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1.
Nano Lett ; 24(15): 4415-4422, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38577835

RESUMO

The increasing demand for personal protective equipment such as single-use masks has led to large amounts of nondegradable plastic waste, aggravating economic and environmental burdens. This study reports a simple and scalable approach for upcycling waste masks via a chemical vapor deposition technique, realizing a trichome-like biomimetic (TLB) N95 respirator with superhydrophobicity (water contact angle ≥150°), N95-level protection, and reusability. The TLB N95 respirator comprising templated silicone nanofilaments with an average diameter of ∼150 nm offers N95-level protection and breathability comparable to those of commercial N95 respirators. The TLB N95 respirator can still maintain its N95-level protection against particulate matter and viruses after 10 disinfection treatment cycles (i.e., ultraviolet irradiation, microwave irradiation, dry heating, and autoclaving), demonstrating durable reusability. The proposed strategy provides new insight into upcycle waste masks, breaking the existing design and preparation concept of reusable masks.


Assuntos
COVID-19 , Dispositivos de Proteção Respiratória , Humanos , Respiradores N95 , Máscaras , SARS-CoV-2
2.
Heliyon ; 10(6): e28262, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38560695

RESUMO

Objective: The aim of this study was to evaluate the prognostic value of coronary artery disease (CAD) detected by coronary computed tomography angiography (CTA) to predict the risk of all-cause mortality in cancer patients in a propensity score matching (PSM) analysis. Methods: A total of 331 patients who previously had cancer and underwent coronary CTA from January 2015 to December 2019 were included. Multivariate Cox proportional hazards regression analysis and propensity-score matching analysis were performed. The primary endpoint was all-cause of mortality. Results: In total, 125 with CAD and 206 with no CAD during a median follow-up of 3.3 years were included in this study. After PSM, age (HR, 1.040; 95%CI, 1.001-1.081; p = 0.014) and CAD (HR, 2.164; 95%CI, 1.057-4.430; p = 0.035) remained significant factors for all-cause mortality. Conclusion: CAD evaluated by coronary CTA was found to be at higher risk for all-cause mortality in cancer patients. Due to the retrospective design and lack of information on some medical history and treatments, especially immune checkpoint inhibitors, a large-scale prospective study is needed to further determine the prognostic value of coronary CTA in cancer patients.

3.
Chemosphere ; : 142065, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636916

RESUMO

Sulfoxaflor is a widely used fourth-generation neonicotinoid pesticide, which has been detected in biological and environmental samples. Sulfoxaflor can potentially be exposed to humans via the food chain, thus understanding its toxic effects and enantioselective bioaccumulation is crucial. In this study, toxicokinetics, bioaccumulation, tissue distribution and enantiomeric profiles of sulfoxaflor in rats were investigated through single oral exposure and 28-days continuous exposure experiment. Sulfoxaflor mainly accumulated in liver and kidney, and the (-)-2R,3R-sufloxaflor and (-)-2S,3R-sufloxaflor had higher enrichment than their enantiomers in rats. The toxicological effects were evaluated after 28-days exposure. Slight inflammation in liver and kidney were observed by histopathology. Sphingolipid, amino acid, and vitamin B6 metabolism pathways were significantly disturbed in metabonomics analysis. These toxicities were in compliance with dose-dependent effects. These results improve understanding of enantioselective bioaccumulation and the potential health risk of sulfoxaflor.

4.
Adv Mater ; : e2311129, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557985

RESUMO

Air pollution threats to human health have increased awareness of the role of filter units in air cleaning applications. As an ideal energy-saving strategy for air filters, the slip effect on nanofiber surfaces can potentially overcome the trade-off between filtration efficiency and pressure drop. However, the potential of the slip effect in nanofibrous structures is significantly limited by the tight nanofiber stacks. In this study, trichome-like biomimetic (TLB) air filters with 3D-templated silicone nanofilaments (average diameter: ≈74 nm) are prepared based on an in situ chemical vapor deposition (CVD) method inspired by plant purification. Theoretical modeling and experimental results indicate that TLB air filters make significant use of the slip effect to overcome the efficiency-resistance tradeoff. The selectable filter class (up to U15, ≈99.9995%) allows TLB air filters to meet various requirements, and their integral filtration performance surpasses that of most commodity air filters, including melt-blown cloth, ePTFE membranes, electrospun mats, and glass fiber paper. The proposed strategy directly transforms commercial filter media and filters into TLB air filters using a bottom-up, one-step approach. As a proof-of-concept, reusable N95 respirators and air purifiers equipped with TLB air filters are fabricated, overcoming the limitations of existing filter designs and fabrication methods.

