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1.
Environ Toxicol Chem ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38695729

ABSTRACT

Persistent organic pollutants pose a great threat to amphibian populations, but information on the bioaccumulation of contaminants in amphibians remains scarce. To examine the tissue distribution and maternal transfer of organic halogenated pollutants (OHPs) in frogs, seven types of tissues from black-spotted frog (muscle, liver, kidney, stomach, intestine, heart, and egg) were collected from an e-waste-polluted area in South China. Among the seven frog tissues, median total OHP concentrations of 2.3 to 9.7 µg/g lipid weight were found (in 31 polychlorinated biphenyl [PCB] individuals and 15 polybrominated diphenyl ether [PBDE], dechlorane plus [syn-DP and anti-DP], bexabromobenzene [HBB], polybrominated biphenyl] PBB153 and -209], and decabromodiphenyl ethane [DBDPE] individuals). Sex-specific differences in contaminant concentration and compound compositions were observed among the frog tissues, and eggs had a significantly higher contaminant burden on the whole body of female frogs. In addition, a significant sex difference in the concentration ratios of other tissues to the liver was observed in most tissues except for muscle. These results suggest that egg production may involve the mobilization of other maternal tissues besides muscle, which resulted in the sex-specific distribution. Different parental tissues had similar maternal transfer mechanisms; factors other than lipophilicity (e.g., molecular size and proteinophilic characteristics) could influence the maternal transfer of OHPs in frogs. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.

2.
Respir Res ; 25(1): 193, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702733

ABSTRACT

BACKGROUND: Influenza A virus (IAV) infection is a significant risk factor for respiratory diseases, but the host defense mechanisms against IAV remain to be defined. Immune regulators such as surfactant protein A (SP-A) and Toll-interacting protein (Tollip) have been shown to be involved in IAV infection, but whether SP-A and Tollip cooperate in more effective host defense against IAV infection has not been investigated. METHODS: Wild-type (WT), Tollip knockout (KO), SP-A KO, and Tollip/SP-A double KO (dKO) mice were infected with IAV for four days. Lung macrophages were isolated for bulk RNA sequencing. Precision-cut lung slices (PCLS) from WT and dKO mice were pre-treated with SP-A and then infected with IAV for 48 h. RESULTS: Viral load was significantly increased in bronchoalveolar lavage (BAL) fluid of dKO mice compared to all other strains of mice. dKO mice had significantly less recruitment of neutrophils into the lung compared to Tollip KO mice. SP-A treatment of PCLS enhanced expression of TNF and reduced viral load in dKO mouse lung tissue. Pathway analysis of bulk RNA sequencing data suggests that macrophages from IAV-infected dKO mice reduced expression of genes involved in neutrophil recruitment, IL-17 signaling, and Toll-like receptor signaling. CONCLUSIONS: Our data suggests that both Tollip and SP-A are essential for the lung to exert more effective innate defense against IAV infection.


Subject(s)
Influenza A virus , Mice, Inbred C57BL , Mice, Knockout , Orthomyxoviridae Infections , Pulmonary Surfactant-Associated Protein A , Animals , Pulmonary Surfactant-Associated Protein A/metabolism , Pulmonary Surfactant-Associated Protein A/genetics , Mice , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/virology , Orthomyxoviridae Infections/metabolism , Influenza A virus/immunology , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Lung/immunology , Lung/metabolism , Lung/virology
3.
Nat Commun ; 15(1): 3900, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724552

ABSTRACT

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC+ mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma.


Subject(s)
Asthma , GPI-Linked Proteins , Interleukin-13 , Lectins , Mucin 5AC , Mucus , Child , Humans , Asthma/genetics , Asthma/metabolism , Cytokines , Epithelial Cells/metabolism , GPI-Linked Proteins/genetics , GPI-Linked Proteins/metabolism , Interleukin-13/genetics , Interleukin-13/metabolism , Lectins/genetics , Lectins/metabolism , Mucin 5AC/genetics , Mucin 5AC/metabolism , Mucus/metabolism , Nasal Mucosa/metabolism , Polymorphism, Genetic , Respiratory Mucosa/metabolism
4.
J Hazard Mater ; 472: 134420, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38691997

