Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 706
Filtrar
1.
Nat Genet ; 56(4): 721-731, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38622339

RESUMO

Coffea arabica, an allotetraploid hybrid of Coffea eugenioides and Coffea canephora, is the source of approximately 60% of coffee products worldwide, and its cultivated accessions have undergone several population bottlenecks. We present chromosome-level assemblies of a di-haploid C. arabica accession and modern representatives of its diploid progenitors, C. eugenioides and C. canephora. The three species exhibit largely conserved genome structures between diploid parents and descendant subgenomes, with no obvious global subgenome dominance. We find evidence for a founding polyploidy event 350,000-610,000 years ago, followed by several pre-domestication bottlenecks, resulting in narrow genetic variation. A split between wild accessions and cultivar progenitors occurred ~30.5 thousand years ago, followed by a period of migration between the two populations. Analysis of modern varieties, including lines historically introgressed with C. canephora, highlights their breeding histories and loci that may contribute to pathogen resistance, laying the groundwork for future genomics-based breeding of C. arabica.


Assuntos
Coffea , Coffea/genética , Café , Genoma de Planta/genética , Metagenômica , Melhoramento Vegetal
2.
Huan Jing Ke Xue ; 45(5): 2971-2982, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629558

RESUMO

In order to study the status and sources of heavy metal pollution in Yinchuan Yellow River floodplain soils, we used inductively coupled plasma mass spectrometry (ICP-MS) to determine the presence of eight heavy metals in 92 soil samples from the Yinchuan Yellow River floodplain and used enrichment factors, geological accumulation index, and potential ecological risk index to analyze and evaluate the characteristics of heavy metal pollution in the study area. Combined correlation analysis, absolute factor analysis-multiple linear regression model (APCS-MLR), positive matrix factorization (PMF), and geostatistics were used to analyze the sources of soil heavy metals. The results showed that the content of eight heavy metals in the surface soil of the Yellow River floodplain in Yinchuan City were lower than the screening value of soil pollution risk in agricultural land; Cu and Pb contents were lower than the background value of Yinchuan City soil, and the contents of the remaining six elements were higher than the background value. The coefficients of variation of Zn and Cd were large and in the medium variation level and were influenced by anthropogenic activities. The heavy metal content varied between different land types and generally showed that wasteland > abandoned farmland > woodland > cultivated land. The average content of Cu and Pb in forest and arable soils was lower than the regional background value, whereas the rest of the heavy metals in different land types were higher than the soil background value. The analysis of enrichment factors showed that Zn and Cd were slightly enriched in the study area, and the cumulative index method and the evaluation of the potential risk of single heavy metals indicated that more than 60% of the sites in the study area were contaminated with Cd at a medium or higher potential ecological hazard. The comprehensive evaluation results of potential ecological risk showed that the overall ecological risk level of the study area was mild. From the distribution of heavy metal ecological risk comprehensive index sample points, only one point was in moderate ecological hazard, and the pollution point showed very few. Comprehensive correlation analysis, APCS-MLR model, PMF model, and geostatistical analysis results confirmed that Zn and Cd in the study area were mainly derived from human activities such as agricultural activities and transportation, and the remaining heavy metals were derived from soil parent materials. The results of this study can provide a scientific basis for the ecological protection and sustainable development of the Yellow River in Yinchuan City.

