Antibiotics are widely used in mariculture industry, and this study attempts to determine the extent of water and sediment pollution by antibiotic residues in 13 major mariculture sites in China. ...Through chemical and molecular biology analysis, the results showed that the total concentrations of sulfonamides and tetracyclines were in the range 62.0–373.8ngL−1 and 0.2–259.1ngL−1 respectively in water samples, and in the range 0.19–1.59ngg−1 dry weight and 3.45–74.84ngg−1 dry weight respectively, in sediments samples. The occurrence of antibiotic resistance genes (ARGs) was detected in all sites. Compared with the tetracyclines resistance genes, the absolute copy number and relative abundance of the sulfonamides resistance genes were 4.3 times and 2.3 times higher in water and sediment from the mariculture sites, with the dominant resistance genes being sul2. The abundance of sul3 in the water phase was significantly correlated with the concentrations of sulfamerazine, while the abundance of sul2 in the sediment phase was significantly with sulfadiazine concentrations. The abundance of tetM in the sediment phase was significantly correlated with the concentrations of oxytetracycline. The findings demonstrate the persistence of antibiotic residues and ARGs in major mariculture sites in Southeast China.
Total concentrations of the target antibiotics in water and sediments from mariculture sites in SE China. Display omitted
•11 antibiotics were detected in water and sediments from mariculture sites in China.•Water samples were dominated by sulfadiazine.•Sediment samples were dominated by doxycyclinehyclate.•Antibiotic resistance genes were dominated by sul2 in both water and sediments.•Linear relationships between log Koc and log Kow, and between log Koc and log MW.
Summary
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major economically significant pathogen that has adversely affected China's swine industry. Currently, a novel type 2 PRRSV, ...called the NADC30‐like strain, is epidemic in numerous provinces of China, and commercial vaccines provide limited protection for infected animals. The extensive recombination phenomenon among NADC30‐like PRRSVs is identified as a unique molecular characteristic of the virus. However, our understanding of how recombination influences NADC30‐like PRRSVs is largely inadequate. In this study, we analysed the genetic characteristics of a recombinant NADC30‐like PRRSV (SC‐d) and examined its pathogenicity compared with a non‐recombinant NADC30‐like PRRSV (SD‐A19) and a highly pathogenic PRRSV (HuN4). SC‐d has three discontinuous deletions in nsp2, consistent with NADC30 isolated from the United States in 2008. Furthermore, we identified four recombination breakpoints in the SC‐d genome, which separated the SC‐d genome into four regions (regions A, B, C and D). Regions A and C are closely related to the JXA1‐like strain, one of the earliest Chinese HP‐PRRSV strains, and regions B and D are closely related to the NADC30 strain. Moreover, SC‐d inoculated piglets exhibited a persistent fever, moderate weight loss, mild thymus atrophy and obvious microscopic lung lesions. In summary, the recombinant NADC30‐like PRRSV SC‐d strain displayed a higher pathogenicity than the non‐recombinant NADC30‐like PRRSV SD‐A19 strain; however, the pathogenicity of the NADC30‐like PRRSV SC‐d was lower compared with the HP‐PRRSV HuN4 strain in piglets. Our findings demonstrate that recombination is responsible for the enormous genetic diversity and pathogenicity variance of the NADC30‐like PRRSV in China. This study provides a theoretical basis for developing a more reasonable PRRSV control and prevention strategy.
Superconductivity arises from two distinct quantum phenomena: electron pairing and long-range phase coherence. In conventional superconductors, the two quantum phenomena generally take place ...simultaneously, while in the underdoped high- Tc cuprate superconductors, the electron pairing occurs at higher temperature than the long-range phase coherence. Recently, whether electron pairing is also prior to long-range phase coherence in single-layer FeSe film on SrTiO3 substrate is under debate. Here, by measuring Knight shift and nuclear spin-lattice relaxation rate, we unambiguously reveal a pseudogap behavior below Tp∼60 K in two kinds of layered FeSe-based superconductors with quasi2D nature. In the pseudogap regime, a weak diamagnetic signal and a remarkable Nernst effect are also observed, which indicates that the observed pseudogap behavior is related to superconducting fluctuations. These works confirm that strong phase fluctuation is an important character in the 2D iron-based superconductors as widely observed in high-Tc cuprate superconductors.