ABSTRACT

In this work, MIL-88A(Fe) was immobilized onto the expanded perlites to fabricate the floating MIL-88A(Fe)@expanded perlites (M@EP) catalyst via high throughput batch synthesis method under room temperature. The as-prepared M@EP could efficiently activate H2O2 to achieve 100% tetracycline antibiotics (TCs) removal under both artificial low power UV light (UVL) and real sunlight (SL) irradiation. The toxicological evaluation, growth experiment of mung beans and antimicrobial estimation revealed the decreasing aquatic toxicity of the TCs intermediates compared to those of the pristine TCs. A self-designed continuous bed reactor was employed to investigate the long-term operation of the M@EP. The findings demonstrated that the antibiotics mixture can be continuously degraded up to 7 days under UVL and 5 daytimes under SL irradiation, respectively. More importantly, ca. 76.9% and 81.6% of total organic carbon (TOC) removal efficiencies were accomplished in continuous bed reactor under UVL and SL irradiation, respectively. This work advances the immobilized MOFs on floating supports for their practical application in large-scale wastewater purification through advanced oxidation processes. ENVIRONMENTAL IMPLICATION: This work presented the high throughput production and photo-Fenton degradation application of floating MIL-88A(Fe)@expanded perlites (M@EP). Three tetracycline antibiotics (TCs) were selected as model pollutants to test the degradation ability of M@EP in batch experiment and continuous operation under artificial light and solar light. The complete TCs degradation could be accomplished in self-designed device up to 7 d under UV light and 5 d under real solar light. This work tapped a new door to push MOFs-based functional materials in the real water purification.

5.
eNeuro ; 11(5)2024 May.
Article in English | MEDLINE | ID: mdl-38658137

ABSTRACT

The primary motor cortex (M1) integrates sensory and cognitive inputs to generate voluntary movement. Its functional impairments have been implicated in the pathophysiology of motor symptoms in Parkinson's disease (PD). Specifically, dopaminergic degeneration and basal ganglia dysfunction entrain M1 neurons into the abnormally synchronized bursting pattern of activity throughout the cortico-basal ganglia-thalamocortical network. However, how degeneration of the midbrain dopaminergic neurons affects the anatomy, microcircuit connectivity, and function of the M1 network remains poorly understood. The present study examined whether and how the loss of dopamine (DA) affects the morphology, cellular excitability, and synaptic physiology of Layer 5 parvalbumin-expressing (PV+) cells in the M1 of mice of both sexes. Here, we reported that loss of midbrain dopaminergic neurons does not alter the number, morphology, and physiology of Layer 5 PV+ cells in M1. Moreover, we demonstrated that the number of perisomatic PV+ puncta of M1 pyramidal neurons as well as their functional innervation of cortical pyramidal neurons were not altered following the loss of DA. Together, the present study documents an intact GABAergic inhibitory network formed by PV+ cells following the loss of midbrain dopaminergic neurons.


Subject(s)
Dopaminergic Neurons , Interneurons , Mesencephalon , Motor Cortex , Parvalbumins , Animals , Female , Male , Mice , Dopaminergic Neurons/metabolism , GABAergic Neurons/metabolism , Interneurons/metabolism , Mesencephalon/metabolism , Mice, Inbred C57BL , Mice, Transgenic , Motor Cortex/metabolism , Neural Inhibition/physiology , Parvalbumins/metabolism
6.
bioRxiv ; 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38659803

ABSTRACT

We present an open-source behavioral platform and software solution for studying fine motor skills in mice performing reach-to-grasp task. The behavioral platform uses readily available and 3D-printed components and was designed to be affordable and universally reproducible. The protocol describes how to assemble the box, train mice to perform the task and process the video with the custom software pipeline to analyze forepaw kinematics. All the schematics, 3D models, code and assembly instructions are provided in the open GitHub repository.

7.
Neural Regen Res ; 19(10): 2107-2108, 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-38488541
8.
Int J Mol Sci ; 25(5)2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38474191

ABSTRACT

Mitochondrial dysfunction and metabolic reprogramming have been extensively studied in many disorders ranging from cardiovascular to neurodegenerative disease. Obesity has previously been associated with mitochondrial fragmentation, dysregulated glycolysis, and oxidative phosphorylation, as well as increased reactive oxygen species production. Current treatments focus on reducing cellular stress to restore homeostasis through the use of antioxidants or alterations of mitochondrial dynamics. This review focuses on the role of mitochondrial dysfunction in obesity particularly for those suffering from asthma and examines mitochondrial transfer from mesenchymal stem cells to restore function as a potential therapy. Mitochondrial targeted therapy to restore healthy metabolism may provide a unique approach to alleviate dysregulation in individuals with this unique endotype.


