Long-term survival outcomes of esophagectomy with off-pump CABG versus esophagectomy alone.

BACKGROUND: This study aimed to evaluate the long-term survival outcomes of esophagectomy with off-pump coronary artery bypass grafting (OPCABG) vs. esophagectomy alone. METHODS: A total of 1798 patients who received esophagectomy between January 2010 and February 2020 were included and divided into the 38 patients who underwent OPCABG followed by esophagectomy (OP + ES group) and 1760 patients had only esophagectomy (ES group). Propensity score matching (PSM) and Cox multivariable analyses were performed to compare postoperative complications, disease-free survival (DFS), and overall survival (OS) between the two groups. RESULTS: There were 37 patients in the OP + ES group matched with 74 in the ES group. The matched OP + ES group had higher total postoperative complications than the ES group, especially more pulmonary infections (P = 0.001) and arrhythmias (P = 0.018), but no other postoperative complications were the difference. The DFS was similar and the OS was a significant difference between the matching 2 groups (log-rank, P = 0.132 and 0.04, respectively). Although pT 3/4 stage, pN (+), and tumor length > 3.0 cm were independently associated with worse OS and DFS in multivariable analysis, CAD and EF < 55% were also found to be a predictive factor for OS and DFS in univariate analysis. CONCLUSION: OPCABG followed by esophagectomy for esophageal cancer associated with coronary artery disease has equivalent DFS and recurrence pattern to esophagectomy for esophageal cancer alone, but with a disadvantage in OS.

Multi-omics analysis on the mechanism of the effect of Isatis leaf on the growth performance of fattening sheep.

Introduction: This study evaluated the effects of Isatis Leaf (ISL) on the growth performance, gastrointestinal tissue morphology, rumen and intestinal microbiota, rumen, serum and urine metabolites, and rumen epithelial tissue transcriptome of fattening sheep. Methods: Twelve 3.5-month-old healthy fattening sheep were randomly divided into two groups, each with 6 replicates, and fed with basal diet (CON) and basal diet supplemented with 80 g/kg ISL for 2.5 months. Gastrointestinal tract was collected for histological analysis, rumen fluid and feces were subjected to metagenomic analysis, rumen fluid, serum, and urine for metabolomics analysis, and rumen epithelial tissue for transcriptomics analysis. Results: The results showed that in the ISL group, the average daily gain and average daily feed intake of fattening sheep were significantly lower than those of the CON group (P < 0.05), and the rumen ammonia nitrogen level was significantly higher than that of the CON group (P < 0.01). The thickness of the reticulum and abomasum muscle layer was significantly increased (P < 0.05). At the genus level, the addition of ISL modified the composition of rumen and fecal microorganisms, and the relative abundance of Methanobrevibacter and Centipeda was significantly upregulated in rumen microorganisms, The relative abundance of Butyrivibrio, Saccharofermentans, Mogibacterium, and Pirellula was significantly downregulated (P < 0.05). In fecal microorganisms, the relative abundance of Papillibacter, Pseudoflavonifractor, Butyricicoccus, Anaerovorax, and Methanocorpusculum was significantly upregulated, while the relative abundance of Roseburia, Coprococcus, Clostridium XVIII, Butyrivibrio, Parasutterella, Macellibacteroides, and Porphyromonas was significantly downregulated (P < 0.05). There were 164, 107, and 77 different metabolites in the rumen, serum, and urine between the ISL and CON groups (P < 0.05). The differential metabolic pathways mainly included thiamine metabolism, niacin and nicotinamide metabolism, vitamin B6 metabolism, taurine and taurine metabolism, beta-Alanine metabolism and riboflavin metabolism. These metabolic pathways were mainly involved in the regulation of energy metabolism and immune function in fattening sheep. Transcriptome sequencing showed that differentially expressed genes were mainly enriched in cellular physiological processes, development, and immune regulation. Conclusion: In summary, the addition of ISL to the diet had the effect of increasing rumen ammonia nitrogen levels, regulating gastrointestinal microbiota, promoting body fat metabolism, and enhancing immunity in fattening sheep.

Roles of Y-27632 on sheep sperm metabolism.

