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The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung’s disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease. Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.

Skeletal muscle aging is a key contributor to age-related frailty and sarcopenia with substantial implications for global health. Here we profiled 90,902 single cells and 92,259 single nuclei from 17 donors to map the aging process in the adult human intercostal muscle, identifying cellular changes in each muscle compartment. We found that distinct subsets of muscle stem cells exhibit decreased ribosome biogenesis genes and increased CCL2 expression, causing different aging phenotypes. Our atlas also highlights an expansion of nuclei associated with the neuromuscular junction, which may reflect re-innervation, and outlines how the loss of fast-twitch myofibers is mitigated through regeneration and upregulation of fast-type markers in slow-twitch myofibers with age. Furthermore, we document the function of aging muscle microenvironment in immune cell attraction. Overall, we present a comprehensive human skeletal muscle aging resource ( https://www.muscleageingcellatlas.org/ ) together with an in-house mouse muscle atlas to study common features of muscle aging across species.

Micro- and nanoplastic pollutants are among the major environmental challenges, and are exacerbated by the continuous degradation of growing amounts of plastic debris in the aquatic environment. The purpose of this study was to investigate the morphology of micro/nanoplastics (M/NPs) formed from polyethylene terephthalate (PET) by mechanical degradation in an aquatic environment, which mimics the processes in the natural environment well, and to determine the impact of these particles on model aquatic organisms. To this end, M/NPs were obtained by ball milling in an aqueous medium and the effect of milling length on particle size and shape was investigated. The particles obtained in an environment simulating natural conditions were irregularly shaped, and those of nanometric size tended to form aggregates of various shapes. The ingestion and toxicity of PET M/NPs to freshwater zooplankton were then assessed. Daphnia magna and Thamnocephalus platyurus were used in a series of acute ecotoxicity tests, by exposure to M/NP dispersions at environmentally realistic concentrations (0.01–1.0 mg/L), as well as at very high concentrations (100–1000 mg/L). A significant uptake of PET particles by both types of invertebrates was observed, and the M/NPs were mainly concentrated in the digestive tracts of the crustaceans. However, they did not cause acute toxicity to the tested organisms or a reduction in their swimming activity, even at concentrations as high as 1000 mg/L.

Nowadays, the most important aspect related to the use of dietary supplements seems to be their quality. There are many reports indicating their insufficient quality primarily related to a much lower content of ingredients or even their absence. Currently, there is an increasing interest in supplementing the diet with various kinds of supplements, including those containing combinations of vitamins and minerals, among which preparations with vitamin D are very popular. This is probably due to the reduced production of this vitamin, depending on the amount of time spent in the sun and the use of UV-filters. Very often, preparations with cholecalciferol also contain vitamin K2, which is associated with their synergistic effect. Therefore, the question arises about the effectiveness of supplementation, which may be correlated with the quality of commonly available dietary supplements. In the presented work, it was undertaken to develop optimal conditions for the qualitative and quantitative determination of vitamins D2, D3 and K2 in dietary supplements available in various forms, using thin-layer chromatography with densitometric detection. As a result, the methodology for analyzing the content of three vitamins from various matrices was developed, optimized and validated in accordance with ICH requirements. The obtained results allow us to conclude that it is reliable and meets the requirements for analytical procedures used in the analysis of medicinal products. Based on the results obtained for examined dietary supplements, it can be stated that the amount of vitamin D3 in analyzed products is basically similar to that declared by the manufacturer, in contrast to vitamin K2, the content of which is diverse. The developed methodology seems to be a good, low-cost and quick way to control the quality of dietary supplements so that they can supplement the human diet and be a wholesome product.

