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A high‐performance liquid chromatography‐tandem mass spectrometry method has been developed for the determination of irinotecan, 7‐ethyl‐10‐hydroxycamptothecin (SN38), and SN38 glucuronide (SN38G) in rat plasma in the present study. The analytes were separated on a C18 column and a triple‐quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. Irinotecan, SN38 and SN38G could be well retained in the C18 column after optimization of mobile phase. A simple protein precipitation was used to pretreat the plasma. The extraction recovery was above 90% and the matrix effect could be negligible. The method was linear over the concentration ranges of 3.46–3458.8 ng/mL for irinotecan, 2.53–2530.0 ng/mL for SN38 and 2.5–2500.0 ng/mL for SN38G. The precision and accuracy was within the acceptable limits. The simple and convenient method was validated and successfully applied to support the pharmacokinetic study and elucidate the mechanism of irinotecan‐induced diarrhea after irinotecan was intravenously injected to the Sprague‐Dawley rats. [ABSTRACT FROM AUTHOR]

Electrochemical synthesis serves as a green and efficient method with great application potential. However, it has not been extensively applied in the synthesis of energetic materials. Nitrogen-rich heterocyclic compounds, as a new generation of energetic materials, enjoy advantages such as eco-friendliness, high energy output, and excellent safety performance. This study reports the electrochemical cathodic synthesis of copper nitrotriazole [Cu(NTz)2] using copper chloride and 3-nitro-1,2,4-triazole as a reaction substrate and triethylamine as a deprotonation agent. The obtained Cu(NTz)2 comprises uniform spherical particles of nano lamellae. As the dosage of triethylamine increased from 50 µL to 150 µL, Cu(NTz)2 gradually grew into compact solid spherical particles, significantly increasing the energy output. Notably, the heat release increased from 711 J g-1 to 1301 J g-1, accompanied by a significant positive elevation of ignition performance and peak combustion pressure in the process of confined combustion. This greatly boosted the energetic performance of Cu(NTz)2. Moreover, Cu (NTz)2 demonstrates insensitivity to electrostatic discharge (E50>225 mJ) and friction (FS>360 N), suggesting excellent safety performance. Owing to its outstanding energetic and safety performance, Cu(NTz)2 boasts great potential for application as pyrotechnic compositions, including military gas-producing and incendiary agents. Moreover, it has been corroborated that Cu(NTz)2 can be applied as a micro ignitor. [ABSTRACT FROM AUTHOR]

A high‐performance liquid chromatography‐tandem mass spectrometry method has been developed for the determination of peramivir in rat plasma in the present study. The analytes were separated on a C18 column and a triple‐quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. Peramivir could be well retained in the C18 column after optimization of the mobile phase. A simple protein precipitation was used to pretreat the plasma. The extraction recovery was about 100% and the matrix effect could be negligible. The method was linear over the concentration ranges of 1.17–2340.0 ng/mL for peramivir. The precision and accuracy were within acceptable limits. The lowest limit of quantification was 1.17 ng/mL. Compared with those methods which have been developed and published since 2001, the present method is very simple and convenient. The method was validated and successfully applied to support the pharmacokinetics study after peramivir was intravenously injected into the Sprague‐Dawley rats. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanism behind the faster volitional reaction time (RT) of open skill sports athletes from the perspective of proactive inhibitory control, with the hypothesis that the superior response speed of athletes from open skill sports is related to their enhanced capacity for releasing inhibition. Methods: Participants were divided into two groups, an experimental group of 27 table tennis players and a control group of 27 non-athletes. By manipulating cue-target onset asynchrony (CTOA) in a simple cue-target detection task, the timing of target presentation occurred in different phases of the disinhibition process. The time needed for disinhibition were compared between groups. Results: For the experimental group, RT varied with CTOA at delays less than 200 ms; for CTOAs greater than 200 ms, RTs were not significantly different. For the control group, RT varied with CTOA for delays as long as 300 ms. Conclusions: Table tennis players took less time (200 ms) than non-athletes (300 ms) to complete the disinhibition process, which might partly explain their rapid response speed measured in unpredictable contexts. Significance: The study provided evidence for disinhibition speed as a new index to assess the capacity of proactive inhibitory control, and provided a new perspective to explore the superior RT of athletes from open skill sports. We also offered support for the fundamental cognitive benefits of table tennis training. [ABSTRACT FROM AUTHOR]

