiogenesis and improves long-term neurological recovery via Src signaling pathway.

Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.

Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injuries, such as stroke, by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of cellular survival and recovery of homeostatic equilibrium. In the acute injury phase, PPARγ directly restricts tissue damage by inhibiting the NFκB pathway to mitigate inflammation and stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic phase of acute brain injuries, PPARγ activation in injured cells culminates in the repair of gray and white matter, preservation of the blood-brain barrier, reconstruction of the neurovascular unit, resolution of inflammation, and long-term functional recovery. Thus, PPARγ lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions. Here, we review the therapeutic potential of PPARγ in stroke and brain trauma and highlight the novel role of PPARγ in long-term tissue repair. We describe its structure and function and identify the genes that it targets. PPARγ regulation of inflammation, metabolism, cell fate (proliferation/differentiation/maturation/survival), and many other processes also has relevance to other neurological diseases. Therefore, PPARγ is an attractive target for therapies against a number of progressive neurological disorders.

Central nervous system (CNS) injuries are one of the leading causes of morbidity and mortality worldwide, accompanied with high medical costs and a decreased quality of life. Brain vascular disorders are involved in the pathological processes of CNS injuries and might play key roles for their recovery and prognosis. Recently, increasing evidence has shown that long non-coding RNAs (lncRNAs), which comprise a very heterogeneous group of non-protein-coding RNAs greater than 200 nucleotides, have emerged as functional mediators in the regulation of vascular homeostasis under pathophysiological conditions. Remarkably, lncRNAs can regulate gene transcription and translation, thus interfering with gene expression and signaling pathways by different mechanisms. Hence, a deeper insight into the function and regulatory mechanisms of lncRNAs following CNS injury, especially cerebrovascular-related lncRNAs, could help in establishing potential therapeutic strategies to improve or inhibit neurological disorders. In this review, we highlight recent advancements in understanding of the role of lncRNAs and their application in mediating cerebrovascular pathologies after CNS injury.

As promising highly-efficient and low-cost photovoltaic devices, perovskite solar cells must be made of compact and pin-hole free perovskite films. One-step solution engineering is a most efficient and low-cost precipitation of high quality perovskite films. However, the difficulty in controlling the precipitation and pin-hole formation in perovskite films makes this one-step solution engineering a great challenge. Here, we report, for the first time, a fast and high performance perovskite film precipitation by tuning the boundary layer during the solution processing of the perovskite film. Theoretical analyses and simulations were carried out alongside the experiments, and the results consistently showed that a high velocity and low temperature of the air flow could effectively reduce the thickness of the boundary layer. Subsequently, evaporated solvent molecules would diffuse through the boundary layer more easily, and then solvent evaporation becomes quicker, resulting in a high quality and pin-hole free perovskite film. As a result, the highest efficiency of 17.87% was achieved for planar perovskite solar cells (with an active area of 0.1 cm2) with the perovskite film precipitated under these air conditions. Furthermore, the efficiency reached as high as 12.72% with a 1.08 V open-circuit voltage for a 1 cm2 planar perovskite device. This essentially opens the door to developing high quality perovskite film precipitation approaches by tuning the boundary layer during facile one-step solution engineering.

Microvascular endothelial cell (EC) injury and the subsequent blood-brain barrier (BBB) breakdown are frequently seen in many neurological disorders, including stroke. We have previously documented that peroxisome proliferator-activated receptor gamma (PPARγ)-mediated cerebral protection during ischemic insults needs Kruppel-like factor 11 (KLF11) as a critical coactivator. However, the role of endothelial KLF11 in cerebrovascular function and stroke outcome is unclear. This study is aimed at investigating the regulatory role of endothelial KLF11 in BBB preservation and neurovascular protection after ischemic stroke. EC-targeted overexpression of KLF11 significantly mitigated BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and infiltration of peripheral immune cells, and less brain water content. Endothelial cell-selective KLF11 transgenic (EC-KLF11 Tg) mice also exhibited smaller brain infarct and improved neurological function in response to ischemic insults. Furthermore, EC-targeted transgenic overexpression of KLF11 preserved cerebral tight junction (TJ) levels and attenuated the expression of pro-inflammatory factors in mice after ischemic stroke. Mechanistically, we demonstrated that KLF11 directly binds to the promoter of major endothelial TJ proteins including occludin and ZO-1 to promote their activities. Our data indicate that KLF11 functions at the EC level to preserve BBB structural and functional integrity, and therefore, confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke and other neurological conditions involving BBB breakdown and neuroinflammation.

