•Review covers current state-of-the-art of PAA-based AOPs.•Various methods of PAA activation as well as their activation mechanisms are summarized.•PAA-based AOPs hold great promise for applications ...in contaminant degradation.•UV/PAA is the most promising technology for water disinfection among PAA-based AOPs.•Existing problems, challenges and solutions for research in PAA-based AOPs are discussed.
Peracetic acid (PAA) has attracted growing attention as an alternative oxidant and disinfectant in wastewater treatment due to the increased demand to reduce chlorine usage and control disinfection byproducts (DBPs). These applications have stimulated new investigations on PAA-based advanced oxidation processes (AOPs), which can enhance water disinfection and remove micropollutants. The purpose of this review is to conduct a comprehensive analysis of scientific information and experimental data reported in recent years on the applications of PAA-based AOPs for the removal of chemical and microbiological micropollutants from water and wastewater. Various methods of PAA activation, including the supply of external energy and metal/metal-free catalysts, as well as their activation mechanisms are discussed. Then, a review on the usage of PAA-based AOPs for contaminant degradation is given. The degradation mechanisms of organic compounds and the influence of the controlling parameters of PAA-based treatment systems are summarized and discussed. Concurrently, the application of PAA-based AOPs for water disinfection and the related mechanisms of microorganism inactivation are also reviewed. Since combining UV light with PAA is the most commonly investigated PAA-based AOP for simultaneous pathogen inactivation and micropollutant oxidation, we have also focused on PAA microbial inactivation kinetics, together with the effects of key experimental parameters on the process. Moreover, we have discussed the advantages and disadvantages of UV/PAA as an AOP against the well-known and established UV/H2O2. Finally, the knowledge gaps, challenges, and new opportunities for research in this field are discussed. This critical review will facilitate an in-depth understanding of the PAA-based AOPs for water and wastewater treatment and provide useful perspectives for future research and development for PAA-based technologies.
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Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better ...prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS prognostication biomarkers in 252 patients with detailed clinical phenotyping. First, we identified, in a longitudinal cohort, miRNAs whose plasma levels remain stable over the course of disease. Next, we showed that high levels of miR-181, a miRNA enriched in neurons, predicts a greater than two-fold risk of death in independent discovery and replication cohorts (126 and 122 patients, respectively). miR-181 performance is similar to neurofilament light chain (NfL), and when combined together, miR-181 + NfL establish a novel RNA-protein biomarker pair with superior prognostication capacity. Therefore, plasma miR-181 alone and a novel miRNA-protein biomarker approach, based on miR-181 + NfL, boost precision of patient stratification. miR-181-based ALS biomarkers encourage additional validation and might enhance the power of clinical trials.
Arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress. Arimoclomol ...has been found to be neuroprotective in a number of neurodegenerative disease models, including Amyotrophic Lateral Sclerosis (ALS), and in mutant Superoxide Dismutase 1 (SOD1) mice that model ALS, Arimoclomol rescues motor neurons, improves neuromuscular function and extends lifespan. The therapeutic potential of Arimoclomol is currently under investigation in a Phase II clinical trial for ALS patients with SOD1 mutations. In this review we summarize the evidence for the neuroprotective effects of enhanced heat shock protein expression by Arimoclomol and other inducers of the Heat Shock Response. ALS is a complex, multifactorial disease affecting a number of cell types and intracellular pathways. Cells and pathways affected by ALS pathology and which may be targeted by a heat shock protein-based therapy are also discussed in this review. For example, protein aggregation is a characteristic pathological feature of neurodegenerative diseases including ALS. Enhanced heat shock protein expression not only affects protein aggregation directly, but can also lead to more effective clearance of protein aggregates via the unfolded protein response, the proteasome-ubiquitin system or by autophagy. However, compounds such as Arimoclomol have effects beyond targeting protein mis-handling and can also affect additional pathological mechanisms such as oxidative stress. Therefore, by targeting multiple pathological mechanisms, compounds such as Arimoclomol may be particularly effective in the development of a disease-modifying therapy for ALS and other neurodegenerative disorders.
