Ultrastructural Features of Neurovascular Units in a Rat Model of Chronic Compressive Spinal Cord Injury

Chronic spinal cord compression is the most common cause of spinal cord impairment worldwide. Objective of this study is to assess the ultrastructural features of the neurovascular unit (NVU) in a rat model of chronic compressive spinal cord injury, 24 SD rats were divided into two groups: the control group (n = 12), and the compression group (n = 12). A C6 semi-laminectomy was performed in the control group, whereas a water-absorbent polyurethane polymer was implanted into the C6 epidural space in the compression group. The Basso Beattie Bresnahan (BBB) scores and the somatosensory evoked potentials (SEP) were used to evaluate neurological functions. Transmission Electron Microscopy (TEM) was performed to investigate the change of NVU at the 28th day after modeling. Compared with the control group, the compression group shows a significant reduction (P < 0.05) of BBB score and a significant severity (P < 0.05) of abnormal SEP. TEM results of the compression group showed a striking increase in endothelial caveolae and vacuoles; a number of small spaces in tight junctions; a significant increase in pericyte processing area and vessel coverage; an expansion of the basement membrane region; swollen astrocyte endfeet and mitochondria; and the degeneration of neurons and axons. Our study revealed that damage to NVU components occurred followed by chronic compressive spinal cord injury. Several compensatory changes characterized by thicker endothelium, expansive BM, increased pericyte processing area and vessel coverage were also observed

Surgical treatment indications and outcomes in patients with spinal metastases in the cervicothoracic junction (CTJ)

Abstract Background The cervicothoracic junction (CTJ) site accounts for approximately 10% of all spinal metastases. The complex anatomical and biomechanical features increase the difficulty in surgical treatment of the CTJ metastases. However, few studies in the literature on surgical treatment for spinal metastases are focusing on this special area. The aim of this study was to evaluate the surgical outcome of patients with CTJ metastases and analyze the prognostic factor for the postoperative survival. Methods Total of 34 patients with CTJ metastases who underwent surgery in our department were retrospectively analyzed. We evaluated records for the details of medical history, treatment, surgery, radiographic imaging, and follow-up. Outcomes were assessed by overall survival as well as modified Tokuhashi score, SINS, Frankel grade, visual analog scale (VAS), and Karnofsky Performance Status (KPS). Results The entire patients’ median survival time was 12.4 months (range, 3.5–36.2 months). Pain improved in 32 patients (94.12%), and the postoperative VAS scores were significantly improved compared with preoperative data. Majority of patients (71%) maintained or improved their Frankel scores 1 year after surgery. KPS scores improved in 13 patients (38%), remained stable in 19 (56%), and worsened in 2 (6%) postoperatively. Notably, patients with neurological deficit that did not improve after surgery had significantly worse median survival than those who had either no deficit or who improved after surgery. There were no instrumentation failures in this study. Conclusions Surgical treatment is effective for patients of CTJ metastases, with a tolerable rate of complications. Remained or regained ambulatory status predicted overall survival. Thus, prompt and aggressive decompressive surgery is recommended for CTJ metastases patients with neurological impairment

Linderane Suppresses Hepatic Gluconeogenesis by Inhibiting the cAMP/PKA/CREB Pathway Through Indirect Activation of PDE 3 via ERK/STAT3