Background and objectives The survival rate of patients with advanced oesophageal cancer is very low and can vary significantly, even among patients with the same TNM stage. It is important to look for indicators that are economical and readily available to predict overall survival. The aim of this study was to determine whether lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) could be potential predictors of survival in patients with advanced oesophageal squamous cell carcinoma (ESCC) undergoing concurrent chemoradiotherapy. Methods Differences in survival among 204 patients with advanced oesophageal cancer who underwent concurrent chemoradiotherapy were collected and analysed. Univariate and multivariate COX regression analyses were used to investigate the association between blood inflammatory markers and patient survival before treatment. Results Univariate COX regression analyses showed that a history of alcohol use, neutrophil count, LMR, NLR, tumour length, and N stage were significantly associated with the survival of tumour patients receiving concurrent chemoradiotherapy. Multivariate COX regression analysis showed that NLR and LMR were predictors of outcome in tumour patients receiving chemoradiotherapy. According to receiver operating characteristic (ROC) curve analysis, the AUC of LMR and NLR was 0.734 and 0.749, and the best cutoff point for LMR and NLR was 3.03 and 2.64, respectively. Conclusions LMR and NLR can be used to predict the survival of patients with advanced oesophageal cancer receiving concurrent chemoradiotherapy, thereby providing clinicians with suggestions for further treatment options.

Introduction: Nitro-oleic acid (OA-NO 2 ), a nitroalkene formed in nitric oxide-dependent oxidative reactions, has been found in human plasma and is thought to regulate pathophysiological functions. Recently, accumulating evidence suggests that OA-NO 2 may function as an anti-inflammatory mediator, and ameliorate the progression of diabetes and cardiovascular diseases. However, the role of OA-NO 2 in ischemic brain injury remains unexplored. Hypothesis: OA-NO 2 stabilizes the blood-brain barrier (BBB), and is a neurovascular-protective regulator in ischemic brain injury. Methods: C57BL/6 mice were subjected to 1h transient middle cerebral artery occlusion (MCAO) followed by 24-72h reperfusion. These mice were intravenously treated with vehicle, OA or OA-NO 2 at 2h after the onset of MCAO. BBB integrity was assessed by using fluorescent-dextrans. Brain water content was measured by using a dry-wet method. Brain infarct was analyzed by 2%TTC staining or anti-map2 immunostaining. Infiltration of peripheral immune cells into brain parenchyma were examined by immunofluorescent methods. Total RNA was extracted from brain tissues and the expression of BBB tight junctions (TJs) and pro-inflammatory cytokines was detected by qPCR, Western blotting, and ELISA. Results: Compared to OA and vehicle controls, intravenous administration of OA-NO 2 led to reduced BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and less brain water content. OA-NO 2 treated mice also exhibited a smaller brain infarct and improved neurological functions in response to ischemic insults. Also, OA-NO 2 significantly reduced BBB leakage-triggered infiltration of neutrophils and macrophages in the ischemic brains. Mechanistically, OA-NO 2 increased major endothelial TJs including Claudin 5 and ZO-1 levels in stroke mice. Treatment of OA-NO 2 also significantly inhibited stroke-induced pro-inflammatory cytokines, IL-6 and MCP-1, in mouse brains. Conclusions: OA-NO 2 preserves BBB integrity and confers neurovascular protection in ischemic brain damage. OA-NO 2 -mediated brain protection may help us to develop a novel therapeutic strategy for the treatment of ischemic stroke.

