PO-020 Aerobic Exercise Attenuates Myocardial Injury Through Activation of SIRT1 Signaling in T2DM Rats

Objective Myocardial injury caused by elevated blood glucose is a major risk factor for type 2 diabetes mellitus (T2DM) cardiomyopathy. Aerobic exercise can significantly improve the energy metabolism and is widely used in clinic to prevent and cure T2DM and other metabolic diseases. Myocardial injury can be attenuated after aerobic exercise. Some researches showed SIRT1 is a histone deacetylation enzyme activated by NAD+/NADH, and mainly distributes in the heart, liver, etc. SIRT1 plays an important role in controlling the insulin secretion, which can regulate glucose and lipid metabolism and some other important biological functions. It is not known whether the myocardial injury was reduced by regulating the level of SIRT1 after aerobic exercise. The purpose of the research was to illustrate the regulatory mechanism of decreased myocardial injury after aerobic exercise, and provided theoretical basis for early prevention and treatment of T2DM myocardial injury.  Methods There were two stages in the experiment. At the first stage, 30 male SD rats,12-month old, were randomly divided into two groups, the control group (CC, fed with standard diet and kept sedentary, 8 rats), the high-sugar-lipid fodder for T2DM model Group (DC, kept sedentary, 22 rats). High sugar and high fat diet formula for 10% lard, 20% sucrose, egg yolk powder 8%, 0.1% sodium deoxycholate, 61.9% basic feed, AIN-93g, provided by animal experimental center of Hebei Province. After 5-week high-sugar-lipid fodder, the DC rats were injected streptozocin (STZ, 35mg/kg), the FBG of the tail vein were measured after 12h, and FBG≥7.0mmol/L was defined as T2DM model. Six rats were excluded because of low FBG (<7.0mmol/L). At the second stage, all of the rats were fed with standard diet. The T2DM rats were randomly assigned to the T2DM group (DC, kept sedentary, 8 rats)  and T2DM combined with aerobic exercise, (DE, run on treadmill at 15m/min～19m/min, 45min/d, slope 5%, 6d/w, 5W, 8 rats). The myocardial tissue sections were stained with hematoxylin and eosin (HE) to observe the histological changes. The level of serum insulin was examined by ELISA kits. The content of serum glucose, the activity of SOD and the content of MDA in heart were examined by reagent kits after 5 weeks. The expression of SIRT1 protein in heart were measured using Western blot. ELISA kits were used for the determination of the NAD+/NADH ratio.  Results (1) The myocardial sections of CC can be observed clear cell contour, bright color, arranged closely and neatly, and nuclear distribution in cells border and nuclei of uniform size. In DC myocardial sections, myocardial cell contour was fuzzy, nuclei were relatively large, reduced the number of nuclei and inward migration. The broken cells and part of the cells and nuclei overflow can also be seen. The shape of nucleus was irregular and shifted to the internal. In myocardial cell sections of DE rats, the cell profile was relatively clear, and arranged more orderly, a larger number of nuclei, generated less shift. (2) The plasma insulin of DE were obviously lower than that of DC (P<0.01). The content of serum glucose of DE was significantly decreased compared with that of DC (P<0.01). (3) The ratio of NAD+/NADH in DE heart was higher than that of DC (P<0.05). (4) The expression of SIRT1 in DE heart was higher than that of DC (P<0.05). (5)The activity of SOD in DE heart was increased while the content of MDA in DE was significantly decreased compared with those in DC (P<0.01).  Conclusions Aerobic exercise can effectively reduced the blood glucose level of T2DM rats. The NAD+/NADH ratio in the myocardium of T2DM rats were increased after the aerobic exercise. As a result, the content of SIRT1 protein in myocardial cells of T2DM rats were increased after the aerobic exercise, which resulted in the increased SOD activity and antioxidant capacity in the cardiac muscle cells, which lead to the attenuated myocardial injury in T2DM rats

Isotopic constraints on lightning as a source of fixed nitrogen in Earth's early biosphere