Subject(s)
Asthma , Mitochondrial Diseases , Neurodegenerative Diseases , Humans , Oxidative Stress/physiology , Metabolic Reprogramming , Obesity , Mitochondrial Diseases/metabolism , Reactive Oxygen Species/metabolism
9.
Inorg Chem ; 63(9): 4185-4195, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38364251

ABSTRACT

Posttreatment of pristine metal-organic frameworks (MOFs) with suitable vapor may be an effective way to regulate their structures and properties but has been less explored. Herein, we report an interesting example in which a crystalline nonporous Eu(III)-MOF was transferred to a porous amorphous MOF (aMOF) via iodine vapor adsorption-desorption posttreatment, and the resulting aMOF showed improved turn-on sensing properties with respect to Ag+ ions. The crystalline Eu-MOF, namely, Eu-IPDA, was assembled from Eu(III) and 4,4'-{4-[4-(1H-imidazol-1-yl)phenyl]pyridine-2,6-diyl}dibenzoic acid (H2IPDA) and exhibited a two-dimensional (2D) coordination network based on one-dimensional secondary building blocks. The close packing of the 2D networks gives rise to a three-dimensional supramolecular framework without any significant pores. Interestingly, the nonporous Eu-IPDA could absorb iodine molecules when Eu-IPDA crystals were placed in iodine vapor at 85 °C, and the adsorption capacity was 1.90 g/g, which is comparable to those of many MOFs with large BET surfaces. The adsorption of iodine is attributed to the strong interactions among the iodine molecule, the carboxy group, and the N-containing group and leads to the amorphization of the framework. After immersion of the iodine-loaded Eu-IPDA in EtOH, approximately 89.7% of the iodine was removed, resulting in a porous amorphous MOF, denoted as a-Eu-IPDA. In addition, the remaining iodine in the a-Eu-IPDA framework causes strong luminescent quenching in the fluorescence emission region of the Eu(III) center when compared with that in Eu-IPDA. The luminescence intensity of a-Eu-IPDA in water suspensions was significantly enhanced when Ag+ ions were added, with a detection limit of 4.76 × 10-6 M, which is 1000 times that of pristine Eu-IPDA. It also showed strong anti-interference ability over many common competitive metal ions and has the potential to sense Ag+ in natural water bodies and traditional Chinese medicine preparations. A mechanistic study showed that the interactions between Ag+ and the absorbed iodine, the carboxylate group, and the N atoms all contribute to the sensing performance of a-Eu-IPDA.

10.
Cell Commun Signal ; 22(1): 15, 2024 01 05.
Article in English | MEDLINE | ID: mdl-38183060

ABSTRACT

BACKGROUND: The dynamic interaction between cancer cells and tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is an active barrier to the effector arm of the antitumour immune response. Cancer-secreted exosomes are emerging mediators of this cancer-stromal cross-talk in the TME; however, the mechanisms underlying this interaction remain unclear. METHODS: Exosomes were isolated with ExoQuick exosome precipitation solution. The polarizing effect of TAMs was evaluated by flow cytometry, western blot analysis, immunofluorescence staining and in vitro phagocytosis assays. Clinical cervical cancer specimens and an in vivo xenograft model were also employed. RESULTS: Our previous study showed that hypoxia increased the expression of ZEB1 in cervical squamous cell carcinoma (CSCC) cells, which resulted in increased infiltration of TAMs. Here, we found that hypoxia-induced ZEB1 expression is closely correlated with CD47-SIRPα axis activity in CSCC, which enables cancer cells to evade phagocytosis by macrophages and promotes tumour progression. ZEB1 was found to directly activate the transcription of the CD47 gene in hypoxic CSCC cells. We further showed that endogenous ZEB1 was characteristically enriched in hypoxic CSCC cell-derived exosomes and transferred into macrophages via these exosomes to promote SIRPα+ TAM polarization. Intriguingly, exosomal ZEB1 retained transcriptional activity and reprogrammed SIRPα+ TAMs via activation of the STAT3 signalling pathway in vitro and in vivo. STAT3 inhibition reduced the polarizing effect induced by exosomal ZEB1. Knockdown of ZEB1 increased the phagocytosis of CSCC cells by macrophages via decreasing CD47 and SIRPα expression. CONCLUSIONS: Our results suggest that hypoxia-induced ZEB1 promotes immune evasion in CSCC by strengthening the CD47-SIRPα axis. ZEB1-targeted therapy in combination with CD47-SIRPα checkpoint immunotherapy may improve the outcomes of CSCC patients in part by disinhibiting innate immunity.


