Flexible multilevel nonvolatile biocompatible memristor with high durability.

Current protein or glucose based biomemristors have low resistance-switching performance and require complex structural designs, significantly hindering the development of implantable memristor devices. It is imperative to discover novel candidate materials for biomemristor with high durability and excellent biosafety for implantable health monitoring. Herein, we initially demonstrate the resistance switching characteristics of a nonvolatile memristor in a configuration of Pt/AlOOH/ITO consisting of biocompatible AlOOH nanosheets sandwiched between a Indium Tin Oxides (ITO) electrode and a platinum (Pt) counter-electrode. The hydrothermally synthesized AlOOH nanosheets have excellent biocompatibility as confirmed through the Cell Counting Kit-8 (CCK-8) tests. Four discrete resistance levels are achieved in this assembled device in responsible to different compliance currents (ICC) for the set process, where the emerging multilevel states show high durability over 103 cycles, outperforming the protein-based biomemristors under similar conditions. The excellent performance of the Pt/AlOOH/ITO memristor is attributed to the significant role of hydrogen proton with pipe effect, as confirmed by both experimental results and density functional theory (DFT) analyses. The present results indicate the nonvolatile memristors with great potential as the next generation implantable multilevel resistive memories for long-term human health monitoring.

Comprehensive treatment of Cronkhite-Canada syndrome: A case report and literature review.

INTRODUCTION: Cronkhite-Canada syndrome (CCS) is currently considered to be a non-hereditary disease, which is relatively rare clinically. It is also known as polyposis hyperpigmentation alopecia nail dystrophy syndrome, it is a syndrome characterized by gastrointestinal polyposis and ectodermal changes, the main manifestations are gastrointestinal symptoms, skin pigmentation, alopecia, and hypothyroidism. CASE PRESENTATION: In this paper, the clinical characteristics, diagnosis and treatment of a case of CCS admitted to Huanghe Sanmenxia Hospital were analyzed. In the course of treatment, traditional Chinese medicine was used, but no hormone, and the patient's clinical symptoms were greatly relieved. CONCLUSIONS: CCS is rare, there is no specific treatment, and traditional Chinese medicine may can greatly relieve the clinical symptoms of patients. However, it's still having to be verified by a large sample, multi-center, long-term treatment follow-up studies.

Probiotics protect against hepatic steatosis in tris (2-chloroethyl) phosphate-induced metabolic disorder of mice via FXR signaling.

Tris (2-chloroethyl) phosphate (TCEP), the most widely useful and most frequently detective organophosphate flame retardants in environment, has been shown potential relationship with adolescent weight. Probiotics is an effective therapy for metabolic diseases such as obesity and NAFLD with gut microbiota dysregulation. This study aims to explore the protective effects of probiotics against lipid metabolic disorder induced by chronic TCEP exposure and demonstrate the mechanism of this event. The data showed that dietary complex probiotics supplement attenuated TCEP-induced obesity, hyperlipidemia, liver dysfunction, and hepatic steatosis. In addition, dietary complex probiotics suppressed TCEP-promoted ileal FXR signaling, and upregulated hepatic FXR/SHP pathway inhibited by TCEP. Moreover, dietary complex probiotics stimulated PPARα-mediated lipid oxidation and suppressed SREBP1c/PPARγ-mediated lipid synthesis via regulation of FXR signaling. Therefore, this study indicates that dietary complex probiotics could protect against hepatic steatosis via FXR-mediated signaling pathway in TCEP-induced metabolism disorder in mice, resulting in attenuation of systemic lipid accumulation.

Low-dose hexavalent chromium(VI) exposure promotes prostate cancer cell proliferation by activating MAGEB2-AR signal pathway.

