Remove legacy perfluoroalkyl acids and emerging per- and polyfluoroalkyl ether acids by single-use and regenerable anion exchange resins: Rapid small-scale column tests and model fits.

Rapid small-scale column tests (RSSCT) are used to study the removal of per- and polyfluoroalkyl substances (PFAS) for drinking water treatment by ion exchange. Breakthroughs of 15 emerging per- and perfluoroalkyl ether acids and six legacy perfluoroalkyl acid analogs are studied using a single-use PFAS-selective anion exchange resin (AER1) and a regenerable, generic anion exchange resin (AER2). The Bohart-Adams model was used to describe and predict breakthrough, with the modeled results reasonably aligned with RSSCT results in most cases, enabling shorter RSSCT duration for future applications. AER1 exhibited high uptake capacity with no breakthrough for 11 of the 21 tested PFAS during the 144,175 BV continuous operation, allowing compliance with the new National Primary Drinking Water Regulation in many application scenarios. AER2 exhibited much faster breakthroughs for most PFAS and is not a promising option for drinking water treatment. However, the summed PFAS capacity via model fit and total PFAS adsorbed via measurement were only <0.01 % of both resin capacities at full breakthrough, suggesting PFAS could only occupy a tiny portion of the ion exchange sites even for the PFAS-selective AER1. Ether group insertion in the PFAS group leads to later breakthrough, and linear isomers were better captured by the resins than the branched isomers. Overall, PFAS uptake capacity increases and kinetics decrease when the PFAS molecular volume increases. Regeneration using 10 % NaCl solutions partially released PFAS from AER2 but not from AER1, with more short-chain PFAS released than long-chain ones. Ether group insertion decreased the PFAS recoveries during the regeneration of AER2. The regenerated resins showed much faster breakthroughs than the pristine resins, making them unfavorable for drinking water treatment applications. Adsorption displacement of short-chain PFAS by long-chain PFAS was observed in pristine AER1, and post-regeneration leaching occurred for both resins, both phenomena making the resins a possible PFAS source in long-term use.

A Low-Cost, Sensitive Reporter System Using Membrane-Tethered Horseradish Peroxidase for Efficient Gene Expression Analysis.

Reporter gene assays are essential for high-throughput analysis, such as drug screening or determining downstream signaling activation/inhibition. However, use of this technology has been hampered by the high cost of the substrate (e.g., d-Luciferin (d-Luc)) in the most common firefly luciferase (FLuc) reporter gene assay. Although alternate luciferase is available worldwide, its substrate has remained expensive, and a more affordable option is still in demand. Here, we present a membrane-tethered horseradish peroxidase (mHRP), a new reporter system composed of a cell membrane expressing HRP that can preserve its enzymatic function on the cell surface, facilitates contact with HRP substrates (e.g., ABTS and TMB), and avoids the cell lysis process and the use of the high-priced luciferase substrate. An evaluation of the light signal sensitivity of mHRP compared to FLuc showed that both had comparable signal sensitivity. We also identified an extended substrate half-life of more than 5-fold that of d-Luc. Of note, this strategy provided a more stable detection signal, and the cell lysis process is not mandatory. Furthermore, with this strategy, we decreased the total amount of time taken for analysis and increased the time of detection limit of the reporter assay. Pricing analysis showed a one-third to one twenty-eighth price drop per single test of reporter assay. Given the convenience and stability of the mHRP reporter system, we believe that our strategy is suitable for use as an alternative to the luciferase reporter assay.

TRIPBASE: a database for identifying the human genomic DNA and lncRNA triplexes.

