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1.
J Nanobiotechnology ; 22(1): 231, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720360

ABSTRACT

BACKGROUND: Circulating tumor cells (CTCs) are considered as a useful biomarker for early cancer diagnosis, which play a crucial role in metastatic process. Unfortunately, the tumor heterogeneity and extremely rare occurrence rate of CTCs among billions of interfering leukocytes seriously hamper the sensitivity and purity of CTCs isolation. METHODS: To address these, we firstly used microfluidic chips to detect the broad-spectrum of triple target combination biomarkers in CTCs of 10 types of cancer patients, including EpCAM, EGFR and Her2. Then, we constructed hybrid engineered cell membrane-camouflaged magnetic nanoparticles (HE-CM-MNs) for efficient capture of heterogeneous CTCs with high-purity, which was enabled by inheriting the recognition ability of HE-CM for various CTCs and reducing homologous cell interaction with leukocytes. Compared with single E-CM-MNs, HE-CM-MNs showed a significant improvement in the capture efficiency for a cell mixture, with an efficiency of 90%. And the capture efficiency of HE-CM-MNs toward 12 subpopulations of tumor cells was ranged from 70 to 85%. Furthermore, by using HE-CM-MNs, we successfully isolated heterogeneous CTCs with high purity from clinical blood samples. Finally, the captured CTCs by HE-CM-MNs could be used for gene mutation analysis. CONCLUSIONS: This study demonstrated the promising potential of HE-CM-MNs for heterogeneous CTCs detection and downstream analysis.


Subject(s)
Biomarkers, Tumor , Cell Membrane , Cell Separation , Magnetite Nanoparticles , Neoplastic Cells, Circulating , Neoplastic Cells, Circulating/pathology , Neoplastic Cells, Circulating/metabolism , Humans , Magnetite Nanoparticles/chemistry , Cell Separation/methods , Cell Line, Tumor , Cell Membrane/metabolism , Cell Membrane/chemistry , Biomarkers, Tumor/blood , Receptor, ErbB-2 , Epithelial Cell Adhesion Molecule/metabolism , ErbB Receptors/genetics , ErbB Receptors/metabolism , Neoplasms
2.
Small Methods ; : e2400159, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38697928

ABSTRACT

Regular blood glucose monitoring and control is necessary for people with type 1 or advanced type 2 diabetes, yet diagnosing and treating patients with diabetes in an accurate, sustained and patient-friendly manner remains limited. Here, a glucose-responsive bifunctional nanosystem (PGOxMns) is constructed via one-pot biomineralisation of manganese dioxide with glucose oxidase and ε-poly-L-lysine. Under hyperglycaemic conditions, the cascade reactions that occur when glucose interacts with PGOxMns can trigger the production of Mn(II), which enhances the magnetic resonance imaging signal. Simultaneously, manganese dioxide catalyses the decomposition of toxic hydrogen peroxide into oxygen, which also maintains glucose oxidase (GOx) activity. In an in vivo model of diabetes, PGOxMns is used to monitor glucose levels (0-20 mm) and allowed identification of diabetic mice via T1-weighted MRI. Furthermore, PGOxMns is found to have a high insulin-loading capacity (83.6%), likely due to its positive charge. A single subcutaneous injection of insulin-loaded nanosystem (Ins-PGOxMns) into diabetic mice resulted in a rapid and efficient response to a glucose challenge and prolonged blood glucose level control (< 200 mg dL-1) for up to 50 h. Overall, this proof-of-concept study demonstrates the feasibility of using biomineralised nanosystems to develop patient-friendly strategies for glucose monitoring and control.

4.
Am J Pathol ; 194(6): 975-988, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38423356

ABSTRACT

Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota remains unknown. The current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as compared to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation after irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice after irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, minigut organoid systems and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, although administration of broad-spectrum antibiotics did not alter the goblet cell numbers or mucin 2 (MUC2) secretion, it effectively attenuated inflammation levels in the ileum of irradiated REGγ absent mice, bringing them down to the wild-type levels. Collectively, these findings highlight the contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.


