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Inflammation plays an important role in ischemia–reperfusion injury. Through its antioxidative effects, uric acid can reduce cell injury. However, its mechanism is unknown. This study investigated the protective mechanism of uric acid in cells during ischemia–reperfusion. We divided hippocampal neurons into six groups: the control, OGD, OGD/R, OGD/R + HMGB1 siRNA, OGD/R + uric acid, and OGD/R + uric acid + HMGB1 groups. The MTT assay was used to evaluate cell viability, while apoptosis was detected by flow cytometry. The expression of HMGB1, TLR4, NF-κB-p65 and phosphorylated NF-κB-p65 was detected by Western blotting. The levels of IL-6, IL-1β and TNF-α in the culture medium were determined by ELISA. The results indicated increased cell viability and decreased apoptosis in the presence of HMGB1 siRNA and uric acid but the opposite findings in the presence of HMGB1 protein after OGD/R. Uric acid and HMGB1 siRNA inhibited HMGB1 acetylation to prevent its transport from the nucleus to the cytoplasm. The expression of HMGB1 downstream proteins (TLR4, NF-κB-p65 and phosphorylated NF-κB-p65) and the levels of inflammatory factors in the presence of HMGB1 siRNA and uric acid was lower than those in the presence of HMGB1 protein after OGD or OGD/R. These data indicated that uric acid may prevent cell injury mainly by inhibiting HMGB1 acetylation to regulate TLR4/NF-κB pathways and reduce the levels of inflammatory factors.

Table S2. The PCR amplification efficiency for each primer pair (DOCX 19 kb)

Table S3. Comparison of the main agronomic traits between lcd1 and WT plants (DOCX 15 kb)

Study question What is the impact of glucocorticoid (GC) on female reproduction? Summary answer Corticosterone (CORT) exposure causes little damage to oocyte quality or developmental competence but has an adverse effect on the uterus, which causes decreased implantation, embryo death and subsequent infertility. What is known already Chronic treatment with high GC doses is effective in controlling most allergic diseases but may lead to metabolic disorders such as obesity that are closely related with reproductive function. Study design, size, duration Hypercortisolism was induced in a female mouse model by supplementing the drinking water with 100 μg/ml of CORT. Controls received vehicle (1% v/v ethanol) only. After 4 weeks treatment mice were either mated or killed in estrus for hormone and organ measurements. In the first experiment, treatment with CORT or control continued during pregnancy but in the second CORT treatment was stopped after mating. To identify the effects of GC exposure on the uterus, blastocysts were generated by IVF of oocytes from CORT and control mice and replaced into recipients receiving the opposite treatment. Participants/materials, setting, methods The effects of hypercortisolism on female mice were first characterized by living body fat content, body weight, food intake, hormone and biochemical measurements, a glucose tolerance test and an insulin resistance test. Fertility was determined with or without CORT-treatment during pregnancy. Oocyte quality was assessed by oocyte maturation, mitochondrial distribution, reactive oxygen species production, mitochondrial DNA mutations and morphology of blastocysts produced in vivo or in vitro. Blastocyst cross-transfer was done to evaluate the causes of embryonic development failure. Fetus development and uterus morphology evaluation as well as culture of oocytes in vitro with gradient concentrations of CORT were also carried out. Main results and the role of chance In the hypercortisolism female mouse model, body weight and food intake were much higher than in the control, and corticosterone, estradiol, cholesterol (CHO) and triglycerides (TG) in the plasma of CORT-treated mice was significantly increased. The hypercortisolism female mice were infertile when CORT-treatment was sustained during pregnancy but fertile if CORT-treatment was stopped after mating. The rate of successful implantation in hypercortisolism mice with sustained CORT-treatment during pregnancy was significantly lower than in the control, and the implanted embryos could not develop beyond 13.5 dpc. Blastocyst cross-transfer showed that blastocysts from CORT-treated mice could develop to term in the uterus of control mice, but blastocysts from control mice failed to develop to term when they were transferred into CORT-treated mice, providing evidence that the infertility was mainly caused by an altered uterine environment. CORT administration did not affect oocyte maturation, mitochondrial distribution, ROS production and blastocyst morphology, but increased mitochondrial DNA mutations. Culture of oocytes in vitro with gradient concentrations of CORT showed that only very high concentrations of CORT caused damage to oocyte developmental competence. Large scale data NA. Limitations, reasons for caution The mouse model has the advantages of a consistent genetic and physiological background and openness to experimental manipulation over clinical studies but may not represent the human situation. Wider implications of the findings Our findings show that special care should be taken when administering CORT during pregnancy, and provide important information concerning female reproduction when treating patients by subjecting them to chronic GC exposure. Study funding/competing interest(s) This study was supported by the National Key R&D Program of China (Nos. 2016YFA0100400 and 2017YFC1000600) and the National Natural Science Foundation of China (31472055). The authors have no conflicts of interest.

Background Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown. Methods We generated a T2D mouse model by using high-fat-diet (HFD) and Streptozotocin (STZ) injection. We examined mtDNA mutations in oocytes of diabetic mice by high-throughput sequencing techniques. Results T2D mice showed glucose intolerance, insulin resistance, low fecundity compared to the control group. T2D oocytes showed increased mtDNA mutation sites and mutation numbers compared to the control counterparts. mtDNA mutation examination in F1 mice showed that the mitochondrial bottleneck could eliminate mtDNA mutations. Conclusions T2D mice have increased mtDNA mutation sites and mtDNA mutation numbers in oocytes compared to the counterparts, while these adverse effects can be eliminated by the bottleneck effect in their offspring. This is the first study using a small number of oocytes to examine mtDNA mutations in diabetic mothers and offspring. Electronic supplementary material The online version of this article (10.1186/s12958-018-0423-1) contains supplementary material, which is available to authorized users.

