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1.
Small ; : e2403553, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38845013

ABSTRACT

Eumelanin, a natural, biocompatible, and biodegradable photothermal agent derived from biomass, has attracted increasingly considerable attention due to its outstanding photothermal conversion efficiency. Unfortunately, its tendency to aggregate in flexible non-polar polymers, owing to its abundant polar groups on the surface, severely restricted the application of eumelanin in photothermal composite field. Herein, a feasible strategy is proposed to disperse eumelanin in non-polar rubber matrix via in situ generation of Zinc dimethacrylate (ZDMA). The graft-polymerization of ZDMA promotes the interfacial compatibility between styrene butadiene rubber (SBR) and eumelanin, achieving a uniform dispersion of eumelanin in SBR. The rubber composite exhibits a considerable tensile strength of 11.4 MPa, acceptable elongation at break of 146%, and outstanding photothermal conversion efficiency of up to 75.2% with only 1 wt% of eumelanin. Furthermore, based on the easy-processing of SBR matrix, the composite is treated with a sandpaper template technique and sprayed with trimethoxy(1H,1H,2H,2H-perfluorodecyl)silane (PFDTMS) to endow the material with near superhydrophobicity (water contact angle of 147.9°) capacity. Hydrophobicity provides excellent icing resistance, with droplet surfaces extending more than twice as long to freeze. Moreover, this hydrophobic photothermal material exhibits remarkable anti-frosting, de-frosting, and de-icing capabilities.

2.
Front Immunol ; 15: 1385696, 2024.
Article in English | MEDLINE | ID: mdl-38770013

ABSTRACT

Background: Recent studies have demonstrated a strong association between acute kidney injury (AKI) and chronic kidney disease (CKD), while the unresolved inflammation is believed to be a driving force for this chronic transition process. As a transmembrane pattern recognition receptor, Mincle (macrophage-inducible C-type lectin, Clec4e) was identified to participate in the early immune response after AKI. However, the impact of Mincle on the chronic transition of AKI remains largely unclear. Methods: We performed single-cell RNA sequencing (scRNA-seq) with the unilateral ischemia-reperfusion (UIR) murine model of AKI at days 1, 3, 14 and 28 after injury. Potential effects and mechanism of Mincle on renal inflammation and fibrosis were further validated in vivo utilizing Mincle knockout mice. Results: The dynamic expression of Mincle in macrophages and neutrophils throughout the transition from AKI to CKD was observed. For both cell types, Mincle expression was significantly up-regulated on day 1 following AKI, with a second rise observed on day 14. Notably, we identified distinct subclusters of Minclehigh neutrophils and Minclehigh macrophages that exhibited time-dependent influx with dual peaks characterized with remarkable pro-inflammatory and pro-fibrotic functions. Moreover, we identified that Minclehigh neutrophils represented an "aged" mature neutrophil subset derived from the "fresh" mature neutrophil cluster in kidney. Additionally, we observed a synergistic mechanism whereby Mincle-expressing macrophages and neutrophils sustained renal inflammation by tumor necrosis factor (TNF) production. Mincle-deficient mice exhibited reduced renal injury and fibrosis following AKI. Conclusion: The present findings have unveiled combined persistence of Minclehigh neutrophils and macrophages during AKI-to-CKD transition, contributing to unresolved inflammation followed by fibrosis via TNF-α as a central pro-inflammatory cytokine. Targeting Mincle may offer a novel therapeutic strategy for preventing the transition from AKI to CKD.


Subject(s)
Acute Kidney Injury , Disease Models, Animal , Lectins, C-Type , Macrophages , Membrane Proteins , Mice, Knockout , Neutrophils , Renal Insufficiency, Chronic , Animals , Lectins, C-Type/metabolism , Lectins, C-Type/genetics , Acute Kidney Injury/etiology , Acute Kidney Injury/immunology , Acute Kidney Injury/metabolism , Macrophages/immunology , Macrophages/metabolism , Neutrophils/immunology , Neutrophils/metabolism , Mice , Renal Insufficiency, Chronic/immunology , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Membrane Proteins/genetics , Membrane Proteins/metabolism , Male , Inflammation/immunology , Mice, Inbred C57BL , Reperfusion Injury/immunology , Reperfusion Injury/metabolism , Fibrosis , Disease Progression
3.
Article in English | MEDLINE | ID: mdl-38605670

