ABSTRACT
Inorganic arsenic is a well-established environmental toxicant linked to acute liver injury, fibrosis, and cancer. While oxidative stress, pyroptosis, and ferroptosis are known contributors, the role of PTEN-induced kinase 1 (PINK1)-mediated mitophagy in arsenic-induced hepatic immunotoxicity remains underexplored. Our study revealed that acute arsenic exposure prompts differentiation of hepatic dendritic cells (DCs) and T helper (Th) 1, Th2, Th17, and regulatory T (Treg) cells, alongside increased transcription factors and cytokines. Inorganic arsenic triggered liver redox imbalance, leading to elevated alanine transaminase (ALT), hydrogen peroxide (H2O2), malondialdehyde (MDA), and activation of nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway. PINK1-mediated mitophagy was initiated, and its inhibition exacerbates H2O2 accumulation while promoting DCs/Th1/Th2/Treg differentiation in the liver of arsenic-exposed mice. Mitoquinone (MitoQ) pretreatment relieved arsenic-induced acute liver injury and immune imbalance by activating Nrf2/HO-1 and PINK1-mediated mitophagy. To our knowledge, this is the first report identifying PINK1-mediated mitophagy as a protective factor against inorganic arsenic-induced hepatic DCs/Th1/Th2 differentiation. This study has provided new insights on the immunotoxicity of inorganic arsenic and established a foundation for exploring preventive and therapeutic strategies targeting PINK1-mediated mitophagy in acute liver injury. Consequently, the application of mitochondrial antioxidant MitoQ may offer a promising treatment for the metalloid-induced acute liver injury.
Subject(s)
Antioxidants , Arsenic , Cell Differentiation , Liver , Mitophagy , Organophosphorus Compounds , Protein Kinases , Animals , Mitophagy/drug effects , Mice , Liver/drug effects , Antioxidants/pharmacology , Antioxidants/metabolism , Protein Kinases/metabolism , Cell Differentiation/drug effects , Organophosphorus Compounds/toxicity , Organophosphorus Compounds/pharmacology , Arsenic/toxicity , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Dendritic Cells/drug effects , Mice, Inbred C57BL , Mitochondria/drug effects , Male , T-Lymphocytes, Regulatory/drug effects , Chemical and Drug Induced Liver Injury/prevention & control , Oxidative Stress/drug effectsABSTRACT
BACKGROUND: Cardiovascular disease (CVD) is an important cause of morbidity and mortality in peritoneal dialysis (PD) patients. Cardiovascular calcification (CVC) is highly prevalent in PD patients and could predict their cardiovascular mortality. Soluble urokinase plasminogen activator receptor (suPAR) is closely associated with coronary artery calcification in hemodialysis patients and is an important predictor of CVD. However, the role of suPAR in PD patients is poorly understood. We investigated the relationship between serum suPAR and CVC in PD patients. METHODS: Abdominal aortic calcification (AAC) was assessed by lateral lumbar radiography, coronary artery calcification (CAC) by multi-slice computed tomography, and cardiac valvular calcification (ValvC) by echocardiography. CVC was defined as confirmed presence of calcification in one site (AAC, CAC, or ValvC). Patients were divided into CVC group and non-CVC group. Demographic characteristics, biochemical variables, comorbidities, PD regimen, serum suPAR, and medication were compared between the two groups. Logistic regression was conducted to determine association between serum suPAR and presence of CVC. The receiver-operator curve (ROC) was plotted to calculate the area under the curve (AUC) for suPAR to identify CVC and ValvC. RESULTS: Of 226 PD patients, 111 (49.1%) had AAC, 155 (68.6%) had CAC, and 26 (11.5%) had ValvC. There were significant differences in age, BMI, diabetes, white blood cell, phosphorus, hs-CRP, suPAR, time on dialysis, total volume of dialysate, ultrafiltration, volume of urine, and Kt/V between CVC and non-CVC group. Serum suPAR was associated with CVC by multivariate logistic regression analysis in PD patients, especially in elderly patients. The levels of serum suPAR were closely related to the degree of AAC, CAC, and ValvC in PD patients. The incidence of CVC was higher in patients with higher levels of suPAR. The ROC curve showed that serum suPAR had a predictive value for CVC (AUC = 0.651), especially for ValvC (AUC = 0.828). CONCLUSION: Cardiovascular calcification is prevalent in PD patients. High levels of serum suPAR are associated with cardiovascular calcification in PD patients, especially in elderly patients.