Context: Continuous glucose monitoring (CGM) overcomes the limitations of glycated hemoglobin (HbA1c).Objective: This study aimed to investigate the relationship between CGM metrics and laboratory HbA1c in pregnant women with type 1 diabetes.Methods: An observational study enrolled pregnant women with type 1 diabetes who wore CGM devices during pregnancy and postpartum from 11 hospitals in China from January 2015 to June 2019. CGM data were collected to calculate time in range (TIR), time above range (TAR), time below range (TBR), and glycemic variability parameters. Relationships between the CGM metrics and HbA1c were explored. Linear and curvilinear regressions were conducted to investigate the best-fitting model to clarify the influence of HbA1c on the TIR-HbA1c relationship during pregnancy.Results: A total of 272 CGM data and corresponding HbA1c from 98 pregnant women with type 1 diabetes and their clinical characteristics were analyzed in this study. Mean HbA1c and TIR were 6.49 ± 1.29% and 76.16 ± 17.97% during pregnancy, respectively. HbA1c was moderately correlated with TIR3.5-7.8(R = -0.429, P = .001), mean glucose (R = 0.405, P = .001) and TAR7.8 (R = 0.435, P = .001), but was weakly correlated with TBR3.5 (R = 0.034, P = .001) during pregnancy. On average, a 1% (11 mmol/mol) decrease in HbA1c corresponded to an 8.5% increase in TIR3.5-7.8. During pregnancy, HbA1c of 6.0%, 6.5%, and 7.0% were equivalent to a TIR3.5-7.8 of 78%, 74%, and 69%, respectively.Conclusion: We found there was a moderate correlation between HbA1c and TIR3.5-7.8 during pregnancy. To achieve the HbA1c target of less than 6.0%, pregnant women with type 1 diabetes should strive for a TIR3.5-7.8 of greater than 78% (18 hours 43 minutes) during pregnancy. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) has been considered as the common pathological basis and developmental driving force for most metabolic diseases. Long noncoding RNAs (lncRNAs) have emerged as pivotal regulators in modulation of glucose and lipid metabolism. However, the comprehensive profile of lncRNAs in skeletal muscle cells under the insulin resistant status and the possible biological effects of them were not fully studied. In this research, using C2C12 myotubes as cell models in vitro, deep RNA-sequencing was performed to profile lncRNAs and mRNAs between palmitic acid-induced IR C2C12 myotubes and control ones. The results revealed that a total of 144 lncRNAs including 70 up-regulated and 74 down-regulated (|fold change| > 2, q < 0.05) were significantly differentially expressed in palmitic acid-induced insulin resistant cells. In addition, functional annotation analysis based on the Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases revealed that the target genes of the differentially expressed lncRNAs were significantly enriched in fatty acid oxidation, lipid oxidation, PPAR signaling pathway, and insulin signaling pathway. Moreover, Via qPCR, most of selected lncRNAs in myotubes and db/db mice skeletal muscle showed the consistent expression trends with RNA-sequencing. Co-expression analysis also explicated the key lncRNA-mRNA interactions and pointed out a potential regulatory network of candidate lncRNA ENSMUST00000160839. In conclusion, the present study extended the skeletalmuscle lncRNA database and provided novel potential regulators for future genetic and molecular studies on insulin resistance, which is helpful for prevention and treatment of the related metabolic diseases. [ABSTRACT FROM AUTHOR]

Obesity is associated with a notable risk for disease, including risk of cardiovascular disorders, type 2 diabetes mellitus (T2DM) and hypertension. Adipose tissue modulates the metabolism by releasing free fatty acids (FFAs) and adipokines, including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6). Altered secretion patterns of FFAs and adipokines have been demonstrated to result in obesity-associated insulin resistance (IR) and inflammatory responses. MicroRNA-199a-3p (miR)-199a-3p expression is significantly induced in differentiated human adipose-derived mesenchymal stem cells and indicates the association with T2DM. However, the association between miR-199a-3p levels in adipocytes and obesity-associated IR, as well as inflammatory responses remains to be elucidated. The present study observed an elevation of miR-199a-3p expression level in mature human adipocytes (visceral) compared with pre-adipocytes. In addition, miR-199a-3p expression was higher in visceral adipose deposits from obese subjects. FFA, TNF-α, IL-6 and leptin significantly induced miR-199a-3p expression in mature human adipocytes, while resistin had the opposite effect. miR-199a-3p may represent a factor in the modulation of obesity-associated IR and inflammatory responses. [ABSTRACT FROM AUTHOR]