The formation of cefuroxime axetil+cyclodextrin (CA+CD) complexes increases the aqueous solubility of CA, improves its physico-chemical properties, and facilitates a biomembrane-mediated drug delivery process. In CD-based tablet formulations, it is crucial to investigate the molecular details of complexes in final pharmaceutical preparation. In this study, Raman spectroscopy and mapping were applied for the detection and identification of chemical groups involved in α-, β-, γ-, and 2-hydroxypropyl-β-CD (2-HP- β-CD)+CA complexation process. The experimental studies have been complemented by molecular dynamics-based investigations, providing additional molecular details of CA+CD interactions. It has been demonstrated that CA forms the guest–host type inclusion complexes with all studied CDs; however, the nature of the interactions is slightly different. It seems that both α- and β-CD interact with furanyl and methoxy moieties of CA, γ-CD forms a more diverse pattern of interactions with CA, which are not observed in other CDs, whereas 2HP-β-CD binds CA with the contribution of hydrogen bonding. Apart from supporting this interpretation of the experimental data, molecular dynamics simulations allowed for ordering the CA+CD binding affinities. The obtained results proved that the molecular details of the host–guest complexation can be successfully predicted from the combination of Raman spectroscopy and molecular modeling.

Lecithin is a mixture of phospholipids which naturally occurs in plants and animals cells. This is a component of drugs as well as dietary supplements, which are used to improve memory and concentration, likewise to decrease cholesterol level in blood, decrease risk of cardiovascular diseases and in a lot of other cases. In this paper the quantitative and qualitative analysis of phosphatidylcholine, which is the main component of lecithin, by thin-layer chromatography with densitometric detection, was described. First, the method was validated according to the International Council for Harmonisation (ICH); validation results have shown that the method was selective, precise, and accurate in the range of the linearity 0.23–3.21 mg mL −1 . Next, described method was used for the quantification of phosphatidylcholine in dietary supplements and drugs containing lecithin. The obtained results, both in terms of the quality of chromatographic separation and statistical evaluation are satisfactory, and the developed analytical procedure may be an alternative to other separation techniques, for the quick analysis of lecithin products.

In recent years, ultra-efficient liquid chromatography (UPLC) has gained particular popularity due to the possibility of faster separation of small molecules. This technique, used to separate the ingredients present in multi-component mixtures, has found application in many fields, such as chemistry, pharmacy, food, and biochemistry. It is an important tool in both research and production. UPLC created new possibilities for analytical separation without reducing the quality of the obtained results. This technique is therefore a milestone in liquid chromatography. Thanks to the increased resolution, new analytical procedures, in many cases, based on existing methods, are being developed, eliminating the need for re-analysis. Researchers are trying to modify and transfer the analytical conditions from the commonly used HPLC method to UPLC. This topic may be of strategic importance in the analysis of medicinal substances. The information contained in this manuscript indicates the importance of the UPLC technique in drug analysis. The information gathered highlights the importance of selecting the appropriate drug control tools. We focused on drugs commonly used in medicine that belong to various pharmacological groups. Rational prescribing based on clinical pharmacology is essential if the right drug is to be administered to the right patient at the right time. The presented data is to assist the analyst in the field of broadly understood quality control, which is very important, especially for human health and treatment. This manuscript shows that the UPLC technique is now an increasingly used tool for assessing the quality of drugs and determining the identity and content of active substances. It also allows the monitoring of active substances and finished products during their processing and storage.

