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In France, information on per- and poly-fluoroalkyl substances (PFAS) in residential tap water is still limited or non-existent. In this study, we conducted a local survey to compare human exposure to PFAS in 28 private family households in a medium-sized French city (Besançon). We present the results on the identification and quantification of 65 PFAS substances in residential tap water. Concentrations of PFAS were assessed by a French accredited laboratory. A total of 74 tap water samples were analyzed, revealing the presence of 12 individual molecules, 8 of which are among the 20 regulated substances. Forty-one samples contained a mixture of 2 to 10 different PFAS substances, the most frequently quantified molecules being trifluoroacetic acid (100%), perfluorooctanoic acid (48.6%), perfluorooctane sulfonic acid (44.6%), perfluorobutanoic acid (27.0%), perfluoropentanoic acid (50.1%), and perfluorohexanoic acid (23.0%). The corresponding cumulative concentrations (sum of 65 substances) ranged from 440 ng/L to 3,805 ng/L, showing significant variability. However, in terms of regulations, all values were below the 100 ng/L limit for the sum of the 20 molecules. Trifluoroacetic acid, which is not on the regulatory PFAS list, was systematically found in all the water samples analyzed and the results clearly highlighted the dominance of this PFAS. In tap water, trifluoroacetic acid was quantified at concentrations ranging from 440 to 3,800 ng/L (average value of 1096 ± 575 ng/L), i.e., 4 to 38 times higher than the regulatory threshold of 100 ng/L. This study underlines the need to monitor not only the 20 substances listed in the European Directive, transposed into French law, but also other PFAS, and, above all, to include trifluoroacetic acid.
The synthesis and property characterization of soft biomaterials has taken precedence in recent years. Although bulk physical-chemical properties are well known for these bio-materials, nanoscale properties still need to be probed and evaluated to fine tune the bio-compatibility (structural as well as functional) with natural tissues for regenerative medicine, prosthetics and other biological applications. In this study, the focus is on a popular soft biomaterial, Elastin-like polypeptide (ELP) which has been prepared under different pH conditions. The topographical features of the ELP at the nanoscale using Atomic Force Microscopy (AFM) are explored. Additionally, the employment of a non linear mode of AFM called Intermodulation-AFM (ImAFM) to correlate the elastic properties (Young's modulus) of ELP probed at the nanoscale with the topographical features gives us a deep insight into the mechanical properties offered by ELP when the structural features are altered by change in the ELP synthesis conditions namely, pH in this study. The noteworthy point is that these properties are measured at a spatial resolution of 0.9 nm. Finally, the change in the structural features of ELP with varying pH is discussed through atomistic Molecular Dynamics Simulations. The interaction mechanisms of the amino acid sequences and crosslinkers with proteins as they form the backbone and sidechain of the ELP at different pH are explored.
In this work, a previous quantum wave-packet time-dependent study (D. De Fazio, A. Aguado and C. Petrongolo, Non-adiabatic quantum dynamics of the dissociative charge transfer He+ + H2 → He + H + H+. Front. Chem., 2019, 7, A249) on the charge-transfer dissociation of the hydrogen molecule by the helium cation is continued, extending the calculation to eight rotational H2 reactant states. New data are required to obtain convergent (within about 1 percent) Boltzmann-averaged thermal rate constants up to 1000 Kelvin, which are necessary to provide reliable reaction yields for astrophysical and cosmological computational models. To the best of our knowledge, these are the first quantum mechanical thermal rate constant calculations for a dissociative charge transfer process. As shown in the previous work for the effect of vibrations, a relevant role of rotations is found, and the use of roto-vibrational ground state rate constant only, as often employed in astrophysical model is a poor approximation, especially above room temperature. The large computational scaling of wave-packet methods for excited rotational reactant states, due to the linear increase of the number of projections of the diatomic rotational angular momentum along the internuclear axis, is handled efficiently in the calculations, providing an accurate documentation for developing approximations that are needed to extend the calculations to higher temperatures. A particular effort has been made to better clarify the reaction mechanism, which indicated the key roles of the geometrical phase and non-adiabatic effects. Additionally, the rich resonance pattern, which is the principal reaction mechanism at these temperatures and represents the main source of the computational load, is analyzed and rationalized in detail according to the resonance analysis.