Purpose: To replicate previously confirmed telomere-length loci in a Chinese Han population with coronary heart disease (CHD), and investigate these loci and the possibility of and age at onset of CHD. Patients and methods: 1514 CHD patients and 2470 normal controls were recruited. Medical data including age, sex, body mass index, lipid profiles, history of hypertension, type 2 diabetes mellitus, and dyslipidemia were collected from all the participants. Seven previously identified single-nucleotide polymorphisms (SNPs) related to leucocyte telomere length were genotyped, including rs10936599 in TERC, rs2736100 in TERT, rs7675998 in NAF1, rs9420907 in OBFC1, rs8105767 in ZNF208, rs755017 in RTEL1, and rs11125529 in ACYP2. Results: No significant difference in genotype frequencies from the Hardy-Weinberg equilibrium test was noted for all tested SNPs both in the CHD patients and the normal controls. No polymorphism was observed for rs9420907, and AA genotype was noted in both the CHD patients and the controls. Neither the genotype nor the allele frequencies of rs2736100, rs8105767, rs11125529, and rs2967374 were significantly different between the CHD patients and the normal controls. For rs10936599 and rs755017, statistical difference was found for the allele frequency but not genotype. Distributions of genotype and allele were significantly different between the two groups for rs7675998. The odds ratio for carriers of CHD was 2.127 (95% confidence interval: 1.909-2.370) for the A allele of rs7675998. By one-way analysis of variance test, rs7675998 was associated with the onset age of CHD. CHD patients with the AA genotype of rs7675998 had significantly lower onset age (P<0.05). Conclusion: In a Chinese Han population, NAF1 gene encoding proteins with known function in telomere biology may influence both the possibility of and the age at onset of CHD, as previously reported in European studies. [ABSTRACT FROM AUTHOR]

Background: The Notch signaling pathway has been shown to be involved in the development of the nervous system. Recent studies showed that Notch receptors and ligands are also expressed in the nervous system of adult animals. However, whether the Notch signaling pathway has a function in adults is not fully understood. The present study is designed to investigate the function of the Notch signaling pathway in nociceptive transmission, especially during neuropathic pain in adult rats. Results: We found that the Notch intracellular domain (NICD) is expressed in the DRG (Dorsal Root Ganglia), sciatic nerve and spinal cord in normal rats, and is upregulated in the sciatic nerve and spinal cord after spared nerve injury (SNI). Moreover, we used the ?-secretase (a key enzyme of the Notch signaling pathway) inhibitor DAPT to observe the effect of the Notch signaling pathway after SNI. We found that intrathecal DAPT significantly increased paw withdrawal thermal latency and mechanical threshold. Mechanical hyperalgesia occurring after SNI could be significantly reversed by DAPT in a dose-dependent manner. Conclusions: These results suggest that the Notch signaling pathway participates in the induction and maintenance of neuropathic pain, which indicates that the Notch pathway maybe a potential drug target for neuropathic pain treatment. [ABSTRACT FROM AUTHOR]

The interdomain instability of single-chain fragment variable (scFv) might result in intermolecular aggregation and loss of function. In the present study, we stabilized H4—an anti-aflatoxin B1 (AFB1) scFv—with an interdomain disulfide bond and studied the effect of the disulfide bond on antibody affinity. With homology modeling and molecular docking, we designed a scFv containing an interdomain disulfide bond between the residues H44 and L100. The stability of scFv (H4) increased from a GdnHCl50 of 2.4 M to 4.2 M after addition of the H44-L100 disulfide bond. Size exclusion chromatography revealed that the scFv (H44-L100) mutant existed primarily as a monomer, and no aggregates were detected. An affinity assay indicated that scFv (H4) and the scFv (H44-L100) mutant had similar IC50 values and affinity to AFB1. Our results indicate that interdomain disulfide bonds could stabilize scFv without affecting affinity. [ABSTRACT FROM AUTHOR]

