A detrimental role of endothelial S1PR2 in cardiac ischemia-reperfusion injury via modulating mitochondrial dysfunction, NLRP3 inflammasome activation, and pyroptosis.

Sphingosine 1-phosphate (S1P), a bioactive lipid molecule, exerts multifaceted effects on cardiovascular functions via S1P receptors, but its effects on cardiac I/R injury are not fully understood. Plasma lipidomics analysis by mass spectrometry revealed that sphingosine lipids, including sphingosine 1-phosphate (S1P), were significantly down-regulated following cardiac I/R injury in mice. The reduced S1P levels were also observed in the plasma of coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI) compared with those without PCI. We found that S1P exerted a cardioprotective effect via endothelial cell (EC)-S1PR1, whereas EC-S1PR2 displayed a detrimental effect on cardiac I/R. Our data showed that EC-specific S1pr2 loss-of-function significantly lessened inflammatory responses and diminished cardiac I/R injury, while EC-specific S1pr2 gain-of-function aggravated cardiac I/R injury. Mechanistically, EC-S1PR2 initiated excessive mitochondrial fission and elevated ROS production via RHO/ROCK1/DRP1 pathway, leading to NLRP3 inflammasome activation and subsequent cell pyroptosis, thereby exacerbating inflammation and I/R injuries. Furthermore, RGD-peptide magnetic nanoparticles packaging S1pr2-siRNA to specifically knockdown S1PR2 in endothelial cells significantly ameliorated cardiac I/R injury. Taken together, our investigations demonstrate that EC-S1PR2 induces excessive mitochondrial fission, which results in NLRP3 inflammasome activation and subsequently triggers cell pyroptosis, ultimately exacerbating inflammatory responses and aggravating heart injuries following I/R.

TRABD modulates mitochondrial homeostasis and tissue integrity.

High TRABD expression is associated with tau pathology in patients with Alzheimer's disease; however, the function of TRABD is unknown. Human TRABD encodes a mitochondrial outer-membrane protein. The loss of TRABD resulted in mitochondrial fragmentation, and TRABD overexpression led to mitochondrial clustering and fusion. The C-terminal tail of the TRABD anchored to the mitochondrial outer membrane and the TraB domain could form homocomplexes. Additionally, TRABD forms complexes with MFN2, MIGA2, and PLD6 to facilitate mitochondrial fusion. Flies lacking dTRABD are viable and have normal lifespans. However, aging flies exhibit reduced climbing ability and abnormal mitochondrial morphology in their muscles. The expression of dTRABD is increased in aged flies. dTRABD overexpression leads to neurodegeneration and enhances tau toxicity in fly eyes. The overexpression of dTRABD also increased reactive oxygen species (ROS), ATP production, and protein turnover in the mitochondria. This study suggested that TRABD-induced mitochondrial malfunctions contribute to age-related neurodegeneration.

Establishment of a diagnostic model of endometriosis based on disulfidptosis-related genes.

OBJECTIVES: We aimed to establish a diagnostic model of endometriosis (EM) based on disulfidptosis-related genes (DRGs). MATERIALS AND METHODS: The mRNA expression data of EM were downloaded from the gene expression omnibus database and subjected to differential analysis, and co-expression analysis was performed based on 10 disulfidptosis genes to acquire DRGs. The differentially expressed DRGs were subjected to biofunctional analysis. Lasso analysis and support vector machine-recursive feature elimination (SVM-RFE) analysis were employed to extract the intersection of feature genes as biomarkers, and the diagnostic values of biomarkers for EM were evaluated based on receiver operating characteristic curves. The correlations between biomarkers and the immune microenvironment were assessed by Pearson analysis of biomarkers and immune cell infiltration levels. RESULTS: Transforming growth factor ß stimulated protein clone 22 domain family member 4 (TSC22D4), and F-box/SPRY domain-containing protein 1 (FBXO45) worked as the diagnostic classifiers in EM, with an obvious decrease in FBXO45 expression and an evident increase in TSC22D4 expression. The areas under the curves of FBXO45 and TSC22D4 were 0.752 and 0.706, respectively, and the area of FBXO45 combined with TSC22D4 reached 0.865, suggesting that TSC22D4 and FBXO45 had high predictive values. The diagnostic markers were closely correlated with immune cell infiltration. CONCLUSION: The diagnostic markers constructed based on disulfidptosis are good predictors for EM, which have close correlations with EM.