Subject(s)
Carcinoma, Squamous Cell , Tumor Escape , Uterine Cervical Neoplasms , Zinc Finger E-box-Binding Homeobox 1 , Female , Humans , CD47 Antigen , Exosomes , Immune Evasion , Tumor Microenvironment , Uterine Cervical Neoplasms/metabolism , Zinc Finger E-box-Binding Homeobox 1/metabolism
11.
Huan Jing Ke Xue ; 45(1): 470-479, 2024 Jan 08.
Article in Chinese | MEDLINE | ID: mdl-38216496

ABSTRACT

Contaminants such as microplastics (MPs) and heavy metals are commonly found in soils, both of which are extremely difficult to degrade and can easily form compound contamination, altering the physicochemical properties of the soil and thus potentially changing the growth and physiological and ecological characteristics of plants. In order to study the effects of the combined contamination of soil MPs and heavy metals on soil properties and plant growth, polystyrene microplastics (PS-MPs) with a particle size of 3 µm and the heavy metal cadmium were selected in the study. The changes in the physicochemical properties of soil and their effects on lettuce (Lactuca sativa) seed germination and seedling growth were studied at various exposure concentrations of PS-MPs (0, 10, 50, 100, 200, and 400 mg·kg-1) and combined with different Cd contamination concentrations (0, 1.2, and 6.0 mg·kg-1), respectively. The results showed that soil organic matter (SOM), available phosphorus (AP), alkali-hydrolysable nitrogen (AHN), and available kalium (AK) showed significant decreases as the intensity of PS-MPs combined with Cd contamination increased. Simultaneously, PS-MPs combined with Cd contamination also significantly reduced the germination rate of lettuce seeds, but low concentrations of PS-MPs slowed down the effect of Cd (6.0 mg·kg-1) contamination on lettuce seeds, and high concentrations of PS-MPs enhanced the effect of Cd (6.0 mg·kg-1). The fresh weight, dry weight, and plant height of lettuce seedlings showed an increasing and then decreasing trend with increasing exposure to PS-MPs. Chlorophyll content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) showed a decreasing trend, whereas malondialdehyde (MDA) content showed an overall increasing trend under different Cd concentrations. The main physicochemical indicators of the soil were negatively correlated with MDA of lettuce seedlings, whereas other indicators of the seedlings were positively correlated. The combined contamination of PS-MPs and Cd could affect the germination of plant seeds and the physiological and ecological characteristics of seedlings by changing the physicochemical properties of the soil. Both exposure to single PS-MPs contaminants and the combination of PS-MPs with Cd inhibited the germination of lettuce seeds and affected the physiological activities of their seedlings, and the inhibition was significantly increased with increasing exposure. Low exposure to PS-MPs or the combination of PS-MPs with Cd contamination exhibited a promotive effect on lettuce seedling growth. High exposure to PS-MPs combined with Cd contamination exhibited significant ecological effects on lettuce seedlings, and high exposure to PS-MPs exacerbated the ecotoxicological effects of Cd contaminants on lettuce seedlings, and PS-MPs and Cd exhibited synergistic effects. The results can provide some reference for assessing the ecological effects of MPs and heavy metal pollution in soil-plant systems.


Subject(s)
Metals, Heavy , Soil Pollutants , Cadmium/toxicity , Cadmium/metabolism , Microplastics , Lactuca , Plastics , Polystyrenes , Soil , Metals, Heavy/metabolism , Seedlings , Soil Pollutants/analysis
12.
J Sci Food Agric ; 104(3): 1431-1440, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37800391