5.
Pestic Biochem Physiol ; 199: 105770, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458664

RESUMO

The extensive application of pesticides in agricultural production has raised significant concerns about its impact on human health. Different pesticides, including fungicides, insecticides, and herbicides, cause environmental pollution and health problems for non-target organisms. Infants and young children are so vulnerable to the harmful effects of pesticide exposure that early-life exposure to pesticides deserves focused attention. Recent research lays emphasis on understanding the mechanism between negative health impacts and early-life exposure to various pesticides. Studies have explored the impacts of exposure to these pesticides on model organisms (zebrafish, rats, and mice), as well as the mechanism of negative health effects, based on advanced methodologies like gut microbiota and multi-omics. These methodologies help comprehend the pathogenic mechanisms associated with early-life pesticide exposure. In addition to presenting health problems stemming from early-life exposure to pesticides and their pathogenic mechanisms, this review proposes expectations for future research. These proposals include focusing on identifying biomarkers that indicate early-life pesticide exposure, investigating transgenerational effects, and seeking effective treatments for diseases arising from such exposure. This review emphasizes how to understand the pathogenic mechanisms of early-life pesticide exposure through gut microbiota and multi-omics, as well as the adverse health effects of such exposure.


Assuntos
Microbioma Gastrointestinal , Inseticidas , Praguicidas , Criança , Humanos , Animais , Ratos , Camundongos , Praguicidas/toxicidade , Multiômica , Peixe-Zebra , Inseticidas/farmacologia
6.
Pestic Biochem Physiol ; 199: 105804, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458671

RESUMO

Chemical fertilizer and pesticide are necessary in agriculture, which have been frequently used, sometimes even at the same time or in combination. To understand the interactions of them could be of significance for better use of these agrochemicals. In this study, the influence of chemical fertilizers (urea, potassium sulfate, ammonium sulfate and superphosphate) on the control efficacy and environmental behavior of abamectin was investigated, which could be applied in soil for controlling nematodes. In laboratory assays, ammonium sulfate at 1 and 2 g/L decreased the LC50 values of abamectin to Meloidogyne incognita from 0.17 mg/L to 0.081 and 0.043 mg/L, indicating it could increase the contact toxicity. In greenhouse trial, ammonium sulfate at 1000 mg/kg increased the control efficacy of abamectin by 1.37 times. Meanwhile, the combination of abamectin with ammonium sulfate could also promote the tomato seedling growth as well as the defense-related enzyme activity under M. incognita stress. The persistence and mobility of abamectin in soil were significantly elevated by ammonium sulfate, which could prolong and promote the control efficacy against nematodes. These results could provide reference for reasonable use of abamectin and fertilizers so as to increase the control efficacy and minimize the environmental risks.


Assuntos
Fertilizantes , Ivermectina/análogos & derivados , Tylenchoidea , Animais , Solo , Sulfato de Amônio
7.
Mol Breed ; 44(4): 25, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38516203

RESUMO

Maize rough dwarf disease (MRDD) caused by pathogenic viruses in the genus Fijivirus in the family Reoviridae is one of the most destructive diseases in maize. The pyramiding of effective resistance genes into maize varieties is a potential approach to reduce the damage resulting from the disease. Two major quantitative trait loci (QTLs) (qMrdd2 and qMrdd8) have been previously identified. The resistance genes ZmGLK36 and ZmGDIα-hel have also been cloned with the functional markers Indel-26 and IDP25K, respectively. In this study, ZmGLK36 and ZmGDIα-hel were introgressed to improve MRDD resistance of maize lines (Zheng58, Chang7-2, B73, Mo17, and their derived hybrids Zhengdan958 and B73 × Mo17) via marker-assisted selection (MAS). The converted lines and their derived hybrids, carrying one or two genes, were evaluated for MRDD resistance using artificial inoculation methods. The double-gene pyramiding lines and their derived hybrids exhibited increased resistance to MRDD compared to the monogenic lines and the respective hybrids. The genetic backgrounds of the converted lines were highly similar (90.85-98.58%) to the recurrent parents. In addition, agronomic trait evaluation demonstrated that pyramiding lines with one or two genes and their derived hybrids were not significantly different from the recurrent parents and their hybrids under nonpathogenic stress, including period traits (tasseling, pollen shedding, and silking), yield traits (ear length, grain weight per ear and 100-kernel weight) and quality traits (protein and starch content). There were differences in plant architecture traits between the improved lines and their hybrids. This study illustrated the successful development of gene pyramiding for improving MRDD resistance by advancing the breeding process. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01466-9.