ABSTRACT

Recently, conductive hydrogels have emerged as promising materials for smart, wearable devices. However, limited mechanical properties and low sensitivity greatly restrict their lifespan. Based on the design of biomimetic-layered structure, the conductive hydrogels with nacre-mimetic structure were prepared by using layered acrylic bentonite (AABT) and phytic acid (PA) as multifunctional "brick" and "mortar" units. Among them, the unique rigid cyclic multihydroxyl structure of the "organic mortar" PA preserves both ultrastretchability (4050.02%) and high stress (563.20 kPa) of the hydrogel, which far exceeds most of the reported articles. Because of the synergistic effect of AABT and PA, the hydrogel exhibits an excellent adhesive strength (87.74 kPa). The role of AABT in the adhesive properties of hydrogels is proposed for the first time, and a general strategy for improving the adhesive properties of hydrogels by using AABT is demonstrated. Furthermore, AABT provides ion channels and PA ionizes abundant H+, conferring a high gauge factor (GF = 14.95) and excellent antimicrobial properties to the hydrogel. Also, inspired by fruit batteries, simple self-powered flexible sensors were developed. Consequently, this study provides knowledge for functional bentonite filler modified hydrogel, and the prepared multifunctional ionic conductive hydrogel shows great application potential in the field of intelligent wearable devices.

4.
Article in English | MEDLINE | ID: mdl-38648756

ABSTRACT

OBJECTIVES: The efficacy of artificial intelligence (AI)-driven chatbots like ChatGPT4 in specialized medical consultations, particularly in rheumatology, remains underexplored. This study compares the proficiency of ChatGPT4' responses with practicing rheumatologists to inquiries from patients with systemic lupus erythematosus (SLE). METHODS: In this cross-sectional study, we curated 95 frequently asked questions (FAQs), including 55 in Chinese and 40 in English. Responses for FAQs from ChatGPT4 and 5 rheumatologists were scored separately by a panel of rheumatologists and a group of patients with SLE across 6 domains (scientific validity, logical consistency, comprehensibility, completeness, satisfaction level, and empathy) on a 0-10 scale (a score of 0 indicates entirely incorrect responses, while 10 indicates accurate and comprehensive answers). RESULTS: Rheumatologists' scoring revealed that ChatGPT4-generated responses outperformed those from rheumatologists in satisfaction level and empathy, with mean differences of 0.537 (95% CI, 0.252-0.823; p < 0.01) and 0.460 (95% CI, 0.227-0.693 p < 0.01), respectively. From the SLE patients' perspective, ChatGPT4-generated responses were comparable to the rheumatologist-provided answers in all 6 domains. Subgroup analysis revealed ChatGPT4 responses were more logically consistent and complete regardless of language, and exhibited greater comprehensibility, satisfaction, and empathy in Chinese. However, ChatGPT4 responses were inferior in comprehensibility for English FAQs. CONCLUSION: ChatGPT4 demonstrated comparable, possibly better in certain domains, to address FAQs from patients with SLE, when compared with the answers provided by specialists. This study showed the potential of applying ChatGPT4 to improve consultation in SLE patients.

5.
Vaccines (Basel) ; 12(3)2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38543908

ABSTRACT

Coronavirus disease 2019 (COVID-19) vaccination is essential for patients with autoimmune inflammatory rheumatic diseases (AIIRD) to reduce the risk of morbidity and mortality associated with serious COVID-19 infection. With endemicity, waning of vaccine- and infection-acquired immunity, and development of SARS-CoV-2 variants, the need for additional doses of vaccines against serious illness in high-risk immunocompromised persons remains imperative. This review examines how immunomodulatory therapies affect vaccine-induced immune response in patients with AIIRD. Glucocorticoids, methotrexate, azathioprine, calcineurin inhibitors, mycophenolate mofetil, tumor necrosis factor inhibitors, and abatacept have been shown to variably attenuate both humoral and cellular immune responses to vaccination. Janus kinase inhibitors reduce humoral immune response. In contrast, sulfasalazine, leflunomide, belimumab, interleukin (IL)-17, IL-12/23, IL-6, and IL-1 inhibitors appear favorable, with mild or no impact on vaccine response. Although rituximab is known to profoundly diminish humoral immune response, cellular immunity is relatively preserved. Administering a third and subsequent vaccine dose or temporally coordinating the dosing of immunomodulatory drugs may improve vaccine effectiveness. Further research is needed to personalise vaccination strategies for AIIRD patients, considering their specific immunomodulatory treatments.