Zeolitic imidazolate framework-67 (ZIF67) has been regarded as an effective energy storage material due to its high surface area and electroactive cobalt center. Carbonizing ZIF67 can enhance ...electrical conductivity by converting 2-methylimidazole (2-melm) to carbon with cobalt doping. In this work, a novel in situ electrospinning is proposed to fabricate carbonized ZIF67 on carbon fiber (C67@PAN-OC) as a freestanding supercapacitor electrode. Polyacrylonitrile solution containing a cobalt precursor is used for electrospinning, and produced fibers are immersed in 2-melm to form ZIF67. Individually grown carbonized ZIF67 on carbon fiber is obtained using the in situ electrospinning method, while the one-body mixed carbon electrode is formed using the ex situ electrospinning method. A highest specific capacitance (C F) of 386.3 F/g at 20 mV/s is obtained for the in situ synthesized C67@PAN-OC electrode due to the largest electrochemical surface area and the smallest resistance, while the ex situ synthesized electrode only shows a C F value of 27.7 F/g. A symmetric supercapacitor (SSC) assembled using the optimized C67@PAN-OC electrodes and gel electrolytes shows a maximum energy density of 9.64 kWh/kg at 0.55 kW/kg and a C F retention of 59.5% after 1000 times charge/discharge process. A C F retention of 75.6% after bending 100 times is also obtained for SSC.
Practical applications of disinfection technologies for engineered waters require an in‒depth understanding of disinfection profiles and mechanisms of pathogenic bacteria in a complex matrix. This ...study investigated the inactivation of E. coli and E. faecalis by SO4•−, an emerging advanced disinfectant, in ultrapure water (UPW) and wastewater effluent (WE). Based on the bacterial inactivation kinetics in UPW in a zerovalent iron/peroxydisulfate system, the second order rate constants (k) for SO4•− reacting with E. coli and E. faecalis were measured to be (1.39 ± 0.1) × 109 M−1 s−1 and (6.71 ± 0.1) × 109 M−1 s−1, respectively. The morphological images of both bacteria by the scanning electron microscope indicated that SO4•− initiates oxidative reactions on the wall/membranes, causing their irreversible damage, ultimately affecting membrane permeability and physiological functions. To profile the inactivation kinetics of two strains of bacteria in WE matrix, a mechanistic process‒based model with the obtained k values was developed. Sensitivity and uncertainty analyses indicated that the key parameters for the model predictions were the concentrations of halide ions (i.e., Br− and Cl−) in WE and their k values reacting with SO4•− accounting for >80% of uncertainty or variance expected in predicted bacterial inactivation. This model allows precise estimation of required disinfectant dose even in complex water matrices, shedding lights on the extension of application of SO4•−‒based technology in wastewater treatments.
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•We investigated inactivation of two bacteria by SO4•−in DI water and wastewater.•k for SO4•− reacting with E. faecalis was higher than that of E. coli.•We developed a mechanistic process‒based disinfection model with the k values.•Halide and their reactions with SO4•− account for large uncertainty in model.•The model allows precise estimation of disinfectant dose in complex water matrices.