8.
J Agric Food Chem ; 72(13): 7423-7437, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38502791

RESUMO

As chlorfenapyr is a commonly used insecticide in agriculture, the health risks of subchronic exposure to chlorfenapyr remained unclear. This study aimed to extensively probe the health risks from subchronic exposure to chlorfenapyr at the NOAEL and 10-fold NOAEL dose in mice. Through pathological and biochemical examinations, the body metabolism, hepatic toxicity, and intestinal homeostasis were systematically assessed. After 12 weeks, a 10-fold NOAEL dose of chlorfenapyr resulted in weight reduction, increased daily food intake, and blood lipid abnormalities. Concurrently, this dosage induced hepatotoxicity and amplified oxidative stress in hepatocytes, a finding further supported in HepG2 cells. Moreover, chlorfenapyr resulted in intestinal inflammation, evidenced by increased inflammatory factors (IL-17a, IL-10, IL-1ß, IL-6, IL-22), disrupted immune cells (RORγt, Foxp3), and compromised intestinal barriers (ZO-1 and occludin). By contrast, the NOAEL dose presented less toxicity in most evaluations. Serum metabolomic analyses unveiled widespread disruptions in pathways related to hepatotoxicity and intestinal inflammation, including NF-κB signaling, Th cell differentiation, and bile acid metabolism. Microbiomic analysis showed an increase in Lactobacillus, a decrease in Muribaculaceae, and diminished anti-inflammatory microbes, which further propelled the inflammatory response and leaded to intestinal inflammation. These findings revealed the molecular mechanisms underlying chlorfenapyr-induced hepatotoxicity and intestinal inflammation, highlighting the significant role of the gut microbiota.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Inflamação , Piretrinas , Camundongos , Animais , Inflamação/induzido quimicamente , Inflamação/patologia , Estresse Oxidativo , Homeostase
9.
Cell Mol Life Sci ; 81(1): 138, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478029

RESUMO

Circular RNAs (circRNAs) have garnered significant attention in the field of neurodegenerative diseases including Alzheimer's diseases due to their covalently closed loop structure. However, the involvement of circRNAs in postoperative cognitive dysfunction (POCD) is still largely unexplored. To identify the genes differentially expressed between non-POCD (NPOCD) and POCD mice, we conducted the whole transcriptome sequencing initially in this study. According to the expression profiles, we observed that circAKT3 was associated with hippocampal neuronal apoptosis in POCD mice. Moreover, we found that circAKT3 overexpression reduced apoptosis of hippocampal neurons and alleviated POCD. Subsequently, through bioinformatics analysis, our data showed that circAKT3 overexpression in vitro and in vivo elevated the abundance of miR-106a-5p significantly, resulting in a decrease of HDAC4 protein and an increase of MEF2C protein. Additionally, this effect of circAKT3 was blocked by miR-106a-5p inhibitor. Interestingly, MEF2C could activate the transcription of miR-106a-5p promoter and form a positive feedback loop. Therefore, our findings revealed more potential modulation ways between circRNA-miRNA and miRNA-mRNA, providing different directions and targets for preclinical studies of POCD.


