Transmission Mechanism and Logical Operation of Graphene-Doped Poly(vinyl alcohol) Composite-Based Memristor.

Memristors are considered the best candidates for nonvolatile memory and advanced computing technologies, and polymer and two-dimensional (2D) materials have been developed as functional layer materials in memristors with high-performance resistive switching characteristics. In this work, a polymer memristor with a graphene (Gr)-doped poly(vinyl alcohol) (PVA) composite acting as the functional layer was prepared. The memristor device exhibited superior performance with good retention and a comparatively large ON/OFF ratio at room temperature. Additionally, excellent logic operations were achieved. These satisfactory properties can be attributed to trap-induced carrier trapping and detrapping. In addition, the device exhibited stable bipolar resistive switching behavior over a moderate temperature range. This work provides insight into the transmission mechanism of polymer-based memristors and the reasons why they become unstable at high temperatures, demonstrating the potential applications of PVA-Gr-based polymer memristors as logic circuit units in integrated chips and artificial intelligence.

Performance Regulation of a ZnO/WOx-Based Memristor and Its Application in an Emotion Circuit.

The development of a memristor is very important for artificial intelligence and new electronic circuits. In this work, Ag(Al)/ZnO/WOx/FTO memristors are fabricated by magnetron sputtering, and the device performance is further improved through annealing and oxygen supply during sputtering. The experimental data show that the FTO/WOx/ZnO-O2/Ag memristor has the largest high resistance state (HRS)/low resistance state (LRS) resistance ratio and the best durability. Through data fitting and analysis, the switching mechanism of memristors with different top electrodes is investigated. Furthermore, the physical model of the best performance memristor was established by Simulink, and an emotion-monitoring circuit was constructed on this basis. The circuit can be used to monitor and record the mood changes, and the feedback of the emotion monitoring can be fed back to the user to help them adjust the mood.

LINC01393, a Novel Long Non-Coding RNA, Promotes the Cell Proliferation, Migration and Invasion through MiR-128-3p/NUSAP1 Axis in Glioblastoma.

Nucleolar and spindle-associated protein 1 (NUSAP1) is a potential molecular marker and intervention target for glioblastoma (GBM). In this study, we aim to investigate upstream regulatory lncRNAs and miRNAs of NUSAP1 through both experimental and bioinformatic methods. We screened upstream lncRNAs and miRNAs of NUSAP1 through multiple databases based on ceRNA theory. Then, in vitro and in vivo experiments were performed to elucidate the relevant biological significance and regulatory mechanism among them. Finally, the potential downstream mechanism was discussed. LINC01393 and miR-128-3p were screened as upstream regulatory molecules of NUSAP1 by TCGA and ENCORI databases. The negative correlations among them were confirmed in clinical specimens. Biochemical studies revealed that overexpression or knockdown of LINC01393 respectively enhanced or inhibited malignant phenotype of GBM cells. MiR-128-3p inhibitor reversed LINC01393 knockdown-mediated impacts on GBM cells. Then, dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to validate LINC01393/miR-128-3p/NUSAP1 interactions. In vivo, LINC01393-knockdown decreased tumor growth and improved mice survival, while restoration of NUSAP1 partially reversed these effects. Additionally, enrichment analysis and western blot revealed that the roles of LINC01393 and NUSAP1 in GBM progression were associated with NF-κB activation. Our findings showed that LINC01393 sponged miR-128-3p to upregulate NUSAP1, thereby promoting GBM development and progression via activating NF-κB pathway. This work deepens understanding of GBM mechanisms and provides potential novel therapeutic targets for GBM.

Angiotensin II receptor blockade alleviates calcineurin inhibitor nephrotoxicity by restoring cyclooxygenase 2 expression in kidney cortex.

AIM: The use of calcineurin inhibitors such as cyclosporine A (CsA) for immunosuppression after solid organ transplantation is commonly limited by renal side effects. CsA-induced deterioration of glomerular filtration rate and sodium retention may be related to juxtaglomerular dysregulation as a result of suppressed cyclooxygenase 2 (COX-2) and stimulated renin biosynthesis. We tested whether CsA-induced COX-2 suppression is caused by hyperactive renin-angiotensin system (RAS) and whether RAS inhibition may alleviate the related side effects. METHODS: Rats received CsA, the RAS inhibitor candesartan, or the COX-2 inhibitor celecoxib acutely (3 days) or chronically (3 weeks). Molecular pathways mediating effects of CsA and RAS on COX-2 were studied in cultured macula densa cells. RESULTS: Pharmacological or siRNA-mediated calcineurin inhibition in cultured cells enhanced COX-2 expression via p38 mitogen-activated protein kinase and NF-kB signalling, whereas angiotensin II abolished these effects. Acute and chronic CsA administration to rats led to RAS activation along with reduced cortical COX-2 expression, creatinine clearance and fractional sodium excretion. Evaluation of major distal salt transporters, NKCC2 and NCC, showed increased levels of their activating phosphorylation upon CsA. Concomitant candesartan treatment blunted these effects acutely and completely normalized the COX-2 expression and renal functional parameters at long term. Celecoxib prevented the candesartan-induced improvements of creatinine clearance and sodium excretion. CONCLUSION: Suppression of juxtaglomerular COX-2 upon CsA results from RAS activation, which overrides the cell-autonomous, COX-2-stimulatory effects of calcineurin inhibition. Angiotensin II antagonism alleviates CsA nephrotoxicity via the COX-2-dependent normalization of creatinine clearance and sodium excretion.