Background The number of periprosthetic joint infections (PJI) after total knee arthroplasty (TKA) is increasing annually. Animal models have been used to clarify their clinical characteristics and the infection mechanism of pathogenic bacteria, However, since the prosthesis design of animal models is not uniform, it is difficult to simulate the environment of clinical PJI. Objectives To retrospect the progress on the prosthesis design of animal models of PJI after TKA and to summarize the criteria for evaluating a clinically representative model of PJI. Methods This systematic review was reported on the basis of Systematic Reviews and Meta-Analyzes (PRISMA). Pubmed, EMbase, Cochrane Library, Web of Science, Wanfang Data and China National Knowledge Infrastructure were researched for animal models of PJI after TKA from database establishment to April 2019 according to Chinese and English retrieval words, including "periprosthetic joint infections and total knee arthroplasty," "periprosthetic joint infections and model," "periprosthetic joint infections and biofilm," and "total knee arthroplasty and model." Results A total of 12 quantitative studies were enrolled in our study finally: 8 representative studies described prosthesis designs used in PJI animal models, 4 studies described prosthesis designs in non-infected animal models which were suitable for infection models. The major problems need to be dealed with were prosthesis, installation location, material, the function of separating the articular and medullary cavity, fixation manner, and the procedure of preserving the posterior cruciate ligament. Conclusion A highly representative design of the animal prosthesis of PJI should meet the following criteria: the surface of the prosthesis is smooth with the formation of biofilm, composed of titanium-6Al-4V or cobalt-chromium-molybdenum alloy; prosthesis can bear weight and is highly stable; and it can connect the joint cavity and medullary cavity simultaneously. To reach a more reliable conclusion, further experiments and improvements are required.

Given the essential role of the blood-brain barrier (BBB) in the central nervous system (CNS), cumulative investigations have been performed to elucidate how modulation of BBB structural and functional integrity affects the pathogenesis of CNS diseases such as stroke, traumatic brain injuries, dementia, and cerebral infection. Recent studies have demonstrated that microRNAs (miRNAs) contribute to the maintenance of the BBB and thereby mediate CNS homeostasis. This review summarizes emerging studies that demonstrate cerebral miRNAs regulate BBB function in CNS disorders, emphasizing the direct role of miRNAs in BBB molecular composition. Evidence presented in this review will encourage a deeper understanding of the mechanisms by which miRNAs regulate BBB function, and facilitate the development of new miRNAs-based therapies in patients with CNS diseases.

Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood–brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.

The Marx generator is an important device in pulse power technology for generating high voltage pulses. In general, the equivalent circuit of Marx generator circuit is a lumped parameter circuit under the condition of electrically small. However, for a Marx generator generating very short pulses such as ultra-wideband pulses, it is necessary to consider the wave process of pulse forming from the original terminal to the output terminal. In this paper, the circuit model of Marx generator involved distributed transmission lines is introduced, which considering the wave process. The difference between the newly raised Marx generator circuit model and the traditional Marx circuit is demonstrated by simulation and experiment. Based on this circuit model, it is useful to explain the pulse forming process accurately and to optimize the pulser design.