Neurofilament proteins (Nf) are a biomarker of disease progression in amyotrophic lateral sclerosis (ALS). This study investigated whether there are major differences in expression from in vivo ...measurements of neurofilament isoforms, from the light chain, NfL (68 kDa), compared with larger proteins, the medium chain (NfM, 150 kDa) and the heavy (NfH, 200‐210 kDa) chains in ALS patients and healthy controls. New immunological methods were combined with Nf subunit stoichiometry calculations and Monte Carlo simulations of a coarse‐grained Nf brush model. Based on a physiological Nf subunit stoichiometry of 7 : 3 : 2 (NfL:NfM:NfH), we found an ‘adaptive’ Nf subunit stoichiometry of 24 : 2.4 : 1.6 in ALS. Adaptive Nf stoichiometry preserved NfL gyration radius in the Nf brush model. The energy and time requirements for Nf translation were 56 ± 27k ATP (5.6 h) in control subjects compared to 123 ± 102k (12.3 h) in ALS with ‘adaptive’ (24:2.4:1.6) Nf stoichiometry (not significant) and increased significantly to 355 ± 330k (35.5 h) with ‘luxury’ (7:3:2) Nf subunit stoichiometry (p < 0.0001 for each comparison). Longitudinal disease progression‐related energy consumption was highest with a ‘luxury’ (7:3:2) Nf stoichiometry. Therefore, an energy and time‐saving option for motor neurons is to shift protein expression from larger to smaller (cheaper) subunits, at little or no costs on a protein structural level, to compensate for increased energy demands.
This study describes a novel concept, adaptive protein stoichiometry, which provides neurons with an efficient strategy to slow neurodegeneration. The data supporting this conclusion come from protein concentrations measured in patients suffering from a rapid neurodegenerative condition, amyotrophic lateral sclerosis (synonymous motor neuron disease, Lou Gehrig disease). Extrapolation to a much boarder disease spectrum is conceivable as ‘adaptive protein stoichiometry’ is based on the fundamental principle of ATP and time requirements for transcription. The results of present data on the neurofilament triplet protein should be applicable to other heteropolymers and offer a new conceptional framework for developing antisense therapies.
Exosomes are secreted into the extracellular space by most cell types and contain various molecular constituents, which play roles in many biological processes. Adipose‐derived mesenchymal stem cells ...(ADSCs) can differentiate into a variety of cell types and secrete a series of paracrine factors through exosomes. ADSC‐derived exosomes have shown diagnostic and therapeutic potential in many clinical diseases. The molecular components are critical for their mechanisms. Several methods have been developed for exosome purification, including ultracentrifugation, ultrafiltration, density gradient purification, size‐based isolation, polymer precipitation and immuno‐affinity purification. Thus, we employed four methods to isolate exosomes from the hADSC culture medium, including ultracentrifugation, size exclusion chromatography, ExoQuick‐TC precipitation and ExoQuick‐TC ULTRA isolation. Following exosome isolation, we performed quantitative proteomic analysis of the exosome proteins using isobaric tags for relative and absolute quantification (iTRAQ) labelling, combined with 2D‐LC‐MS/MS. There were 599 universal and 138 stably expressed proteins in hADSC‐derived exosomes. We proved that these proteins were potential hADSC‐derived exosomes markers, including CD109, CD166, HSPA4, TRAP1, RAB2A, RAB11B and RAB14. From the quantitative proteomic analysis, we demonstrated that hADSC‐derived exosome protein expression varied, with lipopolysaccharide (LPS) treatment, in the different isolation methods. Pathway analysis and proliferation, migration and endothelial tube formation assays showed varying effects in cells stimulated with hADSC‐derived exosomes from different isolation methods. Our study revealed that different isolation methods might introduce variations in the protein composition in exosomes, which reflects their effects on biological function. The pros and cons of these methods are important points to consider for downstream research applications.
•PFOS was associated with breast cancer risk in Taiwanese women.•Young women (age ≤ 50 years) had a high risk of breast cancer by PFOS exposure.•Women in the age less than 50 years had a higher risk ...of estrogen receptor positive tumors than those in the age over 50 years by PFHxS and PFOS exposure.
