Seaweed polysaccharide relieves hexavalent chromium-induced gut microbial homeostasis

Heavy metals released in the environment pose a huge threat to soil and water quality, food safety and public health. Additionally, humans and other mammals may also be directly exposed to heavy metals or exposed to heavy metals through the food chain, which seriously threatens the health of animals and humans. Chromium, especially hexavalent chromium [Cr (VI)], as a common heavy metal, has been shown to cause serious environmental pollution as well as intestinal damage. Thus, increasing research is devoted to finding drugs to mitigate the negative health effects of hexavalent chromium exposure. Seaweed polysaccharides have been demonstrated to have many pharmacological effects, but whether it can alleviate gut microbial dysbiosis caused by hexavalent chromium exposure has not been well characterized. Here, we hypothesized that seaweed polysaccharides could alleviate hexavalent chromium exposure-induced poor health in mice. Mice in Cr and seaweed polysaccharide treatment group was compulsively receive K2Cr2O7. At the end of the experiment, all mice were euthanized, and colon contents were collected for DNA sequencing analysis. Results showed that seaweed polysaccharide administration can restore the gut microbial dysbiosis and the reduction of gut microbial diversity caused by hexavalent chromium exposure in mice. Hexavalent chromium exposure also caused significant changes in the gut microbial composition of mice, including an increase in some pathogenic bacteria and a decrease in beneficial bacteria. However, seaweed polysaccharides administration could ameliorate the composition of gut microbiota. In conclusion, this study showed that seaweed polysaccharides can restore the negative effects of hexavalent chromium exposure in mice, including gut microbial dysbiosis. Meanwhile, this research also lays the foundation for the application of seaweed polysaccharides

Co‐evolutionary adaptations of Acinetobacter baumannii and a clinical carbapenemase‐encoding plasmid during carbapenem exposure

Abstract: OXA‐23 is the predominant carbapenemase in carbapenem‐resistant Acinetobacter baumannii. The co‐evolutionary dynamics of A. baumannii and OXA‐23‐encoding plasmids are poorly understood. Here, we transformed A. baumannii ATCC 17978 with pAZJ221, a blaOXA−23‐containing plasmid from clinical A. baumannii isolate A221, and subjected the transformant to experimental evolution in the presence of a sub‐inhibitory concentration of imipenem for nearly 400 generations. We used population sequencing to track genetic changes at six time points and evaluated phenotypic changes. Increased fitness of evolving populations, temporary duplication of blaOXA−23 in pAZJ221, interfering allele dynamics, and chromosomal locus‐level parallelism were observed. To characterize genotype‐to‐phenotype associations, we focused on six mutations in parallel targets predicted to affect small RNAs and a cyclic dimeric (3′ → 5′) GMP‐metabolizing protein. Six isogenic mutants with or without pAZJ221 were engineered to test for the effects of these mutations on fitness costs and plasmid kinetics, and the evolved plasmid containing two copies of blaOXA−23 was transferred to ancestral ATCC 17978. Five of the six mutations contributed to improved fitness in the presence of pAZJ221 under imipenem pressure, and all but one of them impaired plasmid conjugation ability. The duplication of blaOXA−23 increased host fitness under carbapenem pressure but imposed a burden on the host in antibiotic‐free media relative to the ancestral pAZJ221. Overall, our study provides a framework for the co‐evolution of A. baumannii and a clinical blaOXA−23‐containing plasmid in the presence of imipenem, involving early blaOXA−23 duplication followed by chromosomal adaptations that improved the fitness of plasmid‐carrying cells

Study of the LQRY-SMC Control Method for the Longitudinal Motion of Fully Submerged Hydrofoil Crafts

The control system is one of the important components of the hydrofoil craft. By adjusting the navigation attitude of the craft, the hydrofoil craft can navigate stably and safely in the turbulent environment. Aiming at the problem that existing control algorithms have poor stability in the longitudinal motion control of hydrofoil craft, the longitudinal motion reduction is limited, and there are excessive requirements for accurate disturbance wave data. Based on the fully submerged hydrofoil craft model, this article proposes a joint control method LQRY-SMC combining linear-quadratic optimal control with output regulation (LQRY) and sliding-mode control (SMC), and adds genetic algorithm to optimize the weighting matrix parameters, get better control-feedback gain, improve the global optimal-control stability, thus improving the comfort of the crew, and prevent the attack of the hull, deck wetness and damage to instruments. The simulation results show that compared with the existing methods, the heave displacement and pitch angle obtained by LQRY-SMC under the turbulent flow of different significant wave heights are reduced by about 50%, and the influence of longitudinal motion on hydrofoil crafts is avoided to a large extent, which proves the effectiveness and superiority of the method proposed