Bioavailable nitrogen is thought to be a requirement for the origin and sustenance of life. Before the onset of biological nitrogen fixation, abiotic pathways to fix atmospheric N2 must have been prominent to provide bioavailable nitrogen to Earth's earliest ecosystems. Lightning has been shown to produce fixed nitrogen as nitrite and nitrate in both modern atmospheres dominated by N2 and O2 and atmospheres dominated by N2 and CO2 analogous to the Archaean Earth. However, a better understanding of the isotopic fingerprints of lightning-generated fixed nitrogen is needed to assess the role of this process on the early Earth. Here, we present results from spark discharge experiments in N2-CO2 and N2-O2 gas mixtures. Our experiments suggest that lightning-driven nitrogen fixation may have been similarly efficient in the Archaean atmosphere, compared to modern times. Measurements of the isotopic ratio {\delta}15N of the discharge-produced nitrite and nitrate in solution show very low values of -6 to -15 permil after equilibration with the gas phase with a calculated endmember composition of -17 permil. These results are much lower than most {\delta}15N values documented from the sedimentary rock record, which supports the development of biological nitrogen fixation earlier than 3.2 Ga. However, some Paleoarchean records (3.7 Ga) may be consistent with lightning-derived nitrogen input, highlighting the potential role of this process for the earliest ecosystems.Comment: Accepted manuscript. Version of record published in Nature Geoscience. 29 pages (main text, methods, supplementary material), 5 figures + 4 supplementary figure

Associations between gut microbiota and adverse neurodevelopmental outcomes in preterm infants: a two-sample Mendelian randomization study

Gut microbiota are associated with adverse neurodevelopmental outcomes in preterm infants; however, the precise causal relationship remains unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to comprehensively study the relationship between gut microbiota and adverse neurodevelopmental outcomes in preterm infants and identify specific causal bacteria that may be associated with the occurrence and development of adverse neurodevelopmental outcomes in preterm infants. The genome-wide association analysis (GWAS) of the MiBioGen biogroup was used as the exposure data. The GWAS of six common adverse neurodevelopmental outcomes in premature infants from the FinnGen consortium R9 was used as the outcome data. Genetic variations, namely, single nucleotide polymorphisms (SNPs) below the locus-wide significance level (1 × 10−5) and genome-wide statistical significance threshold (5 × 10−8) were selected as instrumental variables (IVs). MR studies use inverse variance weighting (IVW) as the main method. To supplement this, we also applied three additional MR methods: MR-Egger, weighted median, and weighted mode. In addition, the Cochrane’s Q test, MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out methods were used for sensitivity analysis. Our study shows a causal relationship between specific gut microbiota and neurodevelopmental outcomes in preterm infants. These findings provide new insights into the mechanism by which gut microbiota may mediate adverse neurodevelopmental outcomes in preterm infants

“Seminal testosterone”, rising viewpoint of local spermatogenesis in nonobstructive azoospermia: One center long-term bidirectional cohort study

ObjectiveReproductive hormones are a traditional good method to evaluate spermatogenesis but might not accurately represent local spermatogenesis. To find a more accurate method, seminal reproductive hormones were studied.MethodsA bidirectional cohort study was performed. A total of 126 infertile men from 2018 to 2019 were retrospectively analyzed. They were divided into nonobstructive azoospermia (NOA), oligozoospermia (OLZ) and normal (NOR) groups. A prospective study was conducted on patients in the NOA and OLZ groups for 2 years. Microscopic testicular sperm extraction was performed for NOA patients, who were divided into a focal spermatogenesis group (FS) and an idiopathic azoospermia group (IA). Drug treatment was for OLZ patients, who were divided into a valid group (VA) and an invalid group (IN). The differences in sperm parameters and reproductive hormones were compared. ANOSIM analysis was used between and within groups. Pearson correlation analysis, CO inertia analysis and Proctor’s analysis were for relationships. ROC curve for the specificity and sensitivity. Time series analysis was for the trends between hormones and time.ResultsThe b-FSH, b-LH, s-T and ΔT in the NOA group were significantly higher than those in the OLZ and NOR groups. However, the s-FSH, s-E2, s-P, ΔFSH, ΔLH, ΔP and ΔE2 were lower. Thirty-one NOA patients underwent MTSE, of whom 12 had sperm (FS) and 19 had no sperm (IA). The s-FSH and s-E2 of the FS group were higher than those of the IA group. Twenty-six OLZ patients completed 30 days of treatment, of which 11 had an improved sperm count (VA) and 15 had no (IN). The ΔT of the VA group was higher than that of the IN group. After follow-up for 2 years, 18 patients’ results showed that b-FSH, b-LH and s-T were different over time, with delays of 19, 3 and -19 days. SC is closely related to pH, s-FSH, s-LH, s-E2, s-P, s-T, b-FSH, b-LH, ΔFSH, ΔLH, ΔP, ΔE2 and ΔT. There were complex common trends and relationships between different kinds of hormones. s-FSH, s-LH, s-E2, s-P, s-T, b-FSH and b-LH were useful to judge spermatogenesis, of which s-T, b-FSH and b-LH were more sensitive. If s-T, b-FSH and b-LH reached 64.4, 9.4 and 4.7, respectively, their prediction performance was the strongest.ConclusionSeminal testosterone is sensitive for judging local spermatogenesis in nonobstructive azoospermia patients, which may be the direction of local spermatogenesis in nonobstructive azoospermia.Clinical trial registrationhttp://www.chictr.org.cn/index.aspx, identifier ChiCTR2200060463