Hexavalent chromium [Cr(VI)], one common environmental contaminant, has long been recognized as a carcinogen associated with several malignancies, such as lung cancer, but little information was available about the effects of its low-dose environmental exposure in prostate cancer. Our previous study has shown that low-dose Cr(VI) exposure could promote prostate cancer(PCa) cell growth in vitro and in vivo. In the present study, we furthermore found that low-dose Cr(VI) exposure could induce DNA demethylation in PCa cells. Based on our transcriptome sequencing data and DNA methylation database, we further identified MAGEB2 as a potential effector target that contributed to tumor-promoting effect of low-dose Cr(VI) exposure in PCa. In addition, we demonstrated that MAGEB2 was upregulated in PCa and its knockdown restrained PCa cell proliferation and tumor growth in vitro and in vivo. Moreover, Co-IP and point mutation experiments confirmed that MAGEB2 could bind to the NH2-terminal NTD domain of AR through the F-box in the MAGE homology domain, and then activated AR through up-regulating its downstream targets PSA and NX3.1. Together, low-dose Cr(VI) exposure can induce DNA demethylation in prostate cancer cells, and promote cell proliferation via activating MAGEB2-AR signaling pathway. Thus, inhibition of MAGEB2-AR signaling is a novel and promising strategy to reverse low-dose Cr(VI) exposure-induced prostate tumor progression, also as effective adjuvant therapy for AR signaling-dependent PCa.

CRTAC1 (Cartilage acidic protein 1) inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process in bladder cancer by downregulating Yin Yang 1 (YY1) to inactivate the TGF-ß pathway.

Cartilage acidic protein 1 (CRTAC1) is predicted to be aberrantly expressed in bladder cancer based on bioinformatics analysis. However, its functions and molecular mechanism in bladder cancer remain elusive. This study aimed to explore the role of CRTAC1 in bladder cancer. The mRNA and protein levels of CRTAC1 and Yin Yang 1 (YY1) were detected by reverse transcription quantitative polymerase chain reaction and western blotting. We found that CRTAC1 was downregulated in bladder cancer tissues and cells. Cell Counting Kit-8 assays, colony formation assays, wound healing assays and Transwell assays and western blotting revealed that CRTAC1 overexpression inhibited cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process in bladder cancer, while CRTAC1 knockdown exerted opposite effects on these malignant behaviors. Mechanistically, CRTAC1 targeted YY1 in bladder cancer cells. YY1 was upregulated in bladder cancer tissues and cells. CRTAC1 negatively modulated the mRNA and protein expression of YY1 in bladder cancer cells. Co-localization of CRTAC1 and YY1 expression was assessed using immunofluorescence staining and Co-Immunoprecipitation assays. The interaction between CRTAC1 and YY1 was explored by Chromatin immunoprecipitation and luciferase reporter assays. Moreover, CRTAC1 inactivated the TGF-ß pathway by downregulating YY1 expression. Protein levels of factors associated with the TGF-ß pathway were examined by western blotting. Rescue assays indicated that CRTAC1 inhibited malignant behaviors of bladder cancer cells by targeting YY1. Overall, CRTAC1 inhibited malignant phenotypes of bladder cancer cells by targeting YY1 to inactivate the TGF-ß pathway.

The effect of thermal mineral waters on pain relief, physical function and quality of life in patients with osteoarthritis: A systematic review and meta-analysis.

BACKGROUND: To evaluate the effectiveness and safety of thermal mineral waters therapy for pain relief, and functional improvement, and quality of life (QoL) in patients with osteoarthritis (OA). METHODS: Cochrane Library, Web of science, EMBASE, ClinicalTrials.gov and PubMed were systematically searched for randomized controlled trials. Study inclusion criteria included assessment of the visual analog scale and Western Ontario and McMaster Universities scores and the lequesne index to evaluate the effects of thermal mineral waters on pain relief and functional improvement. Also, studies that used the European quality of life 5-dimension scale and health assessment questionnaire to assess the impact of thermal mineral waters therapy on improving QoL were included. RESULTS: Sixteen studies were included. A meta-analysis showed that thermal mineral waters therapy could significantly reduce pain as measured visual analog scale and Western Ontario and McMaster Universities assessments (P < .001). Thermal mineral waters significantly reduced the lequesne index (P < .001) and improved joint function. Finally, compared with a control group, European quality of life 5-dimension scale and health assessment questionnaire improved significantly in patients with OA receiving thermal mineral waters therapy (P  < .05). There is no evidence that thermal mineral waters is unsafe for treating OA. CONCLUSION: Thermal mineral waters therapy is a safe way to relieve pain, improve physical functions, and QoL in patients with OA.

Puerarin inhibits the development of osteoarthritis through antiinflammatory and antimatrix-degrading pathways in osteoarthritis-induced rat model.

