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Oral administration of BCS class IV anticancer agents has always remained challenging and frequently results in poor oral bioavailability. The goal of the current study was to develop hybrid nanoparticles (HNPs) employing cholesterol and poloxamer-407 to boost paclitaxel's (PTX) oral bioavailability. A series of HNPs with different cholesterol and poloxamer-407 ratios were developed utilizing a single-step nanoprecipitation technique. The PTX loaded HNPs were characterized systematically via particle size, zeta potential, polydispersity index, surface morphology, in vitro drug release, FTIR, DSC, XRD, acute oral toxicity analysis, hemolysis evaluation, accelerated stability studies, and in vivo pharmacokinetic analysis. The HNPs were found within the range of 106.6±55.60 - 244.5±88.24 nm diameter with the polydispersity index ranging from 0.20±0.03 - 0.51±0.11. SEM confirmed circular, nonporous, and smooth surfaces of HNPs. PTX loaded HNPs exhibited controlled release profile. The compatibility between the components of formulation, thermal stability, and amorphous nature of HNPs were confirmed by FTIR, DSC, and XRD, respectively. Acute oral toxicity analysis revealed that developed system have no deleterious effects on the animals' cellular structures. HNPs demonstrated notable cytotoxic effects and were hemocompatible at relatively higher concentrations. In vivo pharmacokinetic profile (AUC 0-∞ , AUMC 0-∞ , t 1/2, and MRT 0-∞ ) of the PTX loaded HNPs was improved as compared to pure PTX. It is concluded from our findings that the developed HNPs are hemocompatible, biocompatible and have significantly enhanced the oral bioavailability of PTX., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aims to design and optimize ondansetron (OND) gastro-retentive floating minitablets for better and prolonged control of postoperative nausea and vomiting (PONV) with improved patient compliance. Minitablets were directly compressed and encapsulated in a size 2 capsule shell with an overall dose of 24 mg. Central composite design (CCD) was applied keeping one cellulose ether derivative HPMC K15M and Carbopol 971 as variable and used as swelling and rate retarding agents. The other cellulose derivative i.e. sodium carboxymethyl cellulose, along with mannitol, sodium bicarbonate, and talc, were used in fixed quantities. The floating lag time, total floating time, swelling index, in-vitro drug release, and zero-order (RSQ value), were critical quality parameters. The optimized formulation (F pred ) was evaluated for all critical parameters, along with surface morphology, thermal stability, chemical interaction, and accelerated stability. The in silico PBPK modeling was applied to compare the bioavailability of F pred with reference OND immediate-release tablets. The numerical optimization model predicted >90 % drug release with zero-order at 12 h. In silico PBPK modeling revealed comparable relative bioavailability of F pred with the reference formulation. The gastroretentive floating minitablets of OND were successfully designed for prolonged emesis control in patients receiving chemotherapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aim: The liver plays a crucial role in biotransformation but it is susceptible to chemical-induced damage, known as hepatotoxicity. Traditional therapies for protecting the liver face significant challenges, including poor bioavailability, off-target effects, adverse reactions, drug breakdown, and inadequate uptake. These issues emphasize the need for precise, targeted therapeutic approaches against hepatotoxicity., Materials and Methods: The objective of our research was to develop a customized, biocompatible, and biodegradable nanodrug delivery system for hepatoprotection. We chose collagen hydrolyzed protein, or gelatin, as the base material and utilized solvent evaporation and nanoprecipitation methods to create nanoparticles with size ranging from 130 to 155 nm. The resulting nanoparticles exhibited a spherical and smooth surface, as confirmed by scanning and transmission electron microscopy., Key Findings: Bioactive aescin (AES), into these gelatin nanoparticles (AES-loaded gel NPs), we tested these nanoparticles using a hepatotoxicity model. The results were indicating a significant reduction in the levels of key biomolecules, including NF-κB, iNOS, BAX, and COX-2 and decreased serum levels of enzymes ALT and AST. This reduction correlated with a notable alleviation in the severity of hepatotoxicity. Furthermore, the treatment with AES-loaded gel NPs resulted in the downregulation of several inflammatory and liver-specific biomarkers, including nitrite, MPO, TNF-α, and IL-6., Significance: In summary, our study demonstrates that the AES-loaded gel NPs were markedly more effective in mitigating experimental hepatotoxicity when compared to the free aescin. The nanoparticles exhibited a propensity for suppressing liver damage, showcasing the potential of this targeted therapeutic approach for safeguarding the liver from harmful chemical insults., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Dissolved organic matter (DOM) in the sediment matrix affects contaminant remediation