Combining Passive Sampling with Suspect and Nontarget Screening to Characterize Organic Micropollutants in Streams Draining Mixed-Use Watersheds.

Organic micropollutants (OMPs) represent an anthropogenic stressor on stream ecosystems. In this work, we combined passive sampling with suspect and nontarget screening enabled by liquid chromatography-high-resolution mass spectrometry to characterize complex mixtures of OMPs in streams draining mixed-use watersheds. Suspect screening identified 122 unique OMPs for target quantification in polar organic chemical integrative samplers (POCIS) and grab samples collected from 20 stream sites in upstate New York over two sampling seasons. Hierarchical clustering established the co-occurrence profiles of OMPs in connection with watershed attributes indicative of anthropogenic influences. Nontarget screening leveraging the time-integrative nature of POCIS and the cross-site variability in watershed attributes prioritized and confirmed 11 additional compounds that were ubiquitously present in monitored streams. Field sampling rates for 37 OMPs that simultaneously occurred in POCIS and grab samples spanned the range of 0.02 to 0.22 L/d with a median value of 0.07 L/d. Comparative analyses of the daily average loads, cumulative exposure-activity ratios, and multi-substance potentially affected fractions supported the feasibility of complementing grab sampling with POCIS for OMP load estimation and screening-level risk assessments. Overall, this work demonstrated a multi-watershed sampling and screening approach that can be adapted to assess OMP contamination in streams across landscapes.

Improved Pharmaceutical Properties of Honokiol via Salification with Meglumine: an Exception to Oft-quoted ∆pKa Rule.

Honokiol (HK), a BCS class II drug with a wide range of pharmacological activities, has poor solubility and low oral bioavailability, severely limiting its clinical application. In the current study, incorporating a water-soluble meglumine (MEG) into the crystal lattice of HK molecule was performed to improve its physicochemical properties. The binary mixture of HK and MEG was obtained by anti-solvent method and characterized by TGA, DSC, FTIR, and PXRD. The SCXRD analysis showed that two HK- molecules and two MEG+ molecules were coupled in each unit cell via the ionic interaction along with intermolecular hydrogen bonds, suggesting the formation of a salt, which was further confirmed by the XPS measurements. However, the ∆pKa value between HK and MEG was found to be less than 1, which did not follow the oft-quoted ∆pKa rule for salt formation. After salification with MEG, the solubility and dissolution rate of HK exhibited 3.50 and 25.33 times improvement than crystalline HK, respectively. Simultaneously, the powder flowability, tabletability and stability of HK-MEG salt was also significantly enhanced, and the salt was not more hygroscopic, and that salt formation did not compromise processability in that regard. Further, in vivo pharmacokinetic study showed that Cmax and AUC0-t of HK-MEG salt were enhanced by 2.92-fold and 2.01-fold compared to those of HK, respectively, indicating a considerable improvement in HK oral bioavailability.

Suspect screening to support source identification and risk assessment of organic micropollutants in the aquatic environment of a Sub-Saharan African urban center.

Organic micropollutants (OMPs) are contaminants of global concern and have garnered increasing attention in Africa, particularly in urban and urbanizing areas of Sub-Saharan Africa (SSA). In this work, we coupled suspect screening enabled by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) with multivariate analysis to characterize OMPs in wastewater, surface water, and groundwater samples collected from Kampala, the capital and largest city of Uganda. Suspect screening prioritized and confirmed 157 OMPs in Kampala samples for target quantification. Many OMPs detected in Kampala samples occurred within concentration ranges similar to those documented in previous studies reporting OMP occurrence in SSA, but some have never or rarely been quantified in environmental water samples from SSA. Hierarchical cluster analysis established the source-related co-occurrence profiles of OMPs. Partial least squares regression and multiple linear regression analyses further pinpointed the concentration of nitrate and the content of a fluorescent organic matter component with excitation/emission maxima around 280/330 nm as predictors for the sample-specific cumulative concentrations of OMPs, suggesting the likely contribution of diffuse runoff and wastewater discharges to OMP occurrence in the aquatic environment of Kampala. Parallel calculations of exposure-activity ratios and multi-substance potentially affected fractions provided insights into the potential for biological effects associated with OMPs and highlighted the importance of expanded analytical coverage for screening-level risk assessments. Overall, our study demonstrates a versatile database-driven screening and data analysis methodology for the multipronged characterization of OMP contamination in a representative SSA urban center.

