Discovering, Characterizing, and Applying Acyl Homoserine Lactone-Quenching Enzymes to Mitigate Microbe-Associated Problems Under Saline Conditions

Quorum quenching (QQ) is proposed as a new strategy for mitigating microbe-associated problems (e.g., fouling, biocorrosion). However, most QQ agents reported to date have not been evaluated for their quenching efficacies under conditions representative of seawater desalination plants, cooling towers or marine aquaculture. In this study, bacterial strains were isolated from Saudi Arabian coastal environments and screened for acyl homoserine lactone (AHL)-quenching activities. Five AHL quenching bacterial isolates from the genera Pseudoalteromonas, Pontibacillus, and Altererythrobacter exhibited high AHL-quenching activity at a salinity level of 58 g/L and a pH of 7.8 at 50°C. This result demonstrates the potential use of these QQ bacteria in mitigating microbe-associated problems under saline and alkaline conditions at high (>37°C) temperatures. Further characterizations of the QQ efficacies revealed two bacterial isolates, namely, Pseudoalteromonas sp. L11 and Altererythrobacter sp. S1-5, which could possess enzymatic QQ activity. The genome sequences of L11 and S1-5 with a homologous screening against reported AHL quenching genes suggest the existence of four possible QQ coding genes in each strain. Specifically, two novel AHL enzymes, AiiAS1-5 and EstS1-5 from Altererythrobacter sp. S1-5, both contain signal peptides and exhibit QQ activity over a broad range of pH, salinity, and temperature values. In particular, AiiAS1-5 demonstrated activity against a wide spectrum of AHL molecules. When tested against three bacterial species, namely, Aeromonas hydrophila, Pseudomonas aeruginosa, and Vibrio alginolyticus, AiiAS1-5 was able to inhibit the motility of all three species under saline conditions. The biofilm formation associated with P. aeruginosa was also significantly inhibited by AiiAS1-5. AiiAS1-5 also reduced the quorum sensing-mediated virulence traits of A. hydrophila, P. aeruginosa, and V. alginolyticus during the mid and late exponential phases of cell growth. The enzyme did not impose any detrimental effects on cell growth, suggesting a lower potential for the target bacterium to develop resistance over long-term exposure. Overall, this study suggested that some QQ enzymes obtained from the bacteria that inhabit saline environments under high temperatures have potential applications in the mitigation of microbe-associated problems

Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC

Environment-economy tradeoff for Beijing–Tianjin–Hebei’s exports

The trade of goods among regions or nations associated with large environmental consequences. Yet balancing economic gains and environmental consequences induced by trade is still hindered by a lack of quantification of these two factors, especially for the environmental problems those are more locally oriented, such as the atmospheric pollution. Based on an environmental input-output analysis for 2010, we contrast economic gains (value added) against atmospheric pollutant emissions (sulfur dioxide (SO2), nitric oxide (NOx), primary fine particulate matter (PM2.5) and non-methane volatile organic compounds (NMVOC)) and the widely concerned CO2 emissions associated with international and interprovincial exports from Beijing-Tianjin-Hebei (BTH), the most polluted area in China. Our results show that exports contributed 55-62% of BTH's production emissions and 54% of its total value added. BTH's large exports of metals and metal products, nonmetal mineral products, chemical and transportation and warehousing, generated a larger share of pollutant emissions (36-46% of BTH's total) than that of value added (17%) along the supply chain. Most of BTH's embodied emissions in exports go to neighboring provinces and the developed east coastal regions in China, although the economic returns are comparatively low. Among BTH, industrial production in Beijing and Tianjin lead to more pollutant emission than value added in Hebei, due to reliance on pollution-intensive product imports from Hebei. Our results call for refocusing and restructuring of BTH's industry and trade structures to balance the economic gains and environmental losses for each region

Combination of Chinese Herbal Medicines and Conventional Treatment versus Conventional Treatment Alone in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention (5C Trial): An Open-Label Randomized Controlled, Multicenter Study

Aims. To evaluate the efficacy of Chinese herbal medicines (CHMs) plus conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods and Results. Participants (n=808) with ACS who underwent PCI from thirteen hospitals of mainland China were randomized into two groups: CHMs plus conventional treatment group (treatment group) or conventional treatment alone group (control group). All participants received conventional treatment, and participants in treatment group additionally received CHMs for six months. The primary endpoint was the composite of cardiac death, nonfatal recurrent MI, and ischemia-driven revascularization. Secondary endpoint was the composite of readmission for ACS, stroke, or congestive heart failure. The safety endpoint involved occurrence of major bleeding events. The incidence of primary endpoint was 2.7% in treatment group versus 6.2% in control group (HR, 0.43; 95% CI, 0.21 to 0.87; P=0.015). The incidence of secondary endpoint was 3.5% in treatment group versus 8.7% in control group (HR, 0.39; 95% CI, 0.21 to 0.72; P=0.002). No major bleeding events were observed in any participant. Conclusion. Treatment with CHMs plus conventional treatment further reduced the occurrence of cardiovascular events in patients with ACS after PCI without increasing risk of major bleeding

Use of nanomaterials in the pretreatment of water samples for environmental analysis

The challenge of providing clean drinking water is of enormous relevance in today’s human civilization, being essential for human consumption, but also for agriculture, livestock and several industrial applications. In addition to remediation strategies, the accurate monitoring of pollutants in water sup-plies, which most of the times are present at low concentrations, is a critical challenge. The usual low concentration of target analytes, the presence of in-terferents and the incompatibility of the sample matrix with instrumental techniques and detectors are the main reasons that renders sample preparation a relevant part of environmental monitoring strategies. The discovery and ap-plication of new nanomaterials allowed improvements on the pretreatment of water samples, with benefits in terms of speed, reliability and sensitivity in analysis. In this chapter, the use of nanomaterials in solid-phase extraction (SPE) protocols for water samples pretreatment for environmental monitoring is addressed. The most used nanomaterials, including metallic nanoparticles, metal organic frameworks, molecularly imprinted polymers, carbon-based nanomaterials, silica-based nanoparticles and nanocomposites are described, and their applications and advantages overviewed. Main gaps are identified and new directions on the field are suggested.publishe