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Pathological reduction in enzymatic activity of the tissue-non-specific alkaline phosphatase (TNSALP) is the molecular hallmark of hypophosphatasia (HPP), a group of rare inborn systemic diseases, mainly characterized by pathological affections of calcified tissue mineralization and the musculoskeletal system. The disease, in all clinical forms, is biochemically characterized by variable degrees of chronically reduced activity of circulating total alkaline phosphatase (ALP). Repeated detection of low values of ALP activity is mandatory to diagnose the presence of HPP, but, alone, it is not sufficient for the diagnosis of the disease. Detection of increased circulating levels of one of the main natural substrates of TNSALP, the pyridoxal 5'-phosphate (PLP), is needed to biochemically confirm the diagnosis of HPP. Urinary and/or blood levels of phosphoethanolamine (PEA) and inorganic pyrophosphate (PPi), two other natural substrates of TNSALP, can be elevated in a percentage of HPP patients. The contemporary biochemical evaluation of ALP activity and its target substrates is of great help in the diagnosis of HPP, and also for the monitoring of a patient's response to enzymatic replacement therapy or other pharmacological treatments. Here, we describe and discuss possibilities and challenges of biochemical screenings for HPP, based also on the experience gained in our analysis laboratory.
Supramolecular nanoparticles offer an efficient strategy to enhance the solubility, stability, and bioavailability of poorly water-soluble therapeutic molecules. In this study, water-dispersible SNPs were successfully prepared from dicarboxyl-bis-pillar[5]arene (H) and cetyltrimethylammonium bromide (CTAB) using a microemulsion method. Dynamic light scattering revealed that the resulting CTAB/H nanoparticles possessed a size distribution centered around 40 nm, a positive surface charge (+15 mV), and exhibited high colloidal stability over three months. 1H NMR, 2D TOCSY, 2D NOESY, diffusion ordered NMR spectroscopy, and UV-Vis investigations confirmed the inclusion of the CTAB alkyl chain within the pillar[5]arene cavity, supporting the formation of stable supramolecular assemblies capable of efficiently encapsulating the poorly water-soluble flavonol quercetin (Q). The CTAB/H system displayed low cytotoxicity (up to 50 µg/mL) and pronounced antioxidant activity, as evidenced by DPPH, ABTS, and FRAP assays. Quercetin-loaded nanoparticles (CTAB/H/Q) enhanced cellular uptake and exhibited a marked cytoprotective effect against H2O2-induced oxidative stress in NIH-3T3 fibroblasts.
The aim of this study is to assess the discrepancies between potassium values obtained from point-of-care testing and laboratory analyzers, and to propose a straightforward method to indirectly assess the likelihood of hemolysis in whole blood samples. The data were collected from 409 hospitalized patients (199 males, 210 females; median age 78 years, interquartile range 55-87) in whom were simultaneously requested the blood gas profile, including electrolytes (Na, K, Cl and Ca2+) on the GEM Premier 5000 blood gas analyzer and K in plasma samples on the Cobas analytical system. The Wilcoxon test showed a significant difference (p<0.0001) for K measurements, with a number of positive differences between Cobas and GEM Premier 5,000 of 110 and negative differences of 293. The median value of the hemolysis index was 7 (95 % CI for the median 6 to 8). The differences between the two K measurements obtained from plasma and whole blood samples showed a lowest and highest differences of -1.7 and 4.6 mmol/L. The median difference was 0.63 (95 % CI for the median: 0.54-0.73) and the interquartile range (IQR) was 0.48-0.9. Overall, 89 samples (21 %) displayed a difference larger than the relative change value. The presence of hemolysis in plasma samples should alert laboratory professionals to carefully evaluate the corresponding whole blood results. Concordant values indicate the presence of hemolysis in the whole blood sample, while discordant values suggest that hemolysis only affects one of the two samples.