N6-methyladenosine (m6A) is the most prevalent and reversible internal modification of mammalian messenger and noncoding RNAs mediated by specific m6A writer, reader, and eraser proteins. As an m6A...

N6-methyladenosine (m6A) is the most prevalent and reversible internal modification of mammalian messenger and noncoding RNAs mediated by specific m6A writer, reader, and eraser proteins. As an m6A writer, the METTL3–METTL14-WTAP complex dynamically regulates m6A modification and plays important roles in diverse biological processes. However, our knowledge about the complete functions of this RNA methyltransferase complex, the contributions of each component to the methylation and their impacts on different biological pathways, are still very limited. Here, by employing both in vivo and in vitro models, we report that METTL14 was indispensable for post-implantation embryonic development by facilitating the conversion from naïve to primed state of the epiblast. Depletion of Mettl14 lead to conspicuous embryonic growth retardation from E6.5 mainly as a result of resistance to differentiation, which further lead to embryonic lethality early in gestation. Our data highlight the critical function of METTL14, as an m6A modification regulator, in orchestrating early mouse embryogenesis.

Thermal insulation and flame-retardant (TIFR) protective clothing, which has good thermal protective performance (TPP), could protect people from high-temperature or flame in casting industry, the petrochemical industry, fire industry and et al. That is, TIFR protective clothing must have certain function of slowing or restraining heat transmission, and insulating radiant heat and convection heat from high temperature heat source. The construction of TIFR protective clothing is being developed from single layer to multi-layer fabrics made by flame-retardant (FR) fibre. In this paper, based on TPP-206 tester, the TPP coefficient of single and multi-layer fabrics with flame-retardant were measured, and the TPP of TIFR protective clothing was analyzed. TPP coefficient of single fabrics included the FR viscose non-woven fabric do not meet the standard. That of all of multi-layer fabrics meet the standard requirement, and the FR viscose/wool blended fabric is not suitable for fire fighter. It is significant and the most observable effect to put the PTFE membrane between the outer layer and the insulating layer. It could improve the overall thermal protection performance.

Oil from rapeseed with high oleic oil content is insensitive to oxidation and long shelf life.In daily diet with high oleic acid oil can reduce low-density lipoprotein cholesterol levels in blood and prevent arteriosclerosis.In addition,high oleic acid content in edible oil is an important fat indicator.Oleic acid can be effectively converted to methyl ester,which is beneficial to produce biodiesel.Oleic acid content in conventional rapeseed is only 17%.However,oleic acid content in low erucic acid rapeseed reaches around 60%.Differential expressed genes of oleic acid have been found in the high oleic acid line(71.71%) and low oleic acid line(55.6%) of Brassica napus by gene chip technique.The results showed that there were 562 differential expressed genes relating to high and low oleic acid contents in rapeseed,among them 194 were up-regulated genes and 368 were down-regulated genes.The up-regulated gene NM_100489 and the down-regulated gene NM_130183 were then taken as the materials.Real time RT-PCR was further used to confirm the results of gene chip,and the results of real time RT-PCR analysis agreed with the results by gene chip.According to the results of gene chip,562 differentially expressed genes were annotated functionally using Go Annotation System.The molecular function of differential expressed genes mainly included catalysis of enzymes,binding,transcriptional regulation,metabolism and others with unknown functions.Some genes related to sugar metabolism and fatty acid synthesis were identified as differential expressed genes.They are pyruvate kinase,fructose diphosphate,acyl transfer/acyl-ACP S lipase,hydrolase acting on ester bond,Δ9 stearoyl acid-N-carrier protein desaturase(ADS1),Δ9 acyl-lipid desaturase 2(ADS2),ω-3 fatty acid desaturation enzymes(fad3) and so on.

Nursing students' and nurses' attitudes toward caring for the dying need to be explored. The Frommelt Attitude Toward Care of the Dying (FATCOD) scale has not previously been used in the Chinese language. The aim of this study was to examine the reliability and validity of the Chinese version of the FATCOD scale. A convenience sample of 154 nurses and 200 nursing students was recruited. The Chinese version of the FATCOD was used to test construct validity, concurrent validity, convergent validity, and internal consistency. The Cronbach's alpha coefficient of the Chinese version of the FATCOD scale, Form B (FATCOD-B-C) was 0.790. The Cronbach's alpha coefficients for each subscale ranged from 0.610 to 0.863. The test-retest reliability was satisfactory (r = 0.959, P < 0.001). The overall content validity index was 0.92. Seven factors were identified in exploratory factor analysis. The results provide preliminary support for the reliability and validity of the FATCOD-B-C in nurses and nursing students. Additional psychometric testing is recommended to confirm the factor analysis, but this study provides further evidence of the applicability of the FATCOD-B-C in clinical care services.

In 1997, the first monoclonal antibody (MoAb), the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug administration for use in cancer patients. Since then, the panel of MoAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has continued to expand, currently encompassing a stunning amount of 20 distinct molecules for 11 targets. We provide a brief scientific background on the use of MoAbs in cancer therapy, review all types of monoclonal antibodies-related adverse events (e.g., allergy, immune-related adverse events, cardiovascular adverse events, and pulmonary adverse events), and discuss the mechanism and treatment of adverse events.