3.
Environ Pollut ; 349: 123959, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608855

RESUMO

The worldwide prevalence of obesity highlights the potential contribution of endocrine-disrupting chemicals (EDCs). However, common epidemiological measures such as body mass index and waist circumference may misrepresent the intricate obesity risks these chemicals pose across genders. This study delves deeper into abdominal fat by differentiating between subcutaneous and visceral regions by analyzing data from National Health and Nutrition Examination Surveys (NHANES). We particularly investigated the gender-specific associations between organophosphorus flame-retardant metabolites (mOPFRs), phthalates (mPAEs) and accumulated fat indexes from 2536 people. Aiding by Bayesian Kernel Machine Regression (BKMR), we found while co-exposure to mOPFRs and mPAEs was linked to general and abdominal obesity across the entire and gender-specific populations, a gender-specific fat distribution emerged. For women, urinary BDCPP and MBzP were linked to an increased subcutaneous fat index (SFI) [BDCPP OR: 1.12 (95% CI: 1.03-1.21), MBzP OR: 1.09 (95% CI: 1.01-1.18)], but not to visceral fat index (VFI). These metabolites had a combined linkage with SFI, with BDCPP (weighting 22.0%) and DPHP (weighting 31.0%) being the most influential in Quantile g-computation model (qgcomp) model. In men, BCEP exposure exclusively associated with the elevated VFI [OR: 1.14 (95% CI: 1.03-1.26)], a trend further highlighted in mixture models with BCEP as the predominant association. Intriguingly, only males displayed a marked correlation between these metabolites and insulin resistance in subpopulation. An attempted mediation analysis revealed that elevated C-reactive protein mediated 12.1% of the association between urinary BCEP and insulin resistance, suggesting a potential role of inflammation. In conclusion, the gender-specific fat distribution and insulin resistance that associated with mOPFRs represented the potential risk of these chemicals to man.

4.
BMC Microbiol ; 24(1): 124, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622529

RESUMO

BACKGROUND: Severe burns may alter the stability of the intestinal flora and affect the patient's recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. METHODS: We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. RESULTS: We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. CONCLUSIONS: Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.


Assuntos
Queimaduras , Microbioma Gastrointestinal , Microbiota , Humanos , Animais , Camundongos , Bactérias/genética , Firmicutes/genética , RNA Ribossômico 16S/genética
5.
Can Respir J ; 2024: 5554886, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38584671

RESUMO

Objective: To investigate the mechanism through which Astragalus and Panax notoginseng decoction (APD) facilitates the treatment of ferroptosis-mediated pulmonary fibrosis. Materials and Methods: First, the electromedical measurement systems were used to measure respiratory function in mice; the lungs were then collected for histological staining. Potential pharmacologic targets were predicted via network pharmacology. Finally, tests including immunohistochemistry, reverse transcription-quantitative polymerase chain reaction, and western blotting were used to evaluate the relative expression levels of collagen, transforming growth factor ß, α-smooth muscle actin, hydroxyproline, and ferroptosis-related genes (GPX4, SLC7A11, ACSL4, and PTGS2) and candidates involved in the mediation of pathways associated with ferroptosis (Hif-1α and EGFR). Results: APD prevented the occurrence of restrictive ventilation dysfunction induced by ferroptosis. Extracellular matrix and collagen fiber deposition were significantly reduced when the APD group compared with the model group; furthermore, ferroptosis was attenuated, expression of PTGS2 and ACSL4 increased, and expression of GPX4 and SLC7A11 decreased. In the APD group, the candidates related to the mediation of ferroptosis (Hif-1α and EGFR) decreased compared with the model group. Discussion and Conclusions. APD may ameliorate restrictive ventilatory dysfunction through the inhibition of ferroptosis. This was achieved through the attenuation of collagen deposition and inflammatory recruitment in pulmonary fibrosis. The underlying mechanisms might involve Hif-1α and EGFR.


Assuntos
Ferroptose , Panax notoginseng , Fibrose Pulmonar , Animais , Camundongos , Fibrose Pulmonar/tratamento farmacológico , Ciclo-Oxigenase 2 , Colágeno , Receptores ErbB
6.
Nat Chem ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38499849

RESUMO

Photoredox catalysis relies on light-induced electron transfer leading to a radical pair comprising an oxidized donor and a reduced acceptor in a solvent cage. For productive onward reaction to occur, the oxidized donor and the reduced acceptor must escape from that solvent cage before they undergo spontaneous reverse electron transfer. Here we show the decisive role that cage escape plays in three benchmark photocatalytic reactions, namely, an aerobic hydroxylation, a reductive debromination and an aza-Henry reaction. Using ruthenium(II)- and chromium(III)-based photocatalysts, which provide inherently different cage escape quantum yields, we determined quantitative correlations between the rates of photoredox product formation and the cage escape quantum yields. These findings can be largely rationalized within the framework of Marcus theory for electron transfer.

