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Journal of Chemical Theory and... Jul 2023Fast and accurate estimation of electronic coupling matrix elements between molecules is essential for the simulation of charge transfer phenomena in chemistry,...
Fast and accurate estimation of electronic coupling matrix elements between molecules is essential for the simulation of charge transfer phenomena in chemistry, materials science, and biology. Here we investigate neural-network-based coupling estimators combined with different protocols for sampling reference data (random, farthest point, and query by committee) and compare their performance to the physics-based analytic overlap method (AOM), introduced previously. We find that neural network approaches can give smaller errors than AOM, in particular smaller maximum errors, while they require an order of magnitude more reference data than AOM, typically one hundred to several hundred training points, down from several thousand required in previous ML works. A Δ-ML approach taking AOM as a baseline is found to give the best overall performance at a relatively small computational overhead of about a factor of 2. Highly flexible π-conjugated organic molecules like non-fullerene acceptors are found to be a particularly challenging case for ML because of the varying (de)localization of the frontier orbitals for different intramolecular geometries sampled along molecular dynamics trajectories. Here the local symmetry functions used in ML are insufficient, and long-range descriptors are expected to give improved performance.
PubMed: 37345885
DOI: 10.1021/acs.jctc.3c00184 -
Cell Reports Methods Dec 2023Glycomics, the comprehensive profiling of all glycan structures in samples, is rapidly expanding to enable insights into physiology and disease mechanisms. However,...
Glycomics, the comprehensive profiling of all glycan structures in samples, is rapidly expanding to enable insights into physiology and disease mechanisms. However, glycan structure complexity and glycomics data interpretation present challenges, especially for differential expression analysis. Here, we present a framework for differential glycomics expression analysis. Our methodology encompasses specialized and domain-informed methods for data normalization and imputation, glycan motif extraction and quantification, differential expression analysis, motif enrichment analysis, time series analysis, and meta-analytic capabilities, synthesizing results across multiple studies. All methods are integrated into our open-source glycowork package, facilitating performant workflows and user-friendly access. We demonstrate these methods using dedicated simulations and glycomics datasets of N-, O-, lipid-linked, and free glycans. Differential expression tests here focus on human datasets and cancer vs. healthy tissue comparisons. Our rigorous approach allows for robust, reliable, and comprehensive differential expression analyses in glycomics, contributing to advancing glycomics research and its translation to clinical and diagnostic applications.
Topics: Humans; Glycomics; Polysaccharides
PubMed: 37992708
DOI: 10.1016/j.crmeth.2023.100652 -
Toxicological Sciences : An Official... Mar 2024Microplastics (MP) derived from the weathering of polymers, or synthesized in this size range, have become widespread environmental contaminants and have found their way...
Microplastics (MP) derived from the weathering of polymers, or synthesized in this size range, have become widespread environmental contaminants and have found their way into water supplies and the food chain. Despite this awareness, little is known about the health consequences of MP ingestion. We have previously shown that the consumption of polystyrene (PS) beads was associated with intestinal dysbiosis and diabetes and obesity in mice. To further evaluate the systemic metabolic effects of PS on the gut-liver-adipose tissue axis, we supplied C57BL/6J mice with normal water or that containing 2 sizes of PS beads (0.5 and 5 µm) at a concentration of 1 µg/ml. After 13 weeks, we evaluated indices of metabolism and liver function. As observed previously, mice drinking the PS-containing water had a potentiated weight gain and adipose expansion. Here we found that this was associated with an increased abundance of adipose F4/80+ macrophages. These exposures did not cause nonalcoholic fatty liver disease but were associated with decreased liver:body weight ratios and an enrichment in hepatic farnesoid X receptor and liver X receptor signaling. PS also increased hepatic cholesterol and altered both hepatic and cecal bile acids. Mice consuming PS beads and treated with the berry anthocyanin, delphinidin, demonstrated an attenuated weight gain compared with those mice receiving a control intervention and also exhibited a downregulation of cyclic adenosine monophosphate (cAMP) and peroxisome proliferator-activated receptor (PPAR) signaling pathways. This study highlights the obesogenic role of PS in perturbing the gut-liver-adipose axis and altering nuclear receptor signaling and intermediary metabolism. Dietary interventions may limit the adverse metabolic effects of PS consumption.