Subject(s)
Enteritis , Gastrointestinal Microbiome , Goblet Cells , Homeostasis , Mice, Knockout , Animals , Enteritis/microbiology , Enteritis/metabolism , Enteritis/pathology , Mice , Goblet Cells/pathology , Goblet Cells/metabolism , Humans , Pancreatitis-Associated Proteins/metabolism , Mucin-2/metabolism , Dysbiosis/microbiology , Dysbiosis/metabolism , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Trefoil Factor-3/metabolism , Mice, Inbred C57BL , Radiation Injuries/metabolism , Radiation Injuries/microbiology , Radiation Injuries/pathology , Radiation Injuries, Experimental/metabolism , Radiation Injuries, Experimental/pathology , Radiation Injuries, Experimental/microbiology
5.
J Hazard Mater ; 466: 133557, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38309168

ABSTRACT

The reactive oxygen species (ROS) photochemically generated from natural iron minerals have gained significant attention. Amidst the previous studies on the impact of heavy metal ions on ROS generation, our study addresses the role of the anion Cr(VI), with its intrinsic photoactivity, in influencing ROS photochemical generation with the co-presence of minerals. We investigated the transformation of inorganic/organic pollutants (Cr(VI) and benzoic acid) at the ferrihydrite interface, considering sunlight-mediated conversion processes (300-1000 nm). Increased photochemical reactivity of ferrihydrite was observed in the presence of aqueous Cr(VI), acting as a photosensitizer. Meanwhile, a positive correlation between hydroxyl radical (•OH) production and concentrations of aqueous Cr(VI) was observed, with a 650% increase of •OH generation at 50 mg L-1 Cr(VI) compared to systems without Cr(VI). Our photochemical batch experiments elucidated three potential pathways for •OH photochemical production under varying wet chemistry conditions: (1) ferrihydrite hole-mediated pathway, (2) chromium intermediate O-I-mediated pathway, and (3) chromium intermediates CrIV/V-mediated pathway. Notably, even in the visible region (> 425 nm), the promotion of aqueous Cr(VI) on •OH accumulation was observed in the presence of ferrihydrite and TiO2 suspensions, attributed to Cr(VI) photosensitization at the mineral interface. This study sheds light on the overlooked role of aqueous Cr(VI) in the photochemical reactivity of minerals, thereby enhancing our understanding of pollutant fate in acid mining-impacted environments.

6.
ACS Biomater Sci Eng ; 10(3): 1494-1506, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38414275

ABSTRACT

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.


Subject(s)
Bacterial Infections , Hemoperfusion , Liver Failure , Nanocomposites , Humans , Bilirubin/chemistry , Polystyrenes/chemistry , Hemoperfusion/methods , Nanocomposites/therapeutic use
7.
Nat Cell Biol ; 26(2): 263-277, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38238450

ABSTRACT

Human in vitro fertilized embryos exhibit low developmental capabilities, and the mechanisms that underlie embryonic arrest remain unclear. Here using a single-cell multi-omics sequencing approach, we simultaneously analysed alterations in the transcriptome, chromatin accessibility and the DNA methylome in human embryonic arrest due to unexplained reasons. Arrested embryos displayed transcriptome disorders, including a distorted microtubule cytoskeleton, increased genomic instability and impaired glycolysis, which were coordinated with multiple epigenetic reprogramming defects. We identified Aurora A kinase (AURKA) repression as a cause of embryonic arrest. Mechanistically, arrested embryos induced through AURKA inhibition resembled the reprogramming abnormalities of natural embryonic arrest in terms of the transcriptome, the DNA methylome, chromatin accessibility and H3K4me3 modifications. Mitosis-independent sequential activation of the zygotic genome in arrested embryos showed that YY1 contributed to human major zygotic genome activation. Collectively, our study decodes the reprogramming abnormalities and mechanisms of human embryonic arrest and the key regulators of zygotic genome activation.