Connexin43 is differentially distributed within renal vasculature and mediates profibrotic differentiation in medullary fibroblasts.

Connexins (Cxs) form gap junctions for intercellular exchange of inorganic ions and messenger molecules. In the kidney, Cxs play essential roles within its compartments, but data on the precise cellular localization and cell type-related function of their isoforms are scarce. We tested whether Cx43 distribution is restricted to vascular and interstitial cells and whether medullary fibroblasts express Cx43 to coordinate profibrotic signaling. Confocal immunofluorescence techniques, ultrastructural labeling, and functional experiments in cell culture were performed. Cx43 was chiefly expressed in the vasculature but was absent from tubular epithelia. All arterial, arteriolar, and lymphatic endothelia showed continuous Cx43 signal along their borders. In the inner medulla, only the interstitium showed Cx43 signals, which were assigned to fibroblasts and their processes. Cultured Cx43-expressing medullary fibroblasts served to study the role of gap junctions in a profibrotic context. In a dye spreading assay, Cx43-sensitive diffusion of Lucifer yellow was dependent on gap junctional passage. The addition of transforming growth factor-ß1 (5 ng/mL for 48 h) activated Cx43 biosynthesis and caused Cx43-sensitive transformation of the fibroblasts into a myofibroblast phenotype. This suggested that Cx43 gap junctional channels enable the coordination of profibrotic signaling between cells of the medullary interstitium. In summary, we demonstrate the presence of Cx43-expressing gap junctions within the two major renal compartments, the vasculature and interstitium. Endothelial Cx43 likely provides functions of an earlier-defined "electrical syncytium" within the vascular wall. Additionally, Cx43 facilitates profibrotic signaling between medullary interstitial fibroblasts.

Calcium-Sensing Receptor and Regulation of WNK Kinases in the Kidney.

The kidney is essential for systemic calcium homeostasis. Urinary calcium excretion can be viewed as an integrative renal response to endocrine and local stimuli. The extracellular calcium-sensing receptor (CaSR) elicits a number of adaptive reactions to increased plasma Ca2+ levels including the control of parathyroid hormone release and regulation of the renal calcium handling. Calcium reabsorption in the distal nephron of the kidney is functionally coupled to sodium transport. Apart from Ca2+ transport systems, CaSR signaling affects relevant distal Na+-(K+)-2Cl- cotransporters, NKCC2 and NCC. NKCC2 and NCC are activated by a kinase cascade comprising with-no-lysine [K] kinases (WNKs) and two homologous Ste20-related kinases, SPAK and OSR1. Gain-of-function mutations within the WNK-SPAK/OSR1-NKCC2/NCC pathway lead to renal salt retention and hypertension, whereas loss-of-function mutations have been associated with salt-losing tubulopathies such as Bartter or Gitelman syndromes. A Bartter-like syndrome has been also described in patients carrying gain-of-function mutations in the CaSR gene. Recent work suggested that CaSR signals via the WNK-SPAK/OSR1 cascade to modulate salt reabsorption along the distal nephron. The review presented here summarizes the latest progress in understanding of functional interactions between CaSR and WNKs and their potential impact on the renal salt handling and blood pressure.

Alteration of Sciatic Nerve Histology and Electrical Function After Compression and After Neurolysis in a Diabetic Rat Model.

BACKGROUND: Diabetic rats are more sensitive to nerve entrapment. This study was conducted to evaluate nerve function and histological changes in diabetic rats after nerve compression and subsequent decompression. METHODS: A total of 35 Wistar rats were included. The experimental group was divided into diabetic sciatic nerve compression group (DSNC, n = 5) and diabetic sciatic nerve decompression group (DSND, n = 20). The DSNC model was created by wrapping a silicone tube circumferentially around the nerve for 4 weeks, and then the DSND group accepted nerve decompression and was followed up to 12 weeks. The DSND group was equally divided into DSND 3 weeks (DSND3), 6 weeks (DSND6), 9 weeks (DSND9), and 12 weeks (DSND12) groups. Five rats were taken as normoglycemic control group (CR, n = 5), and another 5 rats as diabetic control group (DM, n = 5). The mechanical hyperalgesia of rats was detected by Semmes-Weinstein nylon monofilaments (SWMs) and by motor nerve conduction velocity (MNCV). These 2 physiological indicators and histology of sciatic nerves were compared among different groups. RESULTS: The SWM measurements improved toward normal values after decompression. The SWM value was significantly lower (more normal) in the DSNC groups than in the DSND group (P < 0.05). The MNCV was 53.7 ± 0.8 m/s in the CR group, whereas it was 28.4 ± 1.0 m/s in the DSNC group (P < 0.001). Six weeks after decompression, the MNCV was significantly faster than that in the DSNC group (P < 0.001). Histological examination demonstrated chronic nerve compression, which responded toward normal after decompression, but with degree of myelination never recovering to normal. CONCLUSIONS: Chronic compression of the diabetic sciatic nerve has measureable negative effects on sciatic nerve motor nerve function, associated with a decline of touch/pressure threshold and degeneration of myelin sheath and axon. Nerve decompression surgery can reverse these effects and partially restore nerve function.

