Isomer of per- and polyfluoroalkyl substances and red blood cell indices in adults: The Isomers of C8 Health Project in China.

This study aimed to explore the isomer-specific, sex-specific, and joint associations of PFAS and red blood cell indices. We used data of 1,238 adults from the Isomers of C8 Health Project in China. Associations of PFAS isomers and red blood cell indices were explored using multiple linear regression models, Bayesian Kernel Machine Regression models and subgroup analysis across sex. We found that serum concentration of linear (n-) and branched (Br-) isomers of perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) were significantly associated with red blood cell indices in single-pollutant models, with stronger associations observed for n-PFHxS than Br-PFHxS, in women than in men. For instance, the estimated percentage change in hemoglobin concentration for n-PFHxS (3.65%; 95% CI: 2.95%, 4.34%) was larger than that for Br-PFHxS (0.96%; 95% CI: 0.52%, 1.40%). The estimated percentage change in red blood cell count for n-PFHxS in women (2.55%; 95% CI: 1.81%, 3.28%) was significantly higher than that in men (0.12%; 95% CI: -1.04%, 1.29%) (Pinter < 0.001). Similarly, sex-specific positive association of PFAS mixture and outcomes was observed. Therefore, the structure, susceptive population, and joint effect of PFAS isomers should be taken into consideration when evaluating the health risk of chemicals.

Metallacyclobutadienes: Intramolecular Rearrangement from Kinetic to Thermodynamic Isomers.

Metallacyclobutadienes (MCBDs) are key intermediates of alkyne metathesis reactions. There are in principle two isomerization pathway from kinetic to thermodynamic MCBDs, intermolecular and intramolecular. However, systems that simultaneously isolate two kinds of MCBD isomers have not been achieved, thus restricting the mechanistic studies of the isomerization. Here the reactivity of a metallapentalyne that contains an M≡C bond within the aromatic ring, with alkynes to afford a series of MCBD-fused metallapentalenes is studied. In some cases, both kinetic and thermodynamic products are isolated in the same system, which has never been observed in previous MCBD reactions. Furthermore, the isomerization of MCBD-fused metallapentalenes is investigated both experimentally and theoretically, indicating that it is an intramolecular process involving a metallatetrahedrane (MTd) intermediate. This research provides experimental evidence demonstrating that one MCBD can undergo intramolecular rearrangement to transform into another.

The molecular mechanisms underlying optical isomer arbutin permeating the skin: The molecular interaction between arbutin and skin components.

Arbutin, a typical optical isomer, has garnered widespread acclaim in the whitening cosmetics for its favorable efficacy and safety. However, the molecular mechanisms underlying α-arbutin and ß-arbutin permeating across the skin have not elucidated clearly yet. Herein we aimed to unveil how α-arbutin and ß-arbutin interacted with keratin or SC lipids, further demonstrating their relationship with their drug permeability. We found that α-arbutin displayed significantly higher drug accumulation into the porcine skin than ß-arbutin within 24 h through in vitro permeation test. Moreover, α-arbutin predominantly induced the alternations of secondary structure of amide II during the drug permeation, which was favorable for α-arbutin permeation. On the contrary, ß-arbutin exhibited an observable effect on the stretching vibration of SC lipids, possessing a significantly stronger mixing energy, binding energy and compatibility with ceramide (Cer) than that of α-arbutin, which ultimately restricted its permeation. Interestingly, free fatty acids and ceramides of the SC lipids specifically utilized its oxygen atom of carboxyl group to dock the arbutin molecules, enhancing their affinity with ß-arbutin, as confirmed by molecular simulation and 13Carbon Nuclear Magnetic Resonance. Nevertheless, a favorable compatibility between α-arbutin and keratin was observed. It was emphasized that the distinct spatial configuration and opposite optical rotation of arbutin was the leading factor impacting the intermolecular force between arbutin and the SC, and resulted in a diverse drug permeation. In cellular and in vivo skin pharmacokinetic studies, α-arbutin also possessed a higher cellular uptake and topical bioavailability than ß-arbutin. This study revealed the transdermal permeation mechanisms of optical isomer arbutin at the molecular levels, providing methodological reference for the investigations of permeation behaviors of other isomers with similar spatial configuration.