6.
Int J Biol Macromol ; 265(Pt 1): 130798, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479674

ABSTRACT

Controlling ethylene production and microbial infection are key factors to prolong the shelf life of climacteric fruit. Herein, a nanocomposite film, hexanal-loaded ZIF-8/CS (HZCF) with "nano-barrier" structure, was developed by a one-pot co-crystallized of ZIF-8 in situ growth on quaternized chitosan (CS) and encapsulation of hexanal into ZIF-8 via microporous adsorption. The resultant film realized the temperature responsive release of hexanal via the steric hindrance and hierarchical pore structure as "nano-barrier", which can inhibit ethylene production in climacteric fruit on demand. Based on this, the maximum ethylene inhibition rate of HZCF was up to 52.6 %. Meanwhile, the film exhibits excellent antibacterial, mechanical, UV resistance and water retention properties, by virtue of the functional synergy between ZIF-8 and CS. Contributed to the multifunctional features, HZCF prolonged the shelf life of banana and mango for at least 16 days, which is 8 days longer than that of control fruit. More strikingly, HZCF is washable and biodegradable, which is expected to replace non-degradable plastic film. Thus, this study provides a convenient novel approach to simplify the encapsulation of active molecule on metal-organic frameworks (MOFs), develops a packaging material for high-efficient freshness preservation, and helps to alleviate the survival crisis caused by food waste.


Subject(s)
Aldehydes , Chitosan , Climacteric , Refuse Disposal , Chitosan/pharmacology , Chitosan/chemistry , Fruit , Temperature , Ethylenes/chemistry , Anti-Bacterial Agents/pharmacology , Food Packaging
7.
J Nat Prod ; 87(1): 121-131, 2024 01 26.
Article in English | MEDLINE | ID: mdl-38151459

ABSTRACT

A phytochemical investigation of an East China Sea collection of the brown alga Dictyota coriacea has led to the isolation of four novel nitrogen-containing crenulide diterpenoids, named coriaceumins A-D (1-4), two rare nitrogenous xenicane diterpenoids, dictyolactams C (5) and D (6), and one known crenulide diterpenoid, hydroxycrenulide (7). The structures of the new compounds were elucidated by detailed spectroscopic data analyses, including HRESIMS and 1D/2D NMR. The absolute configurations were determined by a comparison of the experimental ECD spectra with the spectra computed by DFT-based quantum chemical calculations. Coriaceumins A-D (1-4) represent the first examples of nitrogen-containing crenulide diterpenoids. In a bioassay, compounds 2, 3, 5, and 7 were found to exhibit different levels of inhibitory effects against protein tyrosine phosphatase 1B (PTP1B) with IC50 values ranging from 7.3 to 19 µM. In addition, the primary structure-activity relationships of all the isolates were summarized.


Subject(s)
Diterpenes , Phaeophyceae , Molecular Structure , Magnetic Resonance Spectroscopy , Diterpenes/pharmacology , Diterpenes/chemistry , China
8.
Front Vet Sci ; 10: 1277293, 2023.
Article in English | MEDLINE | ID: mdl-37901107

ABSTRACT

Introduction: Honeycomb is a traditional natural health medicine and has antioxidant, antibacterial, anti-inflammatory, antiviral and antitumor activities. It is currently unclear whether honeycomb extract supplementation has positive effects on the intensive farming laying duck production. This study aims to evaluate the effects of honeycomb extracts on the laying performance, egg nutritional and flavor quality, serum biochemical indexes, and antioxidant and immune status in laying ducks. Methods: A total of 672 healthy 28-week-old Shanma laying ducks with similar laying performance and body weight were randomly distributed into four dietary treatments with 6 replicates of 28 birds. The birds in each treatment were fed the basal diet supplemented with 0 (control group), 0.5, 1.0 or 1.5 g/kg honeycomb extracts, respectively. Feed and water were provided ad libitum for 45 days. Laying performance, egg quality, egg nutrition and flavor quality, serum parameters were assessed. Results: The results showed that compared with the control group, honeycomb extracts addition significantly increased the average daily feed intake but did not affect the other laying performance indexes, egg quality or serum biochemical indexes of laying ducks. Dietary supplementation with honeycomb extracts significantly increased crude protein content and decreased the contents of cholesterol and trimethylamine in eggs. Diets supplemented with 1.5 g/kg honeycomb extracts significantly improved egg total amino acids and flavor amino acids contents, monounsaturated fatty acids and polyunsaturated fatty acids composition and enhanced the serum antioxidant activity and immune functions of ducks. Discussion: Duck eggs are rich in nutrients and a valuable source of high-quality food for human, while they are rarely consumed directly by consumers because of their stronger fishy odor and lower sensory quality. Many studies have showed that the influence of dietary supplementation on egg components. This study indicated that dietary supplementation with honeycomb extracts positively reduced the contents of egg cholesterol and trimethylamine, improve egg amino acids contents and fatty acid profiles, enhanced serum antioxidant and immune status of laying ducks. The recommended supplemental level of honeycomb extracts was 1.5 g/kg in the diet of laying ducks.