Introduction: Krüppel-like factors (KLFs) belong to zinc finger family of transcription factors and their roles in stroke are poorly explored. KLF11 is highly enriched in vascular endothelium, and we have previously documented that peroxisome proliferator-activated receptor gamma-mediated cerebral protection during ischemic insults needs KLF11 as a critical coactivator. However, the role of endothelial KLF11 itself in cerebrovascular function and stroke outcome is unclear. Hypothesis: We hypothesize that endothelium-targeted overexpression of KLF11 stabilizes the BBB, reduces the progression of brain damage, and improves neurological outcomes after ischemic stroke. Methods: Transient middle cerebral artery occlusion was performed in endothelial cell-selective KLF11 transgenic mice (EC-KLF11 Tg), and WT controls. BBB integrity was assessed by using Evans Blue and TMR-Dextran extravasation assays. Brain water content was measured by using a dry-wet method. Brain infarct was analyzed by 2%TTC staining. A battery of neurobehavioral tests, including rotarod, adhesive tape removal, and foot fault, were performed to assess sensorimotor functions. Total RNA was extracted from brain tissues and the expression of BBB tight junctions (TJs) was detected by qPCR and western blotting. Results: Compared to WT controls, EC-selective transgenic overexpression of KLF11 led to reduced BBB leakage in ischemic brains, evidenced by significantly reduced extravasation of BBB tracers and less brain water content. EC-KLF11 Tg mice also exhibited a smaller brain infarct and improved neurological functions in response to ischemic insults. Mechanistically, we found KLF11 binding sites in the promoter region of major endothelial TJs including Claudin 5 and ZO-1. EC-selective transgenic overexpression of KLF11 significantly increased cerebral TJ levels in mice after ischemic stroke. Conclusions: The present study has demonstrated that KLF11 functions at the EC level to preserve BBB structural and functional integrity and confers brain protection in ischemic stroke. KLF11 may be a novel therapeutic target for the treatment of ischemic stroke.

Introduction: Angiogenesis promotes functional recovery and is associated with longer survival time in stroke patients. Accumulating studies have shown important roles for microRNAs (miRs) in regulating angiogenesis. Previously, we have demonstrated that miR-15a/16-1 cluster in endothelium negatively regulates hindlimb ischemia-induced angiogenesis. Here we further investigate its functional significance and molecular mechanism on post-ischemic cerebral angiogenesis. Hypothesis: Genetic deletion of miR-15a/16-1 cluster in endothelium increases cerebral angiogenesis and improves long-term neurological functions after ischemic stroke. Methods: EC-selective miR-15a/16-1 conditional knockout mice (EC-miR-15a/16-1 cKO) and WT controls were subjected to 1h MCAO followed by 3-28d reperfusion. Neurobehavioral outcomes were determined by the foot fault, rotarod, adhesive tape removal and Morris water maze tests. Brain capillary density and functional vessels were examined by CD31 and tomato-lectin immunofluorescent staining. In vitro angiogenesis assays, including capillary tube formation, scratch assay and BrdU cell proliferation were applied to cultured mBMECs with lentiviral loss- or gain-of-miR-15a/16-1 function. Pro-angiogenic factors were determined by 3’-UTR luciferase reporter assay, ELISA and western blotting. Results: Brain capillary density and the number of functional vessels in the ischemic penumbra of EC-miR-15a/16-1 cKO mice are higher than those of WT controls. Accordingly, EC-miR-15a/16-1 cKO mice exhibit improved sensorimotor and cognitive outcomes. Moreover, loss- or gain-of-miR-15a/16-1 function in mBMECs significantly increases or reduces tube formation, cell migration and cell proliferation, respectively. Mechanistically, gain-of miR-15a/16-1 function decreases luciferase reporter activity of VEGF, and remarkably reduces VEGF expression in mBMECs. Conclusions: Our findings suggest endothelial miR-15a/16-1 cluster is a negative regulator for post-ischemic cerebral angiogenesis and long-term functional recovery. Clinical intervention of miR-15a/16-1 mediated angiogenesis may be helpful for the development of novel neurorestorative therapies after ischemic stroke.