Puerarin Attenuates High-Glucose and High-Lipid-Induced Inflammatory Injury in H9c2 Cardiomyocytes via CAV3 Protein Upregulation.

Background: Inflammation plays a crucial role in the development of diabetic cardiomyopathy (DCM), including inflammation caused by high-glucose and high-lipid (HGHL). Targeting inflammation may provide a useful strategy for preventing and treating DCM. Puerarin has been shown to reduce the inflammation, apoptosis and hypertrophy of cardiomyocytes induced by HGHL, in which this study aims to investigate the underlying mechanisms. Methods: H9c2 cardiomyocytes cultured with HGHL were used to establish a cell model of DCM. Puerarin was then placed to these cells for 24 hours. The effects of HGHL and puerarin on cell viability and apoptosis were investigated by the Cell Proliferation, Toxicity Assay Kit (CCK-8) and flow cytometry. Morphological changes of cardiomyocytes was observed by HE staining. CAV3 proteins in H9c2 cardiomyocytes were altered by transient transfection of CAV3 siRNA. IL-6 was detected by ELISA. The Western blot was performed to determine the CAV3, Bcl-2, Bax, pro-Caspase-3, cleaved-Caspase-3, NF-κB (p65) and p38MAPK proteins. Results: Puerarin treatment reversed the cells viability, hypertrophy in morphology, inflammation (showed by p-p38 and p-p65 and IL-6) and apoptosis-related damage (showed by cleaved-Caspase-3/pro-Caspase-3/Bax, Bcl-2 and flow cytometry) of the H9c2 cardiomyocyte caused by HGHL. Puerarin treatment also restored the decrease of CAV3 proteins of the H9c2 cardiomyocyte caused by HGHL. When silenced the expression of CAV3 proteins with SiRNA, puerarin failed to decreased p-p38 and p-p65 and IL-6, and could not reversed cell viability and morphological damage. In contrast to the simple CAV3 silenced group, the CAV3 silenced with NF-κB pathway or p38MAPK pathway inhibitors, significantly downregulated the p-p38, p-p65 and IL-6. Conclusion: Puerarin upregulated CAV3 protein expression in H9c2 cardiomyocytes and inhibited the NF-κB and p38MAPK pathways, thereby reducing HGHL-induced inflammation and may related to the apoptosis and hypertrophy of cardiomyocytes.

Liver sinusoidal endothelial S1pr2 regulates experimental liver fibrosis through YAP/TGF-ß signaling pathway.

The hepatic vascular niche plays an important role in the pathological process of liver fibrosis. Liver sinusoidal endothelial cells (LSECs) predominantly compose hepatic vascular niches. Endothelial cell (EC)-expressing sphingosine 1-phosphate receptor 2 (S1pr2) plays an essential role in the regulation of vascular functions. Nevertheless, it remains unknown whether liver LSEC-S1pr2 might modulate pathological liver fibrosis. In this study, liver fibrosis was induced by hepatotoxin carbon tetrachloride (CCl4 ). The expression of S1pr2 is significantly downregulated in liver sinusoidal endothelial cells after CCl4 treatment. The loss of S1pr2 in LSECs significantly alleviated liver fibrosis after chronic insult, whereas the overexpression of S1pr2 in LSECs accentuated liver fibrogenesis. In vivo experiments further revealed that the deficiency of S1pr2 in LSECs dampened hepatic stellate cell (HSC) activation, while overexpression of S1pr2 in LSECs enhanced HSC activation with more extracellular matrix component production. Mechanistically, LSEC-S1pr2 activates the YAP signaling pathway to potentiate the transactivation of TGF-ß, which acts on HSCs in a paracrine manner, and thus aggravated liver fibrosis. Taken together, our results uncover a novel pathological mechanism of liver fibrosis in which LSEC-S1pr2 plays an important role in modulating the development of liver fibrosis, providing a future novel therapy target against liver fibrogenesis.

Lymphatic endothelial sphingosine 1-phosphate receptor 1 enhances macrophage clearance via lymphatic system following myocardial infarction.