Subject(s)
Calcinosis , Cardiovascular Diseases , Coronary Artery Disease , Peritoneal Dialysis , Humans , Biomarkers , Coronary Artery Disease/epidemiology , Peritoneal Dialysis/adverse effects , Receptors, Urokinase Plasminogen Activator , Risk FactorsABSTRACT
BACKGROUND: Cardiovascular events (CVE) are the leading cause of death in peritoneal dialysis (PD) patients. The predictive value of cardiac valve calcification (CVC) for CVE in dialysis patients remains controversial. In particular, such studies are limited in PD patients. We aimed to examine the predictive role of CVC for CVE and cardiovascular mortality in PD patients. METHODS: A retrospective analysis was performed on patients who initiated PD in our hospital. According to the result of echocardiography, patients were divided into CVC group and non-CVC group. The differences in baseline demographic characteristics, biochemical variables, comorbidities, and clinical outcomes between the two groups were compared. Kaplan-Meier method was used to obtain survival curves. The Cox regression model was used to evaluate the influence of CVC for cardiovascular outcomes. The inverse probability of treatment weighting (IPTW) was used to eliminate influence of the confounders in the groups. RESULTS: 458 peritoneal dialysis patients were enrolled in this study. 77 patients were in CVC group and 381 patients in non-CVC group. The average follow-up time was (32 ± 21) months. At baseline, the absolute standardized difference (ASD) of age, BMI, history of CVE, diabetes, LVEF, LVMI, albumin, calcium, phosphorus, triglycerides, hsCRP, urine volume, Kt/V, statins and vitamin D intake rate were greater than 0.1 between the two groups. All of ASD dropped to less than 0.1 after IPTW, which meant that the balance had been reached between the two groups. Multivariable logistic analysis showed that advanced age, diabetes, and hyperphosphatemia were associated with CVC. The Kaplan-Meier survival curve showed the cumulative CVE-free survival rate and cardiovascular survival rate of CVC group were significantly lower than that of non-CVC group before and after IPTW (log-rank P < 0.05). After IPTW was used to eliminate the effect of confounders, multivariate Cox regression analysis still showed CVC was an independent risk factor for CVE (HR = 2.383, 95% CI 1.331~4.264, P = 0.003) and cardiovascular mortality (HR = 2.347, 95% CI 1.211~4.548, P = 0.012) in PD patients. CONCLUSION: The prevalence of CVC is high in peritoneal dialysis patients. CVC is an independent risk factor for CVE and cardiovascular mortality in peritoneal dialysis patients.
Subject(s)
Cardiovascular Diseases , Heart Valve Diseases , Peritoneal Dialysis , Humans , Retrospective Studies , Heart Valve Diseases/complications , Heart Valve Diseases/epidemiology , Peritoneal Dialysis/adverse effects , Peritoneal Dialysis/methods , Probability , Heart Valves , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiologyABSTRACT
AIE-active phenyl- and [2.2]paracyclophanyl-based aurones (2-Ph and 2-PCP) were synthesized and investigated with different structures and photophysical properties. The results illustrated that the PCP ring can provide chirality, electron-donating ability and steric hindrance. Accordingly, (Rp)/(Sp)-2-PCP exhibit high sensitivity in trace water detection and aggregation-induced CPL with enhanced quantum yields and luminescence dissymmetry factors.
Subject(s)
Benzofurans , Luminescence , Water , ElectronsABSTRACT
The construction of cluster-based crystalline chalcogenide structures through the traditional solvothermal method relies on synergistic control of precursors, template cations and auxiliary solvents. Generally, the combination of metal precursors plays a crucial role in controlling the size of clusters, while organic templates and auxiliary solvents usually contribute to the type of clusters and architecture of the framework. Decades of synthetic efforts have been mainly devoted to expanding organic amine templates for constructing new structures. However, the important role of auxiliary solvents in enriching the chalcogenide family is usually disregarded. Reported here are several new crystalline In-Se compounds (ISP-1 to 4) with different dimensions, obtained by elaborately regulating auxiliary solvents under the direction of the same organic template, piperidine. Of these four structures, ISP-1 is constructed by irregular supertetrahedral clusters, giving a novel 2D structure with a corner-shared single Se atom and In2Se3 five-member ring as linkers; ISP-2 has a 1D structure composed by interlinked In2Se3 five-member rings; ISP-4 is constructed by supertetrahedral T2 clusters exhibiting an uncommon zeolite-like mog network.
