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ChemPlusChem Jun 2024A set of 211At-astatoarenes were synthesized from corresponding trimethylgermyl arenes with radiochemical conversions (RCCs) of up to 90%. Both electron rich and...
A set of 211At-astatoarenes were synthesized from corresponding trimethylgermyl arenes with radiochemical conversions (RCCs) of up to 90%. Both electron rich and electron poor substrates were successfully radiolabeled at room temperature (RT) using relatively low precursor amounts (0.15 µmol/ 0.02 mL solvent (7.5 mM)). Ready access to ortho-, para- and meta- astatinated arenes was achievable. Optimized reaction conditions were successfully applied to label a poly (ADP-ribose) polymerase (PARP) inhibitor with a RCC of approx. 50%. We believe that trimethylgermanyl derivatives are a viable addition to the astatination precursor toolbox and facilitate astatination of arenes. The developed labeling method should easily be applicable for productions under good manufacturing practice (GMP).
PubMed: 38877386
DOI: 10.1002/cplu.202400254 -
ACS Applied Bio Materials Oct 2023In the field of carbon nanomaterials, carbon dots (CDs) have become a preferable choice in biomedical applications. Based on the concept of green chemistry, CDs derived... (Review)
Review
In the field of carbon nanomaterials, carbon dots (CDs) have become a preferable choice in biomedical applications. Based on the concept of green chemistry, CDs derived from traditional Chinese medicines (TCMs) have attracted extensive attention, including TCM charcoal drugs, TCM extracts, and TCM small molecules. The design and preparation of CDs from TCMs (TCMs-CDs) can improve the inherent characteristics of TCMs, such as solubility, particle size distribution, and so on. Compared with other precursor materials, TCMs-CDs have outstanding intrinsic bioactivities and potential pharmacological effects. However, the research of TCMs-CDs in biomedicine is not comprehensive, and their mechanisms have not been understood deeply either. In this review, we will provide concise insights into the recent development of TCMs-CDs, with a major focus on their preparation, formation, precursors, and bioactivities. Then we will discuss the perfect transformation from TCMs to TCMs-CDs. Finally, we discuss the opportunities and challenges for the application of TCMs-CDs in clinical treatment.
PubMed: 37707491
DOI: 10.1021/acsabm.3c00462 -
Environmental Health : a Global Access... Jun 2024Several legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been regulated around the world. There is growing concern over the proliferation of...
Serum concentrations of legacy, alternative, and precursor per- and polyfluoroalkyl substances: a descriptive analysis of adult female participants in the MIREC-ENDO study.
BACKGROUND
Several legacy and emerging per- and polyfluoroalkyl substances (PFAS) have been regulated around the world. There is growing concern over the proliferation of alternative PFAS, as well as PFAS precursors. Biomonitoring data for PFAS are critical for assessing exposure and human health risk.
METHODS
We collected serum samples from 289 adult female participants in a 2018-2021 follow-up study of the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort. Samples were analyzed for 40 PFAS using ultra-performance liquid chromatography-tandem mass spectrometry. For those compounds with > 50% detection, as well as the sum of these compounds, we describe serum concentrations and patterns of exposure according to sociodemographic and obstetrical history characteristics.
RESULTS
17 out of 40 PFAS were detected in > 50% of samples with 7 of these detected in > 97% of samples. Median [95th percentile] concentrations (µg/L) were highest for PFOS (1.62 [4.56]), PFOA (0.69 [1.52]), PFNA (0.38 [0.81]), and PFHxS (0.33 [0.92]). Geometric mean concentrations of PFOA and PFHxS were approximately 2-fold lower among those with more children (≥ 3 vs. 1), greater number of children breastfed (≥ 3 vs. ≤ 1), longer lifetime duration of breastfeeding (> 4 years vs. ≤ 9 months), and shorter time since last pregnancy (≤ 4 years vs. > 8 years). We observed similar patterns for PFOS, PFHpS, and the sum of 17 PFAS, though the differences between groups were smaller. Concentrations of PFOA were higher among "White" participants, while concentrations of N-MeFOSE, N-EtFOSE, 7:3 FTCA, and 4:2 FTS were slightly higher among participants reporting a race or ethnicity other than "White". Concentrations of legacy, alternative, and precursor PFAS were generally similar across levels of age, education, household income, body mass index, and menopausal status.
CONCLUSIONS
We report the first Canadian biomonitoring data for several alternative and precursor PFAS. Our findings suggest that exposure to PFAS, including several emerging alternatives, may be widespread. Our results are consistent with previous studies showing that pregnancy and breastfeeding are excretion pathways for PFAS.