Spatial heterogeneity of per- and polyfluoroalkyl substances caused by glacial melting in Tibetan Lake Nam Co due to global warming.

Per- and polyfluoroalkyl substances (PFASs) in high-latitude polar regions and the Tibetan Plateau have received widespread international attention. Here, we measured 18 PFASs and 11 major isomers in the lake water, sediment, and surrounding runoff of Lake Nam Co in 2020. The concentrations of ultrashort-chain trifluoroacetic acid (TFA) and perfluoropropanoic acid (PFPrA) and major isomers of perfluoooctanoic acid (PFOA) and perfluoooctane sulfonate acid (PFOS) in water bodies in high-latitude polar regions and the Tibetan Plateau are reported for the first time. The results showed that the concentration of ∑PFASs in glacial runoff was approximately 139 % greater than that in nonglacial runoff. The concentrations of ∑PFASs in the lake water and sediment in the southern lake with multiple glacial runoff events were approximately 113 % and 108 % higher, respectively, than those in the northern lake. The concentrations of short-chain perfluorobutanoic acid (PFBA) and ultrashort-chain TFA and PFPrA, which may be indicators of ice and snow melt, exhibited significant spatial heterogeneity. Overall, the spatial heterogeneity of PFAS concentrations in the water, sediment and surrounding runoff of Lake Nam Co may be caused mainly by glacial melting.

Concerning the structures of Lewis base adducts of titanium(IV) hexafluoroisopropoxide.

The reaction of titanium(IV) chloride with sodium hexafluoroisopropoxide, carried out in hexafluoroisopropanol, produces titanium(IV) hexafluoroisopropoxide, which is a liquid at room temperature. Recrystallization from coordinating solvents, such as acetonitrile or tetrahydrofuran, results in the formation of bis-solvate complexes. These compounds are of interest as possible Ziegler-Natta polymerization catalysts. The acetonitrile complex had been structurally characterized previously and adopts a distorted octahedral structure in which the nitrile ligands adopt a cis configuration, with nitrogen lone pairs coordinated to the metal. The low-melting tetrahydrofuran complex has not provided crystals suitable for single-crystal X-ray analysis. However, the structure of chloridotris(hexafluoroisopropoxido-κO)bis(tetrahydrofuran-κO)titanium(IV), [Ti(C3HF6O)3Cl(C4H8O)2], has been obtained and adopts a distorted octahedral coordination geometry, with a facial arrangement of the alkoxide ligands and adjacent tetrahydrofuran ligands, coordinated by way of metal-oxygen polar coordinate interactions.

Preparation of two amphiphilic dendritic small molecule gelators based on poly (aryl ether) modified silica-based chromatographic stationary phases and molecular shape recognition for shape-restricted isomers.

Geometric isomers tend to have similar polarities and differ only in molecular shape. Vigorously developing new stationary phases to meet the requirements for the separation of isomers that have similar physicochemical properties is still an urgent topic in separation science. Poly (arylene ether)-based dendrimers are known for their multifunctional branched peripheral structures and high self-assembly properties. In this paper, two amphiphilic dendritic organic small molecule gelling agents based on poly (aryl ether), PAE-ANT and PAE-PA, were prepared and conjugated to the silica surface. SiO2@PAE-ANT and SiO2@PAE-PA were used as HPLC stationary phases for the separation of non-polar shape-restricted isomers. Both stationary phases have very high molecular shape selectivity for isomers such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), tocopherols and carotenoids. Separation of cis-trans geometric isomers such as diethylstilbestrol and polar compounds such as monosubstituted benzenes and anilines can also be achieved. These two columns offer more flexible selectivity and higher separation performance than commercial C18 and phenyl columns. There is a difference in molecular shape selectivity between the two stationary phases for the same analyte test probes. SiO2@PAE-ANT showed slightly better linear selectivity for non-polar shape-restricted isomers compared to SiO2@PAE-PA with Janus-type PAE-PA bonding phase. This separation behavior may be attributed to the ordered spatial structure formed by the gel factor on the surface of the stationary phase and the combined effect of multiple weak interaction centers (hydrophobic, hydrophilic, hydrogen bonding and π-π interactions). It was also possible to separate nucleoside and nucleobase strongly polar compounds well in the HILIC mode, suggesting that hydrophilic groups in PAE-ANT and PAE-PA are involved in the interactions, reflecting their amphiphilic nature. The results show that the ordered gelation of dendritic organic small molecule gelators on the SiO2 surface, along with multiple carbonyl-π, π-π and other interactions, play a crucial role in the separating shape-restricted isomers. The integrated and ordered functional groups serve as the primary driving force behind the exceptionally high molecular shape selectivity of SiO2@PAE-ANT and SiO2@PAE-PA phases. Alterations in the structure of dendritic organic small molecule gelators can impact both molecular orientation and recognition ability, while changes in the type of functional groups influences the separation mechanism of shape-restricted isomers.