Topics: Animals; Mice; Plastics; Polystyrenes; Microplastics; Mice, Inbred C57BL; Liver; Non-alcoholic Fatty Liver Disease; Obesity; Weight Gain
PubMed: 38291899
DOI: 10.1093/toxsci/kfae013 -
Advanced Healthcare Materials Mar 2024Premature ovarian failure (POF) features an upward incidence nowadays, and the human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived exosomes (MSC-Exos) have...
Premature ovarian failure (POF) features an upward incidence nowadays, and the human umbilical cord mesenchymal stem cells (hUC-MSCs)-derived exosomes (MSC-Exos) have shown applied values in the recovery of ovarian function. Here, a novel exosome-encapsulated microcarrier prepared by microfluidic technology for ovarian repair after chemotherapy damage is presented. The exosomes derived from lipopolysaccharide (LPS)-preconditioned hUC-MSCs are encapsulated with hyaluronic acid methacryloyl (HAMA) via microfluidic electrospray, which is named HAMA/MSC-Exos. Attributing to the biocompatibility and semipermeable property of HAMA, the encapsulated exosomes show great viability and controllable release behavior from HAMA. It is demonstrated that in situ transplantation of HAMA/MSC-Exos can rescue ovarian functions of cyclophosphamide-induced ovarian failure in mice by increasing ovarian volume, improving the number of antral follicles and restoring fertility. It is believed that the transplantation of HAMA/MSC-Exos will provide a new concept for the treatment of POF in clinical practice.
Topics: Humans; Animals; Mice; Exosomes; Hyaluronic Acid; Lipopolysaccharides; Microfluidics; Mesenchymal Stem Cells
PubMed: 37972286
DOI: 10.1002/adhm.202303068 -
Science Advances Apr 2024The formation of protein precursors, due to the condensation of atomic carbon under the low-temperature conditions of the molecular phases of the interstellar medium,...
The formation of protein precursors, due to the condensation of atomic carbon under the low-temperature conditions of the molecular phases of the interstellar medium, opens alternative pathways for the origin of life. We perform peptide synthesis under conditions prevailing in space and provide a comprehensive analytic characterization of its products. The application of C allowed us to confirm the suggested pathway of peptide formation that proceeds due to the polymerization of aminoketene molecules that are formed in the C + CO + NH reaction. Here, we address the question of how the efficiency of peptide production is modified by the presence of water molecules. We demonstrate that although water slightly reduces the efficiency of polymerization of aminoketene, it does not prevent the formation of peptides.
Topics: Extraterrestrial Environment; Water; Peptides
PubMed: 38630826
DOI: 10.1126/sciadv.adj7179 -
Journal of Chemical Theory and... Jul 2023F. Gygi recently suggested an analytic, norm-conserving, regularized nuclear potential to enable all-electron plane-wave calculations [Gygi 2023, 19, 1300-1309.]. This...
F. Gygi recently suggested an analytic, norm-conserving, regularized nuclear potential to enable all-electron plane-wave calculations [Gygi 2023, 19, 1300-1309.]. This potential () is determined by inverting the Schrödinger equation for the wave function Ansatz ϕ() = exp[-()]/√π with () = erf() + exp(-), where and are parameters. Gygi fixes by demanding ϕ to be normalized, with the value () depending on the strength of the regularization controlled by . We begin this work by re-examining the determination of () and find that the original 10-decimal tabulations of Gygi are only correct to 5 decimals, leading to normalization errors in the order of 10. In contrast, we show that a simple 100-point radial quadrature scheme not only ensures at least 10 correct decimals of but also leads to machine-precision level satisfaction of the normalization condition. Moreover, we extend Gygi's plane-wave study by examining the accuracy of () with high-precision finite element calculations with Hartree-Fock and LDA, GGA, and meta-GGA functionals on first- to fifth-period atoms. We find that although the convergence of the total energy appears slow in the regularization parameter , orbital energies and shapes are indeed reproduced accurately by the regularized potential even with relatively small values of , as compared to results obtained with a point nucleus. The accuracy of the potential is furthermore studied with - excitation energies of Sc-Cu as well as ionization potentials of He-Kr, which are found to converge to sub-meV precision with = 4. The findings of this work are in full support of Gygi's contribution, indicating that all-electron plane-wave calculations can be accurately performed with the regularized nuclear potential.
