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Water Research Jun 2024Metals in the drinking water distribution system (DWDS) play an important role on the fate of disinfection by-products (DBPs). They can increase the formation of DBPs... (Review)
Review
Metals in the drinking water distribution system (DWDS) play an important role on the fate of disinfection by-products (DBPs). They can increase the formation of DBPs through several mechanisms, such as enhancing the proportion of reactive halogen species (RHS), catalysing the reaction between natural organic matter (NOM) and RHS through complexation, or by increasing the conversion of NOM into DBP precursors. This review comprehensively summarizes these complex processes, focusing on the most important metals (copper, iron, manganese) in DWDS and their impact on various DBPs. It organizes the dispersed 'metals-DBPs' experimental results into an easily accessible content structure and presents their underlying common or unique mechanisms. Furthermore, the practically valuable application directions of these research findings were analysed, including the toxicity changes of DBPs in DWDS under the influence of metals and the potential enhancement of generalization in DBP model research by the introduction of metals. Overall, this review revealed that the metal environment within DWDS is a crucial factor influencing DBP levels in tap water.
PubMed: 38941679
DOI: 10.1016/j.watres.2024.121991 -
ACS Nano Jun 2024Solid-state nanochannels (SSNs) have emerged as promising platforms for controlling ionic transport at the nanoscale. SSNs are highly versatile, and this feature can be...
Solid-state nanochannels (SSNs) have emerged as promising platforms for controlling ionic transport at the nanoscale. SSNs are highly versatile, and this feature can be enhanced through their combination with porous materials such as Metal-Organic Frameworks (MOF). By selection of specific building blocks and experimental conditions, different MOF architectures can be obtained, and this can influence the ionic transport properties through the nanochannel. Herein, we study the effects of confined synthesis of Zr-based UiO-66 MOF on the ion transport properties of single bullet-shaped poly(ethylene terephthalate) (PET) nanochannels. We have found that emerging textural properties from the MOF phase play a determinant role in controlling ionic transport through the nanochannel. We demonstrate that a transition from ion current saturation regimes to diode-like regimes can be obtained by employing different synthetic approaches, namely, counterdiffusion synthesis, where MOF precursors are kept separate and forced to diffuse through the nanochannel, and one-pot synthesis, where both precursors are placed at both ends of the channel. Also, by considering the dependence of the charge state of the UiO-66 MOF on the protonation degree, pH changes offered a mechanism to tune the iontronic output (and selectivity) among different regimes, including anion-driven rectification, cation-driven rectification, ion current saturation, and ohmic behavior. Furthermore, Poisson-Nernst-Planck (PNP) simulations were employed to rationalize the different iontronic outputs observed experimentally for membranes modified by different methods. Our results demonstrate a straightforward tool to synthesize MOF-based SSN membranes with tunable ion transport regimes.
PubMed: 38941562
DOI: 10.1021/acsnano.4c04435 -
Journal of the American Chemical Society Jun 2024In recent years, progress has been made in the development of catalytic methods that allow remote functionalizations based on alkene isomerization. In contrast,...
In recent years, progress has been made in the development of catalytic methods that allow remote functionalizations based on alkene isomerization. In contrast, protocols based on alkyne isomerization are comparatively rare. Herein, we report a general Pd-catalyzed long-range isomerization of alkynyl alcohols. Starting from aryl-, heteroaryl-, or alkyl-substituted precursors, the optimized system provides access preferentially to the thermodynamically more stable α,β-unsaturated aldehydes and is compatible with potentially sensitive functional groups. We showed that the migration of both π-components of the carbon-carbon triple bond can be sustained over several methylene units. Computational investigations served to shed light on the key elementary steps responsible for the reactivity and selectivity. These include an unorthodox phosphine-assisted deprotonation rather than a more conventional β-hydride elimination in the final tautomerization event.
PubMed: 38941513
DOI: 10.1021/jacs.4c05136 -
Science Immunology Jun 2024KLRG1 CD8 T cells persist for months after clearance of acute infections and maintain high levels of effector molecules, contributing protective immunity against...