25.71%-Efficiency FACsPbI3 Perovskite Solar Cells Enabled by A Thiourea-based Isomer.

Various isomers have been developed to regulate the morphology and reduce defects in state-of-the-art perovskite solar cells. To insight the structure-function-effect correlations for the isomerization of thiourea derivatives on the performance of the perovskite solar cells (PSCs), we developed two thiourea derivatives [(3,5-dichlorophenyl)amino]thiourea (AT) and N-(3,5-dichlorophenyl)hydrazinecarbothioamide (HB). Supported by experimental and calculated results, it was found that AT can bind with undercoordinated Pb2+ defect through synergistic interaction between N1 and C=S group with a defect formation energy of 1.818 eV, which is much higher than that from the synergistic interaction between two -NH- groups in HB and perovskite (1.015 eV). Moreover, the stronger interaction between AT and Pb2+ regulates the crystallization process of perovskite film to obtain a high-quality perovskite film with high crystallinity, large grain size, and low defect density. Consequently, the AT-treated FACsPbI3 device engenders an efficiency of 25.71% (certified as 24.66%), which is greatly higher than control (23.74%) and HB-treated FACsPbI3 devices (25.05%). The resultant device exhibits a remarkable stability for maintaining 91.0% and 95.2% of its initial efficiency after aging 2000 h in air condition or tracking at maximum power point for 1000 h, respectively.

Serum Mac-2 binding protein glycosylation isomer dynamics in patients achieving sustained virologic response for hepatitis C virus.

BACKGROUND AND AIM: Understanding the dynamics of serum Mac-2 binding protein glycosylation isomer (M2BPGi) remains pivotal for hepatitis C virus (HCV) patients' post-sustained virologic response (SVR12) through direct-acting antivirals (DAAs). METHODS: We compared areas under receiver operating characteristic curves (AUROCs) of M2BPGi, FIB-4, and APRI and assess M2BPGi cutoff levels in predicting fibrosis stages of ≥F3 and F4 utilizing transient elastography in 638 patients. Variations in M2BPGi levels from pretreatment to SVR12 and their association with pretreatment alanine transaminase (ALT) levels and fibrosis stage were investigated. RESULTS: The AUROCs of M2BPGi were comparable to FIB-4 in predicting ≥F3 (0.914 vs 0.902, P = 0.48) and F4 (0.947 vs 0.915, P = 0.05) but were superior to APRI in predicting ≥F3 (0.914 vs 0.851, P = 0.001) and F4 (0.947 vs 0.857, P < 0.001). Using M2BPGi cutoff values of 2.83 and 3.98, fibrosis stages of ≥F3 and F4 were confirmed with a positive likelihood ratio ≥10. The median M2BPGi change was -0.55. Patients with ALT levels ≥5 times ULN or ≥F3 demonstrated more pronounced median decreases in M2BPGi level compared to those with ALT levels 2-5 times ULN and <2 times ULN (-0.97 vs -0.68 and -0.44; P < 0.001) or with < F3 (-1.52 vs -0.44; P < 0.001). CONCLUSIONS: Serum M2BPGi is a reliable marker for advanced hepatic fibrosis. Following viral clearance, there is a notable M2BPGi decrease, with the extent of reduction influenced by ALT levels and fibrosis stage.