Puerarin is an isoflavone isolated from the medicinal plant Pueraria lobata. The purpose of this study was to study the antiinflammatory and antimatrix-degrading effects of puerarin in a rat osteoarthritis (OA) model and its protective effects on joints. The rat OA model was established by anterior cruciate ligament transection (ACLT) surgery. Rats (n = 40) were divided into nontreated OA, OA + celecoxib (2.86 mg/kg), OA + puerarin (50 and 100 mg/kg), and control groups. Two weeks after surgical induction, puerarin was administered by gavage daily for 8 weeks. After 8 weeks, macroscopic observation and histopathological images showed that cartilage damage was reduced after puerarin and celecoxib treatment, the intensity of Safranin O staining was high, and the OARSI scores were significantly reduced compared to the OA group. Puerarin reduced the expression of MMP-3, MMP-13, ADAMTS-5, and COX-2 in the cartilage tissue of ACLT rats, inhibited the production of IL-1ß, IL-6, and TNF-α inflammatory factors, increased Type II collagen content, and altered the expression of serum OA cartilage degradation/bone turnover biomarkers (CTX-I, CTX-II, COMP, and PIINP). Based on these findings, we speculate that puerarin supplement to attain recovery from OA damage.

Glucosamine induces increased musclin gene expression through endoplasmic reticulum stress-induced unfolding protein response signaling pathways in mouse skeletal muscle cells.

Glucosamine (GlcN) is a dietary supplement that is widely used to promote joint health. Reports have demonstrated that oral GlcN adversely affects glucose metabolism. Here, we found that oral administration of GlcN induced insulin resistance (IR) and increased plasma glucose levels in mice. Musclin is a muscle-secreted cytokine that participates in the development and aggravation of diabetes. In this study, we found that increased expression of the musclin plays a pathogenic role in GlcN-induced IR in mice. Additional in vivo and in vitro studies showed that 4-PBA inhibited GlcN-induced endoplasmic reticulum (ER) stress and reduced musclin expression, indicating that ER stress might be closely linked to musclin expression. Moreover, the inhibition of musclin gene expression was also observed when sh-RNAs and small molecular compound inhibitors inhibited ER stress-induced PERK and IRE1-associated unfolding protein response (UPR) signaling pathways, and the CRISPR/Cas9 genome editing technology knockout the ATF6-associated UPR pathway in C2C12 myotubes cells. Silencing of the expression of musclin effectively relieved GlcN-affected phosphorylation of Akt, glucose intake and glycogen synthesis. These results suggest that GlcN increased musclin gene expression though UPR, and musclin represents an important mechanism underlying GlcN-induced IR in mice.

Titanium dioxide nanoparticles increase plasma glucose via reactive oxygen species-induced insulin resistance in mice.

There have been few reports about the possible toxic effects of titanium dioxide (TiO2 ) nanoparticles on the endocrine system. We explored the endocrine effects of oral administration to mice of anatase TiO2 nanoparticles (0, 64 and 320 mg kg(-1) body weight per day to control, low-dose and high-dose groups, respectively, 7 days per week for 14 weeks). TiO2 nanoparticles were characterized by scanning and transmission electron microscopy (TEM) and dynamic light scattering (DLS), and their physiological distribution was investigated by inductively coupled plasma. Biochemical analyzes included plasma glucose, insulin, heart blood triglycerides (TG), free fatty acid (FFA), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 and reactive oxygen species (ROS)-related markers (total SOD, GSH and MDA). Phosphorylation of IRS1, Akt, JNK1, and p38 MAPK were analyzed by western blotting. Increased titanium levels were found in the liver, spleen, small intestine, kidney and pancreas. Biochemical analyzes showed that plasma glucose significantly increased whereas there was no difference in plasma insulin secretion. Increased ROS levels were found in serum and the liver, as evidenced by reduced total SOD activity and GSH level and increased MDA content. Western blotting showed that oral administration of TiO2 nanoparticles induced insulin resistance (IR) in mouse liver, shown by increased phosphorylation of IRS1 (Ser307) and reduced phosphorylation of Akt (Ser473). The pathway by which TiO2 nanoparticles increase ROS-induced IR were included in the inflammatory response and phosphokinase, as shown by increased serum levels of TNF-α and IL-6 and increased phosphorylation of JNK1 and p38 MAPK in liver. These results show that oral administration of TiO2 nanoparticles increases ROS, resulting in IR and increasing plasma glucose in mice.