Dense Multi-Object 3D Glomerular Reconstruction and Quantification on 2D Serial Section Whole Slide Images.

There has been a long pursuit for precise and reproducible glomerular quantification in the field of renal pathology in both research and clinical practice. Currently, 3D glomerular identification and reconstruction of large-scale glomeruli are labor-intensive tasks, and time-consuming by manual analysis on whole slide imaging (WSI) in 2D serial sectioning representation. The accuracy of serial section analysis is also limited in the 2D serial context. Moreover, there are no approaches to present 3D glomerular visualization for human examination (volume calculation, 3D phenotype analysis, etc.). In this paper, we introduce an end-to-end holistic deep-learning-based method that achieves automatic detection, segmentation and multi-object tracking (MOT) of individual glomeruli with large-scale glomerular-registered assessment in a 3D context on WSIs. The high-resolution WSIs are the inputs, while the outputs are the 3D glomerular reconstruction and volume estimation. This pipeline achieves 81.8 in IDF1 and 69.1 in MOTA as MOT performance, while the proposed volume estimation achieves 0.84 Spearman correlation coefficient with manual annotation. The end-to-end MAP3D+ pipeline provides an approach for extensive 3D glomerular reconstruction and volume quantification from 2D serial section WSIs.

Coupling Suspect and Nontarget Screening with Mass Balance Modeling to Characterize Organic Micropollutants in the Onondaga Lake-Three Rivers System.

Characterizing the occurrence, sources, and fate of organic micropollutants (OMPs) in lake-river systems serves as an important foundation for constraining the potential impacts of OMPs on the ecosystem functions of these critical landscape features. In this work, we combined suspect and nontarget screening with mass balance modeling to investigate OMP contamination in the Onondaga Lake-Three Rivers system of New York. Suspect and nontarget screening enabled by liquid chromatography-high-resolution mass spectrometry led to the confirmation and quantification of 105 OMPs in water samples collected throughout the lake-river system, which were grouped by their concentration patterns into wastewater-derived and mixed-source clusters via hierarchical cluster analysis. Four of these OMPs (i.e., galaxolidone, diphenylphosphinic acid, N-butylbenzenesulfonamide, and triisopropanolamine) were prioritized and identified by nontarget screening based on their characteristic vertical distribution patterns during thermal stratification in Onondaga Lake. Mass balance modeling performed using the concentration and discharge data highlighted the export of OMPs from Onondaga Lake to the Three Rivers as a major contributor to the OMP budget in this lake-river system. Overall, this work demonstrated the utility of an integrated screening and modeling framework that can be adapted for OMP characterization, fate assessment, and load apportionment in similar surface water systems.

High-throughput wastewater analysis for substance use assessment in central New York during the COVID-19 pandemic.

Wastewater entering sewer networks represents a unique source of pooled epidemiological information. In this study, we coupled online solid-phase extraction with liquid chromatography-high resolution mass spectrometry to achieve high-throughput analysis of health and lifestyle-related substances in untreated municipal wastewater during the coronavirus disease 2019 (COVID-19) pandemic. Twenty-six substances were identified and quantified in influent samples collected from six wastewater treatment plants during the COVID-19 pandemic in central New York. Over a 12 week sampling period, the mean summed consumption rate of six major substance groups (i.e., antidepressants, antiepileptics, antihistamines, antihypertensives, synthetic opioids, and central nervous system stimulants) correlated with disparities in household income, marital status, and age of the contributing populations as well as the detection frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater and the COVID-19 test positivity in the studied sewersheds. Nontarget screening revealed the covariation of piperine, a nontarget substance, with SARS-CoV-2 RNA in wastewater collected from one of the sewersheds. Overall, this proof-of-the-concept study demonstrated the utility of high-throughput wastewater analysis for assessing the population-level substance use patterns during a public health crisis such as COVID-19.