Filling the gaps in peptide maps with a platform assay for top-down characterization of purified protein samples.

Liquid chromatography-mass spectrometry (LC-MS) intact mass analysis and LC-MS/MS peptide mapping are decisional assays for developing biological drugs and other commercial protein products. Certain PTM types, such as truncation and oxidation, increase the difficulty of precise proteoform characterization owing to inherent limitations in peptide and intact protein analyses. Top-down MS (TDMS) can resolve this ambiguity via fragmentation of specific proteoforms. We leveraged the strengths of flow-programmed (fp) denaturing online buffer exchange (dOBE) chromatography, including robust automation, relatively high ESI sensitivity, and long MS/MS window time, to support a TDMS platform for industrial protein characterization. We tested data-dependent (DDA) and targeted strategies using 14 different MS/MS scan types featuring combinations of collisional- and electron-based fragmentation as well as proton transfer charge reduction. This large, focused dataset was processed using a new software platform, named TDAcquireX, that improves proteoform characterization through TDMS data aggregation. A DDA-based workflow provided objective identification of αLac truncation proteoforms with a two-termini clipping search. A targeted TDMS workflow facilitated the characterization of αLac oxidation positional isomers. This strategy relied on using sliding window-based fragment ion deconvolution to generate composite proteoform spectral match (cPrSM) results amenable to fragment noise filtering, which is a fundamental enhancement relevant to TDMS applications generally.

Spectral and HPLC Analyses of Synthesized Butin and Butein.

Butin and butein are significant bioactive flavanones derived from plants, existing as tautomers of each other. However, their physicochemical attributes, such as their spectral profiles under varying experimental conditions in aqueous solutions and established chromatographic methods for distinguishing between them, remain undetermined. In this study, we determined the basic properties of butin and butein using conventional spectroscopic, reversed-phase, and chiral HPLC analyses. The spectra of the synthesized butin and butein were analyzed using a UV-Vis spectrophotometer in several solvents with different polarities as well as in aqueous solutions at various pH values. Furthermore, the behavior of the measured spectra was reproduced by calculations to reveal the effects of the solvent and pH on the spectra of butin and butein in organic and aqueous solutions. Subsequently, we assessed the structural stability of butin and butein using reversed-phase HPLC, which revealed that butein is unstable compared with butin in a general culture medium. The synthesized butin was effectively separated into R- and S-isomers with positive and negative Cotton effects, respectively, via HPLC using a chiral column. These findings will aid in uncovering the individual properties of both butin and butein that may have been concealed by their tautomerism and enable the synthesis of S-butin, which is typically challenging and time-consuming to isolate.

Successively Controlling Nanoscale Wrinkles of Ultrathin 2D Metal-Organic Framework Nanosheets.

The wrinkles are pervasive in ultrathin two-dimensional (2D) materials, but the regulation of wrinkles is rarely explored systematically. However, the regulation of wrinkles at nanometer scale is merely explored. Here, we employed a series of carboxylic acids (from formic acid to octanoic acid) to control the wrinkles of Zr-BTB (BTB = 1, 3, 5-(4-carboxylphenyl)-benzene) metal-organic framework (MOF) nanosheet. The wrinkles at the micrometer scale were observed with transmission electron microscopy. Furthermore, high-angle annular dark-field (HAADF) images showed lattice distortion in many nanoscale regions, which was precisely matched to the nano-wrinkles. With the changes of hydrophilicity/hydrophobicity, MOF-MOF and MOF-solvent interactions were synergistically regulated and wrinkles with different sizes were obtained, which was supported by HAADF, molecular dynamics and density functional theory calculation. Different wrinkle sizes resulted in different pore sizes between the Zr-BTB nanosheet interlayers, providing highly-oriented thin films and the successive optimization of kinetic diffusion pathways, proved by grazing-incidence wide-angle X-ray scattering and nitrogen adsorption. The most suitable wrinkle pore from Zr-BTB-C4 exhibited highly efficient chromatographic separation of the substituted benzene isomers. Our work provides a rational route for the modulation of nanoscale wrinkles and their stacked pores of MOF nanosheets and improves the separation abilities of MOFs.