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Summary
ADAMTS‐13, a plasma reprolysin‐like metalloprotease, cleaves von Willebrand factor (VWF). Severe deficiency of plasma ADAMTS‐13 activity results in thrombotic thrombocytopenic purpura (TTP), ...while mild to moderate deficiencies of plasma ADAMTS‐13 activity are emerging risk factors for developing myocardial and cerebral infarction, pre‐eclampsia, and malignant malaria. Moreover, Adamts13−/− mice develop more severe inflammatory responses, leading to increased ischemia/perfusion injury and formation of atherosclerosis. Structure–function studies demonstrate that the N‐terminal portion of ADAMTS‐13 (MDTCS) is necessary and sufficient for proteolytic cleavage of VWF under various conditions and attenuation of arterial/venous thrombosis after oxidative injury. The more distal portion of ADAMTS‐13 (TSP1 2–8 repeats and CUB domains) may function as a disulfide bond reductase to prevent an elongation of ultra‐large VWF strings on activated endothelial cells and inhibit platelet adhesion/aggregation on collagen surface under flow. Remarkably, the proteolytic cleavage of VWF by ADAMTS‐13 is accelerated by FVIII and platelets under fluid shear stress. A disruption of the interactions between FVIII (or platelet glycoprotein 1bα) and VWF dramatically impairs ADAMTS‐13‐dependent proteolysis of VWF in vitro and in vivo. These results suggest that FVIII and platelets may be physiological cofactors regulating VWF proteolysis. Finally, the structure–function and autoantibody mapping studies allow us to identify an ADAMTS‐13 variant with increased specific activity but reduced inhibition by autoantibodies in patients with acquired TTP. Together, these findings provide novel insight into the mechanism of VWF proteolysis and tools for the therapy of acquired TTP and perhaps other arterial thrombotic disorders.
Aim
Gastroparesis is a common non‐motor system symptom of Parkinson's disease (PD). However, the mechanism responsible for the gastric motor abnormality is not clear. We previously reported on the ...impaired gastric motility in 6‐hydroxydopamine (6‐OHDA) rats, which were treated with a bilateral microinjection of 6‐OHDA in the substantia nigra (SN). We hypothesize that the enhanced dopamine system and reduced acetylcholine (Ach) in gastric tissues might contribute to the delayed gastric emptying observed in PD.
Methods
A strain gauge force transducer, digital X‐ray imaging system, Western blot, immunofluorescence and Radio Immunoassay were used in this study.
Results
Dopaminergic neurones in the SN were greatly reduced following the bilateral microinjection of 6‐OHDA. 6‐OHDA rats exhibited impaired gastric motility and delayed gastric emptying, accompanied by increased dopamine content and the overexpression of D2 receptors in the stomach. The administration of the D2 receptor antagonist domperidone relieved gastric dysmotility in 6‐OHDA rats, but the D1 receptor antagonist SCH23390 failed to do so. Subdiaphragmatic vagotomy prevented the increase in the gastric dopamine content and D2 receptor expression and improved gastric dysmotility in 6‐OHDA rats.
Conclusion
Dopaminergic deficiency in the SN results in impaired gastric motility, possibly as a result of the enhanced activity of dopamine system and reduced Ach in gastric tissue. The vagus nerve plays an important role in peripheral gastric motility disorder.
Mutual fund managers may decide to deviate from a well-diversified portfolio and concentrate their holdings in industries where they have informational advantages. In this paper, we study the ...relation between the industry concentration and the performance of actively managed U.S. mutual funds from 1984 to 1999. Our results indicate that, on average, more concentrated funds perform better after controlling for risk and style differences using various performance measures. This finding suggests that investment ability is more evident among managers who hold portfolios concentrated in a few industries.
Tumor-derived DNA can be found in the plasma of cancer patients. In this study, we explored the use of shotgun massively parallel sequencing (MPS) of plasma DNA from cancer patients to scan a cancer ...genome noninvasively.
Four hepatocellular carcinoma patients and a patient with synchronous breast and ovarian cancers were recruited. DNA was extracted from the tumor tissues, and the preoperative and postoperative plasma samples of these patients were analyzed with shotgun MPS.
We achieved the genomewide profiling of copy number aberrations and point mutations in the plasma of the cancer patients. By detecting and quantifying the genomewide aggregated allelic loss and point mutations, we determined the fractional concentrations of tumor-derived DNA in plasma and correlated these values with tumor size and surgical treatment. We also demonstrated the potential utility of this approach for the analysis of complex oncologic scenarios by studying the patient with 2 synchronous cancers. Through the use of multiregional sequencing of tumoral tissues and shotgun sequencing of plasma DNA, we have shown that plasma DNA sequencing is a valuable approach for studying tumoral heterogeneity.
Shotgun DNA sequencing of plasma is a potentially powerful tool for cancer detection, monitoring, and research.
