The reversible effects of free fatty acids on sulfonylurea-stimulated insulin secretion are related to the expression and dynamin-mediated endocytosis of KATP channels in pancreatic β cells

Objective: Lipotoxicity-induced pancreatic β cell-dysfunction results in decreased insulin secretion in response to multiple stimulus. In this study, we i nvestigated the reversible effects of palmitate (PA) or oleate (OA) on insulin secretion and the relationship with pancreatic β-cell ATP-sensitive potassium (KATP) channels. Methods: MIN6 cells were treated with PA and OA for 48 h and then washed out for 24 h to determine the changes in expression and endocytosis of the KATP channels and glucose-stimulated insulin secretion (GSIS) and sulfonylurea-stimulated insulin secretion (SU-SIS). Results: MIN6 cells exposed to PA or OA showed both impaired GSIS and SU -SIS; the former was not restorable, while the latter was reversible with washout of PA or OA. Decreased expressions of both total and surface Kir6.2 and SUR1 and endocytosis of KATP channels were observed, which were also recoverable after wash out. When MIN6 cells exposed to free fatty acids (FFAs) were cotreated wi th 5-aminoimidazole- 4-carboxamide ribonucleotide (AICAR) or dynasore, we found that endocytosis of KATP channels did not change significantly by AICAR but was almost co mpletely blocked by dynasore. Meanwhile, the inhibition of endocytosis of K ATP channels after washout could be activated by PIP2. The recovery of SU-SIS after washout was significantly weakened by PIP2, but the decrease of SU-SIS induced by FFAs was not allevi ated by dynasore. Conclusions: FFAs can cause reversible impairment of SU-SIS on pancreatic β cells. The reversibility of the effects is partial because of the changes o f expression and endocytosis of Kir6.2 and SUR1 which was mediated by dynamin

Uterine torsion complicated by severe placental abruption in the second trimester: a case report and literature review

Abstract Background Uterine torsion is a rare obstetric event that can occur during pregnancy and is difficult to diagnose. Its occurrence may lead to serious adverse pregnancy outcomes. Case introduction The patient was a 33-year-old woman at 30+ 5 weeks’ gestation with a singleton pregnancy. The pregnancy course, including fetal growth, and prenatal examinations were regular. Except for a small amount of vaginal bleeding in early pregnancy and treatment with progesterone, there were no prenatal abnormalities, and the patient denied any trauma or sexual history. The patient was admitted to the emergency department with persistent severe pain in the lower abdomen and slight vaginal bleeding during night sleep. Abdominal pain started two hours prior to admission and was accompanied by nausea, vomiting, and dizziness. Examination revealed positive abdominal tenderness, high uterine tone, and no significant intermittent period of uterine contractions, and measurement of the fetal heart rate by means of the nonstress test revealed a rate of 60 beats per minute. Therefore, placental abruption was highly suspected. Subsequently, an emergency cesarean section was performed under general anesthesia. The newborn boy, with Apgar scores of 0–3-4 after birth and weighing 1880 g, was transferred to the neonatal intensive care unit (NICU) and died two days later due to ineffective rescue. After the uterine incision was sutured, the examination revealed that the uterine incision was located on the posterior wall of the uterus, and the uterus was twisted 180° to the right. The diagnosis after cesarean section was 180° uterine torsion to the right, severe placental abruption, and severe neonatal asphyxia. On the fifth day after surgery, the patient recovered and was discharged from the hospital. Conclusions Posterior uterine incision cesarean section may be performed in unexpected circumstances and is also feasible as a safe option for resetting if torsion is not complete. Abdominal pain during pregnancy is less likely to be diagnosed as uterine torsion, which often leads to premature birth, fetal asphyxia, placental abruption, and even perinatal death. Therefore, for abdominal pain during pregnancy, obstetricians should consider the possibility of uterine torsion

Fabrication of PLCL Block Polymer with Tunable Structure and Properties for Biomedical Application

Biodegradable materials are pivotal in the biomedical field, where how to precisely control their structure and performance is critical for their translational application. In this study, poly(L-lactide-b-ε-caprolactone) block copolymers (bPLCL) with well-defined segment structure are obtained by a first synthesis of poly(ε-caprolactone) soft block, followed by ring opening polymerization of lactide to form poly(L-lactide acid) hard block. The pre-polymerization allows for fabrication of bPLCL with the definite compositions of soft/hard segment while preserving the individual segment of their special soft or hard segment. These priorities make the bPLCL afford biodegradable polymer with better mechanical and biodegradable controllability than the random poly(L-lactide-co-ε-caprolactone) (rPLCL) synthesized via traditional one-pot polymerization. 10 mol% ε-caprolactone introduction can result in a formation of an elastic polymer with elongation at break of 286.15% ± 55.23%. Also, bPLCL preserves the unique crystalline structure of the soft and hard segments to present a more sustainable biodegradability than the rPLCL. The combinative merits make the pre-polymerization technique a promising strategy for a scalable production of PLCL materials for potential biomedical application

Improving wood properties for wood utilization through multi-omics integration in lignin biosynthesis.

A multi-omics quantitative integrative analysis of lignin biosynthesis can advance the strategic engineering of wood for timber, pulp, and biofuels. Lignin is polymerized from three monomers (monolignols) produced by a grid-like pathway. The pathway in wood formation of Populus trichocarpa has at least 21 genes, encoding enzymes that mediate 37 reactions on 24 metabolites, leading to lignin and affecting wood properties. We perturb these 21 pathway genes and integrate transcriptomic, proteomic, fluxomic and phenomic data from 221 lines selected from ~2000 transgenics (6-month-old). The integrative analysis estimates how changing expression of pathway gene or gene combination affects protein abundance, metabolic-flux, metabolite concentrations, and 25 wood traits, including lignin, tree-growth, density, strength, and saccharification. The analysis then predicts improvements in any of these 25 traits individually or in combinations, through engineering expression of specific monolignol genes. The analysis may lead to greater understanding of other pathways for improved growth and adaptation