PubMed: 37354116
DOI: 10.1021/acs.jctc.3c00530 -
The Journal of Headache and Pain Mar 2024The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The burden and disability associated with headaches are conceptualized and measured differently at patients' and populations' levels. At the patients' level, through patient-reported outcome measures (PROMs); at population level, through disability weights (DW) and years lived with a disability (YLDs) developed by the Global Burden of Disease Study (GBD). DW are 0-1 coefficients that address health loss and have been defined through lay descriptions. With this literature review, we aimed to provide a comprehensive analysis of disability in headache disorders, and to present a coefficient referring to patients' disability which might inform future GBD definitions of DW for headache disorders.
METHODS
We searched SCOPUS and PubMed for papers published between 2015 and 2023 addressing disability in headache disorders. The selected manuscript included a reference to headache frequency and at least one PROM. A meta-analytic approach was carried out to address relevant differences for the most commonly used PROMs (by headache type, tertiles of medication intake, tertiles of females' percentage in the sample, and age). We developed a 0-1 coefficient based on the MIDAS, on the HIT-6, and on MIDAS + HIT-6 which was intended to promote future DW iterations by the GBD consortium.
RESULTS
A total of 366 studies, 596 sub-samples, and more than 133,000 single patients were available, mostly referred to cases with migraine. Almost all PROMs showed the ability to differentiate disability severity across conditions and tertiles of medication intake. The indexes we developed can be used to inform future iterations of DW, in particular considering their ability to differentiate across age and tertiles of medication intake.
CONCLUSIONS
Our review provides reference values for the most commonly used PROMS and a data-driven coefficient whose main added value is its ability to differentiate across tertiles of age and medication intake which underlie on one side the increased burden due to aging (it is likely connected to the increased impact of common comorbidities), and by the other side the increased burden due to medication consumption, which can be considered as a proxy for headache severity. Both elements should be considered when describing disability of headache disorders at population levels.
Topics: Female; Humans; Global Burden of Disease; Headache; Headache Disorders; Migraine Disorders; Aging
PubMed: 38433202
DOI: 10.1186/s10194-024-01735-0 -
Colloids and Surfaces. B, Biointerfaces Oct 2023The coenzyme Q10 is a compound widely used in pharmaceutical and cosmetic formulations because it is a potent eliminator of free radicals, giving it antioxidant and... (Review)
Review
The coenzyme Q10 is a compound widely used in pharmaceutical and cosmetic formulations because it is a potent eliminator of free radicals, giving it antioxidant and anti-aging properties. It is naturally synthesized by the human body, but its production wanes with age, leading to the formation of wrinkles. The efficacy of topical application of the coenzyme to counteract this process is subject to several difficulties, due to its instability in the presence of light, low solubility in water and high lipophilicity. Because of these drawbacks, many studies have been conducted of release systems. Lipid nanoparticles stand out in this sense due to the advantages of skin compatibility, protection of the active ingredient against degradation in the external medium, capacity to increase penetration of that ingredient in the skin, and its controlled and prolonged release. In this context, this article presents a review of the main studies of the coenzyme Q10 encapsulated in lipid nanoparticles for topical use, focusing on the analytic methods used to characterize the systems regarding morphology, zeta potential, release profile, Q10 content, encapsulation efficiency, crystalline organization and structure of the lipid matrix, rheology, antioxidant activity, skin penetration and efficacy, among other aspects. We also describe the main results of the different studies and discuss the critical aspects - the simplest, most reproducible, best, and most relevant - that characterize lipid nanoparticles with encapsulated Q10 for topical use.