Assuntos
MicroRNAs , Complicações Cognitivas Pós-Operatórias , Animais , Camundongos , Complicações Cognitivas Pós-Operatórias/genética , RNA Circular/genética , Retroalimentação , MicroRNAs/genética , MicroRNAs/metabolismo , Hipocampo/metabolismo
10.
Plants (Basel) ; 13(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38475468

RESUMO

Drought stress is seriously affecting the growth and production of crops, especially when agricultural irrigation still remains quantitatively restricted in some arid and semi-arid areas. The identification of drought-tolerant genes is important for improving the adaptability of maize under stress. Here, we found that a new member of the actin-depolymerizing factor (ADF) family; the ZmADF5 gene was tightly linked with a consensus drought-tolerant quantitative trait locus, and the significantly associated signals were detected through genome wide association analysis. ZmADF5 expression could be induced by osmotic stress and the application of exogenous abscisic acid. Its overexpression in Arabidopsis and maize helped plants to keep a higher survival rate after water-deficit stress, which reduced the stomatal aperture and the water-loss rate, as well as improved clearance of reactive oxygen species. Moreover, seventeen differentially expressed genes were identified as regulated by both drought stress and ZmADF5, four of which were involved in the ABA-dependent drought stress response. ZmADF5-overexpressing plants were also identified as sensitive to ABA during the seed germination and seedling stages. These results suggested that ZmADF5 played an important role in the response to drought stress.

12.
J Agric Food Chem ; 72(12): 6167-6177, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38500001

RESUMO

Antibiotics can be accidentally introduced into farmland by wastewater irrigation, and the environmental effects are still unclear. In this study, the effects of oxytetracycline on the residue of imidacloprid in soil and radishes were investigated. Besides, the rhizosphere microbiome and radish metabolome were analyzed. It showed that the persistence of imidacloprid in soil was unchanged, but the content of olefin-imidacloprid was increased by oxytetracycline. The residue of imidacloprid in radishes was increased by nearly 1.5 times, and the hazard index of imidacloprid was significantly raised by 1.5-4 times. Oxytetracycline remodeled the rhizosphere microbiome, including Actinobe, Elusimic, and Firmicutes, and influenced the metabolome of radishes. Especially, some amino acid metabolic pathways in radish were downregulated, which might be involved in imidacloprid degradation. It can be assumed that oxytetracycline increased the imidacloprid residue in radish through disturbing the plant-rhizosphere microbiome holobiont and, thus, increased the pesticide dietary risk.


Assuntos
Microbiota , Neonicotinoides , Nitrocompostos , Oxitetraciclina , Raphanus , Raphanus/química , Oxitetraciclina/metabolismo , Oxitetraciclina/farmacologia , Rizosfera , Solo/química
13.
Int J Surg ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38445452

RESUMO

BACKGROUND: Early identification of patients at high risk of postoperative acute kidney injury (AKI) can facilitate the development of preventive approaches. This study aimed to develop prediction models for postoperative AKI in noncardiac surgery using machine learning algorithms. We also evaluated the predictive performance of models that included only preoperative variables or only important predictors. MATERIALS AND METHODS: Adult patients undergoing noncardiac surgery were retrospectively included in the study (76,457 patients in the discovery cohort and 11,910 patients in the validation cohort). AKI was determined using the KDIGO criteria. The prediction model was developed using 87 variables (56 preoperative variables and 31 intraoperative variables). A variety of machine learning algorithms were employed to develop the model, including logistic regression, random forest, extreme gradient boosting, and gradient boosting decision trees (GBDT). The performance of different models was compared using the area under the receiver operating characteristic curve (AUROC). Shapley Additive Explanations (SHAP) analysis was employed for model interpretation. RESULTS: The patients in the discovery cohort had a median age of 52 years (IQR: 42-61 y), and 1179 patients (1.5%) developed AKI after surgery. The GBDT algorithm showed the best predictive performance using all available variables, or only preoperative variables. The AUROCs were 0.849 (95% CI, 0.835-0.863) and 0.828 (95% CI, 0.813-0.843), respectively. The SHAP analysis showed that age, surgical duration, preoperative serum creatinine and gamma-glutamyltransferase, as well as American Society of Anesthesiologists physical status III were the most important five features. When gradually reducing the features, the AUROCs decreased from 0.852 (including the top 40 features) to 0.839 (including the top 10 features). In the validation cohort, we observed a similar pattern regarding the models' predictive performance. CONCLUSIONS: The machine learning models we developed had satisfactory predictive performance for identifying high-risk postoperative AKI patients. Further, we found that model performance was only slightly affected when only preoperative variables or only the most important predictive features were included.