Rupture of an intracranial aneurysm is a life-threatening acute cerebrovascular event. The purpose of this study was to investigate whether aneurysmal subarachnoid haemorrhage (SAH) incidence rate is higher or lower in elderly population than in middle aged population.Aneurysmal SAH cases were collected retrospectively from the archives of 21 hospitals in Mainland China. All the cases were collected from September 2016 and backward consecutively for a period of time up to 8 years. SAH was initially diagnosed by brain computed tomography (CT). CT angiography (CTA) or digital subtraction angiography (DSA) was followed and SAH was confirmed to be due to cerebral aneurysm rupture. For cases when multiple bleeding occurred, the age of the first SAH was used in this study. The total incidence from all hospitals at each age group were summed together for females and males respectively; then adjusted by the total population number at each age group for females and males which was from the 2010 population census of the People's Republic of China.In total there were 8,144 cases of intracranial aneurysmal SAH, with 4,861 females and 3,283 males. For females the relative aneurysmal SAH incidence rate started to decrease after around 65 years old, while for males the relative aneurysmal SAH incidence rate started to decrease after around 53 years old.Our data tentatively suggest elderly patients may be at a reduced risk of rupture compared with patients who are younger while have similar other risk factors.

This paper proposes an effective test setup and method for quantitative determination of critical parameters of surge protective devices (SPDs) when excited by nanosecond level pulse (normally rise time less than 2 ns). The experimental results of SPDs validate the accuracy and reliability of the proposed method. By using the proposed method, the response time and time-varying response characteristics can be evaluated; meanwhile, the incoming voltage and residual voltage of SPDs can be retrieved by simple mathematical operations. These parameters obtained from the proposed method are critical to the device selection when designing the fast response protective module and examining the performance of SPDs by the manufacturers.

Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and post-stroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke-associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis.

With the increase capacity of wind turbines, grounding device's influence on the equipment and personal safety is becoming more and more significant. In order to calculate the grounding resistance of a wind turbine more accurately, in this paper, based on the Neumann integral formula and the average potential method is applied to derive a formula which can calculate the value of grounding resistance. A general MATLAB program corresponding to the calculation formula is compiled. By comparing the numerical value with the empirical analysis results and building a grounding resistance measurement test platform the correctness of the formulas and program is verified.

According to the requirements of the clean-up locomotive in the industrial production process, the locomotive in rail need to automatic complete "moving, locating, parking" reciprocating operation. Accurate locating is realized in the case of no-man control and operation safely. The principle of the locating system is to use the encoder installed on the locomotive to count for the rack fixed on the rail. The pulse number of encoder count is compared with locating parameter which was originally set, and the locomotive is adjusted and located to the accurate position. The discontinuous racks are installed on the rail at the corresponding pithead to solve the absolute accuracy of locating. The minimum locating error can be 2mm, and the maximum is 6mm when debugging on a rail up to 30000mm. This locating error meets the requirement of the system permitting error 20mm.

Creativity, one of the important abilities of industrial designers, can help designing and realizing innovative products. Today industrial design requires group collaboration too. How to effectively stimulate group creativity is an important issue on promoting innovation on products. Both the 635 brainstorming method and the C-Sketch method realize team-based divergent thinking techniques. The former uses words while the latter uses pictures as a way to stimulate group creativity. This study fuses the 635 brainstorming method and the C-Sketch method in an attempt to help group designers, by alternatively passing pictures and words in the divergent thinking phase, stimulating and integrating their ideas from different aspects for developing innovative products. To evaluate the feasibility of this hybrid technique, this study conducts two experiments. The results in the first experiment, using the proposed method, the originality and elaboration of the group creativity are significantly better than using the 635 brainstorming method, but the fluency and flexibility are not. In the second experiment, using the proposed method, the originality and elaboration of the group creativity are significantly better than using the C-Sketch method, but the flexibility is not. The C-Sketch method performs significantly better, nevertheless, than the proposed method in the fluency of group creativity. The proposed method is significantly better than the 635 brainstorming method and the C-Sketch method in improving designers' creativity thinking. Nevertheless, the measurements on the performances on the final products yield no significant differences between the proposed method and the 635 brainstorming method or the C-Sketch method.