7.
Protein Cell ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38482631

RESUMO

Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation at specific CpG sites. However, available DNA methylation (DNAm) age predictors are based on datasets with limited ethnic representation. Moreover, a systematic comparison between DNAm data and other omics datasets has not yet been performed. To address these knowledge gaps, we generated and analyzed DNA methylation datasets from two independent Chinese cohorts, revealing age-related DNAm changes. Additionally, a DNA methylation (DNAm) aging clock (iCAS-DNAmAge) and a group of DNAm-based multi-modal clocks for Chinese individuals were developed, with most of them demonstrating strong predictive capabilities for chronological age. The clocks were further employed to predict factors influencing aging rates. The DNAm aging clock, derived from multi-modal aging features (compositeAge-DNAmAge), exhibited a close association with multi-omics changes, lifestyles, and disease status, underscoring its robust potential for precise biological age assessment. Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace, providing basis for evaluating aging intervention strategies.

8.
J Prosthet Dent ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38519327

RESUMO

STATEMENT OF PROBLEM: The esthetic assessment of smile lines by laypersons is a subject of ongoing debate. However, smile lines often appear with different types of upper lip curvature, which further complicates the esthetic assessment process, and studies on this combination are lacking. PURPOSE: The purpose of this clinical study was to investigate a layperson's esthetic perception of smile lines and upper lip combined images. MATERIAL AND METHODS: Twenty-six smile images resulting from combinations of 3 upper lip types, 4 anterior smile line types, and 3 posterior smile line types were generated by an image editing software program. Eighty-three laypersons (39 men and 44 women; 18 to 35 years of age) completed rating images using a visual analog scale. Unattractive smiles were designated to be those with scores <50 and attractive ones with scores ≥50. Data were analyzed using 1-way analysis of variance and Bonferroni post hoc tests (α=.05). RESULTS: High anterior smile line with gingival display >4 mm obtained significantly lower scores of <50 when combined with all upper lip curvatures (upward: 28.29 ±22.79, straight: 38.74 ±23.00, downward: 30.67 ±22.25, P<.01). High anterior smile lines with gingival display ≤4 mm combined with upward and straight upper lip curvature images obtained significantly higher scores, and all were ≥50 (upward: 63.24 ±22.22, straight: 61.40 ±21.58, P<.01). CONCLUSIONS: From a layperson's perspective, high anterior smile lines with gingival display >4 mm combined with any lip type were determined to be unattractive. If gingival display was ≤4 mm combined with both upward and straight lip types, the smile was assessed as attractive.

9.
J Ethnopharmacol ; 328: 118080, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38521426

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The use of antineoplastic drugs, such as cisplatin, in clinical practice can cause adverse effects in patients, such as liver injury, which limits their long-term use. Therefore, there is an urgent need to develop alternative therapeutic strategies or drugs to minimize cisplatin-induced liver injury. Huangqi, the root of Astragalus membranaceus, is extensively used in traditional Chinese medicine (TCM) and has been employed in treating diverse liver injuries. Astragalus membranaceus contains several bioactive constituents, including triterpenoid saponins, one of which, astragaloside IV (ASIV), has been reported to have anti-inflammatory and antioxidant stress properties. However, its potential in ameliorating cisplatin-induced liver injury has not been explored. AIM OF THE STUDY: The objective of this study was to examine the mechanism by which ASIV protects against cisplatin-induced liver injury. MATERIALS AND METHODS: This study established a model of cisplatin-induced liver injury in mice, followed by treatment with various doses of astragaloside IV (40 mg/kg, 80 mg/kg). In addition, a model of hepatocyte ferroptosis in AML-12 cells was established using RSL3. The mechanism of action of astragaloside IV was investigated using a range of methods, including Western blot assay, qPCR, immunofluorescence, histochemistry, molecular docking, and high-content imaging system. RESULTS: The findings suggested a significant improvement in hepatic injury, inflammation and oxidative stress phenotypes with the administration of ASIV. Furthermore, network pharmacological analyses provided evidence that a major pathway for ASIV to attenuate cisplatin-induced hepatic injury entailed the cell death cascade pathway. It was observed that ASIV effectively inhibited ferroptosis both in vivo and in vitro. Subsequent experimental outcomes provided further validation of ASIV's ability to hinder ferroptosis through the inhibition of PPARα/FSP1 signaling pathway. The current findings suggest that ASIV could function as a promising phytotherapy composition to alleviate cisplatin-induced liver injury. CONCLUSIONS: The current findings suggest that astragaloside IV could function as a promising phytotherapy composition to alleviate cisplatin-induced liver injury.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Ferroptose , Saponinas , Triterpenos , Humanos , Camundongos , Animais , Cisplatino/toxicidade , Simulação de Acoplamento Molecular , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Saponinas/farmacologia , Saponinas/uso terapêutico , Saponinas/química , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Triterpenos/química
10.
Exp Ther Med ; 27(4): 157, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38476896