KLRG1 CD8 T cells persist for months after clearance of acute infections and maintain high levels of effector molecules, contributing protective immunity against systemic pathogens. Upon secondary infection, these long-lived effector cells (LLECs) are incapable of forming other circulating KLRG1 memory subsets such as central and effector memory T cells. Thus, KLRG1 memory T cells are frequently referred to as a terminally differentiated population that is relatively short lived. Here, we show that after viral infection of mice, effector cells derived from LLECs rapidly enter nonlymphoid tissues and reduce pathogen burden but are largely dependent on receiving antigen cues from vascular endothelial cells. Single-cell RNA sequencing reveals that secondary memory cells in nonlymphoid tissues arising from either KLRG1 or KLRG1 memory precursors develop a similar resident memory transcriptional signature. Thus, although LLECs cannot differentiate into other circulating memory populations, they still retain the flexibility to enter tissues and establish residency.
Topics: Animals; Receptors, Immunologic; Mice; Lectins, C-Type; Mice, Inbred C57BL; Memory T Cells; Immunologic Memory; CD8-Positive T-Lymphocytes; Female; Mice, Knockout
PubMed: 38941479
DOI: 10.1126/sciimmunol.adj8356 -
Science Advances Jun 2024Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer's disease (AD). We found that deoxycholic acid (DCA) increased in brains of AD mice...
Bile acids (BAs) metabolism has a significant impact on the pathogenesis of Alzheimer's disease (AD). We found that deoxycholic acid (DCA) increased in brains of AD mice at an early stage. The enhanced production of DCA induces the up-regulation of the bile acid receptor Takeda G protein-coupled receptor (TGR5), which is also specifically increased in neurons of AD mouse brains at an early stage. The accumulation of exogenous DCA impairs cognitive function in wild-type mice, but not in TGR5 knockout mice. This suggests that TGR5 is the primary receptor mediating these effects of DCA. Furthermore, excitatory neuron-specific knockout of TGR5 ameliorates Aβ pathology and cognition impairments in AD mice. The underlying mechanism linking TGR5 and AD pathology relies on the downstream effectors of TGR5 and the APP production, which is succinctly concluded as a "p-STAT3-APH1-γ-secretase" signaling pathway. Our studies identified the critical role of TGR5 in the pathological development of AD.
Topics: Animals; Receptors, G-Protein-Coupled; Alzheimer Disease; Amyloid beta-Protein Precursor; Neurons; Mice; Mice, Knockout; Humans; Disease Models, Animal; Deoxycholic Acid; Amyloid Precursor Protein Secretases; Signal Transduction; Brain
PubMed: 38941459
DOI: 10.1126/sciadv.ado1855 -
ACS Applied Materials & Interfaces Jun 2024Sequential infiltration synthesis (SIS) is a scalable and valuable technique for the synthesis of organic-inorganic materials with several potential applications at the...
Sequential infiltration synthesis (SIS) is a scalable and valuable technique for the synthesis of organic-inorganic materials with several potential applications at the industrial level. Despite the increasing interest for this technique, a clear picture of the fundamental physicochemical phenomena governing the SIS process is still missing. In this work, infiltration of AlO into thin poly(methyl methacrylate) (PMMA) films using trimethyl aluminum (TMA) and HO as precursors is investigated by operando dynamic spectroscopic ellipsometry (SE) analysis. The TMA diffusion coefficient values at temperatures ranging from 70 to 100 °C are determined, and the activation energy for the TMA diffusion process in PMMA is found to be = 2.51 ± 0.03 eV. Additionally, systematic data about reactivity of TMA molecules with the PMMA matrix as a function of temperature are obtained. These results provide important information, paving the way to the development of a comprehensive theory for the modeling of the SIS process.
PubMed: 38941159
DOI: 10.1021/acsami.4c06887 -
European Journal of Nuclear Medicine... Jun 2024The radionuclide pair cerium-134/lanthanum-134 (Ce/La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (Ac)....