ABSTRACT

BACKGROUND: Pea protein, as a by-product of peas (Pisum sativum L.), is rich in a variety of essential amino acids that can meet the body's protein needs and is a valuable source of protein. Since the function of pea protein is closely related to its structure, pea protein has been subjected to different modifications in recent years to improve its application in food and to develop new products. RESULTS: The effects of sonication frequency (primary and secondary time) on pea protein isolate's (PPI's) structural and functional properties were investigated. Sodium dodecyl sulfate polyacrylamide gel electrophoresis demonstrated that different sonication frequencies at the same power (600 W) treatment had no effect on PPI's molecular weight. Fourier-transform infrared spectroscopy revealed that treatment at different sonication frequencies caused secondary structural changes in PPI. The particle size distribution, foaming, stability, surface hydrophobicity, emulsification, and oxidation resistance of PPI were improved after primary and secondary sonication, but secondary sonication was not more effective than primary sonication for an extended period of time. CONCLUSION: Overall, ultrasound is able to improve the structural and functional properties of pea proteins within a suitable range. It provides a theoretical basis for elucidating the modification of the structure and function of plant proteins by ultrasound and lays the foundation for the development of plant proteins in food applications as well as development. © 2023 Society of Chemical Industry.


Subject(s)
Pea Proteins , Ultrasonics , Plant Proteins , Hydrophobic and Hydrophilic Interactions
13.
Clin Cardiol ; 47(1): e24168, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37805965

ABSTRACT

BACKGROUND: Persistent acute kidney injury (AKI) after cardiac surgery is not uncommon and linked to poor outcomes. HYPOTHESIS: The purpose was to develop a model for predicting postoperative persistent AKI in patients with normal baseline renal function who experienced AKI after cardiac surgery. METHODS: Data from 5368 patients with normal renal function at baseline who experienced AKI after cardiopulmonary bypass cardiac surgery in our hospital were retrospectively evaluated. Among them, 3768 patients were randomly assigned to develop the model, while the remaining patients were used to validate the model. The new model was developed using logistic regression with variables selected using least absolute shrinkage and selection operator regression. RESULTS: The incidence of persistent AKI was 50.6% in the development group. Nine variables were selected for the model, including age, hypertension, diabetes, coronary heart disease, cardiopulmonary bypass time, AKI stage at initial diagnosis after cardiac surgery, postoperative serum magnesium level of <0.8 mmol/L, postoperative duration of mechanical ventilation, and postoperative intra-aortic balloon pump use. The model's performance was good in the validation group. The area under the receiver operating characteristic curve was 0.761 (95% confidence interval: 0.737-0.784). Observations and predictions from the model agreed well in the calibration plot. The model was also clinically useful based on decision curve analysis. CONCLUSIONS: It is feasible by using the model to identify persistent AKI after cardiac surgery in patients with normal baseline renal function who experienced postoperative AKI, which may aid in patient stratification and individualized precision treatment strategy.


Subject(s)
Acute Kidney Injury , Cardiac Surgical Procedures , Humans , Retrospective Studies , Cardiac Surgical Procedures/adverse effects , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Cardiopulmonary Bypass/adverse effects , Kidney , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Risk Factors
14.
Vet Microbiol ; 288: 109943, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38113574

ABSTRACT

O-acetyl-homoserine sulfhydrylase (OAHS) is a pyridoxal 5'-phosphate-dependent enzyme involved in microbial methionine biosynthesis, which catalyzes the conversion of o-acetyl-homoserine (OAH) to homocysteine. In our previous study, we found that OAHS of Streptococcus suis serotype 2 (SS2) can interact with the porcine blood-brain barrier (BBB) model, but whether OAHS regulates the penetration of BBB during SS2 infection is still unclear. To explore the role of OAHS in SS2 infection, OAHS-deficient SS2 mutant strain (SC19-ΔOAHS) and gene complemental strain (SC19-cΔOAHS) were constructed. Compared to the parent strain, with the loss of oahs, the chain length of SC19-ΔOAHS was shortened, the virulence was significantly reduced, the survival rate of mice infected with SC19-ΔOAHS was obviously increased accompanied by the relieved clinical symptoms. And the survival ability of SC19-ΔOAHS in whole blood was also remarkably decreased. Interestingly, the adhesion of SC19-ΔOAHS to endothelial cells was markedly increased, but the deficiency of OAHS significantly inhibited the strain penetrating BBB both in vivo and in vitro. Most of these phenomena can be reversed by the complemental strain (SC19-cΔOAHS). Further study showed that the deficiency of OAHS severely reduced SC19-induced endothelial cell apoptosis, tight junctions (TJs) protein impairment and the expression of SS2 virulence factor Enolase (Eno), involved in the destruction of BBB. Additionally, SC19-ΔOAHS immunized mice were able to resist SC19 or JZLQ022 infection. In conclusion, we confirmed that OAHS promoted the pathogenicity by enhancing host's BBB permeability and immune escape, and SC19- ΔOAHS is a potential live vaccine.