To investigate the effect of Y-27632 on low-temperature metabolism of sheep sperm, different concentrations of Y-27632 were added to sheep semen at 4 °C in this experiment to detect indicators such as sperm motility, plasma membrane, acrosome, antioxidant performance, mitochondrial membrane potential (MMP), and metabolomics. The results showed that the addition of 20 µM Y-27632 significantly increased sperm motility, plasma membrane integrity rate, acrosome integrity rate, antioxidant capacity, MMP level, significantly increased sperm adenosine triphosphate (ATP) and total cholesterol content, and significantly reduced sperm Ca2+ content. In metabolomics analysis, compared with the control group, the 20 µM Y-27632 group screened 20 differential metabolites, mainly involved in five metabolic pathways, with the most significant difference in Histidine metabolism (P = 0.001). The results confirmed that Y-27632 significantly improved the quality of sheep sperm preservation under low-temperature conditions.

Sheep semen preservation and artificial insemination is an important reproductive technology that supports the large-scale and intensive development of the sheep farming industry. Under low-temperature condition, sperm metabolic activity slows down or pauses, energy consumption decreases, thereby prolonging sperm preservation time and motility. During the process of sperm preservation, sperm are susceptible to cold shock damage, which affects the quality of sperm preservation. Y-27632 is a rho-associated cooled-coil kinase (ROCK) inhibitor that competes with ATP to inhibit the kinase activity of ROCK-I and ROCK-II. However, the study of Y-27632 used in sheep semen preservation and its protective mechanism is less. In this study, we used the ROCK inhibitor Y-27632 and the ROCK activator arachidonic acid (AA) for low-temperature preservation of sheep semen and related metabolic regulation mechanisms. This experiment confirmed that Y-27632 played a significant protective role by regulating sperm metabolism and protecting sperm plasma membrane in sheep.

Antioxidant activity and metabolic regulation of sodium salicylate on goat sperm at low temperature.

OBJECTIVE: The purpose of this study was to explore the effect of sodium salicylate (SS) on semen preservation and metabolic regulation in goats. METHODS: Under the condition of low temperature, SS was added to goat semen diluent to detect goat sperm motility, plasma membrane, acrosome, antioxidant capacity, mitochondrial membrane potential (MMP) and metabonomics. RESULTS: The results show that at the 8th day of low-temperature storage, the sperm motility of the 20 µM SS group was 66.64%, and the integrity rates of the plasma membrane and acrosome were both above 60%, significantly higher than those of the other groups. The activities of catalase and superoxide dismutase in the sperm of the 20 µM SS group were significantly higher than those of the control group, the contents of reactive oxygen species and malondialdehyde were significantly lower than those in the control group, the MMP was significantly higher than that in the control group, and the contents of Ca2+ and total cholesterol were significantly higher than those in the control group. Through metabonomics analysis, there were significant metabolic differences between the control group and the 20 µM SS group. Twenty of the most significant metabolic markers were screened, mainly involving five metabolic pathways, of which nicotinic acid and nicotinamide metabolic pathways were the most significant. CONCLUSION: The results indicate that SS can effectively improve the low-temperature preservation quality of goat sperm.

Multi-Omics Analysis of the Mechanism of Mentha Haplocalyx Briq on the Growth and Metabolic Regulation of Fattening Sheep.

Mentha haplocalyx Briq (MHB) and its components have been proven to improve the growth performance of livestock and poultry. The aim of this experiment was to investigate the effects of MHB addition on growth performance, rumen and fecal microbiota, rumen fluid, serum and urine metabolism, and transcriptomics of rumen epithelial cells in meat sheep. Twelve Hu sheep were selected for the experiment and fed with basic diet (CON) and a basal diet supplemented with 80 g/kg DM of Mentha haplocalyx Briq (MHB). The experimental period was 10 weeks with the first 2 weeks as the pre-trial period. The results showed that compared with the CON group, the average daily weight gain of meat sheep in the MHB group increased by 20.1%; the total volatile fatty acid (VFA) concentration significantly increased (p < 0.05); The thickness of the cecal mucosal layer was significantly reduced (p < 0.01), while the thickness of the colonic mucosal layer was significantly increased (p < 0.05), the length of ileal villi significantly increased (p < 0.01), the thickness of colonic mucosal layer and rectal mucosal muscle layer significantly increased (p < 0.05), and the thickness of cecal mucosal layer significantly decreased (p < 0.05); The serum antioxidant capacity has increased. At the genus level, the addition of MHB changed the composition of rumen and fecal microbiota, increased the relative abundance of Paraprevotella, Alloprevotella, Marinilabilia, Saccharibacteria_genera_incertae_sedis, Subdivision5_genera_incertae_sedis and Ornatilinea in rumen microbiota, and decreased the relative abundance of Blautia (p < 0.05). The relative abundance of Prevotella, Clostridium XlVb and Parasutterella increased in fecal microbiota, while the relative abundance of Blautia and Coprococcus decreased (p < 0.05). There were significant differences in the concentrations of 105, 163, and 54 metabolites in the rumen, serum, and urine between the MHB group and the CON group (p < 0.05). The main metabolic pathways of the differences were pyrimidine metabolism, taurine and taurine metabolism, glyceride metabolism, and pentose phosphate pathway (p < 0.05), which had a significant impact on protein synthesis and energy metabolism. The transcriptome sequencing results showed that differentially expressed genes were mainly enriched in immune regulation, energy metabolism, and protein modification. Therefore, adding MHB improved the growth performance of lambs by altering rumen and intestinal microbiota, rumen, serum and urine metabolomics, and transcriptome.