Topics: Humans; Female; Fluorocarbons; Adult; Environmental Pollutants; Canada; Biological Monitoring; Pregnancy; Young Adult; Cohort Studies
PubMed: 38858670
DOI: 10.1186/s12940-024-01085-z -
Small (Weinheim An Der Bergstrasse,... Jan 2024Bone mineralization is a ubiquitous process among vertebrates that involves a dynamic physical/chemical interplay between the organic and inorganic components of bone... (Review)
Review
Bone mineralization is a ubiquitous process among vertebrates that involves a dynamic physical/chemical interplay between the organic and inorganic components of bone tissues. It is now well documented that carbonated apatite, an inorganic component of bone, is proceeded through transient amorphous mineral precursors that transforms into the crystalline mineral phase. Here, the evolution on mineral precursors from their sources to the terminus in the bone mineralization process is reviewed. How organisms tightly control each step of mineralization to drive the formation, stabilization, and phase transformation of amorphous mineral precursors in the right place, at the right time, and rate are highlighted. The paradigm shifts in biomineralization and biomaterial design strategies are intertwined, which promotes breakthroughs in biomineralization-inspired material. The design principles and implementation methods of mineral precursor-based biomaterials in bone graft materials such as implant coatings, bone cements, hydrogels, and nanoparticles are detailed in the present manuscript. The biologically controlled mineralization mechanisms will hold promise for overcoming the barriers to the application of biomineralization-inspired biomaterials.
Topics: Animals; Calcification, Physiologic; Biomimetics; Minerals; Bone and Bones; Biocompatible Materials
PubMed: 37621037
DOI: 10.1002/smll.202207951 -
Current Organic Synthesis 2024Click Chemistry, as a powerful tool, has been used for the synthesis of a variety of 1,2,3-triazoles. Among click cycloaddition reactions, intramolecular click reactions...
Click Chemistry, as a powerful tool, has been used for the synthesis of a variety of 1,2,3-triazoles. Among click cycloaddition reactions, intramolecular click reactions carried out in azido-alkyne precursors has not been thoroughly reviewed. Hence, in this review, we have summarized and categorised the recent literature (from 2012 on) based on the azidoalkynyl precursor's type and a brief and concise description of the involved mechanisms is presented. Accordingly, we have classified the relevant literature into three categories: (1) substitution precursors (2) addition and (3) multi-component reaction (MCR) products.
PubMed: 37026493
DOI: 10.2174/1570179420666230407103320 -
Nature Communications Oct 2023Solid-state synthesis plays an important role in the development of new materials and technologies. While in situ characterization and ab-initio computations have...
Solid-state synthesis plays an important role in the development of new materials and technologies. While in situ characterization and ab-initio computations have advanced our understanding of materials synthesis, experiments targeting new compounds often still require many different precursors and conditions to be tested. Here we introduce an algorithm (ARROWS) designed to automate the selection of optimal precursors for solid-state materials synthesis. This algorithm actively learns from experimental outcomes to determine which precursors lead to unfavorable reactions that form highly stable intermediates, preventing the target material's formation. Based on this information, ARROWS proposes new experiments using precursors it predicts to avoid such intermediates, thereby retaining a larger thermodynamic driving force to form the target. We validate this approach on three experimental datasets, containing results from over 200 synthesis procedures. In comparison to black-box optimization, ARROWS identifies effective precursor sets for each target while requiring substantially fewer experimental iterations. These findings highlight the importance of domain knowledge in optimization algorithms for materials synthesis, which are critical for the development of fully autonomous research platforms.
PubMed: 37907493
DOI: 10.1038/s41467-023-42329-9 -
Water Research Jun 2024Biological activated carbon filter (BAC) is one of the most effective technologies for removing disinfection by-product (DBP) precursors from water. Biochar is a...
Biological activated carbon filter (BAC) is one of the most effective technologies for removing disinfection by-product (DBP) precursors from water. Biochar is a lower-cost medium that has the potential to replace granular activated carbon in BAC applications, thus leading to the development of biological biochar filter (BCF). This study compared BCF with BAC for the removal of DBP precursors using column experiments. Both BCF and BAC achieved the removal of DBP precursors, resulting in concentrations of all DBP formation potential below the World Health Organization guideline values for drinking water. Bromodichloromethane and unknown DBP precursor removal by BCF was comparable to that by BAC. However, BAC removed more chloroform and dichloroacetontrile precursors than BCF. For microbial community analysis, cell numbers in a bottom layer (inlet) of BCF and BAC columns were higher than those in the top layer. The abundances of Nordella and a microbial genus from Burkholderiaceae at the bottom layer showed a strong correlation to the number of DBP precursors removed and were comparable in BCF and BAC. This finding likely contributes to the similarities between DBPs species removed and the removal performances of some known and unknown DBP precursors by BCF and BAC. Overall results from this study revealed that biochar can be served as a low-cost and sustainable replacement of activated carbon in water filter for DBP precursor removal.
PubMed: 38955037
DOI: 10.1016/j.watres.2024.121994 -
Frontiers in Immunology 2023Early recovery of donor-derived invariant natural killer T (iNKT) cells are associated with reduced risk of graft-versus-host disease (GvHD) and overall survival....