ABSTRACT
The development of small organic CPL-active molecules with large luminescent dissymmetry factors is highly demanded due to their promising applications in chiroptical devices and sensors. This work describes the design and synthesis of a new family of CPL-active BF2 complexes, (Rp)/(Sp)-3a-3e, which were constructed by fusing a NÌO-chelated BF2 complex with [2.2]paracyclophane. These complexes display aggregation-amplified CPL with moderate dissymmetry factors values and moderate quantum yields both in solution and in the solid state. In addition, these photophysical properties were rationalized via X-ray diffraction and TD-DFT calculations.
ABSTRACT
Planar chiral [2.2]paracyclophanyl-based boron fluoride complexes (3a-3d) were designed and facilely synthesized. The X-ray structure study, theoretical calculations and CD spectra reveal the intense emission and planar chiral structures of these complexes. In particular, 3a-3d show moderate quantum yields and large Stokes shifts both in solution and solid state. Furthermore, the blue-shifted mechanochromic properties of 3a and 3b were both investigated in the solid state. This work is the first study on planar chiral boron monofluoride complexes within the boron fluoride complex field.
ABSTRACT
One bonded- and one discreted-Lindqvist hexatungstate-based copper hybrids (Cu-POMs) ([Cu2(O)OH(phen)2]2[W6O19]·6H2O (1) and [Cu2(phen)4Cl] [HW6O19]·2H2O (2) (phen = 1,10-phenanthroline)) were controllably synthesized and routinely characterized. Cu-POMs 1-2 consisted of identical [W6O19] unit and similar copper-phen complexes, the two units are bonded via four Cu-O chemical bonds in compound 1; however, compound 2 is discreted and stabilized by intermolecular electrostatic interactions. Importantly, these Cu-POMs catalysts were first applied in the novel reaction for the preparation of 2-phenylquinoxalines via the one-pot coupling and oxidation reactions of 2-haloanilines with vinyl azides or 3-phenyl-2H-azirines under mild conditions, and Cu-POMs 1 showed higher catalytic performance in good yields (79-84%). The reactions exhibit some functional group tolerance and allow for the preparation of a number of 2-phenylquinoxalines.
ABSTRACT
A synthetic pathway for the directed preparation of three novel polyoxovanadate-based copper frameworks (POVCFs), i.e., [Cu0.5(1-ipIM)2]2[V4O11] (POVCF 1), [Cu(1-ipIM)2](VO3)2 (POVCF 2) and [Cu(1-pIM)4](HpIM)4[V10O28] (POVCF 3) (1-ipIM = 1-isopropylimidazole; 1-pIM = 1-propylimidazole) using bifunctional imidazole molecules as organic ligands and base has been developed. Systematic studies revealed that the variable base enviroment in the reaction is the key step in the preparation of 1D to 3D supermolecular networks of POVCFs 1-3. Single crystal X-ray diffraction analyses demonstrated that the Cu2+ atoms of POVCFs 1-2 were coordinated with four imidazole derivative molecules and two different polyoxovanadate {[V4O11]2- and [V10O28]6-} clusters, respectively, exhibiting a [CuN4O2] binding set and a distorted octahedral geometry. Specifically, POVCF 1 exhibited adjacent [V4O11]2- that dangle up and down arranged in a parallel 2D network and further coordinated with [Cu(1-ipIM)4]2+ to form a 3D supramolecular structure. However, POVCF 3 presented one tetrahedral coordinated vanadium atom and one four-coordinated copper atom and they further gave rise to a 1D network by the Cu-O and V-O bonds. More importantly, these POVCFs were further studied in the construction of C-N bond reactions of primary amines under mild conditions, and it was found that POVCF 1 displayed efficient heterogeneous catalytic activities in the Chan-Lam reaction (yields up to 89%).