RESUMO

In humans, gut microbiota can determine the health status. The regulatory mechanisms of the gut microbiota in asthma must be elucidated. Although antibiotics (ABXs) can clear infections, they markedly alter the composition and abundance of gut microbiota. The present study used ABX-treated mice to examine the time-dependent effects of ABX administration on the gut microbiota and intestinal mucosal barrier. The mouse asthma model was established using ovalbumin (OVA) and gavaged with an ABX cocktail for different durations (1 or 2 weeks) and stacked sequences. The pathology of the model, model 2, OVA-ABX, OVA-ABX 2, ABX-OVA and ABX-OVA was severe when compared with the control group as evidenced by the following results: i) significantly increased pulmonary and colonic inflammatory cell infiltration; ii) enhanced pause values and iii) OVA-induced immunoglobulin E (IgE) and TGF-ß expression levels, and significantly downregulated Tight Junction Protein 1 (TJP1), claudin 1 and Occludin expression levels. Furthermore, the intestinal bacterial load in the OVA-ABX and OVA-ABX 2 groups was significantly lower than that in the ABX-OVA and ABX-OVA 2 groups, respectively. The predominant taxa were as follows: phyla, Firmicutes and Proteobacteria, genera, Escherichia-Shigella, Lactobacillus and Lachnospira. The abundances of Lachnospira and Escherichia-Shigella were correlated with the expression of OVA-induced IgE and TJPs. These findings indicated that ABX administration, which modifies microbiome diversity and bacterial abundance, can disrupt colonic integrity, downregulate TJ proteins, damage the intestinal barrier, enhance enterocyte permeability, and promote the release of inflammatory factors, adversely affecting asthma alleviation and long-term repair.

11.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38473842

RESUMO

The N6-methyladenosine (M6A) modification is the most common internal chemical modification of RNA molecules in eukaryotes. This modification can affect mRNA metabolism, regulate RNA transcription, nuclear export, splicing, degradation, and translation, and significantly impact various aspects of physiology and pathobiology. Radiotherapy is the most common method of tumor treatment. Different intrinsic cellular mechanisms affect the response of cells to ionizing radiation (IR) and the effectiveness of cancer radiotherapy. In this review, we summarize and discuss recent advances in understanding the roles and mechanisms of RNA M6A methylation in cellular responses to radiation-induced DNA damage and in determining the outcomes of cancer radiotherapy. Insights into RNA M6A methylation in radiation biology may facilitate the improvement of therapeutic strategies for cancer radiotherapy and radioprotection of normal tissues.


Assuntos
Neoplasias , RNA , Humanos , Metilação , RNA/metabolismo , Neoplasias/metabolismo , Reparo do DNA
12.
Ying Yong Sheng Tai Xue Bao ; 35(1): 177-185, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38511454

RESUMO

Microbial necromass carbon (MNC) is a crucial source for stable soil carbon pool, and understanding its response to carbon inputs from both aboveground (litter) and belowground (roots) in subtropical forest soils is essential for assessing soil carbon stocks in global ecosystems. In a Castanopsis carlesii plantation at the Sanming Forest Ecosystem National Observation and Research Station in Fujian Province, we conducted an experiment with five treatments, including root removal (NR), aboveground litter removal (NL), no litter input (removals of both aboveground litter and roots, NI), double aboveground litter addition (DL), and control (CK). After seven years, we collected soil samples in the 0-10 cm soil layer to examine changes in MNC content and its contribution to soil organic carbon (SOC). Results showed that NR treatment reduced MNC, bacterial necromass carbon (BNC), and fungal necromass carbon (FNC) by 15.9%, 20.2%, and 14.5%, respectively, while other treatments did not induce significant changes. The NR, NL, NI, and DL treatments did not affect the contributions of BNC, FNC, and MNC to SOC. Correlation and path analyses revealed that litter and root carbon input treatments could alter the MNC content directly or indirectly through changing soil available substrates and microbial community structure. Our results suggested that roots exert a stronger influence on the maintenance of MNC than aboveground carbon source in the mid-subtropical plantations.