Linear isomer but not branched isomers of perfluorooctane sulfonate in plasma is associated with eicosapentaenoic acid, a seafood consumption biomarker.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are global contaminants. Seafood consumption is a possible PFAS exposure route to humans while the isomer specific analysis has not been conducted. METHODS: Perfluorooctane sulfonate (PFOS), perfluoroheptane sulfonate (PFHpS) and perfluorohexane sulfonate (PFHxS) were investigated in residents of Kyoto, Japan (n = 51). The relationship between plasma PFAS and seafood consumption biomarker, the ratio of eicosapentaenoic acid to arachidonic acid (EPA/AA) was examined by multiple regression analysis. RESULTS: Linear PFOS concentrations showed a significant positive correlation with the EPA/AA ratio in plasma samples (ß = 6.80, p = 0.0014). Linear PFHpS was marginally associated with EPA/AA ratio (ß = 0.178, p = 0.0874). Branched PFOS isomers and PFHxS had no associations with EPA/AA ratios. CONCLUSION: Seafood intake may be a significant exposure pathway for PFAS, such as PFOS but the isomers differ.

Open and Closed Cage Silsesquioxane Dimers.

Polyhedral oligomeric silsesquioxane (POSS) is an organic-inorganic hybrid molecule with two structural variations, closed- and open-cage configurations, referred to as completely condensed POSS (CC-POSS) and corner-opened POSS (CO-POSS), respectively. In this study, we synthesized 12 dimers by combining CC- and CO-POSS variants decorated with isobutyl or phenyl substituents to explore their structure-property relationships. The choice of substituents, both at the cage vertices and open sites, significantly affected the thermal and optical properties of the materials. Modifying the substituents on CO- and CC-POSS, which are isomers, led to significant alterations in the material properties. Notably, isomer-bearing carbazole substituents exhibited a substantially higher quantum yield (0.32) than its counterpart isomer (0.13), underscoring the crucial role of structural nuances in determining material performance. These results offer valuable insights for the design of novel silsesquioxane-based materials.

Determination of 16 ultraviolet-absorbing compounds in marine invertebrates by using LC-USI-MS/MS coupled with QuEChERS.

In this study, we examined multiple endocrine-disrupting ultraviolet-absorbing compounds (UVACs) in marine invertebrates used in personal care products and packaging. Modified QuEChERS and liquid chromatography UniSpray ionization tandem mass spectrometry were used to identify 16 UVACs in marine invertebrates. Matrix-matched calibration curves revealed high linearity (r ≥ 0.9929), with limits of detection and quantification of 0.006-1.000 and 0.020-3.000 ng/g w.w., respectively. In oysters, intraday and interday analyses revealed acceptable accuracy (93%-120%) and precision (≤18%), except for benzophenone (BP) and ethylhexyl 4-(dimethylamino) benzoate. Analysis of 100 marine invertebrate samples revealed detection frequencies of 100%, 98%, 89%, 64%, and 100% for BP, 4-hydroxybenzophenone, 4-methylbenzophenone, 4-methylbenzylidene camphor, and benzophenone-3 (BP-3), respectively. BP and BP-3 were detected at concentrations of 4.40-27.39 and < 0.020-0.560 ng/g w.w., respectively, indicating their widespread presence. Overall, our proposed method successfully detected UVACs in marine invertebrates, raising concerns regarding their potential environmental and health effects.

Accumulation of Per- and Polyfluoroalkyl Substances (PFAS) in Coastal Sharks from Contrasting Marine Environments: The New York Bight and The Bahamas.