ABSTRACT
The synthesis of hierarchical nanosized zeolite materials without growth modifiers and mesoporogens remains a substantial challenge. Herein, we report a general synthetic approach to produce hierarchical nanosized single-crystal aluminophosphate molecular sieves by preparing highly homogeneous and concentrated precursors and heating at elevated temperatures. Accordingly, aluminophosphate zeotypes of LTA (8-rings), AEL (10-rings), AFI (12-rings), and -CLO (20-rings) topologies, ranging from small to extra-large pores, were synthesized. These materials show exceptional properties, including small crystallites (30-150â nm), good monodispersity, abundant mesopores, and excellent thermal stability. A time-dependent study revealed a non-classical crystallization pathway by particle attachment. This work opens a new avenue for the development of hierarchical nanosized zeolite materials and understanding their crystallization mechanism.
ABSTRACT
Hydrogen polysulfides (H2Sn, n > 1), as the oxidized forms of H2S, have attracted increasing attention these years due to their involvement in signaling transduction and cytoprotective processes. It is necessary to detect H2Sn in living systems for the study of their functions. In this work, we report a BODIPY-based near-infrared emitting fluorescence probe NIR-PHS1, with "turn-on" response, rapid response rate (within 10 min), outstanding selectivity and excellent sensitivity (detection limit = 12 nM) response towards H2Sn. The probe was successfully applied to the visualizing of endogenous H2Sn in living cells. Moreover, it can be used for near-infrared in vivo imaging of H2Sn in living mice. Therefore, NIR-PHS1 could be a potential imaging tool to study the biological roles of H2Sn in living systems.
Subject(s)
Fluorescent Dyes/chemistry , Hydrogen Sulfide/chemistry , Hydrogen Sulfide/metabolism , Infrared Rays , Optical Imaging/methods , Animals , Boron Compounds/chemistry , Cell Survival , HeLa Cells , Humans , MiceABSTRACT
Hydrogen polysulfides (H2Sn, nâ¯>â¯1) have attracted increasing attention in biological systems due to its redox signaling effect. To illustrate the process of the physiological and pathological roles played by H2Sn, accurate detection is highly desired. In this work, we report a BODIPY-based fluorescent probe (BDP-PHS) for ratiometric H2Sn sensing. BDP-PHS shows higher sensitivity and selectivity ratiometric response toward H2Sn than various biological related species. Moreover, BDP-PHS has been successfully applied in imaging of H2Sn in living cells.
Subject(s)
Biosensing Techniques/methods , Boron Compounds/chemistry , Hydrogen/analysis , Molecular Imaging , Molecular Probes/chemistry , Sulfides/analysis , Boron Compounds/chemical synthesis , Cell Survival , HeLa Cells , Humans , Hydrogen-Ion Concentration , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , Time FactorsABSTRACT
By combining the fluorophores of axially chiral 1,1'-binaphthol (BINOL) and 1,4-dihydropyridine derivatives, axially chiral 1,4-dihydropyridine derivatives ((R)-/(S)-2) with aggregation-induced emission (AIE) in exciplexes were designed and synthesized. (R)-/(S)-2 emitted low fluorescence in THF solutions of their locally excited states; however, they emitted red-shifted fluorescence in the aggregate state upon exciplex formation. Moreover, (R)-/(S)-2 showed linear and multi-exponential relationships between their local excited and exciplex fluorescence intensities and the viscosity of the medium, which allowed us to determine the viscosities of different mixed solvents. In addition, as an axially chiral viscosity probe, (R)-/(S)-2 show excellent CD signals and have potential applications in the fields of chiral recognition and fluorescence imaging, which will broaden the new family of AIE fluorophores. To the best of our knowledge, there are few reports of axially chiral intramolecular exciplex-mediated AIE molecules.
ABSTRACT
Propeller-shaped pyridyl-enolato-catecholate/-salicyl spiroborates (Sborepy1-6) were synthesized. The complexes Sborepy3-6 show weak emission in fluid solution and aggregation-induced emission enhancement in the aggregation state with large Stokes shifts of 4025-5237 cm-1. Moreover, intense solid-state emissions with high Φf ranging from 25% to 37% were observed for Sborepy3-6 owing to the weak intermolecular interactions in their solid-state. The AIE and intense solid-state emission have been revealed via the X-ray diffraction analysis and theoretical calculations. Furthermore, the solvatochromism in the solution state and the potential application as a fluorescent acidic vapour sensor in the solid state of Sborepy3 and Sborepy6 were also demonstrated.