9.
Adv Rheumatol ; 63(1): 38, 2023 08 01.
Article in English | MEDLINE | ID: mdl-37528453

ABSTRACT

OBJECTIVE: To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). METHODS: A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least 3 months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI 1.22-2.31; HR: 2.28, 95% CI 1.50-3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI 1.20-4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI 0.06-0.10). HRs of flares were not significantly different among RA, PsA and SpA. CONCLUSION: About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.


Subject(s)
Arthritis, Psoriatic , Arthritis, Rheumatoid , COVID-19 , Spondylarthritis , Humans , Arthritis, Psoriatic/epidemiology , Cohort Studies , Prevalence , COVID-19/epidemiology , COVID-19/prevention & control , Arthritis, Rheumatoid/epidemiology , Spondylarthritis/epidemiology , Vaccination
10.
Singapore Med J ; 2023 Jul 27.
Article in English | MEDLINE | ID: mdl-37530384

ABSTRACT

Introduction: This review aims to provide evidence-based recommendations for an enhanced primary series (third dose) coronavirus disease 2019 (COVID-19) vaccination in people with rheumatic diseases (PRDs) in the local and regional context. Methods: Literature reviews were performed regarding the necessity, efficacy, safety and strategies for enhanced primary series COVID-19 vaccination in PRDs. Recommendations were developed based on evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Evidence was synthesised by eight working group members, and the consensus was achieved by a Delphi method with nine members of an expert task force panel. Results: Two graded recommendations and one ungraded position statement were developed. PRDs have impaired immunogenicity from the COVID-19 vaccine and are at an increased risk of postvaccine breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and poor clinical outcomes, compared to the general population. We strongly recommend that PRDs on immunomodulatory drugs be offered a third dose of the messenger RNA (mRNA) vaccine as part of an enhanced primary series, after the standard two-dose regimen. We conditionally recommend that the third dose of mRNA vaccine against SARS-CoV-2 be given at least 4 weeks after the second dose or as soon as possible thereafter. There is insufficient data to inform whether the third mRNA vaccine should be homologous or heterologous in PRDs. Conclusion: These recommendations that were developed through evidence synthesis and formal consensus process provide guidance for an enhanced primary series COVID-19 vaccination in PRDs.

11.
Poult Sci ; 102(10): 102986, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37566964

ABSTRACT

Traditional Chinese herbs have been widely researched as a green, safe, and effective feed additive for poultry. The purpose of this study was to investigate the effects of traditional Chinese prescription (TCP) based on various herbs in a specific ratio on the growth performance, carcass traits, immunity, antioxidant level, and intestinal health of Ningdu yellow chickens. A total of 420 female Ningdu yellow chickens were randomly divided into 5 groups, with 6 replicates of 14 each. The chickens were fed with a basal diet supplemented with 0 (CON), 0.2, 0.4, 0.6, or 0.8% TCP from d 43 to 105. Body weight, feed intake, and serum biochemical indicators were recorded at d 70 and 105, intestinal morphology and microflora of the carcass were determined at d 105. Compared to the control group, chickens fed with TCP, particularly at the level of 0.6%, showed improved average daily gain and breast muscle percentage, as well as a lower feed-to-gain ratio with statistical significance (P < 0.05). Between 43 and 70 d of age, chickens fed with TCP exhibited higher levels of serum glutathione peroxidase activity, total antioxidant capacity, and superoxide dismutase, particularly in the group fed with the 0.6% level of TCP (P < 0.05). Between 43 and 105 d of age, feeding chickens with 0.4 and 0.6% TCP resulted in a decrease in serum IL-2 concentration, and increase in the IL-4 content (P < 0.05). Chickens fed with 0.4, 0.6, and 0.8% TCP had significantly higher jejunum villous height (P < 0.05), TCP supplementation also led to a marked increase in the relative abundance of Bacteroidota compared to the control group (P < 0.05). Collectively, the study suggests that TCP supplementation can enhance immune and antioxidant functions, improve jejunum morphology, and positively impact cecum microflora in chickens. Based on these results, a level of 0.6% TCP could be considered an optimum level as a feed supplement for Ningdu yellow chickens aged 43 to 105 d.


