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1.
Chemistry ; : e202401074, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697944

RESUMO

The backwardness of n-type organic semiconductors still exists compared with the p-type counterparts. Thus, the development of high-performance n-type organic semiconductors is of great importance for organic electronic devices and their integrated circuits. In recent years, azabenzannulated perylene diimide (PDI), as one of immense bay-region-annulated PDI derivatives, has drawn considerable attentions. However, the electronic mobilities of azabenzannulated PDI derivatives are barely satisfactory. In this contribution, the peripheral benzene ring in azabenzannulated PDI 2 was fused to the ortho position by intermolecular C-H arylation cyclization. This endows the resultant azabenzannulated PDI 4 a planar configuration as well as electron deficient pentagonal ring. As a result, the electronic mobility of 4 is almost two orders of magnitude higher than that of the nonfused azabenzannulated PDI 2. This work shall pave a new avenue in elevating the performance of azabenzannulated PDI in organic electronics.

2.
Front Immunol ; 15: 1385696, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38770013

RESUMO

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.


Assuntos
Injúria Renal Aguda , Modelos Animais de Doenças , Lectinas Tipo C , Macrófagos , Proteínas de Membrana , Camundongos Knockout , Neutrófilos , Insuficiência Renal Crônica , Animais , Lectinas Tipo C/metabolismo , Lectinas Tipo C/genética , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Camundongos , Insuficiência Renal Crônica/imunologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Masculino , Inflamação/imunologia , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Fibrose , Progressão da Doença
3.
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
4.
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.

5.
Eur J Pediatr ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652266

RESUMO

It is unclear whether there is any postnatal abnormality in brainstem auditory function in late preterm small-for-gestational-age (SGA) infants. We investigated the functional integrity of the brainstem auditory pathway at 4 months after term in late preterm SGA infants and defined differences from appropriate-for-gestational age (AGA) infants. The maximum length sequence brainstem evoked response (MLS BAER) was recorded and analyzed in 24 SGA (birthweight < 3rd centile) infants and 28 AGA infants (birthweight > 10th centile). All infants were born at 33-36-week gestation without major perinatal and postnatal problems. We found that I-V interval in SGA infants was shorter than in AGA infants at higher click rates and significantly shorter at the highest rate of 910/s. Of the two smaller intervals, I-III interval was significantly shorter in SGA infants than in AGA infants at higher click rates of 455 and 910/s clicks, whereas III-V interval was similar in the two groups. The III-V/I-III interval ratio in SGA infants tended to be greater than in AGA infants at all rates and was significantly greater at 455 and 910/s clicks. The slope of I-III interval-rate functions in SGA infants was moderately smaller than in AGA infants.  Conclusions: The main and fundamental difference between late preterm SGA and AGA infants was a significant shortening in the MLS BAER I-III interval in SGA infants at higher click rates, suggesting moderately faster neural conduction in the caudal brainstem regions. Postnatal neural maturation in the caudal brainstem regions is moderately accelerated in late preterm SGA infants. What is Known: • At 40 weeks of postconceptional age, late preterm SGA infants manifested a mild delay in neural conduction in the auditory brainstem. What is New: • At 56 weeks of postconceptional age, late preterm SGA infants manifested moderately faster neural conduction in the caudal brainstem regions. • Postnatal neural maturation is moderately accelerated in the caudal brainstem regions of late preterm SGA infants.