Study of the LQRY-SMC Control Method for the Longitudinal Motion of Fully Submerged Hydrofoil Crafts

The control system is one of the important components of the hydrofoil craft. By adjusting the navigation attitude of the craft, the hydrofoil craft can navigate stably and safely in the turbulent environment. Aiming at the problem that existing control algorithms have poor stability in the longitudinal motion control of hydrofoil craft, the longitudinal motion reduction is limited, and there are excessive requirements for accurate disturbance wave data. Based on the fully submerged hydrofoil craft model, this article proposes a joint control method LQRY-SMC combining linear-quadratic optimal control with output regulation (LQRY) and sliding-mode control (SMC), and adds genetic algorithm to optimize the weighting matrix parameters, get better control-feedback gain, improve the global optimal-control stability, thus improving the comfort of the crew, and prevent the attack of the hull, deck wetness and damage to instruments. The simulation results show that compared with the existing methods, the heave displacement and pitch angle obtained by LQRY-SMC under the turbulent flow of different significant wave heights are reduced by about 50%, and the influence of longitudinal motion on hydrofoil crafts is avoided to a large extent, which proves the effectiveness and superiority of the method proposed

Stratified analysis of clinical pregnancy outcomes of sequential embryo transfer in frozen embryo transfer cycles based on different factors: a retrospective study

Abstract Objective To explore the effect of sequential embryo transfer (ET) on the pregnancy outcome of frozen-thawed embryo transfer (FET) cycle and the indications of sequential transfer. Methods A total of 1440 FET cycles were enrolled in this retrospective study, of which 1080 patients received conventional ET and 360 patients received sequential ET. Further stratified analysis was performed according to the number of previous failed cycles, the number of embryos transferred and the stage of blastocyst (day 5 or 6, denoted D5 or D6) transferred. Comparison of pregnancy rates, implantation rate, miscarriage rate and multiple pregnancy rate among the groups of patients. Results The clinical pregnancy rate and implantation rate of the sequential ET group were higher than those of the conventional ET group (P  0.05). In sequential transfer, the number of transferred embryos (2 or 3) and the stage of transferred blastocysts (D5 or D6) had no effect on clinical pregnancy rate, implantation rate, multiple pregnancy rate and miscarriage rate (P > 0.05). In patients with three or more previous failure cycles, the sequential ET group showed higher clinical pregnancy rate and implantation rate (P > 0.05). Conclusions Compared with conventional ET in FET cycle, sequential ET strategy could significantly improve the clinical pregnancy rate and implantation rate. In sequential transfer, patients with three embryos transferred don’t have higher pregnancy rate and implantation rate. Besides, sequential transfer is more suitable for patients with repeated implantation failures (RIF), and increase the utilization rate of D6 blastocysts

Experimental study on the mechanical properties of cement-based grouting materials after exposed to high temperatures

This paper experimentally investigates the compressive and flexural strengths of cement-based grouting materials used in grouted sleeve connections at both room temperature and after exposure to high temperatures. The tests were conducted at three different temperatures (200°C, 400°C, and 600°C) using two cooling methods (natural-cooled and water-cooled), and various durations of constant temperature and dwell times after high-temperature exposure were considered. The mechanical properties of the grout after high temperature were comparatively analyzed, and the changes in the microstructure were observed and analyzed using a scanning electron microscope. The experimental results demonstrate a linear decrease in the dynamic elastic modulus as the temperature rises. Moreover, the sample tested at 200°C exhibits an upward trend in its mechanical properties due to the development of stable phases of calcium silicate hydrate (C-S-H) and the additional effects of secondary hydration. However, beyond 400°C, a substantial decomposition of C-S-H occurs, leading to severe internal structural damage and a sharp decline in mechanical performance.Furthermore, the cooling method employed also influences the mechanical properties of the grouting material after exposure to high temperatures. The sample cooled by water displays a slight increase (up to 10%) in the dynamic elastic modulus, attributed to the secondary hydration of surface hydration products, compared to the naturally cooled sample. Nevertheless, the water-cooled sample experiences an uneven temperature distribution caused by the temperature disparity between its interior and exterior, exacerbating internal damage. As a result, their flexural strength and compressive strength exhibited varying degrees of decline, up to 43.9% and 27.9%, respectively, compared to natural-cooled specimens. Microscopic observations revealed that exposure to high temperature induced significant physical and chemical changes in the cement-based grouting materials, which were closely correlated with their macro mechanical properties. Based on the experimental study, a calculation formula for the discount coefficient of flexural and compressive strengths of the cement-based grouting materials after exposure to high temperatures was established through data analysis. The computational results demonstrated good agreement with the experimental findings. Finally this study provides reliable and valuable test data for investigating the bonding properties between reinforcement and grouting materials in grouted sleeve connections