CRISPR-based m6A modification and its potential applications in telomerase regulation.

Telomerase determines cell lifespan by controlling chromosome stability and cell viability, m6A epigenetic modification plays an important role in the regulation of telomerase activity. Using CRISPR epigenome editing to analyze specific m6A modification sites in telomerase will provide an important tool for analyzing the molecular mechanism of m6A modification regulating telomerase activity. In this review, we clarified the relevant applications of CRISPR system, paid special attention to the regulation of m6A modification in stem cells and cancer cells based on CRISPR system, emphasized the regulation of m6A modification on telomerase activity, pointed out that m6A modification sites regulate telomerase activity, and discussed strategies based on telomerase activity and disease treatment, which are helpful to promote the research of anti-aging and tumor related diseases.

Metabolomics Analysis of Sodium Salicylate Improving the Preservation Quality of Ram Sperm.

The aim of this study was to investigate the effects of sodium salicylate (SS) on the preservation and metabolic regulation of sheep sperm. Under 4 °C low-temperature conditions, SS (at 10 µM, 20 µM, 30 µM, and 50 µM) was added to the semen diluent to detect sperm motility, plasma membrane, and acrosome integrity. Based on the selected optimal concentration of SS (20 µM), the effects of 20 µM of SS on sperms' antioxidant capacity and mitochondrial membrane potential (MMP) were evaluated, and metabolomics analysis was conducted. The results showed that on the 20th day of low-temperature storage, the sperm motility of the 20 µM SS group was 62.80%, and the activities of catalase (CAT) and superoxide dismutase (SOD) were significantly higher than those of the control group (p < 0.01). The content of Ca2+, reactive oxygen species (ROS), and malondialdehyde (MDA) were significantly lower than those of the control group (p < 0.01), and the total antioxidant capacity (T-AOC) was significantly higher than that of the control group (p < 0.05); mitochondrial activity and the total cholesterol (TC) content were significantly higher than those in the control group (p < 0.01). An ultrastructural examination showed that in the SS group, the sperm plasma membrane and acrosome were intact, the fibrous sheath and axoneme morphology of the outer dense fibers were normal, and the mitochondria were arranged neatly. In the control group, there was significant swelling of the sperm plasma membrane, rupture of the acrosome, and vacuolization of mitochondria. Using metabolomics analysis, 20 of the most significant differential metabolic markers were screened, mainly involving 6 metabolic pathways, with the amino acid biosynthesis pathway being the most abundant. In summary, 20 µM of SS significantly improved the preservation quality of sheep sperm under low-temperature conditions of 4 °C.

Numerical study on the wall-impinging diesel spray soot generation and oxidation in the cylinder under cold-start conditions of a diesel engine.

The combustion of wall-impinging diesel spray of heavy-duty diesel engines deteriorates combustion quality under cold-start conditions, making it difficult to control soot emissions. To investigate the causes of soot increase in the combustion of wall-impinging spray at low temperature and low speed starting conditions, the effect of the starting fuel mass on the soot formation and oxidation process was analyzed using a multidimensional computational fluid dynamics (CFD) model. The results show that the diesel spray is guided by the piston wall and the limited space, the spray impinged on the wall and the vapor-phase fuel flowed in the spray interaction zone. Thus, the soot mainly accumulates in the spray interaction zone, the region near the cylinder head and the bowl wall in the combustion chamber bowl. The soot from the vapor of deposited fuel film in the piston bowl wall and near wall region accumulates continuously in the after combustion stage, becoming the main source of soot emissions at the time of exhaust valve opening (EVO). Increasing the mass of starting fuel raises the mass of the rich mixture and wall-impinging fuel, which enhances the mismatch between fuel and air, resulting in higher soot generation, while soot is more difficult to be completely oxidized by OH radicals, and ultimately soot emissions increase significantly. It can be deduced that the engine-optimized injection strategy may mitigate the increase in soot emissions at high start-up fuel injection conditions.