Per- and polyfluoroalkyl substances (PFAS) enter the marine food web, accumulate in organisms, and potentially have adverse effects on predators and consumers of seafood. However, evaluations of PFAS in meso-to-apex predators, like sharks, are scarce. This study investigated PFAS occurrence in five shark species from two marine ecosystems with contrasting relative human population densities, the New York Bight (NYB) and the coastal waters of The Bahamas archipelago. The total detected PFAS (∑PFAS) concentrations in muscle tissue ranged from 1.10 to 58.5 ng g-1 wet weight, and perfluorocarboxylic acids (PFCAs) were dominant. Fewer PFAS were detected in Caribbean reef sharks (Carcharhinus perezi) from The Bahamas, and concentrations of those detected were, on average, ∼79% lower than in the NYB sharks. In the NYB, ∑PFAS concentrations followed: common thresher (Alopias vulpinus) > shortfin mako (Isurus oxyrinchus) > sandbar (Carcharhinus plumbeus) > smooth dogfish (Mustelus canis). PFAS precursors/intermediates, such as 2H,2H,3H,3H-perfluorodecanoic acid and perfluorooctanesulfonamide, were only detected in the NYB sharks, suggesting higher ambient concentrations and diversity of PFAS sources in this region. Ultralong-chain PFAS (C ≥ 10) were positively correlated with nitrogen isotope values (δ15N) and total mercury in some species. Our results provide some of the first baseline information on PFAS concentrations in shark species from the northwest Atlantic Ocean, and correlations between PFAS, stable isotopes, and mercury further contextualize the drivers of PFAS occurrence.

Improved hydrophobic subtraction model of reversed-phase liquid chromatography selectivity based on a large dataset with a focus on isomer selectivity.

Reversed-phase (RP) liquid chromatography is an important tool for the characterization of materials and products in the pharmaceutical industry. Method development is still challenging in this application space, particularly when dealing with closely-related compounds. Models of chromatographic selectivity are useful for predicting which columns out of the hundreds that are available are likely to have very similar, or different, selectivity for the application at hand. The hydrophobic subtraction model (HSM1) has been widely employed for this purpose; the column database for this model currently stands at 750 columns. In previous work we explored a refinement of the original HSM1 (HSM2) and found that increasing the size of the dataset used to train the model dramatically reduced the number of gross errors in predictions of selectivity made using the model. In this paper we describe further work in this direction (HSM3), this time based on a much larger solute set (1014 solute/stationary phase combinations) containing selectivities for compounds covering a broader range of physicochemical properties compared to HSM1. The molecular weight range was doubled, and the range of the logarithm of the octanol/water partition coefficients was increased slightly. The number of active pharmaceutical ingredients and related synthetic intermediates and impurities was increased from four to 28, and ten pairs of closely related structures (e.g., geometric and cis-/trans- isomers) were included. The HSM3 model is based on retention measurements for 75 compounds using 13 RP stationary phases and a mobile phase of 40/60 acetonitrile/25 mM ammonium formate buffer at pH 3.2. This data-driven model produced predictions of ln α (chromatographic selectivity using ethylbenzene as the reference compound) with average absolute errors of approximately 0.033, which corresponds to errors in α of about 3 %. In some cases, the prediction of the trans-/cis- selectivities for positional and geometric isomers was relatively accurate, and the driving forces for the observed selectivity could be inferred by examination of the relative magnitudes of the terms in the HSM3 model. For some geometric isomer pairs the interactions mainly responsible for the observed selectivities could not be rationalized due to large uncertainties for particular terms in the model. This suggests that more work is needed in the future to explore other HSM-type models and continue expanding the training dataset in order to continue improving the predictive accuracy of these models. Additionally, we release with this paper a much larger data set (43,329 total retention measurements) at multiple mobile phase compositions, to enable other researchers to pursue their own lines of inquiry related to RP selectivity.

In vitro metabolic studies and machine learning analysis of mass spectrometry data: A dual strategy for differentiating alpha-pyrrolidinohexiophenone (α-PHP) and alpha-pyrrolidinoisohexanophenone (α-PiHP) in urine analysis.