Subject(s)
Streptococcal Infections , Streptococcus suis , Swine Diseases , Animals , Mice , Endothelial Cells , Homoserine/genetics , Serogroup , Streptococcal Infections/veterinary , Swine , Swine Diseases/metabolism , Virulence
15.
Front Immunol ; 14: 1304758, 2023.
Article in English | MEDLINE | ID: mdl-38124753

ABSTRACT

Toll-interacting protein (Tollip) is a negative regulator of the pro-inflammatory response to viruses, including influenza A virus (IAV). Genetic variation of Tollip has been associated with reduced airway epithelial Tollip expression and poor lung function in patients with asthma. Whether Tollip deficiency exaggerates type 2 inflammation (e.g., eosinophils) and viral infection in asthma remains unclear. We sought to address this critical, but unanswered question by using a Tollip deficient mouse asthma model with IAV infection. Further, we determined the underlying mechanisms by focusing on the role of the ATP/IL-33 signaling axis. Wild-type and Tollip KO mice were intranasally exposed to house dust mite (HDM) and IAV with or without inhibitors for IL-33 (i.e., soluble ST2, an IL-33 decoy receptor) and ATP signaling (i.e., an antagonist of the ATP receptor P2Y13). Tollip deficiency amplified airway type 2 inflammation (eosinophils, IL-5, IL-13 and mucins), and the release of ATP and IL-33. Blocking ATP receptor P2Y13 decreased IL-33 release during IAV infection in HDM-challenged Tollip KO mice. Furthermore, soluble ST2 attenuated airway eosinophilic inflammation in Tollip KO mice treated with HDM and IAV. HDM challenges decreased lung viral load in wild-type mice, but Tollip deficiency reduced the protective effects of HDM challenges on viral load. Our data suggests that during IAV infection, Tollip deficiency amplified type 2 inflammation and delayed viral clearance, in part by promoting ATP signaling and subsequent IL-33 release. Our findings may provide several therapeutic targets, including ATP and IL-33 signaling inhibition for attenuating excessive airway type 2 inflammation in human subjects with Tollip deficiency and IAV infection.


Subject(s)
Asthma , Receptors, Purinergic P2 , Humans , Mice , Animals , Interleukin-1 Receptor-Like 1 Protein , Allergens , Interleukin-33 , Asthma/metabolism , Inflammation/metabolism , Pyroglyphidae , Dermatophagoides pteronyssinus , Adenosine Triphosphate , Intracellular Signaling Peptides and Proteins
16.
Kidney Dis (Basel) ; 9(4): 298-305, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37900000

ABSTRACT

Background: Patients receiving chronic dialysis are usually with multiple comorbidities and at high risk for hospitalization, which lead to tremendous health care resource utilization. This study aims to explore the characteristics of hospitalizations among chronic dialysis patients in China. Methods: Hospital admissions from January 2013 to December 2015 were extracted from a national inpatient database in China. Chronic dialysis, including hemodialysis and peritoneal dialysis, was identified according to inpatient discharge records and International Classification of Diseases-10 (ICD-10) codes. The primary kidney disease, causes of admissions, modalities of dialysis, and comorbidities were analyzed. Multivariable logistic regression model was used to assess the association of patient characteristics with multiple hospitalizations per year. Results: Altogether, 266,636 hospitalizations from 124,721 chronic dialysis patients were included in the study. The mean age was 54.46 ± 15.63 years and 78.29% of them were receiving hemodialysis. The leading cause of hospitalizations was dialysis access-related, including dialysis access creation (25.06%) and complications of access (21.09%). The following causes were nonaccess surgery (1.89%), cardiovascular disease (1.66%), and infectious diseases (1.43%). One-fourth of the patients were hospitalized more than once per year. Multivariate logistic regression models indicated that the primary kidney disease of diabetic kidney disease (odds ratio [OR]: 1.16, 95% confidence interval [CI]: 1.11-1.22) or hypertensive nephropathy (OR: 1.33, 95% CI: 1.27-1.40), coronary heart disease (OR: 1.09, 95% CI: 1.05-1.14), cancer (OR: 1.21, 95% CI: 1.13-1.30), or modality of peritoneal dialysis (OR: 2.67, 95% CI: 2.59-2.75) was risk factors for multiple hospitalizations. Conclusion: Our study described characteristics and revealed the burden of hospitalizations of chronic dialysis patients in China. These findings highlight the importance of effective and efficient management strategies to reduce the high burden of hospitalization in dialysis population.