INTRODUCTION
Early recovery of donor-derived invariant natural killer T (iNKT) cells are associated with reduced risk of graft-versus-host disease (GvHD) and overall survival. Patients with severe GvHD, however, had much slower iNKT cell reconstitution relative to conventional T cells.
METHODS
To characterize the delay of iNKT cell reconstitution and explore its possible causes, we used a haploidentical bone marrow transplantation (haplo-BMT) mouse model with GvHD. We found the delayed recovery of thymic and peripheral iNKT cell numbers with markedly decreased thymic NKT1 subset in GvHD mice. The defective generation of thymic iNKT precursors with egress capability contributed to the reduced peripheral iNKT cells in GvHD mice. We further identified intermediate NK1.1 NKT1 precursor subpopulations under steady-state conditions and found that the differentiation of these subpopulations was impaired in the thymi of GvHD mice. Detailed characterization of iNKT precursors and thymic microenvironment showed a close association of elevated TCR/co-stimulatory signaling provided by double positive thymocytes and macrophages with defective down-regulation of proliferation, metabolism, and NKT2 signature in iNKT precursor cells. Correspondingly, NKT2 but not NKT1 differentiation was favored in GvHD mice.
DISCUSSION
These data underline the important roles of TCR and co-stimulatory signaling in the differentiation of thymic iNKT subsets under transplantation conditions.
Topics: Animals; Mice; Bone Marrow Transplantation; Natural Killer T-Cells; Graft vs Host Disease; Cell Differentiation; Receptors, Antigen, T-Cell
PubMed: 37600815
DOI: 10.3389/fimmu.2023.1203614 -
EMBO Reports Apr 2024Most mitochondrial proteins are synthesized on cytosolic ribosomes and imported into mitochondria in a post-translational reaction. Mitochondrial precursor proteins...
Most mitochondrial proteins are synthesized on cytosolic ribosomes and imported into mitochondria in a post-translational reaction. Mitochondrial precursor proteins which use the ER-SURF pathway employ the surface of the endoplasmic reticulum (ER) as an important sorting platform. How they reach the mitochondrial import machinery from the ER is not known. Here we show that mitochondrial contact sites play a crucial role in the ER-to-mitochondria transfer of precursor proteins. The ER mitochondria encounter structure (ERMES) and Tom70, together with Djp1 and Lam6, are part of two parallel and partially redundant ER-to-mitochondria delivery routes. When ER-to-mitochondria transfer is prevented by loss of these two contact sites, many precursors of mitochondrial inner membrane proteins are left stranded on the ER membrane, resulting in mitochondrial dysfunction. Our observations support an active role of the ER in mitochondrial protein biogenesis.
Topics: Mitochondria; Mitochondrial Membranes; Mitochondrial Membrane Transport Proteins; Protein Transport; Mitochondrial Proteins; Endoplasmic Reticulum; Saccharomyces cerevisiae Proteins
PubMed: 38565738
DOI: 10.1038/s44319-024-00113-w -
Nucleic Acids Research Feb 2024Regulation of RNA helicase activity, often accomplished by protein cofactors, is essential to ensure target specificity within the complex cellular environment. The...
Regulation of RNA helicase activity, often accomplished by protein cofactors, is essential to ensure target specificity within the complex cellular environment. The largest family of RNA helicase cofactors are the G-patch proteins, but the cognate RNA helicases and cellular functions of numerous human G-patch proteins remain elusive. Here, we discover that GPATCH4 is a stimulatory cofactor of DHX15 that interacts with the DEAH box helicase in the nucleolus via residues in its G-patch domain. We reveal that GPATCH4 associates with pre-ribosomal particles, and crosslinks to the transcribed ribosomal DNA locus and precursor ribosomal RNAs as well as binding to small nucleolar- and small Cajal body-associated RNAs that guide rRNA and snRNA modifications. Loss of GPATCH4 impairs 2'-O-methylation at various rRNA and snRNA sites leading to decreased protein synthesis and cell growth. We demonstrate that the regulation of 2'-O-methylation by GPATCH4 is both dependent on, and independent of, its interaction with DHX15. Intriguingly, the ATPase activity of DHX15 is necessary for efficient methylation of DHX15-dependent sites, suggesting a function of DHX15 in regulating snoRNA-guided 2'-O-methylation of rRNA that requires activation by GPATCH4. Overall, our findings extend knowledge on RNA helicase regulation by G-patch proteins and also provide important new insights into the mechanisms regulating installation of rRNA and snRNA modifications, which are essential for ribosome function and pre-mRNA splicing.
Topics: Humans; Methylation; Ribosomes; RNA Helicases; RNA Precursors; RNA, Ribosomal; RNA, Small Nucleolar
PubMed: 38113271
DOI: 10.1093/nar/gkad1202