ABSTRACT
A versatile Lewis acid catalyzed tandem cyclization of in situ generated alkynyl o-quinone methides ( o-AQMs) with electron-rich phenols has been developed on the basis of the mode involving an intermolecular 1,4-conjugate addition/6-endo cyclization/1,3-aryl shift/intramolecular 1,4-conjugate addition cascade. This reaction provides a new method for expeditious assembly of synthetically and biologically interesting tetracyclic bridged dioxabicyclo[3.3.1]nonane skeletons featuring a congested bridgehead oxa-quaternary stereocenter.
ABSTRACT
A new family of aggregation-induced emission (AIE)-active monoboron and bisboron complexes based on benzothiazole-hydrazone chelates was synthesized. These complexes showed very weak fluorescence in fluid solution due to active intramolecular rotation and were emissive in high-viscosity solvents or in the aggregation state. Single crystal X-ray diffraction analyses and theoretical calculations were carried out to explain AIE behavior. The large Stokes shifts (3590-7400 cm-1) and relatively highly efficient solid-state emission make these complexes valuable AIE luminophores for further potential applications.
ABSTRACT
A heteropoly acid based organic hybrid heterogeneous catalyst, HMQ-STW, was prepared by combining 8-hydroxy-2-methylquinoline (HMQ) with Keggin-structured H4SiW12O40 (STW). The catalyst was characterized via elemental analysis, X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), thermogravimetric analysis (TG) and potentiometric titration analysis. The catalytic performance of the catalyst was assessed in the ketalization of ketones with glycol or 1,2-propylene glycol. Various reaction parameters, such as the glycol to cyclohexanone molar ratio, catalyst dosage, reaction temperature and time, were systematically examined. HMQ-STW exhibited a relatively high yield of corresponding ketal, with 100% selectivity under the optimized reaction conditions. Moreover, catalytic recycling tests demonstrated that the heterogeneous catalyst exhibited high potential for reusability, and it was revealed that the organic modifier HMQ plays an important role in the formation of a heterogeneous system and the improvement of structural stability. These results indicated that the HMQ-STW catalyst is a promising new type of heterogeneous acid catalyst for the ketalization of ketones.
ABSTRACT
Recent studies have shown that as members of the reactive sulfur species family and the oxidized forms of H2S, hydrogen polysulfides (H2Sn) play important roles in physiological and pathological processes. Therefore, accurate detection of H2Sn levels in living systems is of great significance. In this study, we report an isophorone-based far-red emitting fluorescent probe (RPHS1) for selective ratiometric sensing and imaging of H2Sn. RPHS1 shows specific ratiometric response towards H2Sn with fast reaction rate and low detection limit in aqueous media. Furthermore, confocal fluorescence microscopy experiments demonstrate that RPHS1 can be applied for H2Sn imaging in living cells.
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A new family of pyrimidine-based BF2 complexes () with aggregation-induced emission (AIE) and mechanochromic luminescence properties were developed. These compounds exhibit intense fluorescence in their aggregation/solid-state resulting from their large Stokes shift and AIE. X-ray crystallographic analysis shows that the weak intermolecular interactions by fixing the molecular conformations of are responsible for the intense fluorescence in solid-state. In addition to their pronounced AIE behaviour, also exhibits a reversible chromic response to grinding, and a distinct red-shift of emission is observed. The high solid-state luminescence and grinding-stimuli response properties of these compounds make them potential candidates for smart materials.
ABSTRACT
Due to the similar structure and reactivity of cysteine (Cys), homocysteine (Hcy) and glutathione (GSH), the simultaneous discrimination of Cys over Hcy and GSH by a single fluorescent sensor is still a great challenge. In this work, a benzothiazole-pyimidine-based boron difluoride complex (BPB) was developed as a new fluorescent sensor for Cys. The sensor exhibits a highly selective "turn-on" response to cysteine over Hcy, GSH and other amino acids in aqueous solution at physiological pH. The observed pseudo-first-order rate constant for the reaction of BPB with Cys was calculated to be about 0.062â min(-1) . The detection limit of this sensor for Cys was determined to be 332â nm, and bioimaging of exogenous Cys by this sensor was successfully applied in living cells, thus indicating that this sensor holds great potential for biological applications.