A Validated HPLC-MS/MS Assay for 14-<i>O</i>-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] Mutilin in Biological Samples and Its Pharmacokinetic, Distribution and Excretion via Urine and Feces in Rats

14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] mutilin (DPTM), a novel pleuromutilin candidate with a substituted pyrimidine moiety, has been confirmed to possess excellent antibacterial activity against Gram-positive bacteria. To illustrate the pharmacokinetic profile after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations with DPTM, as well as tissue distribution and excretion via urine and feces in vivo, a specific, sensitive and robust HPLC-MS/MS method was first developed to determine DPTM in rat plasma, various tissues, urine and feces. The plasma, tissues, urine and feces samples were treated by protein precipitation with acetonitrile using tiamulin fumarate as an internal standard (IS). This method which was achieved on an HPLC system detector equipped with an ESI interface, was sensitive with 5 ng/mL as the lower limit of detection and exhibited good linearity (R2 &gt; 0.9900) in the range of 5&#8315;4000 ng/mL for plasma, various tissues, urine and feces, as well as intra-day precision, inter-day precision and accuracy. The matrix effects ranged from 94.2 to 109.7% with RSD &#8804; 9.4% and the mean extraction recoveries ranged from 95.4 to 109.5% in plasma, tissue homogenates, urine and feces (RSD &#8804; 9.9). After i.v., i.m. and p.o. administrations, DPTM was rapidly absorbed and metabolized in rats with the half-life (t1/2) of 1.70&#8315;1.86, 3.23&#8315;3.49 and 4.38&#8315;4.70 for 10, 25 and 75 mg/kg doses, respectively. The tissue distribution showed that DPTM was diffused into all the tested tissues, especially into the intestine and lung. Excretion via urine and feces studies demonstrated that DPTM was mainly excreted by feces after administration

Synthesis and Biological Activity Evaluation of Novel Heterocyclic Pleuromutilin Derivatives

A series of pleuromutilin derivatives were synthesized by two synthetic procedures under mild reaction conditions and characterized by Nuclear Magnetic Resonance (NMR), Infrared Spectroscopy (IR), and High Resolution Mass Spectrometer (HRMS). Most of the derivatives with heterocyclic groups at the C-14 side of pleuromutilin exhibited excellent in vitro antibacterial activities against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and vancomycin-resistant Enterococcus (VRE) in vitro antibacterial activity. The synthesized derivatives which contained pyrimidine rings, 3a, 3b, and 3f, displayed modest antibacterial activities. Compound 3a, the most active antibacterial agent, displayed rapid bactericidal activity and affected bacterial growth in the same manner as that of tiamulin fumarate. Moreover, molecular docking studies of 3a and lefamulin provided similar information about the interactions between the compounds and 50S ribosomal subunit. The results of the study show that pyrimidine rings should be considered in the drug design of pleuromutilin derivatives

In Vitro and In Vivo Activity of 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] Mutilin against Methicillin-Resistant Staphylococcus aureus

Staphylococcus aureus (S. aureus) is a major human pathogen that requires new antibiotics with unique mechanism. A new pleuromutilin derivative, 14-O-[(4,6-Diamino-pyrimidine-2-yl) thioacetyl] mutilin (DPTM), has been synthesized and proved as a potent antibacterial agent using in vitro and in vivo assays. In the present study, DPTM was further in vitro evaluated against methicillin-resistant Staphylococcus aureus (MRSA) isolated from dairy farms and outperformed tiamulin fumarate, a pleuromutilin drug used for veterinary. Moreover, a murine skin wound model caused by MRSA infection was established, and the healing effect of DPTM was investigated. The results showed that DPTM could promote the healing of MRSA skin infection, reduce the bacterial burden of infected skin MRSA and decrease the secretion of IL-6 and TNF-α inflammatory cytokines in plasma. These results provided the basis for further in-depth drug targeted studies of DPTM as a novel antibacterial agent