Subject(s)
Aurora Kinase A , Multiomics , Humans , Aurora Kinase A/genetics , Blastocyst , Chromatin/genetics , Cytoskeleton , Embryonic Development/genetics
8.
Molecules ; 28(18)2023 Sep 21.
Article in English | MEDLINE | ID: mdl-37764514

ABSTRACT

Phthalic acid esters (PAEs), which are widespread environmental contaminants, can be efficiently biodegraded, mediated by enzymes such as hydrolases. Despite great advances in the characterization of PAE hydrolases, which are the most important enzymes in the process of PAE degradation, their molecular catalytic mechanism has rarely been systematically investigated. Acinetobacter sp. LUNF3, which was isolated from contaminated soil in this study, demonstrated excellent PAE degradation at 30 °C and pH 5.0-11.0. After sequencing and annotating the complete genome, the gene dphAN1, encoding a novel putative PAE hydrolase, was identified with the conserved motifs catalytic triad (Ser201-Asp295-His325) and oxyanion hole (H127GGG130). DphAN1 can hydrolyze DEP (diethyl phthalate), DBP (dibutyl phthalate) and BBP (benzyl butyl phthalate). The high activity of DphAN1 was observed under a wide range of temperature (10-40 °C) and pH (6.0-9.0). Moreover, the metal ions (Fe2+, Mn2+, Cr2+ and Fe3+) and surfactant TritonX-100 significantly activated DphAN1, indicating a high adaptability and tolerance of DphAN1 to these chemicals. Molecular docking revealed the catalytic triad, oxyanion hole and other residues involved in binding DBP. The mutation of these residues reduced the activity of DphAN1, confirming their interaction with DBP. These results shed light on the catalytic mechanism of DphAN1 and may contribute to protein structural modification to improve catalytic efficiency in environment remediation.


Subject(s)
Acinetobacter , Hydrolases , Acinetobacter/genetics , Molecular Docking Simulation , Cloning, Molecular
9.
Sci Adv ; 9(26): eadg6004, 2023 06 28.
Article in English | MEDLINE | ID: mdl-37379385

ABSTRACT

Recent discoveries of methyl-coenzyme M reductase-encoding genes (mcr) in uncultured archaea beyond traditional euryarchaeotal methanogens have reshaped our view of methanogenesis. However, whether any of these nontraditional archaea perform methanogenesis remains elusive. Here, we report field and microcosm experiments based on 13C-tracer labeling and genome-resolved metagenomics and metatranscriptomics, revealing that nontraditional archaea are predominant active methane producers in two geothermal springs. Archaeoglobales performed methanogenesis from methanol and may exhibit adaptability in using methylotrophic and hydrogenotrophic pathways based on temperature/substrate availability. A five-year field survey found Candidatus Nezhaarchaeota to be the predominant mcr-containing archaea inhabiting the springs; genomic inference and mcr expression under methanogenic conditions strongly suggested that this lineage mediated hydrogenotrophic methanogenesis in situ. Methanogenesis was temperature-sensitive , with a preference for methylotrophic over hydrogenotrophic pathways when incubation temperatures increased from 65° to 75°C. This study demonstrates an anoxic ecosystem wherein methanogenesis is primarily driven by archaea beyond known methanogens, highlighting diverse nontraditional mcr-containing archaea as previously unrecognized methane sources.


Subject(s)
Archaea , Hot Springs , Archaea/genetics , Archaea/metabolism , Ecosystem , Methane/metabolism , Temperature , Phylogeny
10.
Environ Sci Technol ; 57(26): 9843-9853, 2023 07 04.
Article in English | MEDLINE | ID: mdl-37342885