new manifold learning method, called incremental alignment method (IAM), is proposed for nonlinear dimensionality reduction of high dimensional data with intrinsic low dimensionality. The main idea is to incrementally align low-dimensional coordinates of input data patch-by-patch to iteratively generate the representation of the entire dataset. The method consists of two major steps, the incremental step and the alignment step. The incremental step incrementally searches neighborhood patch to be aligned in the next step, and the alignment step iteratively aligns the low-dimensional coordinates of the neighborhood patch searched to generate the embeddings of the entire dataset. Compared with the existing manifold learning methods, the proposed method dominates in several aspects: high efficiency, easy out-of-sample extension, well metric-preserving, and averting of the local minima issue. All these properties are supported by a series of experiments performed on the synthetic and real-life datasets. In addition, the computational complexity of the proposed method is analyzed, and its efficiency is theoretically argued and experimentally demonstrated. [ABSTRACT FROM AUTHOR]

To evaluate the relationship between reproduction and migratory flight, we examined ovaries, tethered flight, and egg laying in the beet armyworm, Spodoptera exigua (Hübner). Ovarian development in female S. exigua was classified into five stages in relation to the postemergence age of the moths. Oviposition peaked at ovarian stages III and IV. Mating accelerated ovarian development in this species, and thus the mated females developed faster than the virgin moths in ovaries. In virgin adults, flight capacity increased from the first day to the third day after emergence and remained at a high level until the moths were 7 d old. In contrast, the mated moths reached the maximum flight capacity in 2 d after emergence and maintained a high level until the age of 7 d. However, mating status could not influence the flight capacity of the beet armyworm, although there were general differences in flight capacity between virgin and mated adults at the same age. Moreover, significant correlations between the number of eggs laid and the flight capacity were not performed by the mated moths. These results showed that mating status and ovarian development did not seem to influence flight capacity in the beet armyworm, which was not in agreement with the definitions of the oogenesis-flight syndrome observed in many other migratory insects. [ABSTRACT FROM AUTHOR]

Nilaparvata lugens (Stål) is a typical vascular feeder, primarily sucking the phloem sap of host plants. Its feeding on rice, Oryza sativa L., plants changes the pattern of allocation of assimilates between roots and shoots, and the root:shoot (R/S) ratio of assimilates is often measured as an index of physiological responses to N. lugens. The current study investigated changes in the R/S ratio of biomass, sucrose, and soluble sugar contents of rice plants in a susceptible variety (TN1) and a resistant variety (Xieyou 963). The results demonstrated that root and shoot biomasses in the two varieties linearly decreased with the increase of N. lugens infestation density. However, the relationship between changes in the RI S ratio of biomass and N. lugens density differed between rice varieties, with the R/S increasing with infestation density in TN1 and decreasing in Xieyou 963. Sucrose and soluble sugar contents and their R/S values were also significantly different between the two varieties. Compared with the control that was not infested by N. lugens, the R/S values of sucrose and soluble sugar at 3 days after infestation (DAI) increased but decreased at 6 DAI in TN1. The R/S values of sucrose and soluble sugar were higher at 6 DAI than those at 3 DAI in TN1, whereas these values were lower at 6 DAI than at 3 DAI in Xieyou 963. These contrasting results suggest that physiological responses to N. lugens infestation differ between the susceptible and tolerant rice varieties. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to observe the effects of resistin on insulin sensitivity and glucose output in rat-derived hepatocytes. Methods: The rat hepatoma cell line H4IIE was cultured and stimulated with resistin; supernant glucose and glycogen content were detected. The insulin receptor substrate (IRS)-1 and IRS-2, protein kinase B/Akt, glycogen synthase kinase-3β (GSK-3β), the suppressor of cytokine signaling 3 (SOCS-3) protein content, as well as the phosphorylation status were assessed by Western blotting. Specific antisense oligodeoxynucleotides directed against SOCS-3 were used to knockdown SOCS-3. Results: Resistin induced insulin resistance, but did not affect glucose output in rat hepatoma cell line H4IIE. Resistin attenuated multiple effects of insulin, including insulin-stimulated glycogen synthesis and phosphorylation of IRS, protein kinase B/Akt, as well as GSK-3β. Resistin treatment markedly induced the gene and protein expression of SOCS-3, a known inhibitor of insulin signaling. Furthermore, a specific antisense oligodeoxynucleotide directed against SOCS-3 treatment prevented resistin from antagonizing insulin action. Conclusion: The major function of resistin on liver is to induce insulin resistance. SOCS-3 induction may contribute to the resistin-mediated inhibition of insulin signaling in H4IIE hepatocytes. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects and mechanisms of the action of resistin on basal and insulin-stimulated glucose uptake in rat skeletal muscle cells. Methods: Rat myo-blasts (L6) were cultured and differentiated into myotubes followed by stimulation with single commercial resistin (130 ng/mL, 0-24 h) or cultured supernatant from 293-T cells transfected with resistin-expressing vectors (130 ng/mL, 0-24 h). Liquid scintillation counting was used to quantitate [3H] 2-deoxyglucose uptake. The translocation of insulin-sensitive glucose transporters GLUT4 and GLUT1, synaptosomal-associated protein 23 (SNAP23) and GLUT protein content, as well as the tyrosine phosphorylation status and protein content of insulin receptor substrate (IRS) -1, were assessed by Western blotting. Results: Treatment of L6 myotubes with single resistin or cultured supernatant containing recombinant resistin reduced basal and insulin-stimulated 2-deoxyglucose uptake and impaired insulin-stimulated GLUT4 translocation. While SNAP23 protein content was decreased, no effects were noted in GLUT4 or GLUT1 protein content. Resistin also diminished insulin-stimulated IRS-1 tyrosine phosphorylation levels without affecting its protein content. The effects of recombinant resistin from 293-T cells transfected with resistin-expressing vectors were greater than that of single resistin treatment. Conclusion: Resistin regulated IRS-1 function and decreased GLUT4 translocation and glucose uptake in response to insulin. The downregulated expression of SNAP23 may have been partly attributed to the decrease of glucose uptake by resistin treatment. These observations highlight the potential role of resistin in the pathophysiology of type 2 diabetes related to obesity. [ABSTRACT FROM AUTHOR]

