Impact of coronary artery disease on clinical outcomes after TAVR: Insights from the BRAVO-3 randomized trial.

OBJECTIVE: To determine the prognostic impact of coronary artery disease (CAD) in patients randomized to bivalirudin or unfractionated heparin (UFH) during transcatheter aortic valve replacement (TAVR). BACKGROUND: CAD is a common comorbidity among patients undergoing TAVR and studies provide conflicting data on its prognostic impact. METHODS: The Bivalirudin on Aortic Valve Intervention Outcomes-3 (BRAVO-3) randomized trial compared the use of bivalirudin versus UFH in 802 high-surgical risk patients undergoing transfemoral TAVR for severe symptomatic aortic stenosis. Patients were stratified according to the presence or absence of history of CAD as well as periprocedural anticoagulation. The coprimary endpoints were net adverse cardiac events (NACE; a composite of all-cause mortality, myocardial infarction, stroke, or major bleeding) and major Bleeding Academic Research Consortium (BARC) bleeding ≥3b at 30 days postprocedure. RESULTS: Among 801 patients, 437 (54.6%) had history of CAD of whom 223 (51.0%) received bivalirudin. There were no significant differences in NACE (adjusted odds ratio [OR]: 1.04; 95% confidence interval [CI]: 0.69-1.58) or BARC ≥ 3b bleeding (adjusted OR: 0.84; 95% CI: 0.51-1.39) in patients with vs without CAD at 30 days. Among CAD patients, periprocedural use of bivalirudin was associated with similar NACE (OR: 0.80; 95% CI: 0.47-1.35) and BARC ≥ 3b bleeding (OR: 0.64; 95% CI: 0.33-1.25) compared with UFH, irrespective of history of CAD (p-interaction = 0.959 for NACE; p-interaction = 0.479 for major bleeding). CONCLUSION: CAD was not associated with a higher short-term risk of NACE or major bleeding after TAVR. Periprocedural anticoagulation with bivalirudin did not show any advantage over UFH in patients with and without CAD.

Microplastics in different municipal solid waste treatment and disposal systems: Do they pose environmental risks?

Microplastic (MP) pollution is a significant worldwide environmental and health challenge. Municipal solid waste (MSW) can be an important source of MPs in the environment if treated and disposed of inappropriately, causing potential ecological risks. MSW treatment and disposal methods have been gradually shifting from landfilling/dumping to more sustainable approaches, such as incineration or composting. However, previous studies on MP characteristics in different MSW treatment and disposal systems have mainly focused either on landfills/dumpsites or composts. The lack of knowledge of multiple MSW treatment and disposal systems makes it difficult to ensure effective MP pollution control during MSW treatment and disposal. Therefore, this study systematically summarizes the occurrence of MPs in different MSW treatment and disposal systems (landfill/dumpsite, compost, and incineration) on the Eurasian scale, and discusses the factors that influence MPs in individual MSW treatment and disposal systems. In addition, the paper assesses the occurrence of MPs in the surrounding environment of MSW treatment and disposal systems and their ecological risks using the species sensitivity distribution approach. The study also highlights recommendations for future research, to more comprehensively describe the occurrence and fate of MPs during MSW treatment and disposal processes, and to develop appropriate pollution control measures to minimize MP pollution.

Unravelling and reconstructing the biosynthetic pathway of bergenin.

Bergenin, a rare C-glycoside of 4-O-methyl gallic acid with pharmacological properties of antitussive and expectorant, is widely used in clinics to treat chronic tracheitis in China. However, its low abundance in nature and structural specificity hampers the accessibility through traditional crop-based manufacturing or chemical synthesis. In the present work, we elucidate the biosynthetic pathway of bergenin in Ardisia japonica by identifying the highly regio- and/or stereoselective 2-C-glycosyltransferases and 4-O-methyltransferases. Then, in Escherichia coli, we reconstruct the de novo biosynthetic pathway of 4-O-methyl gallic acid 2-C-ß-D-glycoside, which is the direct precursor of bergenin and is conveniently esterified into bergenin by in situ acid treatment. Moreover, further metabolic engineering improves the production of bergenin to 1.41 g L-1 in a 3-L bioreactor. Our work provides a foundation for sustainable supply of bergenin and alleviates its resource shortage via a synthetic biology approach.

Effect of aggregation behavior on microplastic removal by magnetic Fe3O4 nanoparticles.

Magnetic nanotechnologies have been shown to be an efficient approach to the reduction of microplastic (MP) pollution in aquatic environments. However, uncertainties remain regarding the relationship between particle stability and MP removal under varying water conditions, hindering the practical application of magnetic nanotechnologies for MP removal. Herein, the influence of particle aggregation behavior on nano-scale MP removal by Fe3O4 nanoparticles (FNPs) was investigated, by monitoring dynamic light scattering parameters and analyzing the microstructures of particle aggregates. Results showed that 83.1 %-92.9 % of MPs could be removed by FNPs within 1 h, and MP removal exhibited a high degree of Pearson correlation (R = 0.95; P = 0.04) with particle aggregation behavior mediated by the FNPs dosage. Furthermore, pH-dependent electrostatic interactions significantly influenced particle aggregation behavior and the removal of MPs. Under pH <6.7 conditions, electrostatic attraction between electropositive FNPs and electronegative MPs led to charge neutralization-induced aggregation and efficient removal MP performance. Under increasingly saline conditions, compression of the electrical double layer enhanced the self-aggregation behavior of MPs, weakening the electrostatic repulsion between FNPs and MPs under alkaline conditions. Therefore, salinity improved the MP removal efficiency, especially under alkaline conditions, with MP removal increasing from 4.47 % to 55.1 % when the mass fraction of NaCl was increased from 0 % to 1 %. These findings further our understanding of the effect of aggregation behavior on MP removal by FNPs and highlight the potential for magnetic nanotechnology application in the removal of nano-scale MPs from aquatic environments, while also providing valuable insights for the design of FNP-based materials.