Lymphatic endothelial cell homeostasis plays important roles in normal physiological cardiac functions, and its dysfunction significantly influences pathological cardiac remodeling after myocardial infarction (MI). Our results revealed that sphingosine 1-phosphate receptor 1 (S1pr1) expression in cardiac lymphatic endothelial cells (LECs) was sharply changed after MI. It has been shown that S1pr1 tightly controlled LEC functions and homeostasis. We thus hypothesized that lymphatic endothelial S1pr1 might be involved in post-MI cardiac remodeling. We generated LEC-conditional S1pr1 transgenic mice, in which S1pr1 expression was reduced in cardiac LECs. We performed the left anterior descending coronary artery (LAD) ligation operation to induce MI in these mice. Cardiac functions and remodeling were examined by echocardiography analysis and serial histological analysis. Meanwhile, we performed adoptive cell transfer experiments to monitor macrophage trafficking in post-MI myocardium and their draining lymphatic system. Furthermore, in vitro cell culture experiments and mechanism studies were undertaken to uncover the molecular mechanism by which LEC-S1pr1 regulated cardiac inflammation and remodeling after MI. Our results showed that S1pr1 expression significantly decreased in cardiac LECs after MI. Our in vivo experiments showed that the reduced expression of LEC-S1pr1 deteriorated cardiac function and worsened pathological cardiac remodeling after MI. Our further results demonstrated that the reduced expression of LEC-S1pr1 did not influence macrophage infiltration in an early inflammatory phase of MI, but significantly affected macrophages clearance in the later phase of MI via afferent cardiac lymphatics, and thus influenced inflammatory responses and cardiac outcome after MI. Further study showed that S1P/S1pr1 activated ERK signaling pathway and enhanced CCL2 expression, which promoted macrophage trafficking in a paracrine manner. This study reveals that cardiac lymphatic endothelial cells tightly control macrophage trafficking via lymphatic vessels in injured hearts via S1P/S1pr1/ERK/CCL2 pathway and thus regulate post-MI immune modulation and heart repair. This study highlights the importance of cardiac lymphatic vessel system in orchestrating post-MI immune responses and cardiac remodeling by regulating macrophage transit in injured hearts. Our finding implies that a feasible modulation of S1pr1 signaling in LECs might provide a promising target to resolve excessive inflammation and to ameliorate adverse cardiac remodeling after MI.

Endothelial S1pr2 regulates post-ischemic angiogenesis via AKT/eNOS signaling pathway.

Aims: It is important to understand the mechanism that regulates post-ischemic angiogenesis and to explore a new therapeutic target for an effective improvement of revascularization in peripheral artery disease (PAD) patients. Post-ischemic angiogenesis is a highly orchestrated process, which involves vascular endothelial cells (ECs) proliferation, migration and assembly into capillaries. We found a significant reduction of S1pr2 (sphingosine 1-phosphate receptor 2) in endothelial cells after hindlimb ischemia (HLI). We thus hypothesized that EC-S1pr2 might be involved in the regulation of post-ischemic angiogenesis and blood flow recovery during peripheral arterial disease (PAD). Methods and Results: We generated both EC-specific S1pr2 loss-of-function and S1pr2 gain-of-function mice. Our study showed that EC-specific S1pr2 loss-of-function significantly enhanced post-ischemic angiogenesis and improved blood flow recovery upon femoral artery ligation, whereas the EC-specific S1pr2 gain-of-function severely hindered post-ischemic angiogenesis and reduced blood flow recovery in ischemic limbs. We next identified that S1pr2 inhibited AKT/eNOS signaling pathway, and thus inhibited EC proliferation/migration and angiogenic activity. As expected, pharmacological inhibition of S1pr2 by JTE013 improved post-ischemic angiogenesis and improved blood flow perfusion after femoral artery ligation. Moreover, we developed RGD-peptide magnetic nanoparticles packaging S1pr2-siRNA which specifically targeted ECs and achieved an efficient silencing of S1pr2 expression in ECs in vivo. This EC-targeted strategy to dampen S1pr2 significantly enhanced post-ischemic angiogenesis and boosted blood perfusion after HLI, supplying a novel therapy target for patients with peripheral arterial disease. Conclusions: This present study demonstrates that EC-expressing S1pr2 tightly controls post-ischemic angiogenesis and blood flow perfusion recovery. This research provides a novel strategy for EC-target knockdown of S1pr2 as a new therapeutic intervention for patients with peripheral artery disease.

Psychometric properties of a simplified Chinese version of the cancer predisposition perception scale.