Background and Purpose— Dysregulation of the miR-15a/16-1 cluster in plasma has been reported in patients with stroke as a potential biomarker for diagnostic and prognostic use. However, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. This study is aimed at investigating the regulatory role of the miR-15a/16-1 cluster in ischemic brain injury and insight mechanisms. Methods— Adult male miR-15a/16-1 knockout and wild-type mice, or adult male C57 BL/6J mice injected via tail vein with the miR-15a/16-1–specific inhibitor (antagomir, 30 pmol/g), were subjected to 1 hour of middle cerebral artery occlusion and 72 hours of reperfusion. The neurological scores, brain infarct volume, brain water content, and neurobehavioral tests were then evaluated and analyzed. To explore underlying signaling pathways associated with alteration of miR-15a/16-1 activity, major proinflammatory cytokines were measured by quantitative polymerase chain reaction or ELISA and antiapoptotic proteins were examined by Western blotting. Results— Genetic deletion of the miR-15a/16-1 cluster or intravenous delivery of miR-15a/16-1 antagomir significantly reduced cerebral infarct size, decreased brain water content, and improved neurological outcomes in stroke mice. Inhibition of miR-15a/16-1 significantly decreased the expression of the proinflammatory cytokines interleukin-6, monocyte chemoattractant protein-1, vascular cell adhesion molecule 1, tumor necrosis factor alpha, and increased Bcl-2 and Bcl-w levels in the ischemic brain regions. Conclusions— Our data indicate that pharmacological inhibition of the miR-15a/16-1 cluster reduces ischemic brain injury via both upregulation of antiapoptotic proteins and suppression of proinflammatory molecules. These results suggest that the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.

Kruppel-like factors (KLFs) are members of the zinc finger family of transcription factors and the function of the KLFs in the central nervous system is largely unexplored. KLF11 is a member of the KLF family and we have previously demonstrated that peroxisome proliferator-activated receptor gamma-mediated cerebral protection during ischemic insults needs recruitment of KLF11 as its critical coactivator. In this study we sought to determine the role of KLF11 itself in cerebrovascular function and the pathogenesis of ischemic stroke. Transient middle cerebral artery occlusion (MCAO) was performed in KLF11 knockout and wild-type control mice, and brain infarction size was analyzed by TTC staining. BBB integrity was assessed by using Evans Blue and TMR-Dextran extravasation assays. KLF11 KO mice exhibited significantly larger brain infarct volume and worse neurological outcomes in response to ischemic insults. Genetic deficiency of KLF11 in mice also significantly aggravated ischemia-induced BBB disruption by increasing cerebrovascular permeability and edema in comparison with wild-type mice. Mechanistically, KLF11 was found to directly regulate several key inflammatory cytokines in the brains of ischemic mice. These findings suggest that KLF11 acts as a novel protective factor in ischemic stroke. Elucidating the functional importance of KLF11 in ischemic process may lead us to discover novel pharmaceutical targets for the development of effective therapies against ischemic stroke.

MicroRNAs (miRs) are small endogenous RNA molecules that repress gene translation by hybridizing to 3’-UTRs of mRNAs. Accumulating evidence has shown that miRs play a critical regulatory role in the pathogenesis of ischemic stroke. MiR-15a and miR-16-1 are two highly conserved miRs, which act similarly by binding to their common mRNA targets, thus forming both a structural and functional cluster. Dysregulated plasma levels of miR-15a/16-1 have been reported in stroke patients. Inhibition of miR-15a has been shown to protect against myocardial infarction and selected by pharmaceutical companies as one of the most attractive miR-based therapeutics. Up to now, the essential role and therapeutic potential of the miR-15a/16-1 cluster in ischemic stroke are poorly understood. In this study, adult male miR-15a/16-1 knockout and wildtype mice were subjected to 45 min of middle cerebral artery occlusion (MCAO) and 72h of reperfusion. In a separate experiment, miR-15a/16-1 specific inhibitor (antagomir, 30 pmol/g) was injected into tail vein of stroke mice and the animals were allowed to survive for 72h. The neurological scores, brain infarct volume, and edema content were then evaluated and analyzed. To explore the underlying mechanism, inflammatory factors were measured by qPCR or ELISA and anti-apoptotic proteins were examined by western blotting. We found that genetic deletion of miR-15a/16-1 or intravenous delivery of miR-15a/16-1 antagomir significantly reduced cerebral infarct size, decreased brain edema and improved neurological outcomes in stroke mice. Mechanistically, treatment of miR-15a/16-1 antagomir significantly ameliorated the expression of several key inflammatory factors and increased the Bcl-2 and Bcl-w levels in the ischemic brain regions. These results demonstrated that pharmacological inhibition of miR-15a/16-1 reduces ischemic brain injury via both anti-apoptotic and anti-inflammatory mechanisms and the miR-15a/16-1 cluster is a novel therapeutic target for ischemic stroke.