A magnetic chitosan for efficient adsorption of vanadium (V) from aqueous solution.

The all-vanadium redox flow battery (VRFB) is becoming a promising technology for large-scale energy storage due to its advantages such as scalability and flexibility. In recent years, the VRFB has been successfully developed and put into use in many countries. It is expected that the abandoned VRFB will generate a large amount of vanadium waste. To our knowledge, there are few reports on the disposal of spent VRFBs. Herein, chitosan-coated nano-zero-valent iron (CS-Fe0) is proposed for the first time as adsorbents for the treatment of spent VRFBs. It can provide a new approach to deal with the upcoming large number of spent VRFBs. The calculated maximum adsorption capacity for V(V) of chitosan and CS-Fe0 reached 209.5 and 511.3 mg/g at 288 K, respectively. CS-Fe0 showed better adsorption performance than chitosan under different pH conditions and is easy to be separated from the liquid phase. The Freundlich isotherm was suitable for the adsorption process of chitosan, and CS-Fe0 was more consistent with the Langmuir isotherm. Ionic strength (0.05-0.5 M) had a positive effect on the adsorption capacity of CS-Fe0, and the influence of coexisting anions on CS-Fe0 could be negligible. FTIR and XPS analyses revealed that the primary mechanisms were the electrostatic attraction of chitosan and redox of Fe0. The present study confirmed that CS-Fe0 could be a potential material to efficiently trap V(V) from the VRFB electrolyte.

Alteration of the p53 gene during tree shrews' hepatocarcinogenesis.

OBJECTIVE: To detect the expression and variation of the p53 gene in hepatocarcinogenesis of tree shrews induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1). METHODS: Tree shrews were divided into four groups: group A, infected with HBV and fed with AFB1; group B, only infected with HBV; group C, fed with AFB1 alone; and group D normal control. The tree shrews underwent liver biopsy every 15 weeks. Liver and tumor tissues were detected by immunohistochemistry and molecular biotechnologies. RESULTS: The incidence of hepatocellular carcinoma (HCC) was higher in group A (66.7%) than in groups B (0) and C (30%). HCC occurrence was earlier in group A than in group C (120.0+/-16.6 wk vs 153.3+/-5.8 wk, t=3.336, P<0.01). Mutated p53 protein was not found in all groups before 75 weeks of experiment. At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60.0% and 71.4% in groups A, B and C respectively, which were significantly higher than that in group D (10%) (chi2> or =5.03, P<0.05). An abnormal band of the p53 gene was detected in groups A and C. The mutational points of the p53 gene in liver cancer of tree shrews were at codon 275, 78 and 13. Nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 were 91.7% and 93.4% in homology compared with those of human p53, respectively. CONCLUSIONS: Remarkable synergistic effect on HCC exists between HBV and AFB1. Mutated p53 protein expressed before occurrence of HCC promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation.

[Alteration of p53 gene during tree shrews' hepatocarcinogenesis].

OBJECTIVE: To detect the expression and variation of p53 gene during tree shrews' hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1). METHODS: Tree shrews were divided into four groups: the tree shrews were infected with HBV and fed with AFB1 in group A, only infected with HBV in group B, fed with AFB1 alone in group C, and normal control in group D. All the tree shrews were performed liver biopsy every 15 weeks. The tissues of liver and tumor were detected by immunohistochemistry and molecular biotechnologies. RESULTS: (1) The incidence of hepatocellular carcinoma (HCC) in group A (66.7%) was higher than that in Group B and C (30%). HCC appearance in group A was earlier than that in group C (120.0 weeks +/-16.6 weeks vs 153.3 weeks +/-5.8 weeks, t = 3.336, P<0.01). (2) Mutated p53 protein was not found before the 75th week of the experiment in each group. (3) At the 105th week, the expression rates of mutated p53 protein were 78.6%, 60% and 71.4% in group A, B and C respectively, which were much higher than that (10%) in group D (x2 > or = 5.03, P<0.05). An abnormal band of p53 gene was detected in both group A and C. (4) The mutation points of p53 gene in liver cancer of tree shrew were at codon 275, 78 and 13. The nucleotide sequence and amino acids sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homology with those of human p53 respectively. CONCLUSIONS: There is a remarkable synergistic effect between HBV and AFB1 on HCC. Mutated p53 protein is expressed before HCC occurrence, which promotes the development and progress of HCC. HBV and AFB1 may synergistically induce p53 gene mutation.