through consumption of oxidants and binding with contaminants. Yet the change in DOM during remediation processes, particularly during electrokinetic remediation (EKR), remains under-investigated. In this work, we elucidated the fate of sediment DOM in EKR using multiple spectroscopic tools under abiotic and biotic conditions. We found that EKR led to significant electromigration of the alkaline-extractable DOM (AEOM) toward the anode, followed by transformation of the aromatics and mineralization of the polysaccharides. The AEOM remaining in the cathode (largely polysaccharides) was resistant to reductive transformation. Limited difference was noted between abiotic and biotic conditions, indicating the dominance of electrochemical processes when relatively high voltages were applied (1-2 V/cm). The water-extractable organic matter (WEOM), in contrast, showed an increase at both electrodes, which was likely attributable to pH-driven dissociations of humic substances and amino acid-type constituents at the cathode and the anode, respectively. Nitrogen migrated with the AEOM toward the anode, but phosphorus remained immobilized. Understanding the redistribution and transformation of DOM could inform studies on contaminant degradation, carbon and nutrient availability, and sediment structural changes in EKR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Applications of electrochemical advanced oxidation processes are rising in drinking water treatment for effective mitigation of refractory organic compounds. This study explored the fate of natural organic matter (NOM) (lake water and standard NOM (SRNOM solution)) at molecular-level in the reactive electrochemical membrane (REM) system utilizing Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Fluorescence spectroscopy showed above 90 % removal of the humic-like component in both lake water and SRNOM solution in 10 min of REM operation compared to 70-80 % removal of the fulvic-like component after 30 min. REM-based treatment effectively eliminated (>70 %) the disinfection byproduct precursors. The lake water, sharing ~70 % of similar compounds with SRNOM, displayed a different propensity toward electrochemical oxidation, and its finished water was characterized with relatively lower double-bond equivalent (DBE), nominal oxidation state of carbon (NOSC), and aromaticity compared to that of SRNOM. The chloride ions in the water matrix of lake water impacted the electrochemical oxidation and generated significantly different transformation products than SRNOM solution. The heteroatoms (N and S) containing compounds (CHON and CHOS) were preferentially degraded in lake water; however, CHOS compounds were removed fewer in SRNOM. The electrosorption and electrochemical oxidation on the REM surface were the significant contributors for NOM removal. The newly formed compounds were mostly retained on the REM surface and fewer were released in finished water. This study is believed to help understand the fate of NOM in real source drinking water during electrochemical treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The increasing release of nutrients to aquatic environments has led to great concern regarding eutrophication and the risk of unwanted algal blooms. Based on observational data of 20 water quality parameters measured on a monthly basis at 40 stations from 2011 to 2020, this study applied different Machine Learning (ML) algorithms to suggest the best option for algal bloom prediction in the Han River, a large river in South Korea. Eight different ML algorithms were categorized into several groups of statistical learning, regression family, and deep learning, and were then compared for their suitability to predict the chlorophyll-derived trophic index (TSI-Chla). ML algorithms helped identify the most important water quality parameters contributing to algal bloom prediction. The ML results confirmed that eutrophication and algal proliferation were governed by the complex interplay between nutrients (nitrogen and phosphorus), organic contaminants, and environmental factors. Of the models tested, the adaptive neuro-fuzzy inference system (ANFIS) exhibited the best performance owing to its consistent and outperforming prediction both quantitatively (i.e., via regression) and qualitatively (i.e., via classification), which was evidenced by the lowest value of mean absolute error (MAE) of 0.09, and the highest F1-score, Recall and Precision of 0.97, 0.98 and 0.96, respectively. In a further step, a representative web application was constructed to assist common users to predict the trophic status of the Han River. This study demonstrated that ML techniques are not only promising for highly accurate water quality modeling of urban rivers, but also reduce time and labor intensity for experiments, which decreases the number of monitored water quality parameters, providing further insights into the driving factors of water quality deterioration. They ultimately help devise proactive strategies for sustainable water management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, we used stable isotope-labeled soluble microbial products (SMP) and substrates to explore their assimilation into the formation