Assuntos
Ecossistema , Fagaceae , Solo/química , Carbono/análise , Microbiologia do Solo , Florestas , Bactérias
13.
Sci Rep ; 14(1): 6547, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503900

RESUMO

This study assessed the global and regional burden of IS (ischemic stroke) deaths due to LPA (low physical activity) from 1990 to 2019, analyzed regional, sex, and age differences in ASMR (age-standardized mortality rate), and provided a comprehensive understanding of the impact of age, period, and cohort on low physical activity related ischemic stroke ASMR. We conducted an APC (age-period-cohort) analysis of the global and four World Bank income level regions' IS mortality data attributed to LPA from 1990 to 2019, using the GBD2019 database, and the results showed that the global net drift of the Ischemic stroke age-standardized mortality attributable to low physical activity was - 1.085%[95% CI: - 1.168, - 1.003].The ASMR drop is most pronounced in the high-income zone, with a net drift of - 2.473% [95% CI: - 2.759, - 2.187] across the four income groups. The influence of age on mortality is increasing in the worldwide old population, while the period and cohort effects are decreasing. We also performed a Joinpoint regression analysis, which revealed that the specific time of considerable drop in ASMR of IS in the global LPA population was 2002-2007, with an APC of -2.628%. The specific period of considerable drop in ASMR in high-income regions with the highest variation was 1999-2007, with an APC = - 4.726%. The global burden of public health deaths caused by LPA is diminishing, with the most notable progress observed in high-income regions. However, in low and lower-middle income areas, the situation continues to deteriorate. Within the global elderly population, the effects of age on mortality is increasing, while the effects of period and cohort are diminishing. These trends vary across income levels, highlighting the necessity for enhanced international collaboration to formulate context-specific public health strategies aimed at enhancing cardiovascular health on a global, regional, and national scale.


Assuntos
AVC Isquêmico , Humanos , Idoso , Comportamento Sedentário , Renda , Saúde Pública , Estudos de Coortes , Saúde Global
14.
Clinics (Sao Paulo) ; 79: 100341, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38457938

RESUMO

AIMS: Very Low Birthweight (VLBW) infants with neonatal Chronic Lung Disease (CLD) have been found to have functional impairment of the brainstem auditory pathway at term. This study investigated the functional status of the brainstem auditory pathway in VLBW infants with CLD after term for any abnormality. METHODS: Fifty-two VLBW infants were recruited at 50 weeks of Postconceptional Age: 25 with neonatal CLD and 27 without CLD. None had any other major complications to minimize confounding effects. Brainstem Auditory Evoked Responses were studied at 21‒91/s click rates. RESULTS: Compared with those without CLD, VLBW infants with CLD had relatively shorter latencies of BAER waves I and III, associated with a slightly lower BAER threshold. Wave V latency and I‒V interpeak interval did not differ significantly between the two groups of infants. The I‒III interval in infants with CLD was shorter than in those without CLD at 91/s clicks. However, the III‒V interval was significantly longer than in those without CLD at all click rates (all p < 0.05). There were no significant differences in the amplitudes of BAER wave components between the two groups of infants. CONCLUSIONS: The main BAER abnormality in VLBW infants with CLD was a prolonged III‒V interval. Auditory conduction is delayed or impaired at more central regions of the brainstem in CLD infants. After term central auditory function is adversely affected by neonatal CLD. Monitoring post-term change is required to provide valuable information for post-term care of CLD infants.