Breast cancer (BC) is a common cancer in women worldwide; however, the incidence of BC is increasing in younger women, possibly associated with the environment. Perfluoroalkyl substances (PFAS) are one of endocrine disruptors that accumulate in environment and impact human health. This study aimed to investigate whether the PFAS and BC are associated. We enrolled 120 BCE patients and 119 controls at National Taiwan University Hospital (NTUH) and also collected bio-specimen and questionnaire from 2013 to 2015. All subjects’ plasma PFAS levels were analyzed by ultra-performance liquid chromatography tandem mass spectrometry method with electrospray ionization (UHPLC-ESI-MS/MS). A logistic regression model was used to estimate the association between PFAS and BC. In the ≤50 years age group, the adjusted odds ratio (OR) was 2.34 (95% CI = 1.02, 5.38) for perfluorooctane sulfonate (PFOS) exposure per natural log unit increase. After stratifying the estrogen receptor (ER) status and age group, we obtained a positive association for PFHxS and PFOS concentrations with respect to the risk of ER positive tumors for ≤50 years age group. In conclusion, we found that PFAS were associated with the BC risk of ER positive tumors in young Taiwanese women. Further studies are needed to follow and explore whether these associations are causal.
The lack of biomarkers for early diagnosis, clinical stratification and to monitor treatment response has hampered the development of new therapies for amyotrophic lateral sclerosis (ALS), a ...clinically heterogeneous neurodegenerative disorder with a variable site of disease initiation and rate of progression. To identify new biomarkers and therapeutic targets, two separate proteomic workflows were applied to study the immunological response and the plasma/brain proteome in phenotypic variants of ALS. Conventional multiplex (TMT) proteomic analysis of peripheral blood mononuclear cells (PBMCs) was performed alongside a recently introduced method to profile neuronal-derived proteins in plasma using brain tissue-enhanced isobaric tagging (TMTcalibrator). The combined proteomic analysis allowed the detection of regulated proteins linked to ALS pathogenesis (RNA-binding protein FUS, superoxide dismutase Cu-Zn and neurofilaments light polypeptide) alongside newly identified candidate biomarkers (myosin-9, fructose-bisphosphate aldolase and plectin). In line with the proteomic results, orthogonal immunodetection showed changes in neurofilaments and ApoE in bulbar versus limb onset fast progressing ALS. Functional analysis of significantly regulated features showed enrichment of pathways involved in regulation of the immune response, Rho family GTPases, semaphorin and integrin signalling. Our cross-phenotype investigation of PBMCs and plasma/brain proteins provides a more sensitive biomarker exploratory platform than conventional case-control studies in a single matrix. The reported regulated proteins may represent novel biomarker candidates and potentially druggable targets.
The lack of biomarkers for an early diagnosis of neurodegenerative disorders (NDs) has hampered the development of therapeutics whose effect would be enhanced by a timely intervention. Neurofilaments ...light chain (Nf-L), an integral part of the axonal structure, has emerged as a robust fluid biomarker for fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). To facilitate large-scale studies into early-stage neurodegeneration, reduce costs of samples collection/processing and cold-chain storage, we describe the measurement of Nf-L in blood fractions obtained from dry blood spots (DBS) and dry plasma spots (DPS), two filter paper-based remote blood collection tools. To test the feasibility of using this approach, Nf-L analysis in DBS/DPS is compared to that in plasma obtained from the same blood sample, looking at Nf-L discriminatory power in the clinical stratification of ALS compared to healthy controls. With the best pre-analytical treatment for total protein recovery and using highly sensitive immunoassays, we report the detection of different Nf-L levels in DBS elute compared to reference plasma and DPS from the same blood samples. However, Nf-L measurement in DBS elutes provides a very good discrimination of ALS from healthy controls which is comparable to that obtained using plasma Nf-L assays. With the available immunodetection methods, we show that Nf-L measurement based on DPS microsampling is similar to that in plasma. The filter-paper biophysical characteristics and the interference of high haemoglobin concentration released by erythrocyte lysis is likely to perturb Nf-L detection in DBS elute. Further studies into DBS-based Nf-L detection and its analytical optimization are needed to make this method suitable for routine Nf-L blood analyses in neurodegeneration.
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