Bone defect repair is challenging in orthopaedic clinics. For treatment of large bone defects, bone grafting remains the method of choice for the majority of surgeons, as it fills spaces and provides ...support to enhance biological bone repair. As therapeutic agents are desirable for enhancing bone healing, this study was designed to develop such a bioactive composite scaffold (PLGA/TCP/ICT) made of polylactide-co-glycolide (PLGA) and tricalcium phosphate (TCP) as a basic carrier, incorporating a phytomolecule icaritin (ICT), i.e., a novel osteogenic exogenous growth factor. PLGA/TCP/ICT scaffolds were fabricated as PLGA/TCP (control group) and PLGA/TCP in tandem with low/mid/high-dose ICT (LICT/MICT/HICT groups, respectively). To evaluate the in vivo osteogenic and angiogenic potentials of these bioactive scaffolds with slow release of osteogenic ICT, the authors established a 12mm ulnar bone defect model in rabbits. X-ray and high-resolution peripheral quantitative computed tomography results at weeks 2, 4 and 8 post-surgery showed more newly formed bone within bone defects implanted with PLGA/TCP/ICT scaffolds, especially PLGA/TCP/MICT scaffold. Histological results at weeks 4 and 8 also demonstrated more newly mineralized bone in PLGA/TCP/ICT groups, especially in the PLGA/TCP/MICT group, with correspondingly more new vessel ingrowth. These findings may form a good foundation for potential clinical validation of this innovative bioactive scaffold incorporated with the proper amount of osteopromotive phytomolecule ICT as a ready product for clinical applications.
Postmenopausal osteoporosis (PMO) is a risk factor for periodontitis, and current therapeutics against PMO prevent the aggravated alveolar bone loss of periodontitis in estrogen-deficient women. Gut ...microbiota is recognized as a promising therapeutic target for PMO. Berberine extracted from Chinese medicinal plants has shown its effectiveness in the treatment of metabolic diseases such as obesity and diabetes via regulating gut microbiota. Here, we hypothesize that berberine ameliorates periodontal bone loss by improving the intestinal barriers by regulating gut microbiota under an estrogen-deficient condition. Experimental periodontitis was established in ovariectomized (OVX) rats, and the OVX-periodontitis rats were treated with berberine for 7 wk before sacrifice for analyses. Micro–computed tomography and histologic analyses showed that berberine treatment significantly reduced alveolar bone loss and improved bone metabolism of OVX-periodontitis rats as compared with the vehicle-treated OVX-periodontitis rats. In parallel, berberine-treated OVX-periodontitis rats harbored a higher abundance of butyrate-producing gut microbiota with elevated butyrate generation, as demonstrated by 16S rRNA sequencing and high-performance liquid chromatography analysis. Berberine-treated OVX-periodontitis rats consistently showed improved intestinal barrier integrity and decreased intestinal paracellular permeability with a lower level of serum endotoxin. In parallel, IL-17A-related immune responses were attenuated in berberine-treated OVX-periodontitis rats with a lower serum level of proinflammatory cytokines and reduced IL-17A+ cells in alveolar bone as compared with vehicle-treated OVX-periodontitis rats. Our data indicate that gut microbiota is a potential target for the treatment of estrogen deficiency–aggravated periodontal bone loss, and berberine represents a promising adjuvant therapeutic by modulating gut microbiota.
Background
Dopamine (DA) is a negative modulator of gut motility. Monoamine oxidase‐B (MAO‐B) is an important metabolic enzyme degrading DA. Rasagiline, an irreversible MAO‐B inhibitor, is used to ...treat Parkinson’s disease because of its neuroprotective effect and increasing central DA. However, it is unclear whether MAO‐B exists in the colon and rasagiline increases colonic DA, thereby affecting colonic motility.
Methods
Immunohistochemistry, western blotting, enzyme activity assay, colonic motility recording, gut transit test, and high‐performance liquid chromatography‐electrochemical detection were employed in this study.
Key Results
Monoamine oxidase‐B was distributed in the colonic muscular layers including neurons and glias of rat and human. When oral treatment of rats with rasagiline for 4 weeks, in vitro colonic motility was significantly reduced, but it was greatly reversed by SCH‐23390, an antagonist of DA D1 receptor. The rasagiline‐treated rats also manifested decreased MAO‐B activity and increased DA content in the colonic muscular layer, but no alterations were detected in the protein expressions of D1 and D2 receptors, and MAO‐A and MAO‐B, as well as in the content of 5‐hydroxytryptamine and noradrenaline. Moreover, acute administration of rasagiline did not affect the colonic motility in vitro and the colonic DA level in rats, although MAO‐B activity was significantly inhibited.
Conclusions & Inferences
Monoamine oxidase‐B is abundant in the colonic muscular layer including myenteric plexus of rat and human. Long‐term administration of rasagiline can increase colonic DA thereby inhibiting colonic motility, suggesting that colonic MAO‐B could be a potential drug target for colonic dysmotility.
Monoamine oxidase‐B was distributed in the colonic muscular layers including neurons and glias of rat and human. Long‐term treatment of rasagiline significantly inhibited colonic monoamine oxidase‐B activity and increased the dopamine content, which may contribute to colonic hypomotility.
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