PURPOSE
The radionuclide pair cerium-134/lanthanum-134 (Ce/La) was recently proposed as a suitable diagnostic counterpart for the therapeutic alpha-emitter actinium-225 (Ac). The unique properties of Ce offer perspectives for developing innovative in vivo investigations that are not possible with Ac. In this work, Ac- and Ce-labelled tracers were directly compared using internalizing and slow-internalizing cancer models to evaluate their in vivo comparability, progeny meandering, and potential as a matched theranostic pair for clinical translation. Despite being an excellent chemical match, Ce/La has limitations to the setting of quantitative positron emission tomography imaging.
METHODS
The precursor PSMA-617 and a macropa-based tetrazine-conjugate (mcp-PEG-Tz) were radiolabelled with Ac or Ce and compared in vitro and in vivo using standard (radio)chemical methods. Employing biodistribution studies and positron emission tomography (PET) imaging in athymic nude mice, the radiolabelled PSMA-617 tracers were evaluated in a PC3/PIP (PC3 engineered to express a high level of prostate-specific membrane antigen) prostate cancer mouse model. The Ac and Ce-labelled mcp-PEG-Tz were investigated in a BxPC-3 pancreatic tumour model harnessing the pretargeting strategy based on a trans-cyclooctene-modified 5B1 monoclonal antibody.
RESULTS
In vitro and in vivo studies with both Ac and Ce-labelled tracers led to comparable results, confirming the matching pharmacokinetics of this theranostic pair. However, PET imaging of the Ce-labelled precursors indicated that quantification is highly dependent on tracer internalization due to the redistribution of Ce's PET-compatible daughter La. Consequently, radiotracers based on internalizing vectors like PSMA-617 are suited for this theranostic pair, while slow-internalizing Ac-labelled tracers are not quantitatively represented by Ce PET imaging.
CONCLUSION
When employing slow-internalizing vectors, Ce might not be an ideal match for Ac due to the underestimation of tumour uptake caused by the in vivo redistribution of La. However, this same characteristic makes it possible to estimate the redistribution of Ac's progeny noninvasively. In future studies, this unique PET in vivo generator will further be harnessed to study tracer internalization, trafficking of receptors, and the progression of the tumour microenvironment.
PubMed: 38940841
DOI: 10.1007/s00259-024-06811-w -
MBio Jun 2024The purine nucleotides ATP and GTP are made from the common precursor inosine monophosphate (IMP). Maintaining the correct balance of these nucleotides for optimal cell...
UNLABELLED
The purine nucleotides ATP and GTP are made from the common precursor inosine monophosphate (IMP). Maintaining the correct balance of these nucleotides for optimal cell growth is controlled in part by the enzyme IMP dehydrogenase (IMPDH), which catalyzes the first dedicated step of GTP biosynthesis. The regulation of IMPDH mRNA and protein levels in the yeast grown in liquid culture has been studied in some detail, but regulation of IMPDH protein under conditions of cellular crowding on a solid substrate has not been examined. Here, we report real-time, live-cell analysis of the accumulation of the Imd2 isoform of IMPDH in yeast cells forming a monolayer colony in a microfluidic device over a 50-hour time course. We observe two distinct phases of increased Imd2 accumulation: a guanine-insensitive phase early in outgrowth and a guanine-sensitive phase later, when cells become crowded. We show that the IMPDH inhibitor mycophenolic acid enhances both phases of increase. Deletion of a transcription attenuator upstream of the mRNA start site that decreases Imd2 mRNA synthesis in the presence of high GTP increases the baseline level of Imd2 protein 10-fold and abolishes guanine-sensitive but not guanine-insensitive induction. Our results suggest that at least two mechanisms of yeast Imd2 regulation exist, the known GTP-dependent attenuation of RNA polymerase II elongation and a GTP concentration-independent pathway that may be controlled by cell growth state. Live-cell analysis of IMPDH protein levels in a growing yeast colony confirms a known mechanism of regulation and provides evidence for an additional mode of regulation.