Subject(s)
Antioxidants , Chickens , Animals , Female , Chickens/physiology , Animal Feed/analysis , Dietary Supplements , Diet/veterinary
13.
Int J Biol Macromol ; 248: 125811, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37467831

ABSTRACT

Circular RNA (circRNA) has been implicated in liver fibrosis and modulated by multiple elusive molecular mechanisms, while the effects of N6-methyladenosine (m6A) modification on circRNA are still elusive. Herein, we identify circIRF2 from our circRNA sequencing data, which decreased in liver fibrogenesis stage and restored in resolution stage, indicating that dysregulated circIRF2 may be closely associated with liver fibrosis. Gain/loss-of-function analysis was performed to evaluate the effects of circIRF2 on liver fibrosis at both the fibrogenesis and resolution in vivo. Ectopic expression of circIRF2 attenuated liver fibrogenesis and HSCs activation at the fibrogenesis stage, whereas downregulation of circIRF2 impaired mouse liver injury repair and inflammation resolution. Mechanistically, YTHDF2 recognized m6A-modified circIRF2 and diminished circIRF2 stability, partly accounting for the decreased circIRF2 in liver fibrosis. Microarray was applied to investigate miRNAs regulated by circIRF2, our data elucidate cytoplasmic circIRF2 may directly harbor miR-29b-1-5p and competitively relieve its inhibitory effect on FOXO3, inducing FOXO3 nuclear translocation and accumulation. Clinically, circIRF2 downregulation was prevalent in liver fibrosis patients compared with healthy individuals. In summary, our findings offer a novel insight into m6A modification-mediated regulation of circRNA and suggest that circIRF2 may be an exploitable prognostic marker and/or therapeutic target for liver fibrosis.


Subject(s)
MicroRNAs , RNA, Circular , Mice , Animals , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , Hepatic Stellate Cells/metabolism , Liver Cirrhosis/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , Transcription Factors/metabolism , Forkhead Box Protein O3/genetics , RNA-Binding Proteins/metabolism
14.
Int J Biol Macromol ; 249: 126020, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37516221

ABSTRACT

Ionic hydrogels used as ideal and flexible strain sensor materials should have excellent mechanical, adhesive and antimicrobial properties. However, it is challenging to achieve these multifunctional requirements simultaneously. Herein, we designed and prepared a multifunctional ionic hydrogel with a multi-length tentacle bentonite backbone to initiate the free radical polymerization of acrylic acid bentonite (AABT) and acrylamide (AAm). The interactions of covalent cross-linking, hydrogen bonding cross-linking, charge interactions and physical entanglement between hybrid polyacrylamide-AABT (PAAm-AABT), sodium carboxymethyl starch (SCMS) and PAAm form an multi-in-one hybrid supramolecular network hydrogel (CABZ). This CABZ ion-conductive hydrogel is capable of detecting weak deformation with a detection limit of 1 % strain, high tensile properties of 995 %, excellent strength of 254.5 kPa, fast response (≈0.21 s), high sensitivity of 0.86 and high conductivity of 0.37 S/m. In addition, this CABZ ion-conductive hydrogel has impressive adhesion properties with shear adhesion strength up to 50.78 kPa and broad-spectrum antibacterial properties achieved by AABT-loaded ZnO nanoparticles. Through special AABT hybrid cross-linking, the CABZ ion-conductive hydrogel achieves stable mechanical properties, highly sensitive signal response and antimicrobial properties, which will make it a good choice for flexible wearable sensor materials.