Chronic Nerve Compression Accelerates the Progression of Diabetic Peripheral Neuropathy in a Rat Model: A Study of Gene Expression Profiling.

OBJECTIVE: This article investigates the role of chronic nerve compression in the progression of diabetic peripheral neuropathy (DPN) by gene expression profiling. METHODS: Chronic nerve compression was created in streptozotocin (STZ)-induced diabetic rats by wrapping a silicone tube around the sciatic nerve (SCN). Neurological deficits were evaluated using pain threshold test, motor nerve conduction velocity (MNCV), and histopathologic examination. Differentially expressed genes (DGEs) and metabolic processes associated with chronic nerve compression were analyzed. RESULTS: Significant changes in withdrawal threshold and MNCV were observed in diabetic rats 6 weeks after diabetes induction, and in DPN rats 4 weeks after diabetes induction. Histopathologic examination of the SCN in DPN rats presented typical changes of myelin degeneration in DPN. Function analyses of DEGs demonstrated that biological processes related to inflammatory response, extracellular matrix component, and synaptic transmission were upregulated after diabetes induction, and chronic nerve compression further enhanced those changes. While processes related to lipid and glucose metabolism, response to insulin, and apoptosis regulation were inhibited after diabetes induction, chronic nerve compression further enhanced these inhibitions. CONCLUSION: Our study suggests that additional silicone tube wrapping on the SCN of rat with diabetes closely mimics the course and pathologic findings of human DPN. Further studies are needed to verify the effectiveness of this rat model of DPN and elucidate the roles of the individual genes in the progression of DPN.

Surgical Decompression in the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review and Meta-analysis.

Background Over the last decade, surgical decompression procedures have been commonly used in the treatment of diabetic peripheral neuropathy. However, the effectiveness of them remains to be proved. Methods A comprehensive literature search of databases including PubMed-Medline, Ovid-EMBASE, and Cochrane Library was performed to collect the related literatures. The Medical Subject Headings used were "diabetic neuropathy," "surgical decompression," and "outcomes." The methodological index for nonrandomized studies was adopted for assessing the studies included in this review. Analyses were performed with Review Manager (Version 5.3, Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration, 2014). Results A total of 12 literatures (including 8 prospective and 4 retrospective) encompassing 1,825 patients with DPN were included in the final analysis. Only one literature was identified as a randomized controlled trial. The remaining 11 literatures were observational studies; 7 of them were classified as upper-extremity nerve decompression group and 4 of them were classified as lower-extremity nerve decompression group. Meta-analysis shows that Boston questionnaire symptom severity and functional status of upper extremities, and distal motor latency and sensory conduction velocity of median nerve of DPN patients are significantly improved after carpal tunnel release. Besides, visual analog scale and two-point discrimination are considered clinically and statistically significant in lower extremities after operation. Conclusions The findings from our review have shown the efficacy of surgical decompression procedures in relieving the neurologic symptoms and restoring the sensory deficits in DPN patients. As there are few high-quality randomized controlled trials or well-designed prospective studies, more data are needed to elucidate the role of surgical procedures for DPN treatment in the future.

Graphene based solid phase extraction combined with ultra high performance liquid chromatography-tandem mass spectrometry for carbamate pesticides analysis in environmental water samples.

In this paper, graphene, a new sorbent material, was synthesized and used for solid-phase extraction (SPE) of the six carbamate pesticides (pirimicarb, baygon, carbaryl, isoprocarb, baycarb and diethofencarb) in environmental water samples. The target analytes can be extracted on the graphene-packed SPE cartridge, and then eluted with acetone. The eluate was collected and dried by high purity nitrogen gas at room temperature. 1mL of 20% (v/v) acetonitrile aqueous solution was used to redissolve the residue. The final sample solution was analyzed by ultra performance liquid chromatography-tandem quadrupole mass spectrometry (UPLC-MS/MS) system. Under optimum conditions, good linearity was obtained for the carbamates with correlation coefficient in the range of 0.9992-0.9998. The limits of detection (S/N=3) for the six carbamate pesticides were in the range of 0.5-6.9ngL(-1). Relative standard deviations (RSD) for five replicate determinations were below 5.54%. RSD values for cartridge-to-cartridge precision (n=7) were in the range of 1.27-8.13%. After proper regeneration, the graphene-packed SPE cartridge could be re-used over 100 times for standard solution without significant loss of performance. The enrichment factors for the target analytes were in the range of 34.2-51.7. The established method has been successfully applied to the determination of carbamate pesticide residues in environmental water samples such as river water, well water and lake water.