Objective: Cancer predisposition perception refers to the subjective estimation of the likelihood of being diagnosed with cancer in the future. It affects people's behavior concerning cancer screening and prevention. At present, there is no available tool to evaluate cancer predisposition perception. The aim of this study was to translate the cancer predisposition perception scale into simplified Chinese (C-CPPS), and then test its psychometric properties among Chinese patients. Methods: In phase I, the CPPS was translated into Chinese, and validated by an expert panel. In phase II, data on reliability and validity was evaluated in terms of construct validity, criterion validity, internal consistency, test-retest reliability, and item-total correlations, with a convenience sample of 208 patients recruited from the colorectal cancer surgical ward. Results: The C-CPPS had desirable validity and reliability. The scale-level content validity index was 0.96. Exploratory factor analysis indicated that the six-factor structure of the C-CPPS was good fit to the data. Correlation between the C-CPPS and the Brief Illness Perception Questionnaire was statistically significant. Cronbach's α for the entire scale was 0.90 and 0.71-0.95 for five of the six subscales. Item-total correlations ranged from 0.309 to 0.775, and the intraclass correlation coefficient was 0.97. Conclusions: The C-CPPS appears to be culturally appropriate, reliable, and valid for assessing cancer predisposition perception among patients with colorectal cancer in China.

Histochemical localization of putative stem cells in irreversible pulpitis.

OBJECTIVES: Our study aimed to observe the distribution of putative stem cells in irreversible pulpitis and to investigate the expression of specific molecules. SUBJECTS AND METHODS: Extracted third molar teeth were collected and divided into two groups: the normal pulp group and inflamed pulp group. Real-time PCR was applied to detect the expression of several embryonic and dentinogenic genes. The expression of mesenchymal cell markers (STRO-1, CD90, and CD146) and stromal cell-derived factor 1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) proteins was examined by immunohistochemical analysis. RESULTS: The expression levels of most embryonic and dentinogenic genes were not statistically different between the two groups. Immunohistochemical analysis revealed that in inflamed pulp, cells with positive expression for STRO-1, CD90, and CD146 mainly resided in two specific niches, both adjacent to inflammatory sites: one in the pulp core and another in the odontoblast layer. SDF-1α- and CXCR4-positive cells were significantly correlated with STRO-1-positive cells. Double immunofluorescence analysis indicated that STRO-1-positive cells overlapped with SDF-1α- and CXCR4-positive cells near the inflammatory site. CONCLUSIONS: This study gave a direct observation of putative stem cells distributed in irreversible pulpitis and implied a role of SDF-1α/CXCR4 signaling in stem cell-based therapies for reparative dentinogenesis.

Ligand based 3D-QSAR model, pharmacophore, molecular docking and ADME to identify potential fibroblast growth factor receptor 1 inhibitors.

The FGF/FGFR system may affect tumor cells and stromal microenvironment through autocrine and paracrine stimulation, thereby significantly promoting oncogene transformation and tumor growth. Abnormal expression of FGFR1 in cells is considered to be the main cause of tumorigenesis and a potential target for the treatment of cancer. In this study, a combination of structure-based drug carriers and molecular docking-based virtual screening was used to screen new potential FGFR1 inhibitors. Forty eight known inhibitors were collected to establish 3 D-QSAR models and pharmacophore models, investigate the relationship between the activity and conformation of compounds, and verify the efficiency of pharmacophore. In Accelrys Discovery Studio 2016, the ZINC database was filtered by Lipinski's Rule of Five and SMART's filtration. Then, Hypo01 was used for virtual screening of ZINC database. Compounds with predicted activity values less than 1 µM were molecularly docked with FGFR1 protein crystals, the docking results were observed, and the interaction between compounds and targets was studied. The absorption, distribution, metabolism and excretion (ADME) and toxicity of potential inhibitors were studied, and a compound with new structural scaffolds were obtained. It could be further studied to explore their better therapeutic effects. Communicated by Ramaswamy H. Sarma.

Platelet-Rich Plasma Induces Autophagy and Promotes Regeneration in Human Dental Pulp Cells.

