Effect of Metformin on Lactate Metabolism in Normal Hepatocytes under High Glucose Stress in Vitro

Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress. In vitro LO2 cells, liver cells were randomly divided into blank control group, 25 tendency/L glucose solution, 27 tendency/L glucose solution,29 tendency/L glucose solution, 31 tendency/L glucose solution, 33 tendency/L glucose solution,35 tendency/L glucose solution treatment group, the optimal concentration of 31 tendency after L, use 30 tendency for L metformin solution, and then divided into blank control group, the optimal concentration of glucose solution, normal liver cells + metformin solution normal liver cells. The optimal concentration of glucose solution normal liver cells + metformin solution respectively in the 12 h, 24 h,48 h on cell count plate to calculate the number of liver cells, and using lactic acid determination kit the optimal concentration of glucose solution + normal liver cells and normal liver cells + the optimal concentration of glucose solution + metformin solution respectively in the 12 h, 24 h, 48 h of cell cultures of lactic acid value. There was no significant change in the lactic acid concentration but significant increase in the number of surviving hepatocytes in the highglycemic control group compared with that in the high-glycemic control group without metformin. Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stress in vitro, and has a protective effect on hepatocytes under high glucose stress. Based on this,it is preliminarily believed that metformin is not the direct factor leading to diabetic lactic acidosis

Increased susceptibility to metabolic syndrome in adult offspring of Angiotensin type 1 receptor autoantibody-positive rats.

Abstract Aims: Abnormal fetal and early postnatal growth is closely associated with adult-onset metabolic syndrome (MetS). However, the underlying etiological factors remain complex. The presence of the autoantibody against the angiotensin II type 1 receptor (AT1-Ab), a known risk factor for pre-eclampsia, may create a suboptimal intrauterine fetal environment. The current study investigated whether middle-aged offspring of AT1-Ab-positive mothers were prone to metabolic disorder development. Results: The AT1-Abs was detected in placental trophoblastic cells, capillary endothelium, and milk of pregnant rats actively immunized with the second extracellular loop of the AT1 receptor. AT1-Abs in newborn rats induced vasoconstriction, increased intracellular-free Ca(2+) in vitro, and was undetectable 7 weeks later. Immunized group offspring exhibited increased weight variability and insulin resistance at 40 weeks of age under a normal diet, evidenced by elevated fasting serum insulin and homeostasis model assessment score compared with the vehicle control. To further observe metabolic alterations, the offspring were given a high-sugar diet (containing 20% sucrose) 40-48 weeks postnatally. The fasting plasma glucose in immunized group offspring was markedly increased. Concomitantly, these offspring manifested increased visceral adipose tissue, increased fatty liver, increased triglycerides, decreased high-density lipoprotein cholesterol, and decreased adiponectin levels, indicative of MetS. Innovation: AT1-Abs could be transferred from mother to offspring via the placenta and milk. Moreover, offspring of an AT1-Ab-positive mother were more vulnerable to MetS development in middle age. Conclusion: AT1-Ab-positivity of mothers during pregnancy is a previously unrecognized silent risk factor for MetS development in their offspring. Antioxid. Redox Signal. 17, 733-743

Steering on-surface reactions through molecular steric hindrance and molecule-substrate van der Waals interactions.

UNLABELLED On-surface synthesis is a rapidly developing field involving chemical reactions on well-defined solid surfaces to access synthesis of low-dimensional organic nanostructures which cannot be achieved via traditional solution chemistry. On-surface reactions critically depend on a high degree of chemoselectivity in order to achieve an optimum balance between target structure and possible side products. Here, we demonstrate synthesis of graphene nanoribbons with a large unit cell based on steric hindrance-induced complete chemoselectivity as revealed by scanning probe microscopy measurements and density functional theory calculations. Our results disclose that combined molecule-substrate van der Waals interactions and intermolecular steric hindrance promote a selective aryl-aryl coupling, giving rise to high-quality uniform graphene nanostructures. The established coupling strategy has been used to synthesize two types of graphene nanoribbons with different edge topologies inducing a pronounced variation of the electronic energy gaps. The demonstrated chemoselectivity is representative for n-anthryl precursor molecules and may be further exploited to synthesize graphene nanoribbons with novel electronic, topological and magnetic properties with implications for electronic and spintronic applications. SUPPLEMENTARY INFORMATION The online version contains supplementary material available at 10.1007/s44214-022-00023-9

Effects of Combined Simultaneous and Sequential Endostar and Cisplatin Treatment in a Mice Model of Gastric Cancer Peritoneal Metastases