ABSTRACT

The association of arsenic (As) with colloidal particles could facilitate its transport to adjacent water systems or alter its availability in soil-rice systems. However, little is known about the size distribution and composition of particle-bound As in paddy soils, particularly under changing redox conditions. Here, we incubated four As-contaminated paddy soils with distinctive geochemical properties to study the mobilization of particle-bound As during soil reduction and subsequent reoxidation. Using transmission electron microscopy-energy dispersive spectroscopy and asymmetric flow field-flow fractionation, we identified organic matter (OM)-stabilized colloidal Fe, most likely in the form of (oxy)hydroxide-clay composite, as the main arsenic carriers. Specifically, colloidal As was mainly associated with two size fractions of 0.3-40 and >130 kDa. Soil reduction facilitated the release of As from both fractions, whereas reoxidation caused their rapid sedimentation, coinciding with solution Fe variations. Further quantitative analysis demonstrated that As concentrations positively correlated with both Fe and OM concentrations at nanometric scales (0.3-40 kDa) in all studied soils during reduction and reoxidation, yet the correlations are pH-dependent. This study provides a quantitative and size-resolved understanding of particle-bound As in paddy soils, highlighting the importance of nanometric Fe-OM-As interactions in paddy As geochemical cycling.


Subject(s)
Arsenic , Oryza , Soil Pollutants , Arsenic/chemistry , Environmental Pollution/analysis , Soil/chemistry , Colloids/metabolism
11.
Proc Natl Acad Sci U S A ; 120(20): e2219588120, 2023 May 16.
Article in English | MEDLINE | ID: mdl-37155894

ABSTRACT

Aerosol microdroplets as microreactors for many important atmospheric reactions are ubiquitous in the atmosphere. pH largely regulates the chemical processes within them; however, how pH and chemical species spatially distribute within an atmospheric microdroplet is still under intense debate. The challenge is to measure pH distribution within a tiny volume without affecting the chemical species distribution. We demonstrate a method based on stimulated Raman scattering microscopy to visualize the three-dimensional pH distribution inside single microdroplets of varying sizes. We find that the surface of all microdroplets is more acidic, and a monotonic trend of pH decreasing is observed in the 2.9-µm aerosol microdroplet from center to edge, which is well supported by molecular dynamics simulation. However, bigger cloud microdroplet differs from small aerosol for pH distribution. This size-dependent pH distribution in microdroplets can be related to the surface-to-volume ratio. This work presents noncontact measurement and chemical imaging of pH distribution in microdroplets, filling the gap in our understanding of spatial pH in atmospheric aerosol.

12.
Environ Sci Ecotechnol ; 16: 100278, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37251519

ABSTRACT

The global problem of petroleum contamination in soils seriously threatens environmental safety and human health. Current studies have successfully demonstrated the feasibility of bioelectrokinetic and bioelectrochemical remediation of petroleum-contaminated soils due to their easy implementation, environmental benignity, and enhanced removal efficiency compared to bioremediation. This paper reviewed recent progress and development associated with bioelectrokinetic and bioelectrochemical remediation of petroleum-contaminated soils. The working principles, removal efficiencies, affecting factors, and constraints of the two technologies were thoroughly summarized and discussed. The potentials, challenges, and future perspectives were also deliberated to shed light on how to overcome the barriers and realize widespread implementation on large scales of these two technologies.

13.
BMC Gastroenterol ; 23(1): 107, 2023 Apr 05.
Article in English | MEDLINE | ID: mdl-37020202

ABSTRACT

BACKGROUND: The role of chemoradiotherapy in unresectable locally advanced pancreatic cancer is still unclear. METHODS: Data from patients with unresectable locally advanced pancreatic cancer were extracted from the Surveillance, Epidemiology, and End Results Program database. Univariate and multivariate Cox regression analyses were conducted to identify the independent prognostic factors of survival. Propensity score matching was carried out to minimize the interference of confounding factors. Subgroup analysis was performed to screen the characteristics of patients who would benefit from chemoradiotherapy. RESULTS: A total of 5002 patients with unresectable locally advanced pancreatic cancer were included. Among them, 2423 (48.4%) received chemotherapy, and 2579 (51.6%) received chemoradiotherapy. The median overall survival of all patients was 11 months. Multivariate Cox analysis showed that age (p < 0.001), marital status (p < 0.001), tumor size (p = 0.001), N stage (p = 0.015) and radiotherapy (p < 0.001) were independent prognostic factors of survival. Both before (HR, 0.817; 95% CI, 0.769-0.868; p < 0.001) and after (HR, 0.904; 95% CI, 0.876-0.933; p < 0.001) propensity score matching, chemoradiotherapy significantly improved the median overall survival of patients from 10 to 12 months. Subgroup analysis showed that chemoradiotherapy was significantly associated with improved survival regardless of sex, primary site or N stage. In addition, the following subgroups all significantly benefited from chemoradiotherapy: age ≥ 50 years, not divorced, grade 2-4, tumor size > 2 cm, adenocarcinoma, mucinous adenocarcinoma and white race. CONCLUSIONS: Chemoradiotherapy is highly recommended for patients with unresectable locally advanced pancreatic cancer.