The role of phosphodiesterase 3 (PDE3), a cyclic AMP (cAMP)-degrading enzyme, in modulating gluconeogenesis remains unknown. Here, linderane, a natural compound, was found to inhibit gluconeogenesis by activating hepatic PDE3 in rat primary hepatocytes. The underlying molecular mechanism and its effects on whole-body glucose and lipid metabolism were investigated. The effect of linderane on gluconeogenesis, cAMP content, phosphorylation of cAMP-response element-binding protein (CREB) and PDE activity were examined in cultured primary hepatocytes and C57BL/6J mice. The precise mechanism by which linderane activates PDE3 and inhibits the cAMP pathway was explored using pharmacological inhibitors. The amelioration of metabolic disorders was observed in ob/ob mice. Linderane inhibited gluconeogenesis, reduced phosphoenolpyruvate carboxykinase (Pck1) and glucose-6-phosphatase (G6pc) gene expression, and decreased intracellular cAMP concentration and CREB phosphorylation in rat primary hepatocytes under both basal and forskolin-stimulated conditions. In rat primary hepatocytes, it also increased total PDE and PDE3 activity but not PDE4 activity. The suppressive effect of linderane on the cAMP pathway and gluconeogenesis was abolished by the non-specific PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the specific PDE3 inhibitor cilostazol. Linderane indirectly activated PDE3 through extracellular regulated protein kinase 1/2 (ERK1/2) and signal transducer and activator of transcription 3 (STAT3) activation. Linderane improved glucose and lipid metabolism after chronic oral administration in ob/ob mice. Our findings revealed linderane as an indirect PDE3 activator that suppresses gluconeogenesis through cAMP pathway inhibition and has beneficial effects on metabolic syndromes in ob/ob mice. This investigation highlighted the potential for PDE3 activation in the treatment of type 2 diabetes

The Organic diamond disk (ODD) versus brazed diamond disk (BDD) for chemical mechanical planarization

Diamond pad conditioners can determine the efficiency of CMP processes and the quality of polished wafers. Conventional pad conditioners are made with metal bonded diamond grits, such as brazed diamond disks (BDD). In this research, we evaluated pad conditioners manufactured with polymer bonded diamond grits known as organic diamond disk (ODD). The latter is not only metal free that avoids the possible contamination of the dissolved metal in slurry, but also its diamond tips are better leveled by a reverse casting technology that has never been adapted in making metallized diamond disks. ODD and BDD were fabricated in the form of dressing bars and used in the CMP for polishing tungsten slugs that bridged circuits at different levels of IC wafers. The results demonstrated that ODD dressed pads generated lower defect counts on IC wafers than BDD. Although the dressing rate of pads may be slower for ODD, the removal rate of wafers can be actually higher. Hence, by using ODD in mass production, not only the longevities of both disks and pads may be increased, but also the throughput of IC wafers produced during CMP. Finally, ODD is made metal free and there is nothing that is soluble in slurry, so in-situ CMP can be adapted to further boost of manufacturing throughput

Atomically dispersed Pd electrocatalyst for efficient aqueous phase dechlorination reaction

High atom utilization is important for practical application of Pd catalysts in dechlorination of chlorinated organic pollutants (COPs). Herein, we report atomically dispersed Pd (coordinated with 2 pyridinic N) anchored on N-doped carbon (A-Pd-NC) as an efficient catalyst toward electrochemical dechlorination of COPs in aqueous solution. Constant current electrolysis showed that the A-Pd-NC catalyst possessed a much higher dechlorination activity (DA, 98.9 mmol•g−1•h−1) than commercial Pd/C (2.4 mmol•g−1•h−1). Using A-Pd-NC as an effective electrocatalyst, near 100% product selectivity of 4-chlorophenol to phenol could be achieved at pH = 3. Constant potential electrolysis, cyclic voltammetry (CV), electron spin resonance (ESR), X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculation results suggested that the dechlorination stability of A-Pd-NC was dependent on the potential applied on the catalyst and the dechlorination reaction followed the hydrodechlorination mechanism with electrochemically adsorbed H as the reductant.Ministry of Education (MOE)This research was supported by the funds from the National Natural Science Foundation of China (21576238, 21106133, 22075195), the Natural Science Foundation of Zhejiang Province, China (LY16B060012), the Jiangsu Specially-Appointed Professor program, Zhejiang Provincial Key Research and Development Program (2020C03085), and Singapore Ministry of Education Academic Research Fund (AcRF) Tier 1: RG10/16 and RG111/15, and Tier 2: MOE2016-T2-2-004

Additional file 1 of Effect of an increase in Lp(a) following statin therapy on cardiovascular prognosis in secondary prevention population of coronary artery disease

Additional file 1: Table S1. Statins used in study subjects. Table S2. Endpoint events for study subjects. Table S3. Univariate COX analysis of risk factors for MACE