Regenerative endodontic procedures using autologous platelet-rich plasma (PRP) can improve the biologic outcome of treatment. However, its mechanism of action on improving pulp regeneration is not fully elucidated. Autophagy was recently shown to be related to tissue repair and osteogenesis. Therefore, the objective of this study was to investigate the effect of PRP in dental pulp regeneration and to elucidate the role of autophagy involved in this process. Human dental pulp cells (hDPCs) were isolated from healthy dental pulp and co-cultured with an increasing concentration of PRP. Cellular migration and proliferation were determined by scratch assay, transwell assay, and cell-counting kit 8 assay. Osteogenic differentiation was clarified by using alkaline phosphatase staining, alizarin red staining, and real-time polymerase chain reaction (RT-PCR) to measure the gene expression levels of alkaline phosphatase, collagen-1, osteocalcin, dentin matrix protein 1, and dentin sialophosphoprotein. Autophagic bodies were observed by transmission electron microscopy and the expression of autophagy marker light chain 3B (LC3B) was determined by immunofluorescence staining. The mRNA and protein expression level of LC3B and Beclin-1 were quantified by qRT-PCR and western blotting. The effect of PRP on cellular migration, proliferation, and osteogenic differentiation was further investigated in the milieu of autophagy activator, rapamycin, and inhibitor, 3-methyladenine. Results showed that PRP promoted cell migration, proliferation, and osteogenic differentiation. Autophagic bodies were strongly activated and the expression level of LC3B and Beclin-1 was significantly promoted by PRP. Autophagy inhibition suppressed PRP-induced hDPCs migration, proliferation, and osteogenic differentiation, whereas autophagy activator substantially augmented PRP-stimulated migration, proliferation, and differentiation. Taken together, these findings suggested that PRP could effectively promote regenerative potentials associated with autophagy.

Prognostic Value of the C-Reactive Protein/Albumin Ratio and Systemic Immune-Inflammation Index for Patients With Colorectal Liver Metastasis Undergoing Curative Resection.

Background: We evaluated the prognostic value of C-reactive protein/albumin (CAR) and systemic immune-inflammation index (SII), which we calculated as neutrophil × platelet/lymphocyte) in patients with colorectal liver metastasis (CRLM) after curative resection. Methods: We retrospectively enrolled 283 consecutive patients with CRLM who underwent curative resection between 2006 and 2016. We determined the optimal cutoff values of CAR and SII using receiver operating curve (ROC) analysis. Overall survival (OS)- and recurrence-free survival (RFS)-related to CAR and SII were analyzed using the log-rank test and multivariate Cox regression methods. Results: We found that a high CAR was significantly associated with poor OS (P < 0.001) and RFS (P = 0.008) rates compared with a low CAR; a high SII was significantly associated with poor RFS (P = 0.003) rates compared with a low SII. The multivariate analysis indicated that CAR was an independent predictor of OS (hazard ratio [HR] = 2.220; 95% confidence interval [CI] = 1.387-3.550; P = 0.001) and RFS (HR = 1.494; 95% CI = 1.086-2.056; P = 0.014). The SII was an independent predictor of RFS (HR = 1.973; 95% CI = 1.230-3.162; P = 0.005) in patients with CRLM. Conclusion: We proved that CAR was an independent predictor of OS and RFS in patients with CRLM who underwent curative resection, and that the prognostic value of CAR was superior to that of SII.

TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability.

Resistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

Optimal extraction, purification and antioxidant activity of total flavonoids from endophytic fungi of Conyza blinii H. Lév.

BACKGROUND: Flavonoids are widely used in the market because of their antibacterial, antiviral, and antioxidant activities. But the production speed of flavonoids is limited by the growth of plants. CBL9 (Chaetomium cruentum) is a flavonoid-producing endophytic fungi from Conyza blinii H. Lév, which has potential to produce flavonoids. METHODS: In this study, we isolated total flavonoids from endophytic fungus CBL9 of Conyza blinii H. Lév using macroporous resin D101. The process was optimized by response surface and the best extraction process was obtained. The antioxidant activities of total flavonoids were analyzed in vitro. RESULTS: It was found that the best parameters were 25 °C pH 2.80, 1.85 h, and the adsorption ratio reached (64.14 ± 0.04)%. A total of 60% ethanol was the best elution solvent. The elution ratio of total flavonoid reached to (81.54 ± 0.03)%, and the purity was 7.13%, which was increased by 14.55 times compared with the original fermentation broth. Moreover its purity could rise to 13.69% after precipitated by ethanol, which is very close to 14.10% prepared by ethyl acetate extraction. In the antioxidant research, the clearance ratio of L9F-M on DPPH, ABTS, •OH, •O2-, (96.44 ± 0.04)% and (75.33 ± 0.03)%, (73.79 ± 0.02)%, (31.14 ± 0.01)% at maximum mass concentration, was higher than L9F. CONCLUSION: The result indicated using macroporous resin in the extraction of total flavonoid from endophytic fungus is better than organic solvents with higher extraction ratio, safety and lower cost. In vitro testing indicated that the flavonoid extracted by macroporous resin have good antioxidant activity, providing more evidence for the production of flavonoid by biological fermentation method.