of new biological products (i.e., extracellular polymeric substances and biomass) in two adjacent sequencing batch reactors. The isotope labeling approach along with fluorescence spectroscopy allowed us to distinguish between refractory and labile portions of SMP constituents as well as their roles in the formation of extracellular polymeric substances (EPS). Comparison of SMP fluorescence and the specific UV absorbance values between the two reactors revealed the presence of humic-like aromatic substances in the non-consumable part of SMP, which can be ultimately released as effluent organic matter. Parallel factor analysis modeling of fluorescence spectra showed that the hydrolysis of EPS contents mostly resulted in humic-like components in SMP rather than protein-like components, which were initially abundant in EPS (>80%). From variations in carbon and nitrogen isotopic contents in EPS and biomass, it was found that carbon-containing substrates were enriched faster than their nitrogenous counterparts. The contributions to new EPS formation reached 87.5% for carbon and 60.5% for nitrogen. Meanwhile, the isotopic tracking of the labeled SMP revealed that only 11.0% and 11.9% of carbon and 13.3% and 11.6% of nitrogen from the influent SMP were finally assimilated into EPS and biomass, respectively. In contrast, the isotopic enrichment in SMP was higher (~50%) than that of EPS and biomass, indicating the low bioavailability and refractory nature of the feed SMP. This study proposed a promising approach for estimating the relative contributions of different forms of labile substrate and SMP to the formation of EPS in activated sludge processes. This approach could be suggested as a versatile method for establishing the kinetics, substrate element flow, mass balance on organic substrates and nutrients, as well as for tracking the consumption and uptake pathways of hazardous materials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The occurrence of mutagenic and carcinogenic N-nitrosamines in drinking water is of great concern. In this study, dynamics and removal of nine N-nitrosamines in three drinking water treatment systems of a southern city of China are monitored during one year of sampling. The impacts of physicochemical treatment units on the removal and generation of N-nitrosamines were evaluated. The O 3 and KMnO 4 based pre-oxidation units have caused an increase in N-nitrosamines concentration, with O 3 showing the substantial generation of N-nitrosamines. The carbon filter and ultrafiltration membrane units were found effective in removing N-nitrosamine precursors. These drinking water treatment systems have been useful in removing N-nitrosamine precursors; meanwhile, a slight decrease was found in already formed N-nitrosamines concentration. However, N-nitrosomorpholine (NMOR) and N-nitrosodiphenylamine (NDPhA) were found resistant toward all kinds of physicochemical treatments, and negligible changes in concentration were noted in all drinking water treatment systems. The distribution networks in the city provided an effective contact period to residual chlorine and precursors, which caused an increase in N-nitrosamines concentration. Overall, N-nitrosodimethylamine (NDMA) and N-nitroso-diethylamine (NDEA) have been found near the cancer risk threshold (10 -6 ) in all of the drinking water treatment systems, while the remaining seven N-nitrosamines were found below the risk level., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The presence of carcinogenic N-nitrosamines and dissolved organic matter (DOM) in freshwater is a significant concern from the perspective of public health and drinking water treatment plant operation. This study investigated the N-nitrosamines concentration and their precursors' distributions, and DOM composition in four reservoirs located in a southern city of China. A total of 22 renowned precursors were identified. Precursors from industrial and pharmaceutical origins were found to be dominant in all reservoirs; however, traces of pesticide-based precursors, i.e. pirimicarb and cycluron were also found. The distribution of nine N-nitrosamines was substantially different among the reservoirs. N-Nitrosodibutylamine (NDBA), N-Nitrosopiperidine (NPIP), N-Nitrosodimethylamine (NDMA), and N-Nitrosopyrrolidine (NPYR) were abundantly present in all reservoirs. Most of N-nitrosamines except NDMA and N-nitrosodiethylamine (NDEA) were far below the generally accepted cancer risk of 10 -6 , and NDMA/NDEA were found close to the risk level (10 -6 ). Anthropogenic DOM was dominant in three reservoirs as depicted by a higher biological index (BIX) than the humification index (HIX). By the principle component analysis, BIX appeared as an indicator of N-nitrosamines (except NDEA and NPIP). A strong and direct relationship was observed between the NDMA-formation potential (FP) and concentration of total N-nitrosamines (∑NA), and BIX. These results confirmed that the anthropogenic activities were the leading source of DOM and N-nitrosamines in this city based on land-use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Delivering drinking water with stable quality in metropolitan cities is a big challenge. This study