Assuntos
Pneumopatias , Recém-Nascido , Lactente , Humanos , Adulto , Pneumopatias/complicações , Audição , Vias Auditivas , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Tronco Encefálico
15.
Chemistry ; : e202400856, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38523568

RESUMO

There has been much progress on mononuclear chromium(III) complexes featuring luminescence and photoredox activity, but dinuclear chromium(III) complexes have remained underexplored in these contexts until now. We identified a tridentate chelate ligand able to accommodate both meridional and facial coordination of chromium(III), to either access a mono- or a dinuclear chromium(III) complex depending on reaction conditions. This chelate ligand causes tetragonally distorted primary coordination spheres around chromium(III) in both complexes, entailing comparatively short excited-state lifetimes in the range of 400 to 800 ns in solution at room temperature and making photoluminescence essentially oxygen insensitive. The two chromium(III) ions in the dimer experience ferromagnetic exchange interactions that result in a high spin (S = 3) ground state with a coupling constant of +9.3 cm-1. Photoinduced energy transfer from the luminescent ferromagnetically coupled dimer to an anthracene derivative results in sensitized triplet-triplet annihilation upconversion. Based on these proof-of-principle studies, dinuclear chromium(III) complexes seem attractive for the development of fundamentally new types of photophysics and photochemistry enabled by magnetic exchange interactions.

16.
Int J Biol Macromol ; 263(Pt 2): 130347, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38401583

RESUMO

Polypeptide N-acetylgalactosamine transferase 9 (GALNT9) catalyzes the initial step of mucin-type O-glycosylation via linking N-acetylgalactosamine (GalNAc) to serine/threonine in a protein. To unravel the association of GALNT9 with Parkinson's disease (PD), a progressive neurodegenerative disorder, GALNT9 levels were evaluated in the patients with PD and mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and statistically analyzed based on the GEO datasets of GSE114918 and GSE216281. Glycoproteins with exposing GalNAc were purified using lectin affinity chromatography and identified by LC-MS/MS. The influence of GALNT9 on cells was evaluated via introducing a GALNT9-specific siRNA into SH-SY5Y cells. Consequently, GALNT9 deficiency was found to occur under PD conditions. GALNT9 silencing contributed to a causative factor in PD pathogenesis via reducing the levels of intracellular dopamine, tyrosine hydroxylase and soluble α-synuclein, and promoting α-synuclein aggregates. MS identification revealed 14 glycoproteins. 5 glycoproteins, including ACO2, ATP5B, CKB, CKMT1A, ALDOC, were associated with energy metabolism. GALNT9 silencing resulted in mitochondrial dysfunctions via increasing ROS accumulation, mitochondrial membrane depolarization, mPTPs opening, Ca2+ releasing and activation of the CytC-related apoptotic pathway. The dysfunctional mitochondria then triggered mitophagy, possibly intermediated by adenine nucleotide translocase 1. Our study suggests that GALNT9 is potentially developed into an auxiliary diagnostic index and therapeutic target of PD.


Assuntos
Doenças Mitocondriais , N-Acetilgalactosaminiltransferases , Neuroblastoma , Doença de Parkinson , Humanos , Camundongos , Animais , Doença de Parkinson/metabolismo , alfa-Sinucleína/química , Acetilgalactosamina/química , Transferases , Cromatografia Líquida , Espectrometria de Massas em Tandem , Peptídeos , Glicoproteínas , N-Acetilgalactosaminiltransferases/genética , N-Acetilgalactosaminiltransferases/metabolismo , Creatina Quinase
17.
Sci Total Environ ; 921: 171109, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38387563

RESUMO

Microplastics (MPs), an emerging environmental contaminant, have raised growing health apprehension due to their detection in various human biospecimens. Despite extensive research into their prevalence in the environment and the human body, the ramifications of their existence within the enclosed confines of the human eye remain largely unexplored. Herein, we assembled a cohort of 49 patients with four ocular diseases (macular hole, macular epiretinal membrane, retinopathy and rhegmatogenous retinal detachment) from two medical centers. After processing the samples with an optimized method, we utilized Laser Direct Infrared (LD-IR) spectroscopy and Pyrolysis Gas Chromatography/Mass Spectrometry (Py-GC/MS) to analyze 49 vitreous samples, evaluating the characteristics of MPs within the internal environment of the human eye. Our results showed that LD-IR scanned a total of 8543 particles in the composite sample from 49 individual vitreous humor samples, identifying 1745 as plastic particles, predominantly below 50 µm. Concurrently, Py-GC/MS analysis of the 49 individual samples corroborated these findings, with nylon 66 exhibiting the highest content, followed by polyvinyl chloride, and detection of polystyrene. Notably, correlations were observed between MP levels and key ocular health parameters, particularly intraocular pressure and the presence of aqueous humor opacities. Intriguingly, individuals afflicted with retinopathy demonstrated heightened ocular health risks associated with MPs. In summary, this research provides significant insights into infiltration of MP pollutants within the human eye, shedding light on their potential implications for ocular health and advocating for further exploration of this emerging health risk.