14.
J Hazard Mater ; 469: 133974, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38518695

RESUMO

Pesticides and fertilisers are frequently used and may co-exist on farmlands. The overfertilisation of soil may have a profound influence on pesticide residues, but the mechanism remains unclear. The effects of chemical fertilisers on the environmental behaviour of atrazine and their underlying mechanisms were investigated. The present outcomes indicated that the degradation of atrazine was inhibited and the half-life was prolonged 6.0 and 7.6 times by urea and compound fertilisers (NPK) at 1.0 mg/g (nitrogen content), respectively. This result, which was confirmed in both sterilised and transfected soils, was attributed to the inhibitory effect of nitrogen fertilisers on soil microorganisms. The abundance of soil bacteria was inhibited by nitrogen fertilisers, and five families of potential atrazine degraders (Micrococcaceae, Rhizobiaceae, Bryobacteraceae, Chitinophagaceae, and Sphingomonadaceae) were strongly and positively (R > 0.8, sig < 0.05) related to the decreased functional genes (atzA and trzN), which inhibited hydroxylation metabolism and ultimately increased the half-life of atrazine. In addition, nitrogen fertilisers decreased the sorption and vertical migration behaviour of atrazine in sandy loam might increase the in-situ residual and ecological risk. Our findings verified the weakened atrazine degradation with nitrogen fertilisers, providing new insights into the potential risks and mechanisms of atrazine in the context of overfertilisation.


Assuntos
Atrazina , Herbicidas , Poluentes do Solo , Atrazina/química , Solo/química , Fertilizantes , Nitrogênio , Metaboloma , Microbiologia do Solo , Poluentes do Solo/metabolismo , Herbicidas/metabolismo , Biodegradação Ambiental
15.
Heliyon ; 10(4): e25678, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38370251

RESUMO

[Research Purpose] In the era of the digital economy, there is an urgent need to explore solutions to various problems faced by enterprises in their digital transformation, such as the lack of data resources, data silos, and information asymmetry within supply chains. [Method/Contribution] Leveraging evolutionary game theory and adopting a supply chain perspective, this study integrates the government and upstream/downstream enterprises into a unified analysis framework. In this study, a three-party evolutionary game model under government coordination aimed at fostering data openness and sharing among supply chain enterprises is constructed. Simulation analyses are conducted on decision-making strategies concerning data sharing between the government and supply chain enterprises across different scenarios. [Research Conclusion] It is observed that the high level of benefits and low costs associated with data sharing incentivize supply chain enterprises to actively open and share their data. Notably, government incentives significantly encourage data openness among these enterprises by subsidizing the cost of data sharing, "especially evident when the incentive coefficient exceeds 0.6," thereby guiding them toward collaborative data-sharing initiatives. Finally, it is also found that data sharing further promotes the digital transformation of the supply chain, optimizing decision-making processes, resource allocation, and operational efficiency. Through data sharing, better forecasting, inventory management, and risk mitigation strategies can be implemented. Moreover, data sharing fosters collaboration among supply chain partners enhances transparency and trust, and makes the supply chain more synchronized and responsive, which leads to value cocreation within the supply chain, with downstream enterprises being more incentivized than upstream enterprises by this value cocreation.

16.
Gut Microbes ; 16(1): 2310603, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38332676

RESUMO

Chronic pain is commonly linked with diminished working memory. This study explores the impact of the anesthetic (S)-ketamine on spatial working memory in a chronic constriction injury (CCI) mouse model, focusing on gut microbiome. We found that multiple doses of (S)-ketamine, unlike a single dose, counteracted the reduced spontaneous alteration percentage (%SA) in the Y-maze spatial working memory test, without affecting mechanical or thermal pain sensitivity. Additionally, repeated (S)-ketamine treatments improved the abnormal composition of the gut microbiome (ß-diversity), as indicated by fecal 16S rRNA analysis, and increased levels of butyrate, a key gut - brain axis mediator. Protein analysis showed that these treatments also corrected the upregulated histone deacetylase 2 (HDAC2) and downregulated brain-derived neurotrophic factor (BDNF) in the hippocampi of CCI mice. Remarkably, fecal microbiota transplantation from mice treated repeatedly with (S)-ketamine to CCI mice restored %SA and hippocampal BDNF levels in CCI mice. Butyrate supplementation alone also improved %SA, BDNF, and HDAC2 levels in CCI mice. Furthermore, the TrkB receptor antagonist ANA-12 negated the beneficial effects of repeated (S)-ketamine on spatial working memory impairment in CCI mice. These results indicate that repeated (S)-ketamine administration ameliorates spatial working memory impairment in CCI mice, mediated by a gut microbiota - brain axis, primarily through the enhancement of hippocampal BDNF - TrkB signaling by butyrate.