17.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(5): 818-824, 2023 Oct 18.
Article in Chinese | MEDLINE | ID: mdl-37807734

ABSTRACT

OBJECTIVE: Constructing a predictive model for urinary incontinence after laparoscopic radical prostatectomy (LRP) based on prostatic gland related MRI parameters. METHODS: In this study, 202 cases were included. All the patients were diagnosed with prostate cancer by prostate biopsy and underwent LRP surgery in Peking University Third Hospital. The preoperative MRI examination of all the patients was completed within 1 week before the prostate biopsy. Prostatic gland related parameters included prostate length, width, height, prostatic volume, intravesical prostatic protrusion length (IPPL), prostate apex shape, etc. From the first month after the operation, the recovery of urinary continence was followed up every month, and the recovery of urinary continence was based on the need not to use the urine pad all day long. Logistic multivariate regression analysis was used to analyze the influence of early postoperative recovery of urinary continence. Risk factors were used to draw the receiver operator characteristic (ROC) curves of each model to predict the recovery of postoperative urinary continence, and the difference of the area under the curve (AUC) was compared by DeLong test, and the clinical net benefit of the model was evaluated by decision curve analysis (DCA). RESULTS: The average age of 202 patients was 69.0 (64.0, 75.5) years, the average prostate specific antigen (PSA) before puncture was 12.12 (7.36, 20.06) µg/L, and the Gleason score < 7 points and ≥ 7 points were 73 cases (36.2%) and 129 cases (63.9%) respectively, with 100 cases (49.5%) at T1/T2 clinical stage, and 102 cases (50.5%) at T3 stage. The prostatic volume measured by preoperative MRI was 35.4 (26.2, 51.1) mL, the ratio of the height to the width was 0.91 (0.77, 1.07), the membranous urethral length (MUL) was 15 (11, 16) mm, and the IPPL was 2 (0, 6) mm. The prostatic apex A-D subtypes were 67 cases (33.2%), 80 cases (39.6%), 24 cases (11.9%) and 31 cases (15.3%), respectively. The training set and validation set were 141 cases and 61 cases, respectively. The operations of all the patients were successfully completed, and the urinary continence rate was 59.4% (120/202) in the 3 months follow-up. The results of multivariate analysis of the training set showed that the MUL (P < 0.001), IPPL (P=0.017) and clinical stage (P=0.022) were independent risk factors for urinary incontinence in the early postoperative period (3 months). The nomogram and clinical decision curve were made according to the results of multivariate analysis. The AUC value of the training set was 0.885 (0.826, 0.944), and the AUC value of the validation set was 0.854 (0.757, 0.950). In the verification set, the Hosmer-Lemeshow goodness-of-fit test was performed on the model, and the Chi-square value was 5.426 (P=0.711). CONCLUSION: Preoperative MUL, IPPL, and clinical stage are indepen-dent risk factors for incontinence after LRP. The nomogram developed based on the relevant parameters of MRI glands can effectively predict the recovery of early urinary continence after LRP. The results of this study require further large-scale clinical research to confirm.


Subject(s)
Laparoscopy , Prostatic Neoplasms , Urinary Incontinence , Male , Humans , Prostate/diagnostic imaging , Prostate/surgery , Prostatectomy/adverse effects , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Urinary Incontinence/etiology , Laparoscopy/adverse effects , Laparoscopy/methods , Magnetic Resonance Imaging/adverse effects , Recovery of Function , Retrospective Studies
18.
Biomedicines ; 11(10)2023 Oct 20.
Article in English | MEDLINE | ID: mdl-37893223