Osteopetrosis is a heterogeneous group of bone diseases with increased bone density as a result of defective osteoclast function or differentiation. The clinical presentations range from the early, often lethal, infantile malignant forms to the mild autosomal dominant forms. This review provides recent updates in preclinical findings regarding molecular genetics, diagnosis, and novel therapeutic approaches in osteopetrosis. The diagnosis is radiologic, supported by biochemical and genetic examination to identify mutations in the key genes involved in osteoclasts, TCIRG1, CLCN7, OSTM1, SNX10, RANK, and RANKL. Treatment is at present largely the management of complications and includes vitamin D and calcium supplements, IFN-γ therapy, and hematopoietic stem cell transplantation (HSCT), the latter being the treatment of choice for most forms of osteopetrosis. Two gene therapy- and iPSCs-derived strategies, based on reconstituting the function of osteoclasts, have been recently developed for the management of this hereditary bone disease. Furthermore, emerging findings suggest the possible involvement of epigenetic mechanisms, such as non-coding RNAs (ncRNAs), in osteopetrosis pathophysiology, paving the way for potential novel diagnostic biomarkers and tailored molecular treatments. The aim of this review is to provide an overview of recent progress in molecular genetics, diagnosis, and novel therapeutic strategies in osteopetrosis and to illustrate conceivable scenarios in regenerative and gene-based therapy.
The use of the abundant and easily available solar energy is central towards a carbon-free society and represents the most sustainable strategy for the increasing energy demand. Rhodobacter (R.) sphaeroides is a versatile photosynthetic purple non sulfur bacteria able to harvest sunlight, particularly in the Near InfraRed (NIR) region, and to efficiently transform it into photochemical energy. In this work, whole wild-type, metabolically-active photosynthetic bacterial cells of R. sphaeroides, and their carotenoid-less mutant strain, were integrated in a two-electrode architecture, to output a positive photovoltage upon illumination. The photovoltage amplitude of the mutant strain is almost three times higher than that obtained with wild-type cells. Photosynthetic bacteria were also integrated in a light-electrolyte-gated organic transistor to produce a photomodulated electronic current, as well as in a biophotonic power cell working on direct sunlight. This proves that bio-organic hybrid optoelectronic devices may enable environmentally safe and cost-effective energy production.
In this study, 28 fossil resins of amber samples from various localities in Europe, Asia and America. Infrared spectroscopy was used to identify the molecular features that characterize these ambers. Through the development of a tailored chemometric approach, we reduced the impact of non-significant spectral contributions and highlighted the most relevant features for classifying amber samples. This was achieved by applying second-derivative processing to the spectra and segmenting them into specific wavenumber ranges. Our novel approach successfully groups ambers based on both age and geographical provenance using their FTIR spectral profiles. Additionally, it isolates the molecular vibrations that have the greatest influence on this classification, particularly the contributions from functional groups that differentiate these samples. This method offers a valuable tool for researchers engaged in amber provenance studies, especially for succinites originated from Eastern Europe, providing a new approach to identify and classify unknown resin samples based on their unique molecular signatures.
Early lipid-lowering therapy with "high-intensity" statins is recommended post-acute myocardial infarction (AMI), yet the optimal dose within such regimens remains uncertain. We compared efficacy and safety of very high-intensity versus high-intensity statin regimens, both combined with ezetimibe, initiated during AMI hospitalization. In a stepped-wedge cluster randomized controlled single-center trial, patients with ST- or non-ST-elevation AMI were assigned in sequential 6-month blocks to either very high-intensity statin (Group A: atorvastatin 80 mg or rosuvastatin 40 mg) or high-intensity statin (Group B: atorvastatin 40 mg or rosuvastatin 20 mg), both combined with ezetimibe 10 mg, daily. The primary endpoint was achieving both LDL-C < 55 mg/dL and ≥ 50% LDL-C reduction at 30 days post-discharge. Secondary endpoints included each primary endpoint component, mean LDL-C levels, safety, and need for dose reduction. Two-hundred-and-twenty patients (mean age 67 years, 63% men) were enrolled. Groups were balanced at baseline for demographic, clinical, and laboratory characteristics. At 30 days, the primary (efficacy) endpoint occurred in 63% of patients in Group A and 52% of patients in Group B (p = 0.13). LDL-C < 55 mg/dL was achieved in 86% of Group A and 73% of Group B (p = 0.02). No significant difference was seen in ≥50% LDL-C reduction. Group A had lower mean LDL-C (43 ± 16 mg/dL vs 48 ± 14 mg/dL; p = 0.046). Statin dose reduction due to intolerance occurred, however, more often in Group A (8% vs 2%, p = 0.03). No differences in liver enzymes were observed. Very high-intensity and high-intensity statin regimens differed minimally in achieving LDL-C targets, but very high-intensity regimens had higher rates of intolerance-related dose reduction.