Assuntos
Dor Crônica , Microbioma Gastrointestinal , Ketamina , Camundongos , Animais , Ketamina/farmacologia , Ketamina/uso terapêutico , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Memória de Curto Prazo , Dor Crônica/tratamento farmacológico , RNA Ribossômico 16S , Hipocampo/metabolismo , Transtornos da Memória/tratamento farmacológico , Butiratos/farmacologia
17.
BMC Surg ; 24(1): 34, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267970

RESUMO

OBJECTIVES: To investigate the effect of a three-dimensional (3D) exoscope for decompression of single-segment massive lumbar disc herniation (LDH). METHODS: The study included 56 consecutive patients with single segment massive LDH who underwent decompression assisted by a 3D exoscope from October 2019 to October 2022 at a university hospital. The analysis was based on comparison of perioperative metrics including decompression time, estimated blood loss (EBL) during decompression and postoperative length of stay (PLS); clinical outcomes including assessment using the visual analogue scale (VAS) and the Oswestry disability index (ODI); and incidence of reoperation and complications. RESULTS: The mean decompression time was 28.35 ± 8.93 min (lumbar interbody fusion (LIF)) and 15.50 ± 5.84 min (fenestration discectomy (LOVE surgery)), the mean EBL during decompression was 42.65 ± 12.42 ml (LIF) and 24.32 ± 8.61 ml (LOVE surgery), and the mean PLS was 4.56 ± 0.82 days (LIF) and 2.00 ± 0.65 days (LOVE surgery). There were no complications such as cerebrospinal fluid leakage, nerve root injury and epidural hematoma. All patients who underwent decompression assisted by a 3D exoscope were followed up for 6 months. At the last follow-up, the VAS and ODI scores were significantly improved from the preoperative period to the last follow-up (P < 0.05). CONCLUSIONS: A 3D exoscope provides a visually detailed, deep and clear surgical field, which makes decompression safer and more effective and reduces short-term complications. A 3D exoscope may be a good assistance tool during decompression for single-segment massive LDH.


Assuntos
Hematoma Epidural Craniano , Deslocamento do Disco Intervertebral , Humanos , Deslocamento do Disco Intervertebral/cirurgia , Vazamento de Líquido Cefalorraquidiano , Hospitais Universitários , Descompressão
18.
Circ Res ; 134(4): 371-389, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38264909

RESUMO

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common but poorly understood form of heart failure, characterized by impaired diastolic function. It is highly heterogeneous with multiple comorbidities, including obesity and diabetes, making human studies difficult. METHODS: Metabolomic analyses in a mouse model of HFpEF showed that levels of indole-3-propionic acid (IPA), a metabolite produced by gut bacteria from tryptophan, were reduced in the plasma and heart tissue of HFpEF mice as compared with controls. We then examined the role of IPA in mouse models of HFpEF as well as 2 human HFpEF cohorts. RESULTS: The protective role and therapeutic effects of IPA were confirmed in mouse models of HFpEF using IPA dietary supplementation. IPA attenuated diastolic dysfunction, metabolic remodeling, oxidative stress, inflammation, gut microbiota dysbiosis, and intestinal epithelial barrier damage. In the heart, IPA suppressed the expression of NNMT (nicotinamide N-methyl transferase), restored nicotinamide, NAD+/NADH, and SIRT3 (sirtuin 3) levels. IPA mediates the protective effects on diastolic dysfunction, at least in part, by promoting the expression of SIRT3. SIRT3 regulation was mediated by IPA binding to the aryl hydrocarbon receptor, as Sirt3 knockdown diminished the effects of IPA on diastolic dysfunction in vivo. The role of the nicotinamide adenine dinucleotide circuit in HFpEF was further confirmed by nicotinamide supplementation, Nnmt knockdown, and Nnmt overexpression in vivo. IPA levels were significantly reduced in patients with HFpEF in 2 independent human cohorts, consistent with a protective function in humans, as well as mice. CONCLUSIONS: Our findings reveal that IPA protects against diastolic dysfunction in HFpEF by enhancing the nicotinamide adenine dinucleotide salvage pathway, suggesting the possibility of therapeutic management by either altering the gut microbiome composition or supplementing the diet with IPA.