Subject(s)
Pancreatic Neoplasms , Humans , Middle Aged , Retrospective Studies , Pancreatic Neoplasms/pathology , Chemoradiotherapy , Cohort Studies , Pancreatic Neoplasms
14.
Environ Sci Technol ; 57(10): 4342-4353, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36864006

ABSTRACT

The association of poorly crystalline iron (hydr)oxides with organic matter (OM), such as extracellular polymeric substances (EPS), exerts a profound effect on Fe and C cycles in soils and sediments, and their behaviors under sulfate-reducing conditions involve complicated mineralogical transformations. However, how different loadings and types of EPS and water chemistry conditions affect the sulfidation still lacks quantitative and systematic investigation. We here synthesized a set of ferrihydrite-organic matter (Fh-OM) coprecipitates with various model compounds for plant and microbial exopolysaccharides (polygalacturonic acids, alginic acid, and xanthan gum) and bacteriogenic EPS (extracted from Bacillus subtilis). Combining wet chemical analysis, X-ray diffraction, and X-ray absorption spectroscopic techniques, we systematically studied the impacts of C and S loadings by tracing the temporal evolution of Fe mineralogy and speciation in aqueous and solid phases. Our results showed that the effect of added OM on sulfidation of Fh-OM coprecipitates is interrelated with the amount of loaded sulfide. Under low sulfide loadings (S(-II)/Fe < 0.5), transformation to goethite and lepidocrocite was the main pathway of ferrihydrite sulfidation, which occurs more strongly at pH 6 compared to that at pH 7.5, and it was promoted and inhibited at low and high C/Fe ratios, respectively. While under high sulfide loadings (S(-II)/Fe > 0.5), the formation of secondary Fe-S minerals such as mackinawite and pyrite dominated ferrihydrite sulfidation, and it was inhibited with increasing C/Fe ratios. Furthermore, all three synthetic EPS proxies unanimously inhibited mineral transformation, while the microbiogenic EPS has a more potent inhibitory effect than synthetic EPS proxies compared at equivalent C/Fe loadings. Collectively, our results suggest that the quantity and chemical characteristics of the associated OM have a strong and nonlinear influence on the extent and pathways of mineralogical transformations of Fh-OM sulfidation.


Subject(s)
Carbon , Extracellular Polymeric Substance Matrix , Oxidation-Reduction , Ferric Compounds/chemistry , Minerals/chemistry , Sulfur , Water
15.
Environ Sci Technol ; 57(14): 5988-5998, 2023 04 11.
Article in English | MEDLINE | ID: mdl-36995950

ABSTRACT

Methylmercury (MeHg) is a potent neurotoxin and has great adverse health impacts on humans. Organisms and sunlight-mediated demethylation are well-known detoxification pathways of MeHg, yet whether abiotic environmental components contribute to MeHg degradation remains poorly known. Here, we report that MeHg can be degraded by trivalent manganese (Mn(III)), a naturally occurring and widespread oxidant. We found that 28 ± 4% MeHg could be degraded by Mn(III) located on synthesized Mn dioxide (MnO2-x) surfaces during the reaction of 0.91 µg·L-1 MeHg and 5 g·L-1 mineral at an initial pH of 6.0 for 12 h in 10 mM NaNO3 at 25 °C. The presence of low-molecular-weight organic acids (e.g., oxalate and citrate) substantially enhances MeHg degradation by MnO2-x via the formation of soluble Mn(III)-ligand complexes, leading to the cleavage of the carbon-Hg bond. MeHg can also be degraded by reactions with Mn(III)-pyrophosphate complexes, with apparent degradation rate constants comparable to those by biotic and photolytic degradation. Thiol ligands (cysteine and glutathione) show negligible effects on MeHg demethylation by Mn(III). This research demonstrates potential roles of Mn(III) in degrading MeHg in natural environments, which may be further explored for remediating heavily polluted soils and engineered systems containing MeHg.