ABSTRACT

PURPOSE: Increased type 2 interferon (i.e., IFN-γ) signaling has been shown to be involved in airway inflammation in a subset of asthma patients who often show high levels of airway neutrophilic inflammation and poor response to corticosteroid treatment. How IFN-γ mediates airway inflammation in a mitochondrial dysfunction setting (e.g., Parkin up-regulation) remains poorly understood. The goal of this study was to determine the role of Parkin, an E3 ubiquitin ligase, in IFN-γ-mediated airway inflammation and the regulation of Parkin by IFN-γ. METHODS: A mouse model of IFN-γ treatment in wild-type and Parkin knockout mice, and cultured human primary airway epithelial cells with or without Parkin gene deficiency were used. RESULTS: Parkin was found to be necessary for the production of neutrophil chemokines (i.e., LIX and IL-8) and airway neutrophilic inflammation following IFN-γ treatment. Mechanistically, Parkin was induced by IFN-γ treatment both in vivo and in vitro, which was associated with less expression of a Parkin transcriptional repressor Thap11. Overexpression of Thap11 inhibited Parkin expression in IFN-γ-stimulated airway epithelial cells. CONCLUSIONS: Our data suggest a novel mechanism by which IFN-γ induces airway neutrophilic inflammation through the Thap11/Parkin axis. Inhibition of Parkin expression or activity may provide a new therapeutic target for the treatment of excessive neutrophilic inflammation in an IFN-γ-high environment.

19.
Anal Chim Acta ; 1277: 341676, 2023 Oct 09.
Article in English | MEDLINE | ID: mdl-37604614

ABSTRACT

The mutual interference in the sensing detection of heavy metal ions (HMIs) is considerably serious and complex. Besides, the co-existed ions may change the stripping peak intensity, shape and position of the target ion, which partly makes peak current analysis inaccurate. Herein, a promising approach of partial peak area analysis was proposed firstly to research the mutual interference. The interference between two species on their electrodeposition processes was investigated by simulating different kinetics parameters, including surface coverage, electro-adsorption, -desorption rate constant, etc. It was proved that the partial peak area is sensitive and regular to these interference kinetics parameters, which is favorable for distinctly identifying different interferences. Moreover, the applicability of the partial peak area analysis was verified on the experiments of Cu2+, As(III) interference at four sensing interfaces: glassy carbon electrode, gold electrode, Co3O4, and Fe2O3 nanoparticles modified electrodes. The interference behaviors between Cu2+ and As(III) relying on solid-solution interfaces were revealed and confirmed by physicochemical characterizations and kinetics simulations. This work proposes a new descriptor (partial peak area) to recognize the interference mechanism and provides a meaningful guidance for accurate detection of HMIs in actual water environment.

20.
Dalton Trans ; 52(34): 12087-12097, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37581335

ABSTRACT

The research on amorphous metal-organic frameworks (aMOFs) is still in its infancy, and designing and constructing aMOFs with functional pores remains a challenge. Two aMOFs based on Co(II) and heterotopic triangular ligands with large conjugated aromatic planes, namely aMOF-1 and aMOF-2, were constructed and characterized by IR, XPS, EA, ICP, XANS and so on. aMOF-1 possesses mesopores, whereas aMOF-2 possesses micropores. The porosity, conjugated aromatic plane and uncoordinated N atoms in the framework allow these aMOFs to adsorb iodine and dyes. The iodine adsorption capacity of aMOF-1 is 3.3 g per g, which is higher than that of aMOF-2 (0.56 g per g), mainly due to the expansion or swelling of aMOF-1 after iodine adsorption. The uptake of cationic dyes by aMOF-2 showed more rapid kinetics and a higher removal rate than that by aMOF-1, mainly due to the difference in the porosity and surface charge. Although the surface charges of aMOF-1 and aMOF-2 are negative, both of them showed significantly faster adsorption kinetics toward anionic dyes, among which methyl orange (MO) and Congo red (CR) can be removed in 5 min. This occurs possibly because the quick adsorption of Na+ ions alters the surface charge of the framework and promotes dye uptake. The adsorption capacities of aMOF-1 for MO and CR reached 921 and 2417 mg g-1, respectively. The correlation data for aMOF-2 are 1042 and 1625 mg g-1, respectively. All adsorption capacities are among the highest compared to many cMOFs. Adsorption in mixed dye solution is found to be charge-dependent, kinetic-dependent, and synergetic in these systems. The porosity, surface charge regulation during adsorption, weak interactions and multiple adsorption processes contribute to the dye adsorption performance.

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