Long-non-coding RNAs (lncRNAs) are defined as RNA sequences which are >200 nt with no coding capacity. These lncRNAs participate in various biological mechanisms, and are widely abundant in a diversity of species. There is well-documented evidence that lncRNAs can interact with genomic DNAs by forming triple helices (triplexes). Previously, several computational methods have been designed based on the Hoogsteen base-pair rule to find theoretical RNA-DNA:DNA triplexes. While powerful, these methods suffer from a high false-positive rate between the predicted triplexes and the biological experiments. To address this issue, we first collected the experimental data of genomic RNA-DNA triplexes from antisense oligonucleotide (ASO)-mediated capture assays and used Triplexator, the most widely used tool for lncRNA-DNA interaction, to reveal the intrinsic information on true triplex binding potential. Based on the analysis, we proposed six computational attributes as filters to improve the in-silico triplex prediction by removing most false positives. Further, we have built a new database, TRIPBASE, as the first comprehensive collection of genome-wide triplex predictions of human lncRNAs. In TRIPBASE, the user interface allows scientists to apply customized filtering criteria to access the potential triplexes of human lncRNAs in the cis-regulatory regions of the human genome. TRIPBASE can be accessed at https://tripbase.iis.sinica.edu.tw/.

A universal in silico V(D)J recombination strategy for developing humanized monoclonal antibodies.

BACKGROUND: Humanization of mouse monoclonal antibodies (mAbs) is crucial for reducing their immunogenicity in humans. However, humanized mAbs often lose their binding affinities. Therefore, an in silico humanization method that can prevent the loss of the binding affinity of mAbs is needed. METHODS: We developed an in silico V(D)J recombination platform in which we used V(D)J human germline gene sequences to design five humanized candidates of anti-tumor necrosis factor (TNF)-α mAbs (C1-C5) by using different human germline templates. The candidates were subjected to molecular dynamics simulation. In addition, the structural similarities of their complementarity-determining regions (CDRs) to those of original mouse mAbs were estimated to derive the weighted interatomic root mean squared deviation (wRMSDi) value. Subsequently, the correlation of the derived wRMSDi value with the half maximal effective concentration (EC50) and the binding affinity (KD) of the humanized anti-TNF-α candidates was examined. To confirm whether our in silico estimation method can be used for other humanized mAbs, we tested our method using the anti-epidermal growth factor receptor (EGFR) a4.6.1, anti-glypican-3 (GPC3) YP9.1 and anti-α4ß1 integrin HP1/2L mAbs. RESULTS: The R2 value for the correlation between the wRMSDi and log(EC50) of the recombinant Remicade and those of the humanized anti-TNF-α candidates was 0.901, and the R2 value for the correlation between wRMSDi and log(KD) was 0.9921. The results indicated that our in silico V(D)J recombination platform could predict the binding affinity of humanized candidates and successfully identify the high-affinity humanized anti-TNF-α antibody (Ab) C1 with a binding affinity similar to that of the parental chimeric mAb (5.13 × 10-10). For the anti-EGFR a4.6.1, anti-GPC3 YP9.1, and anti-α4ß1 integrin HP1/2L mAbs, the wRMSDi and log(EC50) exhibited strong correlations (R2 = 0.9908, 0.9999, and 0.8907, respectively). CONCLUSIONS: Our in silico V(D)J recombination platform can facilitate the development of humanized mAbs with low immunogenicity and high binding affinities. This platform can directly transform numerous mAbs with therapeutic potential to humanized or even human therapeutic Abs for clinical use.

Ion exchange removal and resin regeneration to treat per- and polyfluoroalkyl ether acids and other emerging PFAS in drinking water.