Autoimmune liver diseases (AILDs) are considered rare conditions, though the frequency of their diagnosis is increasing thanks to the introduction of new diagnostic tests and improvements in analytical technologies. In clinical practice, in patients with liver disease of unknown etiology, after a differential diagnosis that excludes other possible causes of hepatic damage, a potential autoimmune origin should be investigated through the evaluation of a specific autoantibody panel. In this context, the diagnostic laboratory plays a pivotal role, since the detection of well-defined autoantibody patterns is essential in the diagnosis and classification of autoimmune liver disorders. In 2009, the Study Group on Autoimmunology (GdS-AI) of the Italian Society of Clinical Pathology and Laboratory Medicine (SIPMeL) issued recommendations pertaining to a rational approach to the interpretation and clinical application of autoantibody testing in autoimmune hepatitis and cholestatic diseases. Then, after fourteen years, the GdS-AI deemed it necessary to revise and update the recommendations for the use of autoantibody testing in the diagnosis and monitoring of AILDs. This updated document provides a summary of the current analytical methodologies and autoantibody markers available for the diagnosis and monitoring of autoimmune liver disorders, together with recommendations regarding the appropriate use of tests and the interpretation of results. The guidelines were prepared after a systematic review of the most recent scientific literature and are structured into 19 specific recommendations, subdivided by disease type into autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The quality of evidence and strength of each recommendation were assessed following the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, ensuring a rigorous and transparent methodology aimed at producing efficient and clinically effective diagnostic recommendations. These guidelines are designed to support laboratory professionals and clinicians in the selection, application, interpretation, and reporting of autoantibody testing in AILDs, improving diagnostic accuracy and clinical outcomes through evidence-based laboratory medicine.
This study reports the optical properties of quercetin encapsulated in self-assembled nanoparticles made from a dicarboxyl-bis-pillar[5]arene/CTAB supramolecular complex, and correlates these properties with the nanoparticle architecture and microenvironment. Experimental evidence indicates that quercetin, in both its neutral and mono-anionic form, is mostly located within the nanoparticle, trapped between the pillararenes. In contrast, only a small fraction of the mono-anionic form is found on the nanoparticle surface. Quercetin is stabilized through hydrogen bonding and hydrophobic interactions, which play a crucial role in protecting the flavonol from oxidation and degradation. This stabilization explains our recent findings on the efficacy of these nanoparticles in delivering and facilitating the cellular internalization of quercetin.
To assess the efficacy of theranostic-guided corneal UV therapy in progressive keratoconus and the association between theranostic imaging biomarkers and 1-year outcomes. Seventy-three consecutive patients (73 eyes; mean age 22 ± 6 years) with progressive keratoconus underwent epithelial removal followed by theranostic-guided corneal UV therapy using 0.22% riboflavin ophthalmic solution. Eyes received either 10- or 15-minute preset riboflavin application protocol, followed by UV irradiation at 10 mW/cm2 for 9 minutes. The device generated 2 intraoperative imaging biomarkers: the riboflavin score, estimating stromal riboflavin concentration, and the theranostic score, quantifying UV-A mediated photoactivation. These scores enabled real-time monitoring to guide effective completion of treatment. A multivariate linear regression model evaluated the relationship between theranostic imaging biomarkers, baseline patient characteristics, and 1-year Kmax change. Theranostic-guided treatment was effective and showed 94% concordance with the 1-year Kmax flattening. Eight eyes (11%) required an additional 15% UV energy (1.3 extra minute at 10 mW/cm2) to surpass the theranostic score threshold of 0.60. Mean Kmax decreased by -1.6 ± 1.6 D (P < 0.001), whereas uncorrected distance visual acuity and corrected distance visual acuity improved significantly (P < 0.001). The regression model explained a limited proportion of outcome variance (R2 = 0.239; P = 0.01) and indicated that the riboflavin score had a greater association with Kmax flattening compared with the other variables included in the model. Real-time monitoring of stromal riboflavin permeation and photoactivation enables precise, individualized treatment, enhancing the ability to halt keratoconus progression by tailoring therapeutic effect to each cornea's molecular response.