investigated the year-long dynamics of dissolved organic matter (DOM) in the tap water and source water of a metropolitan city in southern China using fluorescence spectroscopy. The DOM detected in the tap water, and source water of Shenzhen city was season and location-dependent. A year-long cyclic trend of DOM was found with predominate protein-like fluorescence in the dry season compared to the humic-like enriched DOM in the wet season. A general DOM pattern was estimated by measuring the shift in dominant fluorescence regions on the excitation-emission matrix (EEM). The difference in fluorescent DOM (FDOM) composition (in terms of the ratio of protein-like to humic-like fluorescence) was above 200% between wet and dry seasons. The taps associated with reservoirs receiving water from the eastern tributary of Dongjiang River showed significant changes in protein-like contents than the taps with source water originating from the western part of the river. This study highlights the importance of optimizing drinking water treatment plants' operational conditions after considering seasonal changes and source water characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this study, impacts of in-situ ozonation applied directly in the membrane tank of a ceramic MBR (Oz-MBR) were assessed to elucidate its implications on micropollutant removal, microbial taxa and membrane fouling. The basic effluent quality (i.e., bulk organics and nutrients) of the MBR without and with in-situ ozonation was comparable. Importantly, pollutant-specific (10-26%) improvement in micropollutant removal was achieved by the Oz-MBR, which could be attributed to the increase in the abundance of microbial taxa responsible for the removal of structurally complex pollutants and/or ozone-assisted oxidation. In-situ ozonation affected the abundance of denitrifying bacteria and functional genes but total nitrogen removal by the Oz-MBR was comparable to that achieved by the control (C)-MBR. Improved mixed liquor properties, and the reduced accumulation of foulants on the membrane surface resulted in membrane fouling alleviation (53%) in the Oz-MBR. In addition, fouling models evaluated for the first time in the case of Oz-MBR indicated that the cake-complete model was suitable to explain membrane fouling mechanism. This comprehensive study demonstrates the performance of MBR coupled with in-situ ozonation, and the obtained results would serve as a useful reference for its implementation at pilot- and/or full-scale., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, the effect of a high concentration of powdered activated carbon (PAC) on pollutant removal and microbial communities was systematically investigated. Micropollutant removal by the 'control' MBR (without PAC addition) was pollutant-specific and was mainly controlled by their molecular properties. The PAC-MBR achieved enhanced removal of micropollutant by 10% (ofloxacin) to 40% (caffeine). Analysis of the microbial communities in the sludge samples collected from both MBRs indicated an increase in the abundance of 24 (out of 31) genera following PAC addition. Notably, bacterial diversity enriched, particularly in the anoxic zone of the PAC-MBR, indicating a positive impact of recirculating mixed liquor containing PAC from the aerobic to the anoxic zone. In addition, PAC improved the abundance of Comamonas and Methanomethylovorans (up to 2.5%) that can degrade recalcitrant micropollutants. According to the quantitative PCR (qPCR) analysis, the copies of functional genes (nirS, nosZ and narG) increased in PAC-MBR. This study demonstrated that MBR could be operated at a high PAC concentration without compromising the pollutant removal and microbial community evolution during wastewater treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Integration of an electrochemical process with membrane bioreactor (MBR) has attracted considerable attention in the last decade for simultaneous improvement in pollutant removal and hydraulic performance of MBR. Electrochemical MBR (eMBR) with sacrificial anodes has been observed to achieve enhanced phosphorus (up to 40%) and micropollutant removal (5-60%). This is because direct anodic oxidation, indirect oxidation by reactive oxygen species and electrocoagulation can supplement the biological process. The application of an electric field can substantially reduce membrane fouling by 10% to 95% in the eMBR as compared to the conventional MBR. Sacrificial electrodes (e.g., iron or aluminium) have been reported to be more suitable for fouling mitigation than non-sacrificial electrodes (e.g., titanium). However, during prolonged operation, metal ions released from sacrificial electrodes can adversely affect microbial activity and could accumulate in activated sludge. Depending on the current density and electrode material (sacrificial or non- sacrificial), anodic oxidation, electrocoagulation, electrophoresis and/or electroosmosis mechanisms are responsible for suppressing membrane fouling propensity. This paper critically reviews the current status of the electrochemical MBR technology and presents a concise summary of eMBR configurations and electrode materials. Comparative removal of bulk organics, nutrients