Accumulative studies have demonstrated the important regulatory roles of microRNAs in vascular and neural damage after ischemic stroke. However, the functional significance and mechanisms of other classes of non-coding RNAs in cerebrovascular pathophysiology after stroke are less studied. Using RNA-sequencing technology, we previously profiled long non-coding RNAs (lncRNAs) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD), and identified that metastasis associated lung adenocarcinoma transcript 1 (Malat1) is one of the most highly upregulated OGD-responsive endothelial lncRNAs. Here, we sought to determine the role of Malat1 in cerebrovascular pathogenesis of ischemic stroke. Increased Malat1 levels were found in cultured mouse BMECs after OGD as well as in isolated cerebral microvessels in mice after transient middle cerebral artery occlusion (tMCAO) and 24h reperfusion by quantitative PCR. Loss-of-Malat1 function by LNA-GapmeRs significantly increased OGD-induced cell death and Caspase 3 activity in BMECs. It appears that Malat1 plays anti-apoptotic and anti-inflammatory roles in cerebral endothelium, showing that loss-of-Malat1 function significantly aggravated OGD-induced expression of pre-apoptotic factor Bim, pro-inflammatory cytokines MCP-1, IL-6 and E-selectin at both mRNA and protein levels. Moreover, Malat1 KO mice presented larger brain infarct size and worse neurological score after tMCAO compared to WT controls. A battery of behavioral tests, including adhesive tape removal, foot fault, cylinder were performed to assess sensorimotor functions after ischemic stroke. Malat1 KO mice exhibited reduced ability to perform all the above tests. Consistent with in vitro findings, significantly increased expression of Bim, MCP-1, IL-6 and E-selectin at mRNA and protein levels were also found in Malat1 KO mouse cortex after ischemic stroke in comparison with WT controls. Taken together, these findings suggest that Malat1 plays critical vascular and neuroprotective roles in ischemic stroke.

The performance of a room temperature, zero-field MASER operating at 1.45 GHz has been examined. Nanosecond laser pulses, which are essentially instantaneous on the timescale of the spin dynamics, allow the visible-to-microwave conversion efficiency and temporal response of the MASER to be measured as a function of excitation energy. It is observed that the timing and amplitude of the MASER output pulse are correlated with the laser excitation energy: at higher laser energy, the microwave pulses have larger amplitude and appear after shorter delay than those recorded at lower laser energy. Seeding experiments demonstrate that the output variation may be stabilized by an external source and establish the minimum seeding power required. The dynamics of the MASER emission may be modeled by a pair of first order, non-linear differential equations, derived from the Lotka-Volterra model (Predator-Prey), where by the microwave mode of the resonator is the predator and the spin polarization in the triplet state of pentacene is the prey. Simulations allowed the Einstein coefficient of stimulated emission, the spin-lattice relaxation and the number of triplets contributing to the MASER emission to be estimated. These are essential parameters for the rational improvement of a MASER based on a spin-polarized triplet molecule.