LINC00662 modulates cervical cancer cell proliferation, invasion, and apoptosis via sponging miR-103a-3p and upregulating PDK4.

Cervical cancer (CC) is one of the most common cancers among women with high recurrence rates all over the world. Recently, the molecular mechanism of CC has been gradually uncovered in accumulating reports. This study aimed to investigate the function and upstream regulation mechanism of pyruvate dehydrogenase kinase 4 (PDK4) in CC cells, which was verified as an oncogene in several cancers. Through RT-qPCR assay, we discovered that PDK4 was highly expressed in CC cells. Then, it was demonstrated in function assays that PDK4 facilitated CC cell proliferation and invasion, but inhibited CC cell apoptosis. Next, we sought to determine the upstream genes of PDK4, and miR-103a-3p was identified to target PDK4. Then, through bioinformatics tools and a range of mechanism assays, long intergenic non-protein coding RNA 662 (LINC00662) was verified as the sponge of miR-103a-3p. Moreover, LINC00662 positively modulated PDK4 expression via competitively binding to miR-103a-3p in CC cells. Subsequently, rescue assays demonstrated that LINC00662 accelerated CC cell proliferation and inhibited cell apoptosis through upregulating PDK4. Furthermore, forkhead box A1 (FOXA1) was verified to activate transcription of both LINC00662 and PDK4. Taken together, our study revealed a novel ceRNA pattern of LINC00662/miR-103a-3p/PDK4 with FOXA1 as a transcription factor of LINC00662 and PDK4 in CC cells.

Purification, characterization and antioxidant activities in vitro of polysaccharides from Amaranthus hybridus L.

BACKGROUND: Amaranthus hybridus L. is an annual, erect or less commonly ascending herb that is a member of the Amaranthaceae family. Polysaccharides extracted from traditional Chinese medicines may be effective substances with antioxidant activity. METHODS: In this study, we isolated crude polysaccharides from A. hybridus (AHP-M) using microwave-assisted extraction. Then, the AHP-M was purified by chromatography with DEAE-32 cellulose, and two fractions, AHP-M-1 and AHP-M-2, were obtained. The structural characteristics of AHP-M-1 and AHP-M-2 were investigated, and their antioxidant activities were analyzed in vitro. RESULTS: We found that the monosaccharide composition of AHP-M-1 was different from that of AHP-M-2. The molecular weights of AHP-M-1 and AHP-M-2 were 77.625 kDa and 93.325 kDa, respectively. The results showed that the antioxidant activity of AHP-M-2 was better than that of AHP-M-1. For AHP-M-2, the DPPH radical scavenging rate at a concentration of 2 mg/mL was 78.87%, the hydroxyl radical scavenging rate was 39.34%, the superoxide anion radical scavenging rate was 80.2%, and the reduction ability of Fe3+ was approximately 0.90. The total antioxidant capacity per milligram of AHP-M-2 was 6.42, which was higher than that of Vitamin C (Vc). CONCLUSION: The in vitro test indicated that AHP-M-1 and AHP-M-2 have good antioxidant activity, demonstrating that A. hybridus L. polysaccharide has immense potential as a natural antioxidants.

Synthesis of P-Doped and NiCo-Hybridized Graphene-Based Fibers for Flexible Asymmetrical Solid-State Micro-Energy Storage Device.

Fiber supercapacitors (FSCs) are promising energy storage devices in portable and wearable smart electronics. Currently, a major challenge for FSCs is simultaneously achieving high volumetric energy and power densities. Herein, the microscale fiber electrode is designed by using carbon fibers as substrates and capillary channels as microreactors to space-confined hydrothermal assembling. As P-doped graphene oxide/carbon fiber (PGO/CF) and NiCo2 O4 -based graphene oxide/carbon fiber (NCGO/CF) electrodes are successfully prepared, their unique hybrid structures exhibit a satisfactory electrochemical performance. An all-solid-state PGO/CF//NCGO/CF flexible asymmetric fiber supercapacitor (AFSC) based on the PGO/CF as the negative electrode, NCGO/CF hybrid electrode as the positive electrode, and poly(vinyl alcohol)/potassium hydroxide as the electrolyte is successfully assembled. The AFSC device delivers a higher volumetric energy density of 36.77 mW h cm-3 at a power density of 142.5 mW cm-3 . In addition, a double reference electrode system is adopted to analyze and reduce the IR drop, as well as effectively matching negative and positive electrodes, which is conducive for the optimization and improvement of energy density. For the AFSC device, its better flexibility and electrochemical properties create a promising potential for high-performance micro-supercapacitors. Furthermore, the introduction of the double reference electrode system provides an interesting method for the study on the electrochemical performances of two-electrode systems.