Topics: Humans; Drug Carriers; Ubiquinone; Liposomes; Nanoparticles; Antioxidants; Particle Size
PubMed: 37574615
DOI: 10.1016/j.colsurfb.2023.113491 -
Analytical Methods : Advancing Methods... Sep 2023There is a pressing need for the development of greener liquid chromatographic bioanalytical methods for antidiabetic drugs for plasma monitoring and revisiting... (Review)
Review
There is a pressing need for the development of greener liquid chromatographic bioanalytical methods for antidiabetic drugs for plasma monitoring and revisiting patients' dosage regimens. Besides, analytical methods are also needed for the quality assurance of finished drug products and regulatory approval. Therefore, the present review focuses on the reported liquid chromatographic methods (LC and LC-MS/MS) that are applied for quality control, forced degradation, and pharmacokinetic studies of a newer antidiabetic agent, canagliflozin (CNG). These reported studies are summarized based on liquid chromatographic separation parameters, such as column dimensions, mobile-phase compositions, flow rate, and use of different detection systems (UV, PDA, and mass spectrometry). The sample pretreatment of biological fluids, which is important for minimizing the matrix effect, is dealt with separately. Liquid-liquid extraction was found to be the most preferred methodology adopted for sample pretreatment followed by the solid-phase extraction technique. However, miniaturized novel pretreatment methods are untraceable in the literature for the extraction of CNG. Special emphasis is paid to the assessment of the greenness profiles of the reported analytical methods for the consideration of sustainable development and green analytical chemistry. Based on the National Environmental Method Index (NEMI) assessment tool, most of the reported studies fulfilled around half of the parameters and were found to be about 50% greener. It is proposed that toxic or hazardous solvents, such as acetonitrile or methanol, should be replaced with greener and environmentally friendly solvents. Thus, there is a need to develop more robust, efficient, and greener liquid chromatographic methods for the determination of CNG in biological fluids and drug products.
Topics: Humans; Canagliflozin; Chromatography, Liquid; Tandem Mass Spectrometry; Chemistry, Analytic; Hypoglycemic Agents; Solvents
PubMed: 37694570
DOI: 10.1039/d3ay00896g -
The Journals of Gerontology. Series A,... Aug 2023Osteosarcopenia is a complex geriatric syndrome characterized by the presence of both sarcopenia and osteopenia/osteoporosis. This condition increases rates of...
Osteosarcopenia is a complex geriatric syndrome characterized by the presence of both sarcopenia and osteopenia/osteoporosis. This condition increases rates of disability, falls, fractures, mortality, and mobility impairments in older adults. The purpose of this study was to analyze the Fourier-transform infrared (FTIR) spectroscopy diagnostic power for osteosarcopenia in community-dwelling older women (n = 64; 32 osteosarcopenic and 32 non-osteosarcopenia). FTIR is a fast and reproducible technique highly sensitive to biological tissues, and a mathematical model was created using multivariate classification techniques that denoted the graphic spectra of the molecular groups. Genetic algorithm and support vector machine regression (GA-SVM) was the most feasible model, achieving 80.0% of accuracy. GA-SVM identified 15 wave numbers responsible for class differentiation, in which several amino acids (responsible for the proper activation of the mammalian target of rapamycin) and hydroxyapatite (an inorganic bone component) were observed. Imaging tests and low availability of instruments that allow the observation of osteosarcopenia involve high health costs for patients and restrictive indications. Therefore, FTIR can be used to diagnose osteosarcopenia due to its efficiency and low cost and to enable early detection in geriatric services, contributing to advances in science and technology that are potential "conventional" methods in the future.
Topics: Humans; Female; Aged; Independent Living; Spectroscopy, Fourier Transform Infrared; Osteoporosis; Fractures, Bone; Sarcopenia
PubMed: 36905160
DOI: 10.1093/gerona/glad081