Organic Micropollutants in New York Lakes: A Statewide Citizen Science Occurrence Study.

The widespread occurrence of organic micropollutants (OMPs) is a challenge for aquatic ecosystem management, and closing the gaps in risk assessment of OMPs requires a data-driven approach. One promising tool for increasing the spatiotemporal coverage of OMP data sets is through the active involvement of citizen volunteers to expand the scale of OMP monitoring. Working collaboratively with volunteers from the Citizens Statewide Lake Assessment Program (CSLAP), we conducted the first statewide study on OMP occurrence in surface waters of New York lakes. Samples collected by CSLAP volunteers were analyzed for OMPs by a suspect screening method based on mixed-mode solid-phase extraction and liquid chromatography-high resolution mass spectrometry. Sixty-five OMPs were confirmed and quantified in samples from 111 lakes across New York. Hierarchical clustering of OMP occurrence data revealed the relevance of 11 most frequently detected OMPs for classifying the contamination status of lakes. Partial least squares regression and multiple linear regression analyses prioritized three water quality parameters linked to agricultural and developed land uses (i.e., total dissolved nitrogen, specific conductance, and a wastewater-derived fluorescent organic matter component) as the best combination of predictors that partly explained the interlake variability in OMP occurrence. Lastly, the exposure-activity ratio approach identified the potential for biological effects associated with detected OMPs that warrant further biomonitoring studies. Overall, this work demonstrated the feasibility of incorporating citizen science approaches into the regional impact assessment of OMPs.

Coamorphization combined with complexation enhances dissolution of lurasidone hydrochloride and puerarin with synchronized release.

Coamorphous systems have gained increasing interests due to their ability to enhance solubility and dissolution of poorly soluble drugs. In the current study, coamorphous system of lurasidone hydrochloride (LH), a BCS class II drug, with puerarin (PUE) was prepared by the solvent-evaporation method. The observation of a single Tg at 65.8 °C in differential scanning calorimetry thermogram and the absence of crystalline diffraction peaks in powder X-ray diffraction pattern indicated the formation of coamorphous LH-PUE. Compared to physical mixture of amorphous LH and amorphous PUE, peak shifts in FTIR with principal component analysis indicated potential intermolecular hydrogen bonding formed between the carbonyl group of LH and the hydroxyl group of PUE in the coamorphous system. In comparison to crystalline/amorphous LH and PUE, the coamorphous system exhibited significantly enhanced dissolution with synchronized release behavior of LH and PUE, which was mainly due to the complexation formation between LH and PUE in solution proved by fluorescence quenching test and phase-solubility diagram. In addition, coamorphous LH-PUE showed superior physical stability over pure amorphous LH and PUE under both long-term and accelerated storage conditions.

Improving Tabletability of Excipients by Metal-Organic Framework-Based Cocrystallization: a Study of Mannitol and CaCl2.

PURPOSE: To improve tabletability of pharmaceutical excipient mannitol by forming cocrystal with metal-organic framework (MOF) structure. METHODS: Mannitol was cocrystallized with CaCl2 by slurry method and solvent evaporation method. The obtained cocrystal was characterized by SCXRD, PXRD, and thermal analysis. Comparative study on tabletability between cocrystal and ß-mannitol were then conducted. Differences in tabletability were subsequently analyzed using the bonding area-bonding strength (BA-BS) model and correlated with their crystal structures. RESULTS: The prepared cocrystal contains mannitol, CaCl2 and water in molar ratio of 1:1:2 (i.e. mannitol·CaCl2·2H2O) and all the Ca2+ in the cocrystal are linked together by mannitol molecules through an infinite coordination network, demonstrating a typical MOF structure. Compared with ß-mannitol, such MOF-based cocrystal showed improved tabletability (~2-fold increased tensile strength) and reduced lamination tendency (~3-fold increased minimum compaction pressure to occur lamination). The tabletability improvement of cocrystal was dominated by its higher BS, which is attributed to stronger intermolecular interactions. The reduced lamination tendency was attributed to its lower in-die elastic recovery than ß-mannitol. CONCLUSIONS: MOF-based cocrystallization will be a promising and valuable approach to tailor mechanical properties of pharmaceutical materials in order to achieve better pharmaceutical performance.