Xanthohumol, a prenylated chalcone in the flavonoid group, naturally occurs in many plants and exhibits antioxidant, anticancer, anti-inflammatory, antibacterial, and antiviral effects. The growing interest in xanthohumol due to its potential therapeutic properties has led to the increase in the pool of products available on the market. The novelty of this study is the proposal of a rapid and cost-effective procedure useful for performing quality control on products containing xanthohumol in the form of dietary supplements and cosmetics as well as testing their stability. For this purpose, the thin-layer chromatography method with densitometric detection was used, which was validated in accordance with ICH (International Conference on Harmonization) guidelines. The mobile phase was toluene, 1,4-dioxane, and glacial acetic acid (37:10:1.5 v/v/v), and TLC silica gel 60 F254 plates were used as the stationary phase. The validation process assessed linearity, with a correlation coefficient (r) of 0.9987. The calculated LOD (limit of detection) and LOQ (limit of quantification) values were 3.82 and 11.57 ng/spot, respectively. Accuracy was evaluated by determining percentage recovery at three concentration levels (80, 100, and 120%), with an average recovery of 100% and RSD below 1%, confirming good accuracy. Precision was indicated by an RSD of less than 2.20%. The average content of xanthohumol in dietary supplements ranged from about 8 to 29% of the content declared by the manufacturers. The stability tests showed that XN decomposes most slowly in water (t0.5 = 10.86 h) compared with acidic (t0.5 = 10.80 h) and alkaline solutions (t0.5 = 7.39 h), as well as in the presence of an oxidizing agent (t0.5 = 18.38 h), at all tested temperatures, which is confirmed by the calculated kinetic parameters. In the tests of antioxidant capacity, xanthohumol shows significantly higher radical scavenging capacity than vitamin C in the entire range of analyzed concentrations (0.03–2.40 mmol/L).

Astaxanthin is a red carotenoid pigment known for its strong antioxidant and immune-supporting properties, which are higher than other carotenoids. The aim of this study was the qualitative and quantitative evaluation of dietary supplements containing astaxanthin. First, optimal conditions for conducting analyses using the TLC technique with densitometric detection were developed. The mobile phase consisting of methanol: ethyl acetate: 1,4-dioxane (1:3:6 v/v/v) was selected, while the stationary phase consisted of Silica gel 60 F254. Densitometric detection was performed at 460 nm. Next, the validation process of the developed method was carried out according to the guidelines of the International Conference on Harmonization (ICH). The range of linearity tested was 0.0026–0.0100 µg/spot, and the determined LOD and LOQ values were 0.85 and 2.57 ng/μL, respectively. The variation coefficient at the level of 4.75% proves good precision. The percentage of recovery was in the range of 95.25–104.94%. The obtained results confirmed the good accuracy of the method. Subsequently, quantitative analyses of the preparations were carried out. Analysis of dietary supplements showed significant deviations from the declared astaxanthin content. Astaxanthin solutions were stable in alkaline environments and when exposed to light and oxidizing substances; however, the substance degraded in acidic environments. The performed antioxidant capacity tests confirmed the high antioxidant activity of astaxanthin.

Lipophilicity is a physicochemical parameter well known as a decisive factor for predicting the successful development of a drug. Thus, a balance between potency and physicochemical properties during medicinal chemistry optimization is needed. In this study, the lipophilicity of isoindole-1,3(2 H )-dione derivatives designed as phosphodiesterase 10A (PDE10A) inhibitors was determined by chromatographic [reversed-phase thin-layer chromatography (RP-TLC) and ultra-performance liquid chromatography/mass spectrometry (UPLC/MS)] and in silico methods. To assess the correlation between the obtained lipophilicity parameters, principal component analysis (PCA) was performed. logP values obtained by chromatographic (logP RP-TLC and logP UPLC/MS ) and in silico methods were compared using the PCA method. The results of PCA revealed that logP UPLC/MS and in silico clogP provided by the ChemDraw program were highly correlated. Compounds’ drug likeness was screened, and the pharmacokinetic properties were predicted. All the investigated compounds displayed drug-likeness properties, and they met the criteria of Lipinski’s rule of five, which predicted the oral bioavailability of drug candidates. Analysis of the influence of physicochemical properties on the biological activity showed that the compounds with increased potency on PDE10A had significantly higher topological polar surface area (TPSA) values. The blood‒brain barrier permeability and the hemolytic activity of model compound 18 were examined. The model compound 18 displayed no toxicity effect on erythrocytes in the hemolytic assay and good parallel artificial membrane permeability. The results showed that phthalimide compounds with benzimidazole moiety are a source of compound-targeted inhibition of PDE10A with balanced physicochemical and drug-likeness properties.