Ion exchange (IX) is a promising technology to remove legacy anionic per- and polyfluoroalkyl substances (PFAS) from water. As increasing numbers of per- and polyfluoroalkyl ether acids (PFEA) and other emerging PFAS were detected in the environment, it is necessary to understand how well IX resins remove these emerging PFAS for drinking water treatment. In this study, nine commercially available IX resins were tested to treat a drinking water source spiked with 40 legacy and emerging PFAS at 600 ng/L, including PFEA, perfluoroalkyl carboxylic and sulfonic acids, fluorotelomer sulfonic acids, perfluoroalkane sulfonamides, perfluoroalkane sulfonamidoacetic acids, and zwitterionic species. With limited contact time (15 min), PFAS properties such as the fluorinated chain length, charge, and functional groups all affected PFAS adsorption to resins. However, the impact of PFAS properties on PFAS removal became less pronounced when the contact time increased beyond 2 h, while the resin polymer matrix became the critical factor for PFAS removal. All five tested polystyrene-divinylbenzene (PS-DVB) resins achieved more than 90% removal in 24 h of 35 PFAS compounds, while polymethacrylate and polyacrylic resins achieved >90% removal for less than half of the compounds. Regenerating PS-DVB resin was investigated using different salt species, regenerant pH, brine concentrations, and methanol contents. Sodium chloride and ammonium chloride were found the best brines for regenerating the tested resins. Increasing brine concentrations enhanced the regeneration efficiency, especially for short-chain PFAS. Using simple salt regenerants, up to 94% of selected short-chain PFAS was released from resins designed for general water treatment, but no meaningful regeneration was achieved for long-chain PFAS or PFAS-specific resins when the organic solvent content was less than 20%.

Adsorption of microcystin-LR onto kaolinite, illite and montmorillonite.

In this study, microcystin-LR (MCLR) interactions with three representative silicate clays were studied using equilibrium batch experiments in order to provide insight into the role of clays on determining MCLR fate. The three tested clay minerals (kaolinite, montmorillonite and illite), saturated with sodium or calcium ions, were equilibrated with MCLR across a range of toxin concentrations at pH 5, 7 or 9. The results were fit to Freundlich and linear isotherm models, with the linear isotherm fits deemed most appropriate. In general, adsorption of MCLR was greater in the systems with Ca than in those with Na, however, regardless of the cation present, montmorillonite had the highest adsorption affinity for MCLR. Furthermore, except for Ca-montmorillonite, MCLR adsorption decreased with increasing pH. The pH-dependence of adsorption suggests the polar groups of MCLR, carboxylate associated with the glutamic acid and methylaspartic acid groups and amine associated with the arginine group, were more important in determining MCLR interactions with clays than the nonpolar ADDA group. Increased adsorption in systems enriched with calcium suggests Ca modified the clay interfacial properties and the availability of MCLR groups in a manner that increased MCLR affinity. Overall, the results suggest clays are capable of adsorbing MCLR from the aqueous phase, particularly at low pH and when saturated with Ca2+.

Gallbladder stones and gallbladder polyps associated with increased risk of colorectal adenoma in men.

BACKGROUND AND AIMS: Most cases of colorectal cancer develop via an adenoma to carcinoma sequence. Gallbladder polyps share some risk factors with colorectal polyps. Little is known about the relationship between gallbladder diseases and different status of colorectal polyps by gender. This study was to investigate the association of gallbladder stones and polyps with colorectal adenomas by gender in a Taiwanese population. METHODS: A total of 7066 eligible subjects who underwent a total colonoscopy as a part of health check-up between January 2001 and August 2009 were recruited. Colonoscopic findings were classified into polyp-free, non-neoplastic polyps and colorectal adenomas. Gallbladder stones and gallbladder polyps were diagnosed based on ultrasonographic findings. RESULTS: There was a significant difference in the status of colon polyps between subjects with and without gallbladder polyps. However, the status of colon polyps was not significantly different between subjects with or without gallbladder stones. After adjusting obesity, fasting plasma glucose, and other variables, there was a positive relationship between gallbladder polyps and colorectal adenomas (odds ratio [OR]: 1.396, 95% confidence interval [CI]: 1.115-1.747) but not non-neoplastic polyps in all subjects. In men, gallbladder polyps (OR: 1.560, 95% CI: 1.204-2.019) and gallbladder stones (OR: 1.465, 95% CI 1.081-1.984) were positively associated with colorectal adenomas. In women, neither gallbladder polyps nor gallbladder stones were significantly related to colon polyps. CONCLUSIONS: Both gallbladder polyps and gallbladder stones were associated with an increased risk of colorectal adenomas in men but not in women. Gender difference was significant for the association between gallbladder lesions and colorectal polyps.

Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000-2012.