Subject(s)
Anti-Infective Agents , Bentonite , Anti-Infective Agents/pharmacology , Electric Conductivity , Hydrogels
15.
Int J Biol Macromol ; 243: 125145, 2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37268070

ABSTRACT

The continuous infestation of pests has seriously affected rice growth, yield and quality. How to reduce the use of pesticides and effectively control insect pests is a bottleneck problem. Herein, based on hydrogen bonding and electrostatic interactions, we posed a novel strategy to construct emamectin benzoate (EB) pesticide loading system using self-assembled phosphate-modified cellulose microspheres (CMP) and chitosan (CS). CMP provides more binding sites for EB loading and CS coating further enhances the carrier loading capacity up to 50.75 %, which jointly imparted pesticide photostability and pH-responsiveness. The retention capacity of EB-CMP@CS in rice growth soil reached 101.56-fold that of commercial EB, which effectively improved the absorption of pesticides during rice development. During the pest outbreak, EB-CMP@CS achieved effective pest control by increasing the pesticide content in rice stems and leaves, the control efficiency of the rice leaffolder (Cnaphalocrocis medinalis) reached 14-fold that of commercial EB, and could maintain the effective pest control effect during the booting stage of rice. Finally, EB-CMP@CS-treated paddy fields had improved yields and were free of pesticide residues in the rice grain. Therefore, EB-CMP@CS achieves effective control of rice leaffolder in paddy fields and has potential application value in green agricultural production.


Subject(s)
Chitosan , Moths , Oryza , Pesticides , Animals , Chitosan/pharmacology , Phosphates/pharmacology , Oryza/metabolism , Pesticides/pharmacology
16.
Br J Pharmacol ; 180(20): 2641-2660, 2023 10.
Article in English | MEDLINE | ID: mdl-37248964

ABSTRACT

BACKGROUND AND PURPOSE: Necroptosis plays an essential role in acute kidney injury and is mediated by receptor-interacting protein kinase 1 (RIPK1), receptor-interacting protein kinase 3 (RIPK3), and mixed lineage kinase domain-like pseudokinase (MLKL). A novel RIPK3 inhibitor, compound 42 (Cpd-42) alleviates the systemic inflammatory response. The current study was designed to investigate whether Cpd-42 exhibits protective effects on acute kidney injury and reveal the underlying mechanisms. EXPERIMENTAL APPROACH: The effects of Cpd-42 were determined in vivo through cisplatin- and ischaemia/reperfusion (I/R)-induced acute kidney injury and in vitro through cisplatin- and hypoxia/re-oxygenation (H/R)-induced cell damage. Transmission electron microscopy and periodic acid-Schiff staining were used to identify renal pathology. Cellular thermal shift assay and RIPK3-knockout mouse renal tubule epithelial cells were used to explore the relationship between Cpd-42 and RIPK3. Molecular docking and site-directed mutagenesis were used to determine the binding site of RIPK3 with Cpd-42. KEY RESULTS: Cpd-42 reduced human proximal tubule epithelial cell line (HK-2) cell damage, necroptosis and inflammatory responses in vitro. Furthermore, in vivo, cisplatin- and I/R-induced acute kidney injury was alleviated by Cpd-42 treatment. Cpd-42 inhibited necroptosis by interacting with two key hydrogen bonds of RIPK3 at Thr94 and Ser146, which further blocked the phosphorylation of RIPK3 and mitigated acute kidney injury. CONCLUSION AND IMPLICATIONS: Acting as a novel RIPK3 inhibitor, Cpd-42 reduced kidney damage, inflammatory response and necroptosis in acute kidney injury by binding to sites Thr94 and Ser146 on RIPK3. Cpd-42 could be a promising treatment for acute kidney injury.


Subject(s)
Acute Kidney Injury , Cisplatin , Mice , Animals , Humans , Cisplatin/pharmacology , Necroptosis , Molecular Docking Simulation , Acute Kidney Injury/metabolism , Protein Kinases/metabolism , Mice, Knockout , Apoptosis , Receptor-Interacting Protein Serine-Threonine Kinases
17.
Sci Rep ; 13(1): 7263, 2023 05 04.
Article in English | MEDLINE | ID: mdl-37142713

ABSTRACT

The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.