Aim: To investigate the direct effects of resistin and resistin-binding peptide (RBP) on lipid metabolism and endocrine function in adipose tissue. Methods: Rat white adipose tissue was cultured in vitro and incubated for 24 h with 30 ng/mL recombinant rat resistin protein (rResistin) or combined with RBP of varying concentrations(1×10-12mol/L, 1×10-10mol/L, 1×10-8mol/L). Free fatty acids (FFA) released into medium was measured by a colorimetric kit. The levels of protein secretion and mRNA expression of TNF-α and adiponectin were detected by ELISA kit and RT-PCR respectively. Results: The levels of FFA released into medium were significantly increased after 24 h of exposure to rResistin, but significantly decreased after RBP was applied, although there was no difference between the 3 concentrations. The protein level and gene expression of TNF-α in adipose tissue were significantly increased after 24 h of exposure to rResistin, but only obviously decreased after incubated with 1×10-8mol/L RBP. The levels of protein secretion and mRNA expression of adiponectin in adipose tissue were significantly decreased after 24 h of exposure to rResistin, but increased after incubated with RBP with the higher concentrations. Conclusion: RBP can effectively antagonize the role of resistin on the lipid metabolism and endocrine function of adipose tissue. [ABSTRACT FROM AUTHOR]

The effect of Nilaparvata lugens (Still) (Homoptera: Delphacidae), infestation on the content of zeatin ribosides (ZR) in rice plants was investigated with enzyme-linked immunosorbent assay. Hydroponics experiments were conducted on "Zhendao 2' rice, in which plants were subjected to N. lugens infestation at three nonhopperburn-causing densities (15, 30, and 60 nymphs per hill) for 2, 4, 6, and 8 d and at one hopperburn-eausing density (240 nymphs per hill) for 2, 4, and 6 d, respectively. When rice plants were infested at the nonhopperburn-causing densities, ZR content in leaves varied significantly with the infestation density. Compared with the control plants, ZR content in rice leaves decreased significantly after infestation by 60 nymphs per hill for 2 d, but it tended to increase due to prolonged infestation at all the nonhopperburn-causing densities. In contrast, ZR content in rice roots significantly reduced after the plants being infested at the density of 15 nymphs for 2 d and at all densities for prolonged duration, except for the plants infested by 60 nymphs for 6 and 8 d, in which the ZR content increased or did not change significantly. However, infestation at the hopperburn-causing density caused significant reduction in ZR content in rice roots, regardless of infestation duration, and in rice leaves from the plants subjected to 2-d infestation. These results are discussed in relation to the possible physiological reaction of rice plants to N. lugens infestation and the resultant severe damage or hopperburn. [ABSTRACT FROM AUTHOR]