Assuntos
Doenças Retinianas , Poluentes Químicos da Água , Humanos , Corpo Vítreo/química , Microplásticos , Plásticos/análise , Cromatografia Gasosa-Espectrometria de Massas , Poluentes Químicos da Água/análise
18.
Int Immunopharmacol ; 130: 111699, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38377855

RESUMO

Intracranial infections are among the most common complications of neurosurgery, with their incidence remaining high despite advancements in current neurosurgical techniques and aseptic technology. While the role of mucosal-associated invariant T (MAIT) cells, a subset of innate-like T lymphocytes, in bacterial defense is well-established, their involvement in intracranial infections remains unclear. In this study, we utilized flow cytometry to assess the phenotype and function of circulating and CSF MAIT cells. Our findings revealed that MAIT cells were higher in the CSF compared to blood. Notably, a higher percentage of IL-17A + MAIT cells was detected in the CSF of patients with intracranial infections. Moreover, markers indicating activation and exhaustion were significantly upregulated in CSF MAIT cells. Furthermore, elevated levels of pro-inflammatory cytokines, including IL-1ß, IL-12, and IL-18, were detected in the CSF supernatants. We hypothesized that the elevated levels of IL-1ß, IL-12, and IL-18 in the inflammatory milieu synergistically activate MAIT cells in the CSF. In particular, CD25 and Tim-3 expression of MAIT cells was increased by stimulation with IL-1ß, IL-12, and IL-18 or CSF supernatants of intracranial infection patients. Collectively, these findings provide important information underlying the innate immune response of patients with intracranial infections.


Assuntos
Células T Invariantes Associadas à Mucosa , Humanos , Interleucina-18/metabolismo , Citocinas/metabolismo , Interleucina-12/metabolismo , Craniotomia
19.
Environ Sci Technol ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323904

RESUMO

Neonicotinoid insecticides (neonics) are extensively employed in agriculture and pervade various environmental matrices. However, few studies have documented the occurrence and potential chronic ecological risks of these chemicals in the marine environment. We collected 720 seawater samples from Xiangshan Bay during 2015-2019 and the integrated concentrations of seven neonics were determined using the relative potency factor method. Trend analyses using the Mann-Kendall test in time series, along with the estimation of the flux of neonics into the sea, were conducted. At last, the ecological risk of neonics was evaluated by water quality criteria derivation based on species sensitivity distribution. Our findings revealed that 47.6% of samples contained at least one neonic, with the integrated concentration of neonics ranging from 63.30 to 1684.14 ng/L. Imidacloprid and dinotefuran exhibited the highest frequency of detection in the analysis. The significance level of the Mann-Kendall test ranged from 2.16 × 10-10 to 1.21 × 10-5 (S > 0), indicating all neonics behaved with sharply increasing trends. Approximately 8.47 × 10-2 tons of neonics were discharged into Xiangshan Bay. Notably, the integrated concentrations of neonics represented a potential chronic ecological risk to marine organisms. This study provided novel insights into the spatial distribution, source, and migration of neonic species and their impacts on marine ecosystems.

20.
Small ; : e2310603, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279621

RESUMO

To improve the sluggish kinetics of the hydrogen evolution reaction (HER), a key component in water-splitting applications, there is an urgent desire to develop efficient, cost-effective, and stable electrocatalysts. Strain engineering is proving an efficient strategy for increasing the catalytic activity of electrocatalysts. This work presents the development of Ru-Au bimetallic aerogels by a simple one-step in situ reduction-gelation approach, which exhibits strain effects and electron transfer to create a remarkable HER activity and stability in an alkaline environment. The surface strain induced by the bimetallic segregated structure shifts the d-band center downward, enhancing catalysis by balancing the processes of water dissociation, OH* adsorption, and H* adsorption. Specifically, the optimized catalyst shows low overpotentials of only 24.1 mV at a current density of 10 mA cm-2 in alkaline electrolytes, surpassing commercial Pt/C. This study can contribute to the understanding of strain engineering in bimetallic electrocatalysts for HER at the atomic scale.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...