Subject(s)
COVID-19 , Kidney Transplantation , Female , Humans , Male , Tacrolimus , COVID-19 Vaccines , COVID-19/prevention & control , SARS-CoV-2 , Immunity, Cellular , Bilirubin , Immunity, Humoral , Transplant Recipients , Vaccination , Antibodies, Viral
18.
Int J Biol Macromol ; 242(Pt 1): 124681, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37141968

ABSTRACT

Conventional vulcanized rubbers cause a non-negligible waste of resources due to the formation of 3D irreversible covalently cross-linked networks. The introduction of reversible covalent bonds, such as reversible disulfide bonds, into the rubber network, is an available solution to the above problem. However, the mechanical properties of rubber with only reversible disulfide bonds cannot meet most practical applications. In this paper, a strengthened bio-based epoxidized natural rubber (ENR) composite reinforced by sodium carboxymethyl cellulose (SCMC) was prepared. SCMC forms a mass of hydrogen bonds between its hydroxyl groups and the hydrophilic groups of ENR chain, which gives the ENR/2,2'-Dithiodibenzoic acid (DTSA)/SCMC composites an enhanced mechanical performance. With 20 phr SCMC, the tensile strength of the composite increases from 3.0 to 10.4 MPa, which is almost 3.5 times that of the ENR/DTSA composite without SCMC. Simultaneously, DTSA covalently cross-linked ENR with the introduction of reversible disulfide bonds, which enables the cross-linked network to rearrange its topology at low temperatures and thus endows the ENR/DTSA/SCMC composites with healing properties. The ENR/DTSA/SCMC-10 composite has a considerable healing efficiency of about 96 % after healing at 80 °C for 12 h.


Subject(s)
Carboxymethylcellulose Sodium , Rubber , Rubber/chemistry , Epoxy Compounds/chemistry , Disulfides , Sodium
19.
Small ; 19(23): e2208116, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36890772

ABSTRACT

With the consumption of disposable electronic devices increasing, it is meaningful but also a big challenge to develop reusable and sustainable materials to replace traditional single-use sensors. Herein, a clever strategy for constructing a multifunctional sensor with 3R circulation (renewable, reusable, pollution-reducing biodegradable) is presented, in which silver nanoparticles (AgNPs) with multiple interactions are introduced into a reversible non-covalent cross-linking network composed of biocompatible and degradable carboxymethyl starch (CMS) and polyvinyl alcohol (PVA) to simultaneously obtain high mechanical conductivity and long-term antibacterial properties by a one-pot method. Surprisingly, the assembled sensor shows high sensitivity (gauge factor up to 4.02), high conductivity (0.1753 S m-1 ), low detection limit (0.5%), long-term antibacterial ability (more than 7 days), and stable sensing performance. Thus, the CMS/PVA/AgNPs sensor can not only accurately monitor a series of human behavior, but also identify handwriting recognition from different people. More importantly, the abandoned starch-based sensor can form a 3R circulation. Especially, the fully renewable film still shows excellent mechanical performance, achieving reusable without sacrificing its original function. Therefore, this work provides a new horizon for multifunctional starch-based materials as sustainable substrates for replacing traditional single-use sensors.

20.
Carbohydr Polym ; 306: 120625, 2023 Apr 15.
Article in English | MEDLINE | ID: mdl-36746577

ABSTRACT

Natural polymers with abundant hydrophilic groups are potential candidates for humidity sensor designing. Unfortunately, most of natural polymers lack essential stretchability and high conductivity, which hinder their development in the field of flexible humidity sensor. Cooperation with rubbers and conductive nanometer materials is an effective method to make the best use of natural polymers in flexible humidity sensor. In this paper, a flexible and sensitive sensor with rapid response to humidity change is fabricated based on aldehyde-modified sodium carboxymethyl starch (ACMS), carboxylated styrene-butadiene rubber (XSBR) and Ag nanoflakes through film-forming method. The pre-prepared ACMS owns a better dispersibility in the aqueous phase and serves as reducing agent for formation of Ag nanoflakes. After the film-forming process, the composite film shows a strength of 5.66 MPa and a high stretchability with strain of 367 %. Besides, our sensor shows a rapider response to humidity change than the commercial electronic hygrometer that it takes only 1 s to respond to the humidity change from 25 % RH to 27 % RH. Therefore, the XSBR/ACMS/Ag sensor possesses an impressive sensitive response to slight sweat on human skin and breath, which could find applications in monitoring people's health and distinguish their physical condition.


Subject(s)
Polymers , Rubber , Humans , Humidity , Water
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