The aim of this study was to investigate the stability of leukocyte cell population data (CPD) assessed on Sysmex XN-3000 hematological analyzer in samples stored for up to 24 h at different temperatures. Whole-blood samples from 25 donors were analyzed for 18 CPD parameters at baseline and after storage at room temperature (RT), 4 °C, or 37 °C for 3, 6, 12, and 24 h. Stability was assessed using three complementary approaches: paired Wilcoxon tests with Bonferroni correction, percent difference between medians > 10%, and per-sample percent change > 10% in ≥ 2 samples. In addition, the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) stability protocol was applied, modelling percent differences over time using linear regression through the origin to estimate the rate of change and the stability limit (SL), defined as the time required to exceed a maximum permissible error of 10%. According to predefined stability criteria, several CPD parameters exceeded stability limits within 24 h, particularly under storage at 37 °C. Parameters related to neutrophil, lymphocyte and monocyte complexity and size (e.g., neutrophils complexity (NE-SSC), neutrophils size (NE-FSC), monocytes complexity (MO-X), lymphocytes complexity (LY-X); where SSC = side scatter, FSC = forward scatter) showed slow rates of change with estimated stability limits beyond 24 h across storage conditions. In contrast, fluorescence- and dispersion-related parameters (e.g., neutrophils fluorescence intensity (NE-SFL), width of dispersion of neutrophils complexity (NE-WX), width of dispersion of lymphocytes fluorescence (LY-WY), width of dispersion of monocytes size (MO-WZ); where SFL = side fluorescence, W = width of dispersion) reached the stability limit within 24 h, most frequently at 37 °C. Lymphocyte size (LY-Z) exceeded the stability limit at 17 h also under storage at 4 °C. Leukocyte CPD stability is strongly temperature- and parameter-dependent. Exposure to elevated temperature (37 °C) leads to early exceedance of predefined stability limits for several CPD parameters, whereas storage at RT preserves stability for longer time intervals. Avoiding prolonged exposure to high temperatures is therefore essential for reliable CPD assessment in routine laboratory practice.
The presence of caged dynamics, the Johari-Goldstein (JGβ) relaxation preceding the cooperative α-relaxation, and the fact that their properties are interconnected have been established universally for glass-forming liquids of various kinds [K. L. Ngai, Prog. Mater. Sci. 139, 101130 (2023)]. We apply the universal properties of the three processes in interpreting or reinterpreting the calorimetric and dielectric relaxation data of four amorphous waters: amorphous solid water (ASW), hyperquenched glassy water (HGW), low-density liquid water (LDL), and high-density liquid water (HDL). The presence of the JGβ relaxation and the caged dynamics before the terminal α-relaxation, and the interrelations between their respective properties, are found in the four amorphous waters exactly as in other glass-formers. The existence of the JGβ glass transition temperature, Tgβ, is found indirectly from the response of the caged dynamics in ASW, HGW, and HDL, and its value of ∼113 K is consistent with the extrapolation of the dielectric JGβ relaxation times τβ(T) to long times. The calorimetric data of LDL at a heating rate of 10 K/min show Tgα of LDL is 136 K, which is the same as that of ASW and HGW incidentally. The calorimetric and dielectric data of HDL at temperatures below 125 K, before it transforms to LDL at higher temperatures, are interpreted as originating from the JGβ relaxation and not from the α-relaxation. The value of Tgβ of HDL obtained from calorimetry or deduced from the dielectric JGβ relaxation times τβ(T) is also near 113 K. The α-relaxation glass transition temperature Tgα of HDL, obtained by extrapolating the values from calorimetric and volumetric studies at elevated pressure to ambient pressure, are 137 and 128 K respectively. The 137 K for Tgα is supported by observation of glass transition at the same temperature by DSC in samples of HDL prepared by compressing droplets of HGW. Assuming τα(Tgα) is 100 s, the value of the calorimetric Tgα for HDL is close to the calorimetric and dielectric τα(T) of HGW. The τα(T) of HGW and LDL have Arrhenius temperature dependence with a small fragility index m. The Arrhenius temperature dependence of τβ(T) for HGW, HDL, and LDL are similar as well. Applying the relation between τα(T) and τβ(T) from the Coupling Model, the averaged coupling parameter nav ∼ 0.18 is deduced for all four amorphous waters. Such a small value of nav is consistent with the frequency dependence, ∼ν-nav, on the high-frequency flank of the α-loss peak of HGW and LDL Thus, the small nav correlates with the small m, in accord with the correlation found in other glass-formers.