Synthetic cathinones are some of the most prevalent new psychoactive substances (NPSs) globally, with alpha-pyrrolidinoisohexanophenone (α-PiHP) being particularly noted for its widespread use in the United States, Europe, and Taiwan. However, the analysis of isomeric NPSs such as α-PiHP and alpha-pyrrolidinohexiophenone (α-PHP) is challenging owing to similarities in their retention times and mass spectra. This study proposes a dual strategy based on in vitro metabolic experiments and machine learning-based classification modelling for differentiating α-PHP and α-PiHP in urine samples: (1) in vitro metabolic experiments using pooled human liver microsomes and liquid chromatography tandem quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) were conducted to identify the key metabolites of α-PHP and α-PiHP from the high-resolution MS/MS spectra. After 5 h incubation, 71.4 % of α-PHP and 64.7 % of α-PiHP remained unmetabolised. Nine phase I metabolites were identified for each compound, including primary ß-ketone reduction (M1) metabolites. Comparing the metabolites and retention times confirmed the efficacy of in vitro metabolic experiments for differentiating NPS isomers. Subsequently, analysis of seven real urine samples revealed the presence for various metabolites, including M1, that could be used as suitable detection markers at low concentrations. The aliphatic hydroxylation (M2) metabolite peak counts and metabolite retention times were used to determine α-PiHP use. (2) Classification models for the parent compounds and M1 metabolites were developed using principal component analysis for feature extraction and logistic regression for classification. The training and test sets were devised from the spectra of standard samples or supernatants from in vitro metabolism experiments with different incubation times. Both models had classification accuracies of 100 % and accurately identified α-PiHP and its M1 metabolite in seven real urine samples. The proposed methodology effectively distinguished between such isomers and confirmed their presence at low concentrations. Overall, this study introduces a novel concept that addresses the complexities in analysing isomeric NPSs and suggests a path towards enhancing the accuracy and reliability of NPS detection.

Mac-2 binding protein glycosylation isomer as a novel predictor of early recurrence after resection for hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC) frequently recurs after radical resection, resulting in a poor prognosis. This study assessed the prognostic value of Mac-2 binding protein glycosylation isomer (M2BPGi) for early recurrence (ER) in patients with HCC. METHODS: Patients who underwent radical resection for HCC between 2015 and 2021. HCC recurrence within one year after curative resection was defined as ER. RESULTS: The 150 patients were divided into two groups: non-ER (116, 77.3%) and ER (34, 22.7%). The ER group had a lower overall survival rate (p < 0.0001) and significantly higher levels of M2BPGi (1.06 vs. 2.74 COI, p < 0.0001) than the non-ER group. High M2BPGi levels (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.31-2.41, p < 0.0001) and a large tumor size (OR 1.31, 95% CI, 1.05-1.63; p = 0.0184) were identified as independent predictors of ER. M2BPGi was the best predictor of ER according to a receiver operating characteristic (ROC) analysis (area under the ROC curve 0.82, p < 0.0001). CONCLUSIONS: M2BPGi can predict ER after surgery and is useful for risk stratification in patients with HCC.

PEPICO analysis of catalytic reactor effluents towards quantitative isomer discrimination: DME conversion over a ZSM-5 zeolite.

The methanol-to-hydrocarbons (MTH) process involves the conversion of methanol, a C1 feedstock that can be produced from green sources, into hydrocarbons using shape-selective microporous acidic catalysts - zeolite and zeotypes. This reaction yields a complex mixture of species, some of which are highly reactive and/or present in several isomeric forms, posing significant challenges for effluent analysis. Conventional gas-phase chromatography (GC) is typically employed for the analysis of reaction products in laboratory flow reactors. However, GC is not suitable for the detection of highly reactive intermediates such as ketene or formaldehyde and is not suitable for kinetic studies under well defined low pressure conditions. Photoelectron-photoion coincidence (PEPICO) spectroscopy has emerged as a powerful analytical tool for unraveling complex compositions of catalytic effluents, but its availability is limited to a handful of facilities worldwide. Herein, PEPICO analysis of catalytic reactor effluents has been implemented at the FinEstBeAMS beamline of MAX IV Laboratory. The conversion of dimethyl ether (DME) on a zeolite catalyst (ZSM-5-MFI27) is used as a prototypical model reaction producing a wide distribution of hydrocarbon products. Since in zeolites methanol is quickly equilibrated with DME, this reaction can be used to probe vast sub-networks of the full MTH process, while eliminating or at least slowing down methanol-induced secondary reactions and catalyst deactivation. Quantitative discrimination of xylene isomers in the effluent stream is achieved by deconvoluting the coincidence photoelectron spectra.