Assuntos
Cardiomiopatias , Insuficiência Cardíaca , Propionatos , Sirtuína 3 , Humanos , Camundongos , Animais , Insuficiência Cardíaca/metabolismo , Volume Sistólico/fisiologia , NAD , Sirtuína 3/genética , Indóis/farmacologia , Niacinamida
19.
Talanta ; 270: 125652, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38199125

RESUMO

Monitoring endogenous glutathione (GSH) levels in living cells is essential for cancer diagnose and treatment. In this work, GSH responsive fluorescent nanoprobe with turn-on property was constructed using Zn-modified porphyrinic metal-organic frameworks (PCN-224-Zn). The introduced Zn2+ could quench the fluorescence of PCN-224 by the metallization of organic ligand (TCPP) and serves as sensing site for GSH. When exposed to GSH, the strong binding affinity of GSH generates the formation of Zn-GSH complex, eliminating the fluorescence quenching effect of Zn2+. Based on the constructed PCN-224-Zn nanoprobe, selective determination of GSH was achieved in the range of 0.01-6 µM with a detection limit of 1.5 nM. Furthermore, the constructed nanoprobe can realize the fluorescence imaging of endogenous GSH in MCF-7 and HeLa cells. Meanwhile, PCN-224-Zn could also monitor GSH in cell lysate with recovery rates from 93.8 % to 102.3 %. The performance of PCN-224-Zn demonstrates its capacities in the application of fluorescence sensing and bio-imaging fields.


Assuntos
Corantes , Pontos Quânticos , Humanos , Células HeLa , Glutationa/metabolismo , Pontos Quânticos/química , Zinco/química , Corantes Fluorescentes/toxicidade , Corantes Fluorescentes/química
20.
Pestic Biochem Physiol ; 198: 105753, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38225097

RESUMO

Recently, studies have shown that pesticides may have adverse effects on the flavor quality of the fruits, but there is still a lack of appropriate methods to repair the damage. This study investigated the effects and mechanism of applying the emerging material, nano­selenium, and two fungicides (Boscalid and Pydiflumetofen) alone or together on the flavor quality and antioxidant capacity of strawberries. The results showed that the two fungicides had a negative impact on strawberry color, flavor, antioxidant capacity and different enzymatic systems. The color damage was mainly attributed to the impact on anthocyanin content. Nano­selenium alleviated the quality losses by increasing sugar-acid ratio, volatiles, anthocyanin levels, enzyme activities and DPPH scavenging ability and reducing ROS levels. Results also showed that these damage and repair processes were related to the regulation of flavor and ripening related transcription factors (including FaRIF, FaSnRK1, FaMYB10, FaMYB1, FaSnRK2.6 and FaABI1), the upregulation of genes on sugar-acid, volatile, and anthocyanin synthesis pathways, as well as the increase of sucrose and ABA signaling molecules. In addition, the application of nano-Se supplemented the selenium content in fruits, and was harmless to human health. This information is crucial for revealing the mechanisms of flavor damage caused by pesticides to strawberry and the repaired of nano­selenium, and broadens the researching and applying of nano­selenium in repairing the damage caused by pesticides.


Assuntos
Fragaria , Fungicidas Industriais , Selênio , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/farmacologia , Antocianinas/metabolismo , Antocianinas/farmacologia , Antioxidantes/farmacologia , Selênio/farmacologia , Fungicidas Industriais/farmacologia , Proteínas de Plantas/genética , Açúcares , Frutas , Regulação da Expressão Gênica de Plantas
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