Objective. Aimed to study the effects of endostar and cisplatin using an in vivo imaging system (IVIS) in a model of peritoneal metastasis of gastric cancer. Methods. NUGC-4 gastric cancer cells transfected with luciferase gene (NUGC-4-Luc) were injected i.p. into nude mice. One week later, mice were randomly injected i.p.: group 1, cisplatin (d1–3) + endostar (d4–7); group 2, endostar (d1–4) + cisplatin (d5–7); group 3, endostar + cisplatin d1, 4, and 7; group 4, saline for two weeks. One week after the final administration, mice were sacrificed. Bioluminescent data, microvessel density (MVD), and lymphatic vessel density (LVD) were analyzed. Results. Among the four groups, there were no significant differences in the weights and in the number of cancer cell photons on days 1 and 8 (P>0.05). On day 15, the numbers in groups 3 and 1 were less than that in group 2 (P<0.05). On day 21, group 3 was significantly less than group 2 (P<0.05). MVD of group 4 was less than that of groups 1 and 2 (P<0.01). There was no significant difference between groups 2 and 3 (P>0.05) or in LVD number among the four groups (P>0.05). Conclusions. IVIS® was more useful than weight, volume of ascites, and number of peritoneal nodules. The simultaneous group was superior to sequential groups in killing cancer cells and inhibiting vascular endothelium. Cisplatin-endostar was superior to endostar-cisplatin in killing cancer cells, while the latter in inhibiting peritoneal vascular endothelium

Thermostability enhancement of Escherichia coli phytase by error-prone polymerase chain reaction (epPCR) and site-directed mutagenesis

Phytase efficiently hydrolyzes phytate to phosphate; thus, it is widely used to increase phosphorus availability in animal feeds and reduce phosphorus pollution through excretion. Phytase is easily inactivated during feed pelleting at high temperature, and sufficient thermostability of phytase is essential for industrial applications. In this study, directed evolution was performed to enhance phytase thermostability. Variants were initially expressed in Escherichia coli BL21 for screening, then in Pichia pastoris for characterization. Over 19,000 clones were generated from an error-prone Polymerase Chain Reaction (epPCR) library; 5 mutants (G10, D7, E3, F8, and F9) were obtained with approximately 9.6%, 10.6%, 11.5%, 11.6%, and 12.2% higher residual activities than the parent after treatment at 99°C for 60 min. Three of these mutants, D7, E3, and F8, exhibited 79.8%, 73.2%, and 92.6% increases in catalytic efficiency (kcat/Km), respectively. In addition, the specific activities of D7, E3, and F8 were 2.33-, 1.98-, and 2.02-fold higher than parental phytase; they were also higher than the activities of all known thermostable phytases. Sequence analysis revealed that all mutants were substituted at residue 75 and was confirmed that the substitution of cysteine at position 75 was the main contribution to the improvement of thermostability of mutants by saturation mutagenesis, indicating that this amino acid is crucial for the stability and catalytic efficiency of phytase. Docking structure analysis revealed that substitution of the C75 residue allowed the mutants to form additional hydrogen bonds in the active pocket, thereby facilitating binding to the substrate. In addition, we confirmed that the intrinsic C77-C108 disulfide bond in E. coli phytase is detrimental to its stability

Shear localization behavior in the hat-shaped specimen of near-α Ti-6Al-2Zr-1Mo-1V titanium alloy loaded at a high strain rate

The microstructure characteristics in early stage shear localization of near-α Ti−6Al−2Zr−1Mo−1V titanium alloy were investigated by split Hopkinson pressure bar (SHPB) tests using hat-shaped specimens. The microstructural evolution and deformation mechanisms of hat-shaped specimens were revealed by electron backscattered diffraction (EBSD) method. It is found that the nucleation and expansion of adiabatic shear band (ASB) are affected by both geometric and structural factors. The increase of dislocation density, structure fragment and temperature rise in the deformation-affected regions provide basic microstructural conditions. In addition to the dislocation slips, the extension twins detected in shear region also play a critical role in microstructural fragmentation due to twin-boundaries effect. Interestingly, the sandwich structure imposes a crucial influence on ASB, which finally becomes a mature wide ASB in the dynamic deformation. However, due to much larger width, the sandwich structure in the middle of shear region is also possible to serve as favorable nucleation sites for crack initiation

Highly-stable, flexible delivery of microjoule-level ultrafast pulses in vacuumized anti-resonant hollow-core fibers for active synchronization

We demonstrate the stable and flexible light delivery of multi-{\mu}J, sub-200-fs pulses over a ~10-m-long vacuumized anti-resonant hollow-core fiber (AR-HCF), which was successfully used for high-performance pulse synchronization. Compared with the pulse train launched into the AR-HCF, the transmitted pulse train out of the fiber exhibits excellent stabilities in pulse power and spectrum, with pointing stability largely improved. The walk-off between the fiber-delivery and the other free-space-propagation pulse trains, in an open loop, was measured to be <6 fs root-mean-square (RMS) over 90 minutes, corresponding to a relative optical-path variation of <2x10-7. This walk-off can be further suppressed to ~2 fs RMS simply using an active control loop, highlighting the great application potentials of this AR-HCF set-up in large-scale laser and accelerator facilities