OBJECTIVES: It is not known if the incidences of autoimmune diseases are higher in individuals living with HIV infection or AIDS. Our study investigated the incidences of autoimmune diseases among people living with HIV/AIDS (PLWHA) in Taiwan during 2000-2012. METHODS: The Taiwan National Health Insurance Research Database was used to identify PLWHA. The incidence densities of systemic and organ-specific autoimmune diseases were calculated, and age-adjusted, sex-adjusted and period-adjusted standardised incidence rates (SIRs) were obtained by using two million people from the general population as controls. To examine the effects of highly active antiretroviral therapy (HAART) on the incidence of autoimmune diseases, the incidence densities and SIRs of autoimmune diseases were calculated after stratifying PLWHA by HAART status. RESULTS: Of the 20 444 PLWHA identified, the overall mean (SD) age was 30.1 (11.0) years; 67.2% of the subjects received HAART. As compared with the general population, SIRs were higher for incident Sjögren syndrome (SIR=1.64; 95% CI 1.24 to 2.13), psoriasis (SIR=2.05; 95% CI 1.67 to 2.48), systemic lupus erythematosus (SLE) (SIR=2.59; 95% CI 1.53 to 4.09), autoimmune haemolytic anaemia (SIR=35.06; 95% CI 23.1 to 51.02) and uveitis (SIR=2.50; 95% CI 2.05 to 3.02), but were lower for incident ankylosing spondyloarthritis (SIR=0.70; 95% CI 0.48 to 0.99). When the effect of HAART on incident autoimmune diseases was considered, PLWHA who received HAART had higher SIRs for psoriasis, autoimmune haemolytic anaemia and uveitis, but had lower risks of rheumatoid arthritis (RA) and ankylosing spondyloarthritis. In contrast, PLWHA who did not receive HAART had higher SIRs for Sjögren syndrome, psoriasis, RA, SLE, scleroderma, polymyositis, autoimmune haemolytic anaemia and Hashimoto's thyroiditis. CONCLUSIONS: PLWHA had higher risks of incident Sjögren syndrome, psoriasis, SLE, autoimmune haemolytic anaemia and uveitis.

Association of HIV and Opportunistic Infections With Incident Stroke: A Nationwide Population-Based Cohort Study in Taiwan.

BACKGROUND: HIV-associated vasculopathy and opportunistic infections (OIs) might cause vascular atherosclerosis and aneurysmal arteriopathy, which could increase the risk of incident stroke. However, few longitudinal studies have investigated the link between HIV and incident stroke. This cohort study evaluated the association of HIV and OIs with incident stroke. METHODS: We identified adults with HIV infection in 2000-2012, using the Taiwan National Health Insurance Research Database. A control cohort without HIV infection, matched for age and sex, was selected for comparison. Stroke incidence until December 31, 2012 was then ascertained for all patients. A time-dependent Cox regression model was used to determine the association between OIs and incident stroke among patients with HIV. RESULTS: Among a total of 106,875 patients (21,375 patients with HIV and 85,500 matched controls), stroke occurred in 927 patients (0.87%) during a mean follow-up period of 5.44 years, including 672 (0.63%) ischemic strokes and 255 (0.24%) hemorrhagic strokes. After adjusting for other covariates, HIV infection was an independent risk factor for incident all-cause stroke [adjusted hazard ratio (AHR) 1.83; 95% confidence interval (CI): 1.58 to 2.13]. When the type of stroke was considered, HIV infection increased the risks of ischemic (AHR 1.33; 95% CI: 1.09 to 1.63) and hemorrhagic stroke (AHR 2.01; 95% CI: 1.51 to 2.69). The risk of incident stroke was significantly higher in patients with HIV with cryptococcal meningitis (AHR 4.40; 95% CI: 1.38 to 14.02), cytomegalovirus disease (AHR 2.79; 95% CI: 1.37 to 5.67), and Penicillium marneffei infection (AHR 2.90; 95% CI: 1.16 to 7.28). CONCLUSIONS: Patients with HIV had an increased risk of stroke, particularly those with cryptococcal meningitis, cytomegalovirus, or P. marneffei infection.