IMPORTANCE
This study used live-cell microscopy to track changes in the level of a key enzyme in GTP nucleotide biosynthesis, inosine monophosphate dehydrogenase (IMPDH), during growth of a brewers yeast colony over 2 days in a microfluidic device. The results show that feedback regulation via transcription attenuation allows cells to adapt to nutrient limitation in the crowded environs of a yeast colony. They also identify a novel mode of regulation of IMPDH level that is not driven by guanine nucleotide availability.
PubMed: 38940616
DOI: 10.1128/mbio.01021-24 -
Liver International : Official Journal... Jun 2024The porphyrias are a group of rare inborn errors of metabolism associated with various clinical presentations and long-term complications, making them relevant... (Review)
Review
The porphyrias are a group of rare inborn errors of metabolism associated with various clinical presentations and long-term complications, making them relevant differential diagnoses to consider for many clinical specialities, especially hepatologists, gastroenterologists and dermatologists. To diagnose a patient with porphyria requires appropriate biochemical investigations, as clinical features alone are not specific enough. Furthermore, it is important to be aware that abnormalities of porphyrin accumulation and excretion occur in many other disorders that are collectively far more common than the porphyrias. In this review, we provide an overview of porphyria-related tests with their strengths and limitations, give recommendations on requesting and diagnostic approaches in non-expert and expert laboratories for different clinical scenarios and discuss the role of genetic testing in the porphyrias. To diagnose porphyria in a currently symptomatic patient requires analysis of biochemical markers to demonstrate typical patterns of haem precursors in urine, faeces and blood. The use of genomic sequencing in diagnostic pathways for porphyrias requires careful consideration, and the demonstration of increased porphyrin-related markers is necessary prior to genomic testing in symptomatic patients. In the acute porphyrias, genomic testing is presently a useful adjunct for genetic counselling of asymptomatic family members and the most common cutaneous porphyria, porphyria cutanea tarda, is usually a sporadic, non-hereditary disease. Getting a correct and timely porphyria diagnosis is essential for delivering appropriate care and ensuring best patient outcome.
PubMed: 38940544
DOI: 10.1111/liv.16012 -
Langmuir : the ACS Journal of Surfaces... Jun 2024Surfactants are widely used as foaming agents to remove liquid accumulation in gas wells, enhancing natural gas production. The surfactant used in traditional foam...
Surfactants are widely used as foaming agents to remove liquid accumulation in gas wells, enhancing natural gas production. The surfactant used in traditional foam sticks was dissolved and released as foam in a short period, especially at elevated downhole temperatures. This often requires the addition of foam sticks to maintain foam. To solve this problem, this study studies the utilization of nano silica to incorporate the amphoteric surfactant, cocamidopropyl betaine (CAB), into the mesoporous structure of silica nanocomposite as foam sticks for controlled release of CAB. Mesoporous nano silica was prepared by a sol-gel acid-catalyzed process with a silica precursor. The formation of nanocomposite solid sticks containing the amphoteric surfactant was achieved by aging and drying. The composite was characterized by various techniques: infrared spectroscopy, thermogravimetric analysis, energy-dispersive spectrometry, scanning electron microscopy, transmission electron microscopy, and small-angle X-ray diffraction. Results showed that 49.3% of CAB was encapsulated within the mesoporous structure of 30-50 nm nano silica. CAB release over time in aqueous solution at 130 °C exhibited 10.1% surfactant left in the nanocomposite after 72 h, as determined by thermal analysis. Surfactant release was systematically evaluated through foam performance tests. The study revealed that CAB could be control-released over 168 h via CAB diffusion from mesoporous silica. This study provides a longer-lasting foam method to enhance gas production by utilizing mesoporous silica as a control release medium for gas well deliquification.
PubMed: 38940399
DOI: 10.1021/acs.langmuir.4c01813