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression1,2, is known for its association with fasting glucose levels3,4. The evidence of an association with T2D for PEPD5 and HNF4A6,7 has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D

The complete chloroplast genome sequence of medicinal plant: Cynanchum thesioides (Asclepiadaceae)

Cynanchum thesioides is a medicinal plant. The complete chloroplast genome sequence of is 158,547 bp in length, contains 131 complete genes, including 85 protein-coding genes (85 PCGs), 8 ribosomal RNA genes (8 rRNAs), and 37 tRNA genes (37 tRNAs). The overall AT content of cp DNA is 62.1%, the corresponding values of the LSC, SSC, and IR regions are 63.7, 67.7, and 56.5%. Phylogenetic tree shows that C. thesioides was identified as the most divergent among the sequenced species of Cynanchum used

Isobaric vapor–liquid equilibrium for binary system of aniline + methyl-N-phenyl carbamate

In this study, the quasi-static ebulliometric method was used to measure both of the vapor pressures of methyl N -phenyl carbamate (MPC), and the isobaric vapor–liquid equilibrium (VLE) data of the aniline and MPC binary system. The measured vapor pressure data of MPC, at different temperature ranging from 369.60 to 389.54 K, fitted well with the Antoine equation. The VLE data for the aniline and MPC system at (2.00, 4.00, 6.00, 7.00 and 8.00) kPa were correlated by both of nonrandom two-liquid (NRTL) and Wilson models. The parameters of the two models were obtained by regressing the experimental data, with the absolute temperature deviations of 0.54 K and 0.53 K, respectively. The relative volatility of the binary system calculated was all far more than 1, which gives the conclusion that the high purity MPC can be separated from aniline and MPC binary system by rectification or distillation technology

Isobaric vapor-liquid equilibrium for binary system of aniline plus methyl-N-phenyl carbamate

In this study, the quasi-static ebulliometric method was used to measure both of the vapor pressures of methyl N-phenyl carbamate (MPC), and the isobaric vapor-liquid equilibrium (VLE) data of the aniline and MPC binary system. The measured vapor pressure data of MPC, at different temperature ranging from 369.60 to 389.54 K, fitted well with the Antoine equation. The VLE data for the aniline and MPC system at (2.00, 4.00, 6.00, 7.00 and 8.00) kPa were correlated by both of nonrandom two-liquid (NRTL) and Wilson models. The parameters of the two models were obtained by regressing the experimental data, with the absolute temperature deviations of 0.54 K and 0.53 K, respectively. The relative volatility of the binary system calculated was all far more than 1, which gives the conclusion that the high purity MPC can be separated from aniline and MPC binary system by rectification or distillation technology. (C) 2016 The Chemical Industry and Engineering Society of China, and Chemical Industry Press. All rights reserved.</p

Joint radar communication system design based on filter bank multicarrier modulation scheme

Abstract Since orthogonal frequency division multiplexing (OFDM) signals are sensitive to Doppler shift, OFDM signals with cyclic prefix (CP) not only reduce the communication rate but also result in symmetric pseudo peaks in the ambiguity function of the radar, which eventually lead to the degradation of the performance of the joint radar communication system (JRCS). In this study, a novel JRCS is proposed based on the filter bank multicarrier (FBMC) waveform for the inverse synthetic aperture radar (ISAR) imaging and communication system. On the one hand, FBMC waveforms are capable of low orthogonality between subcarriers, which can counter Doppler and multipath effects. On the other hand, FBMC waveforms do not require CP, so the false targets can be avoided and spectral efficiency can be improved. The influence of multipath effect and Doppler shift on FBMC waveform in an integrated system is analysed in detail, and a Doppler compensation algorithm suitable for FBMC‐integrated waveform is proposed. The phase error caused by target motion can be iteratively compensated to obtain a well‐focussed ISAR image. Finally, considering the ISAR image entropy after motion compensation as the evaluation metric, extensive simulation experiments verify the noise robustness and effectiveness of the proposed algorithm. Compared with the conventional OFDM and CP‐OFDM schemes, the simulation verifies that the proposed waveform design and processing method has better performance in the ISAR imaging and communication integrated system

The characteristics and nomogram for primary lung papillary adenocarcinoma

Primary pulmonary papillary adenocarcinoma (PA) is a specific and rare subtype of invasive pulmonary adenocarcinoma (ADC). The knowledge concerning the clinicopathologic features and prognosis of patients with primary pulmonary PA has not been clarified because of its rarity