Effects of pH, Electrolyte, Humic Acid, and Light Exposure on the Long-Term Fate of Silver Nanoparticles.

We investigated the evolution in silver nanoparticle (AgNP) properties during a series of 10-50 day experiments on suspensions with different pH (5-9), electrolyte type (NaNO3 and NaCl) and concentration (2 and 6 mM), Suwannee River humic acid (SRHA) concentration (0-13.2 mg C/L), and light exposure (artificial sun light exposure for 8 h per day or dark). Of these factors, pH most influenced the AgNPs' properties as it modifies surface charge as well as AgNP dissolution and oxidation and Ag+ reduction reactions. As a result, particle behavior differed in basic and acidic conditions. Trends with pH varied, however, based on the electrolyte and SRHA concentration. In the presence of chloride which forms AgCl(s), for example, we observed the particle size decreased with increasing pH. The opposite was observed in identical systems in NaNO3. This behavior was modified by SRHA, with increasing SRHA reducing dissolution and enhancing stability. Light exposure enhanced processes resulting in AgNP dissolution, resulting in higher dissolved Ag concentrations than under similar conditions in the dark. Overall, our results highlight how AgNP properties evolve over time and provide insight needed to confidently extend model system behavior to predict the environmental fate of AgNPs.

Association of Cytomegalovirus End-Organ Disease with Stroke in People Living with HIV/AIDS: A Nationwide Population-Based Cohort Study.

OBJECTIVES: Cytomegalovirus (CMV) infection might increase the risk of cardiovascular event. However, data on the link between incident stroke and co-infections of CMV and human immunodeficiency virus (HIV) are limited and inconsistent. This nationwide population-based cohort study analyzed the association of CMV end-organ disease and stroke among people living with HIV/AIDS (PLWHA). METHODS: From January 1, 1998, this study identified adult HIV individuals with and without CMV end-organ disease in the Taiwan National Health Insurance Research Database. All patients were observed for incident stroke and were followed until December 31, 2012. Time-dependent analysis was used to evaluate associations of CMV end-organ disease with stroke. RESULTS: Of the 22,581 PLWHA identified (439 with CMV end-organ disease and 22,142 without CMV end-organ disease), 228 (1.01%) had all-cause stroke during a mean follow-up period of 4.85 years, including 169 (0.75%) with ischemic stroke and 59 (0.26%) with hemorrhagic stroke. After adjusting for age, sex, comorbidities, opportunistic infections after HIV diagnosis, and antiretroviral treatment, CMV end-organ disease was found to be an independent risk factor for incident all-cause stroke (adjusted hazard ratio [AHR], 3.07; 95% confidence interval [CI], 1.70 to 5.55). When stroke type was considered, CMV end-organ disease was significantly positively associated with the risk of ischemic stroke (AHR, 3.14; 95% CI, 1.49 to 6.62) but not hemorrhagic stroke (AHR, 2.52; 95% CI, 0.64 to 9.91). CONCLUSIONS: This study suggested that CMV end-organ disease was an independent predictor of ischemic stroke among PLWHA.

Toxic cyanobacteria and drinking water: Impacts, detection, and treatment.

Blooms of toxic cyanobacteria in water supply systems are a global issue affecting water supplies on every major continent except Antarctica. The occurrence of toxic cyanobacteria in freshwater is increasing in both frequency and distribution. The protection of water supplies has therefore become increasingly more challenging. To reduce the risk from toxic cyanobacterial blooms in drinking water, a multi-barrier approach is needed, consisting of prevention, source control, treatment optimization, and monitoring. In this paper, current research on some of the critical elements of this multi-barrier approach are reviewed and synthesized, with an emphasis on the effectiveness of water treatment technologies for removing cyanobacteria and related toxic compounds. This paper synthesizes and updates a number of previous review articles on various aspects of this multi-barrier approach in order to provide a holistic resource for researchers, water managers and engineers, as well as water treatment plant operators.