Genetic Regulation of N6-Methyladenosine-RNA in Mammalian Gametogenesis and Embryonic Development.

Emerging evidence shows that m6A is the most abundant modification in eukaryotic RNA molecules. It has only recently been found that this epigenetic modification plays an important role in many physiological and pathological processes, such as cell fate commitment, immune response, obesity, tumorigenesis, and relevant for the present review, gametogenesis. Notably the RNA metabolism process mediated by m6A is controlled and regulated by a series of proteins termed writers, readers and erasers that are highly expressed in germ cells and somatic cells of gonads. Here, we review and discuss the expression and the functional emerging roles of m6A in gametogenesis and early embryogenesis of mammals. Besides updated references about such new topics, readers might find in the present work inspiration and clues to elucidate epigenetic molecular mechanisms of reproductive dysfunction and perspectives for future research.

DNA methyltransferase 3 beta regulates promoter methylation of microRNA-149 to augment esophageal squamous cell carcinoma development through the ring finger protein 2/Wnt/ß-catenin axis.

Esophageal squamous cell carcinoma (ESCC) is an aggressive form of human squamous cell carcinomas with extremely aggressive pathological features. This study explores the functions of microRNA-149 (miR-149) and its interacted molecules in ESCC. The ESCC-related miRNA and messenger RNA (mRNA) datasets were applied to identify aberrantly expressed genes in ESCC. Forty-two patients with ESCC were included and their tissue samples were collected. miR-149 was poorly expressed whereas DNA methyltransferase 3 beta (DNMT3B) and ring finger protein 2 (RNF2) were abundantly expressed in ESCC tumor samples. Overexpression of miR-149 suppressed growth and invasiveness of ESCC cells in vitro and in vivo. DNMT3B bound to the promoter region of miR-149 to trigger its promoter methylation and downregulation. RNF2 mRNA was a target of miR-149. RNF2 overexpression blocked the inhibitory effect of miR-149 on ESCC cell growth. RNF2 activated the Wnt/ß-catenin pathway to promote ESCC development. In conclusion, this study found that DNMT3B downregulates miR-149 level through methylation modification of the miR-149 promoter, while miR-149 suppresses RNF2 expression and inactivates the Wnt/ß-catenin pathway to suppress growth of ESCC cells.

Numerical Investigation of Negative Temperature Coefficient Effects on Sooting Characteristics in a Laminar Co-flow Diffusion Flame.

It is a common sense that diesel engines produce worse soot emission than gasoline engines, even though gasoline direct injection also brings about terrible sooting tendency. However, reports showed that diesel emits less soot than gasoline in laminar diffusion flames, which implies that soot emission is a combined effect of multiple factors, such as the combustion mode, physical properties of the fuel, and also fuel chemistry. This work, thus, conducted numerical calculations in laminar co-flow diffusion flames of fuels with different negative temperature coefficient (NTC) behaviors in an order of n-heptane > iso-octane > toluene to solely evaluate the chemical effect, especially the role of low-temperature combustion on soot formation. 2-Dimensional simulations were carried out to obtain the soot distributions, and 0-dimensional simulations were performed to analyze the chemical kinetics of polycyclic aromatic hydrocarbon (PAH) formation and low-temperature reaction sensitivities. The grids of the 2-D model converged at 80(r) × 196(z), and the boundary conditions of both models were set to eliminate the influence of physical factors as much as possible. The results showed that there were three main reactions associated to the formation of aromatic hydrocarbons A1 at the first-stage combustion in the n-heptane flame and the iso-octane flame, in which the reaction of C7H15 + O2 = C7H15O2 enhances the NTC behavior. The first two reaction pathways generated larger molecular hydrocarbons and were unfavorable by A1 formation and therefore inhabit the PAH formation, and 49.8% of C7H16 reacted through the large molecular pathways, while the percentage for C8H18, with weaker NTC behavior, was only 37%. Toluene with even weaker NTC behavior showed no low-temperature oxidation. Therefore, in a more general case, fuels with stronger NTC behavior smoke less, and this conclusion could be promising potential to reduce soot emission in future.