Three-Dimensional NiMoO4 Nanosheets Supported on a Carbon Fibers@Pre-Treated Ni Foam (CF@PNF) Substrate as Advanced Electrodes for Asymmetric Supercapacitors.

Herein, we report a nanoarchitectured nickel molybdate/carbon fibers@pre-treated Ni foam (NiMoO4 /CF@PNF) electrode for supercapacitors. The synthesis of NiMoO4 /CF@PNF mainly consists of a direct chemical vapor deposition (CVD) growth of dense carbon fibers (CFs) onto pre-treated Ni foam (PNF) as the substrate, followed by in situ growth of NiMoO4 nanosheets (NSs) on the CF@PNF substrate by means of a hydrothermal process. The NiMoO4 /CF@PNF electrode exhibits a high areal capacitance (5.14 F cm(-2) at 4 mA cm(-2) ) and excellent cycling stability (97 % capacitance retention after 2000 cycles at 10 mA cm(-2) ). Furthermore, we have successfully assembled NiMoO4 NSs//activated carbon (AC) asymmetric supercapacitors, which can achieve an energy density of 45.6 Wh kg(-1) at 674 W kg(-1) , and excellent stability with 93 % capacitance retention after 2000 cycles at 5 mA cm(-2) . These superior properties hold great promise for energy-storage applications.

Risk assessment of mouse gastric tissue cancer induced by dichlorvos and dimethoate.

Cancer hazards from pesticide residues in food have been much discussed in the past decade. In this study, we showed that dichlorvos and dimethoate affect hemoglobin content and hematocrit value, but had no effect on red blood cell counts and total plasma protein in mice. A 40-mg/kg/day dose of dichlorvos upregulated the expression of p16, Bcl-2 and c-myc genes in mouse gastric tissue. By contrast, expression of the p16, Bcl-2 and c-myc genes induced by low doses (5, 10 and 20 mg/kg/day) of dichlorvos demonstrated no change in the control check group (CK; 200 µl sterile saline perfused group; 0 mg/kg/day). Different doses of dimethoate all upregulated the expression of p16, Bcl-2 and c-myc genes in mouse gastric tissue. The results further demonstrated that mouse gastric tissue, exposed in the long-term to low doses of dichlorvos and dimethoate, has the potential to become cancerous.

[Gemcitabine based combination chemotherapy, a new salvage regimen for recurrent platinum resistant epithelial ovarian cancer].

OBJECTIVE: To evaluate the efficacy and toxicities of gemcitabine combined with ifosfamide and anthracycline chemotherapy for recurrent platinum resistant ovarian epithelial cancer. METHODS: Gemcitabine 800 mg/m(2) (day 1, 8), ifosfamide 1.5 g/m(2) (day 1 - 3), adriamycin 40 mg/m(2) or epirubicin 60 mg/m(2) (day 1) or mitoxantrone 10 mg/m(2) (day 1, 8) were used in recurrent platinum resistant/refractory ovarian cancer patients, the cycle was repeated at interval of 21 to 28 days. RESULTS: A total of 60 patients received 172 cycles combined chemotherapy. There were no one cases complete response, while partial response 22 (37%, 22/60), stable 23 (38%, 23/60) and progression 15 (25%, 15/60) were observed, with clinical benefit rate 75% (45/60). The median time of progression-free survival was 7 months, and the median overall survival time was 20 months. The main side effect was hematologic toxicity with leukopenia rate of 82% (49/60), among which III-IV accounted for 31% (15/49). Digestive reaction was all in I-II, accounted for 42% (25/60). CONCLUSION: The regimen of gemcitabine combined with ifosfamide and anthracycline is feasible, tolerable and effective in patients with recurrent platinum resistant/refractory epithelial ovarian cancer.