Correction for 'Dissociative charge transfer through a conical intersection: quantum thermal rate constants up to 1000 K for the He+ + H2 → He + H + H+ reaction' by Dario De Fazio et al., Phys. Chem. Chem. Phys., 2026, 28, 6928-6943, https://doi.org/10.1039/D5CP04927J.
In the original publication [...].
Glucose-6-phosphate dehydrogenase (G6PD) deficiency impairs NADPH generation through the pentose phosphate pathway, resulting in reduced glutathione regeneration and increased vulnerability to oxidative stress. While its clinical significance is well described in hemolytic disorders, its impact on tumor biology and chemosensitivity remains poorly characterized. Cisplatin, a backbone agent in the management of nasopharyngeal carcinoma (NPC), exerts its cytotoxicity through the formation of DNA adducts and the robust induction of reactive oxygen species (ROS) activity. We report a patient with non-keratinizing NPC and a G6PD variant, a (class III) deficiency, who demonstrated a rapid and pronounced objective response to cisplatin-based induction and concurrent chemoradiotherapy. Unfortunately, the patient also exhibited signs of rapid and persistent hematologic (platelets and white cells) toxicity. Notably, no hemolytic events occurred. A narrative review of the available literature indicates that G6PD-deficient cells exhibit a reduced antioxidant reserve, increased cisplatin-induced DNA damage, and impaired activation of ROS-detoxifying pathways. A few clinical observations similarly report enhanced tumor responsiveness in G6PD-deficient individuals, although the evidence is sparse and heterogeneous. Preclinical data support the notion that diminished NADPH availability amplifies cisplatin-triggered oxidative injury, thereby increasing tumor susceptibility. This case adds to emerging evidence that G6PD deficiency may potentiate cisplatin efficacy in NPC by exploiting intrinsic redox vulnerabilities. While preliminary, these findings suggest the potential utility of metabolic phenotyping in treatment stratification. Prospective studies are needed to define the predictive value, safety, and therapeutic implications of G6PD status in cisplatin-based regimens.
The rise of synthetic cathinones (SC), and in particular 3,4-MDPHP (3,4-methylenedioxy-α-pyrrolidinohexanophenone), is a concerning health threat. This paper represents the most extensive case series on 3,4-MDPHP suspected intoxications to date, offering a detailed analysis of its impact. This study presents the analytical findings for 108 hospitalized patients who tested positive for 3,4-MDPHP, out of a total of 465 subjects admitted for suspected new psychoactive substances (NPS) intoxication. Analyses were performed by GC-MS and LC-MS/MS. The potential cross-reactivity of 3,4-MDPHP with the Syva EMIT II Plus urine ecstasy immunoassay is also investigated. 3,4-MDPHP was detected in 56% of NPS positive cases. A wide range of 3,4-MDPHP concentrations was observed in both blood (1-257 ng/mL) and urine (2-32 250 ng/mL). 3,4-MDPHP was the sole detected substance in 73.1% of cases, while 26.9% involved co-consumption with other drugs of abuse, primarily cocaine. Investigations about 3,4-MDPHP cross-reactivity with Syva EMIT II Plus urine ecstasy demonstrated that unmodified 3,4-MDPHP does not trigger a positive result, but its metabolites seem to be involved in a positive cross-reaction. This study confirms the high prevalence (108/465) of 3,4-MDPHP in NPS related intoxication cases in our cohort. It is essential for clinical laboratories and emergency departments to be aware of the potential cross-reactivity in ecstasy immunoassay, as this may lead to significant diagnostic errors and misinterpretation of results.