Switchable Magnetic Anisotropy of Ferromagnets by Dual-Ion-Manipulated Orbital Engineering.

Tailoring magnetic anisotropy of ferromagnetic films is a critical issue in constructing energy-efficient and high-density magnetic memory devices. Presently, the effective tunability was focused on a single-ion-manipulated electronic structure evolution. Here, we reported a new strategy of dual-ion-tuned orbital structure and magnetic anisotropy of ferromagnetic films. N-doped Fe/MgO bilayer films were deposited on shape memory alloy substrates which can generate a significant lattice strain on the films. Before the N ions participate into the manipulation, the Fe/MgO film shows an in-plane magnetic anisotropy, which may be due to excessive Fe-O orbital hybridization. Interestingly, the N and O ions synergistically manipulate electronic coordination of the Fe layer, which can be further modified by the lattice strain through a charge transfer among N-Fe-O. Under such effect, the magnetic anisotropy of the film is switchable from in-plane to perpendicular magnetic anisotropy (PMA). The X-ray line dichroism (XLD) characterization reveals that the anisotropy regulation is related to Fe 3d orbital evolution: N-Fe orbital hybridization promotes the Fe dz2 orbital occupation effectively, which is beneficial in increasing PMA by strengthening Fe-O orbital hybridization along the out-of-plane direction. However, the compressive strain induces a N-Fe-O charge transfer and reduces the Fe dz2 electronic occupation, which weakens the PMA of films. These findings provide a new dimensionality for regulating orbital performance of ferromagnetic materials and developing strain-assisted memory devices.

Preparation and Characteristics of a Novel Sorptive Extraction Stir Bar Based on Cd-Imprinted Polymer Monoliths.

A novel monolithic stir-bar for Cd(II) sorption extraction was prepared by ion-imprinting technology and in situ stepwise polymerization of epoxy resin (EP). The condensation product of diethylenetriamine and thiourea (DETATUC) was used as a curing agent, with Cd ions as template ions and polyethylene glycol 1540 as a porogenic agent. The main parameters of the stir-bar sorption extraction-EP-DETATUC material for the extraction and desorption of Cd(II) in aqueous solution were investigated, and inductively coupled plasma-atomic emission spectrometry was performed. The results showed that the monolithic material possessed good permeability and reusability. The maximum adsorption capacity was 136.58 µmol g(-1) at pH 6.0. The optimized conditions were the following: stirring rate at 300 rpm, adsorption time at 40 min, elution media at 0.25 mol L(-1) EDTA, and elution time at 20 min. The accuracy of the method was assessed by spiking two water samples and one plant sewage sample with Cd at two concentration levels. Recoveries of 96-102% were obtained.

Ionic liquid-based hollow fiber-supported liquid-phase microextraction enhanced electrically for the determination of neutral red.

A method of ionic liquid-based hollow fiber liquid-phase microextraction enhanced electrically was successfully developed and applied to the extraction and determination of neutral red (NR) dye, which was selected as the model analyte. A room temperature ionic liquid, 1-octyl-3-methylimidazolium hexafluorophosphate ([C8mim][PF6]), was placed in the pores of a polytetrafluoethylene hollow fiber, which acts as a liquid membrane and the acceptor solution. The extraction parameters affecting the enrichment factor of NR, such as pH, extraction time, elution time, stirring rate, and the voltage were optimized. In addition, UV-Visible (UV-Vis) or electrochemiluminescence spectra were also determined. The extraction rate and capacity of NR could be improved significantly by cathodic polarization. Under the optimized extraction conditions (organic liquid microextraction phase [C8mim][PF6], pH 7, stirring rate 300 rpm, extraction time 20 minutes, ultrasonic-assisted elution time 3 minutes, voltage -70 V), the detection limit of 0.38 µg/L and linear correlation coefficient of r > 0.99 were obtained. The established method was successfully applied to the analysis of three soft drink samples, which were spiked with NR standards at the concentrations of 0.1, 1.0, and 5.0 mg/L, and satisfactory results were obtained.