Subject(s)
Mercury , Methylmercury Compounds , Humans , Manganese/chemistry , Methylmercury Compounds/metabolism , Oxidants/chemistry , Cysteine
16.
Water Res ; 230: 119595, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36642031

ABSTRACT

The oxidative dissolution of As from arsenopyrite, one important arsenic mineral in reducing conditions, poses an environmental hazard to natural aquatic systems. The dissolution of arsenopyrite occurs slowly due to the surface precipitates of iron oxides in circumneutral oxic environments. However, the presence of natural ligands and coexisting metals may change the release of Fe species, which would be of critical importance to the dissolution of arsenopyrite. Here, we investigated the oxidative dissolution of arsenopyrite induced by pyrophosphate (PP) and dissolved Mn(III) species as a natural occurring Mn species with strong complexation affinity to PP. With the presence of PP, the formation of Fe(II)-PP complexes and its rapid oxidation to dissolved Fe(III)-PP species resulted in a substantial increase in the generation of hydroxyl radicals (•OH) under ambient dark conditions, contributing to faster dissolution of arsenopyrite and higher percentage of As(V) in the dissolved products. Dissolved Mn(III), though considered as an extra oxidant besides oxygen, unexpectedly acted as a radical scavenger for •OH and inhibited the production of As(V). Moreover, the oxidation of sulfur species differed in the two systems as significant formation of thiosulfate was observed with the presence of PP, which did not occur in the system with dissolved Mn(III). Overall, the effects of dissolved Mn(III) and PP on the dissolution of arsenopyrite and the subsequent transformation of Fe, As and S species have important implications for disentangling the interactions among these metastable elements, and for assessing their transport and environmental impacts in aquatic systems.


Subject(s)
Arsenic , Ferric Compounds , Diphosphates , Solubility , Minerals , Oxidation-Reduction
17.
Oxid Med Cell Longev ; 2023: 4743885, 2023.
Article in English | MEDLINE | ID: mdl-36659906

ABSTRACT

Increased accumulation of reactive oxygen species (ROS) and decline of adaptive response of antioxidants to oxidative stimuli has been implicated in the aging process. Nuclear factor erythroid 2-related factor 2 (Nrf2) activation is a core event in attenuating oxidative stress-associated aging. The activity is modulated by a more complex regulatory network. In this study, we demonstrate the proteasome activator REGγ function as a new regulator of Nrf2 activity upon oxidative stress in cell aging model induced by hydrogen peroxide (H2O2). REGγ deficiency promotes cell senescence in primary MEF cells after H2O2 treatment. Accordingly, ROS scavenging is accelerated in WT cells but blunted in REGγ lacking cells during 12-hour recovery from a 1-hour H2O2 treatment, indicating long-lasting antioxidant buffering capacity of REGγ. Mechanistically, through GSK-3ß inhibition, REGγ enhances the nuclear distribution and transcriptional activity of Nrf2, which is surveyed by induction of phase II enzymes including Ho1 and Nqo1. Meanwhile, Nrf2 mediates the transcriptional activation of REGγ upon H2O2 stimulation. More interestingly, short-term exposure to H2O2 leads to transiently upregulation and gradually descent of REGγ transcription, however sustained higher REGγ protein level even in the absence of H2O2 for 24 hours. Thus, our results establish a positive feedback loop between REGγ and Nrf2 and a new layer of adaptive response after oxidative stimulation that is the REGγ-GSK-3ß-Nrf2 pathway.