and micropollutants in the eMBR and conventional MBR is discussed, and performance governing factors are elucidated. Impacts of operating conditions such as current density on mixed liquor properties (e.g., floc size and zeta potential) and microbial activity are elucidated. The extent of membrane fouling mitigation along with associated mechanisms as well as energy consumption is explained and critically analysed. Future research directions are suggested to fast track the scalability of eMBR, which include but are not limited to electrode lifetime, development of self-cleaning conductive membranes, optimisation of operating parameters, removal of emerging micropollutants, accumulation of toxic metals in activated sludge, and degradation by-products and ecotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In biological wastewater treatment systems, extracellular polymeric substances (EPS) are continuously excreted as a response to environmental changes and substrate conditions. It could severely affect the treatment efficacy such as membrane fouling, dewaterability and the formation of carcinogenic disinfection by-products (DBPs). The heterogeneous dissolved organic matter (DOM) with varying size and chemical nature constitute a primary proportion of EPS. In the last few decades, fluorescence spectroscopy has received increasing attention for characterizing these organic substances due to the attractive features of this low-cost spectroscopic approach, including easy sample handling, rapid, non-destructive and highly sensitive nature. In this review, we summarize the application of fluorescence spectroscopy for characterizing EPS and provide the potential implications for online monitoring of water quality along with its limitations. We also link the dynamics of fluorescent dissolved organic matter (FDOM) in EPS with operational and environmental changes in wastewater treatment systems as well as their associations with metal binding, membrane fouling, adsorption, toxicity, and dewaterability. The multiple modes of exploration of fluorescence spectra, such as synchronous spectra with or without coupling with two-dimensional correlation spectroscopy (2D-COS), excitation-emission matrix (EEM) deconvoluted fluorescence regional integration (FRI), and parallel factor analysis (PARAFAC) are also discussed. The potential fluorescence indicators to depict the composition and bulk characteristics of EPS are also of interest. Further studies are highly recommended to expand the application of fluorescence spectroscopy paired with appropriate supplementary techniques to fully unravel the underlying mechanisms associated with EPS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, an indigenous activation of persulfate by iron-bearing minerals was examined using peroxymonosulfate (PMS) and peroxydisulfate (PDS) for the dewaterability and extracellular polymeric substances (EPS) composition of anaerobically digested sludge (ADS). Iron minerals originally present in the ADS seemed to operate as an initiator of the persulfate activation, which was indicated by an increase in the total dissolved iron in the supernatant. The PMS showed higher performance in improving the ADS dewaterability compared to the PDS, with more reduction in the average microbial flocs size. The extracted EPS consisted of three different fluorescent components of tryptophan-like (C1), humic-like (C2), and fulvic-like (C3) components. In the tightly bound (TB)-EPS, two humic-like components (C2 and C3), which were resistant to degradation, exhibited a strong linkage with dewaterability; whereas, in both the PMS and the PDS systems, the C1 was preferentially degraded by the radical-based oxidation, with a greater extent for the PMS-based treatments. The results showed that prior to the actual EPS degradation, the produced radicals were initially involved in cell disruption. The SEC results during the oxidation clearly demonstrated the degradation of a large-sized biopolymer fraction, followed by the production of relatively small sized molecules. They also revealed in the TB-EPS a close association between the ADS dewaterability and the degradation of humic substances., (Copyright © 2019. Published by Elsevier B.V.)

A comprehensive review of the recently published work on asphaltene destabilization and flocculation kinetics is presented. Four different experimental techniques were used to study asphaltenes undergoing flocculation process in crude oils and model oils. The asphaltenes were destabilized by different n-alkanes and a geometric population balance with the Smoluchowski collision kernel was used to model the asphaltene aggregation process. Additionally, by postulating a relation between the aggregation collision efficiency and the solubility parameter of asphaltenes and the solution, a unified model of asphaltene aggregation model was developed. When the aggregation model is applied to the experimental data obtained from several different crude oil and model oils, the detection time curves collapsed onto a universal single line, indicating that the model successfully captures the underlying physics of the observed process., (Copyright © 2016 Elsevier B.V. All rights reserved.)