Stroke is one of the leading cause of death and major cause of long-term disability in the United States. Over years, extensive efforts have been focusing on the development and improvement of diagnostic and therapeutic strategies to reduce stroke-associated neurovascular damages, such as neuronal death, blood-brain barrier (BBB) dysfunction, and brain edema. However, the only clinically approved pharmacological therapy to date for treatment of acute ischemic stroke is still thrombolysis. This is mainly due to the short therapeutic window and the activation of various pathophysiological signaling cascades triggered after ischemic stroke. MicroRNAs (miRNAs) are small sequences of non-protein-coding RNA (~19 to 25 nt) with a variety of gene regulation functions in eukaryotic cells. Ever since being first reported in the pathogenesis of stroke in 2007, miRNAs have emerged as key mediators of posttranscriptional gene silencing in the pathogenesis of ischemic stroke. Also, preclinical and clinical studies have documented miRNAs as interesting novel drug targets, which led to the development of miRNA mimics and antagomirs as miRNA-based therapies. Stroke also alters miRNA expression profiles in the circulation system, and stroke-associated miRNAs have been proposed as potential diagnostic and prognostic biomarkers in ischemia stroke. In this chapter, we summarized current knowledge about miRNAs and cerebral ischemia, focusing on the role of miRNAs as biomarkers for stroke and as targets for regulating large sets of genes in related pathways after ischemic stroke.

In this paper, we propose a novel two-dimension (2-D) cursor control system by using steady state visual evoked potential (SSVEP) and P300 signals to control the direction and speed of the cursor, respectively. A hybrid stimulus interface is developed, where P300 visual stimuli are distributed at the top and bottom edges, representing accelerating and decelerating commands, respectively, and SSVEP stimuli, representing turning clockwise and counterclockwise, respectively, are located at the right and left sides. A classifier built with support vector machine is first used to distinguish between the direction and speed control commands, and if the classification result is the speed control command, a linear classifier is then applied to classify accelerating and decelerating commands. A real-time cursor control system is developed and tested with eight participants. The experimental results show that the cursor control system has satisfactory efficiency and accuracy, and the cursor movement is smooth and continuous. More importantly, it can work for the users, who are unable to produce event-related desynchronization/event-related synchronization (ERD/ERS) well but can produce P300 and SSVEP potentials compared to other 2-D cursor control systems. The proposed system can be used as a complementary, sometimes an alternative, system to the existing 2-D cursor control systems.

Catadioptric panoramic vision system has been widely used in many fields, and also plays a very important role in environment perception of unmanned platform especially. However, the resolution of system is not very high, usually less than 5 million pixels at present. Even if the resolution is high, but the unwrapping and rectification of panoramic video is carried out off-line. Further, the system is also applied in stationary state or low stationary moving. This paper proposes an unwrapping and rectification method based on high-resolution catadioptric panoramic vision system used during non-stationary moving. It can segment dynamic circular mark region accurately and get the coordinates of center of circular image real-timely, shorten the time of image processing, meanwhile the coordinates of center and radius of the circular mark region would be obtained, so the image distortion caused by inaccurate center coordinates can be reduced. During image rectification, after achieving radial distortions parameters (K1, K2, K3), decentering distortions parameters (P1, P2), and the correction factor that has no physical meanings, we can used those for fitting the rectification polynomial, so the panoramic video can be rectified without distortion.

In this paper, we propose a new steady-state visually evoked potential (SSVEP) brain–computer interface (BCI) with visual stimuli presented on a windshield via a head-up display, and we apply this BCI in conjunction with an alpha rhythm to control a simulated vehicle with a 14-DOF vehicle dynamics model. A linear discriminant analysis classifier is applied to detect the alpha rhythm, which is used to control the starting and stopping of the vehicle. The classification models of the SSVEP BCI with three commands (i.e., turning left, turning right, and going forward) are built by using a support vector machine with frequency domain features. A real-time brain-controlled simulated vehicle is developed and tested by using four participants to perform a driving task online, including vehicle starting and stopping, lane keeping, avoiding obstacles, and curve negotiation. Experimental results show the feasibility of using the human “mind” alone to control a vehicle, at least for some users.