Subject(s)
NF-E2-Related Factor 2 , Proteasome Endopeptidase Complex , Antioxidants/pharmacology , Cellular Senescence , Glycogen Synthase Kinase 3 beta/metabolism , Hydrogen Peroxide/pharmacology , Hydrogen Peroxide/metabolism , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Proteasome Endopeptidase Complex/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Animals
18.
Environ Sci Technol ; 57(1): 730-740, 2023 01 10.
Article in English | MEDLINE | ID: mdl-36538415

ABSTRACT

Manganese (Mn) exists as Mn(II), Mn(III), or Mn(IV) in soils, and the Mn oxidation state controls the roles of Mn in numerous environmental processes. However, the variations of Mn oxidation states with climate remain unknown. We determined the Mn oxidation states in highly weathered bulk volcanic soils (primary minerals free) across two rainfall gradients covering mean annual precipitation (MAP) of 0.25-5 m in the Hawaiian Islands. With increasing MAP, the soil redox conditions generally shifted from oxic to suboxic and to anoxic despite fluctuating at each site; concurrently, the proportions of Mn(IV) and Mn(II) decreased and increased, respectively. Mn(III) was low at both low and high MAP, but accumulated substantially, up to 80% of total Mn, in soils with prevalent suboxic conditions at intermediate MAP. Mn(III) was likely hosted in Mn(III,IV) and iron(III) oxides or complexed with organic matter, and its distribution among these hosts varied with soil redox potentials and soil pH. Soil redox conditions and rainfall-driven leaching jointly controlled exchangeable Mn(II) in soils, with its concentration peaking at intermediate MAP. The Mn redox chemistry was at disequilibrium, with the oxidation states correlating with long-term average soil redox potentials better than with soil pH. The soil redox conditions likely fluctuated between oxic and anoxic conditions more frequently at intermediate than at low and high MAP, creating biogeochemical hot spots where Mn, Fe, and other redox-sensitive elements may be actively cycled.


Subject(s)
Ferric Compounds , Manganese , Manganese/analysis , Soil , Iron , Oxidation-Reduction
19.
J Hazard Mater ; 443(Pt B): 130187, 2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36327834

ABSTRACT

Despite of the extensive research in semiconductor photocatalysis with respect to material and device innovations, much of the fundamental aquatic chemistry of those new materials that governs their environmental hazard and implications remains poorly understood. BiVO4 has long been recognized as a promising visible-light-responsive photocatalyst. However, the solubility product (Ksp) of BiVO4 and the mechanistic understanding of the non-stoichiometric dissolution of BiVO4 remain unclear. Here, we investigated the solubility of BiVO4 via the observation on its non-stoichiometric dissolution in the pH range of 4-9. Combining dissolution experiments, adsorption behavior and thermodynamic equilibrium calculations, the Ksp of BiVO4 was determined to be 10-35.81±0.51. The solubility and stability of BiVO4 were strongly pH-dependent, with the lowest solubility and highest stability near pH 5. Furthermore, we tested the effect of illumination on the dissolution of BiVO4, which was significantly enhanced by light. Under both dark and illumination conditions, adsorption of dissolved bismuth by BiVO4 solids was the main reason for the non-stoichiometric dissolution of BiVO4, and could be modeled by including an additional surface complexation reaction. Thus, the results highlighted the importance of considering the dissolution of photocatalysts, and presented a feasible method to evaluate environmental stability and risks of other semiconductor materials.

20.
Curr Drug Deliv ; 20(10): 1405-1424, 2023.
Article in English | MEDLINE | ID: mdl-35993478

ABSTRACT

The disadvantages of active ingredients extracted from medicinal plants due to poor solubility in the body and low bioavailability limit their clinical application. Pharmaceutical cocrystal as a new type of drug in solid form has attracted the attention of researchers. This article reviews the effects of cocrystal in various poorly soluble herbal active ingredients of medicinal plants on their physicochemical properties and biological properties and provides references for the application of pharmaceutical cocrystal in poorly soluble active compounds of medicinal plants.


Subject(s)
Crystallization , Biological Availability , Solubility , Pharmaceutical Preparations
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