6.
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
7.
Heliyon ; 10(8): e29784, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38681589

RESUMO

This study investigated the effects of partially replacing corn with elephant grass dry matter (air drass) on growth performance, serum parameters, carcass traits, and nutrient digestibility in geese. A total of 360 one-day-old Hortobágyi geese were randomly divided into three groups: control (basic diet), 12 % elephant grass, and 24 % elephant grass. The geese were raised for 70 days. The results showed that compared to the control, 12 % elephant grass had no adverse effects on final body weight, feed/gain ratio, mortality, serum liver and kidney function markers. However, 24 % elephant grass significantly reduced the final body weight (P < 0.001) and feed/gain ratio (P = 0.026) compared to the control group. Both experiment groups had decreased serum aspartate aminotransferase (P < 0.001), alanine aminotransferase (P < 0.001), alkaline phosphatase (P < 0.001), triglycerides (P < 0.001), and total cholesterol (P < 0.001). The addition of 12 % and 24 % elephant grass reduced abdominal fat (P = 0.002), but it had no significant effect on slaughter rate, half-bore rate, full-bore rate, breast muscle rate and leg muscle rate. For nutrient digestibility, 12 % elephant grass improved neutral detergent fiber digestibility compared to the control group (P = 0.026). The 24 % grass group had reduced Ca absorption (P = 0.020). Overall, the findings suggest that partially replacing corn with 12 % elephant grass in goose diet can maintain growth performance and carcass traits.It also has no negative effect on nutrient digestibility while improving serum parameters.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38684611

RESUMO

Sustainable manufacturing is crucial to achieving carbon neutrality targets. However, research on the sustainability of manufacturing systems is limited, and high consumption, low efficiency, and high emissions have resulted in high resource consumption and rapid environmental degradation. Therefore, it is of great importance to establish an evaluation and improvement indicator system conducive to sustainable development. To this end, this study developed a data-driven methodology for evaluating and enhancing the sustainability of manufacturing systems. Manufacturing system production process data, with data dimensions unified via the emergy method, were used to construct a sustainable development evaluation model that includes four perspectives: economy, environment, society, and sustainability. The model was applied to a flange production workshop in China to analyze the interrelation mechanisms among energy consumption, resource consumption, and environmental pollution, and identify optimization schemes to improve sustainability. After implementing these optimization schemes, the emergy yield rate (EYR) of the flange increased by 23.40%, the environmental load rate (ELR) decreased by 19.03%, the per capita emergy (EPP) increased by 6.88%, and the emergy-based sustainability index (ESI) increased by 52.76%. The method presented herein offers a novel and effective tool to analyze and visualize sustainable development in manufacturing systems and identify the relationship between technology and management in the manufacturing industry; however, this method is based on historical data and rules, and lacks of flexible response to unknown situations. The results provide a reference for enterprises to achieve sustainable and lean manufacturing.

9.
Environ Pollut ; 349: 123959, 2024 May 15.
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.


Assuntos
Exposição Ambiental , Resistência à Insulina , Ácidos Ftálicos , Humanos , Feminino , Masculino , Ácidos Ftálicos/metabolismo , Adulto , Pessoa de Meia-Idade , Exposição Ambiental/estatística & dados numéricos , Disruptores Endócrinos/metabolismo , Organofosfatos/metabolismo , Gordura Abdominal/metabolismo , Poluentes Ambientais/metabolismo , Ésteres/metabolismo , Retardadores de Chama/metabolismo , Adulto Jovem , Inquéritos Nutricionais , Fatores Sexuais
10.
Acta Med Okayama ; 78(2): 107-113, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38688828

RESUMO

Vertical transmission of hepatitis B virus (HBV), especially in Asia, is a key target in the global elimination of HBV. This study assessed the effects of tenofovir disoproxil fumarate (TDF) in pregnant women for mother-to-infant transmission of HBV. A total of 122 pregnant women at our hospital met the inclusion criteria for high HBV DNA viral loads. They were randomly divided into TDF-treatment (n=70) and placebo (n=52) groups. Maternal liver function and serum HBV DNA load were tested before and after treatment. Clinical and laboratory data of infants were assayed at delivery and 7-months post-partum visit and compared between the two groups. There was no difference in clinical characteristics of participants between the two groups. There were no significant differences in liver function markers, including alanine aminotransferase, total bilirubin, blood creatinine, and blood urea nitrogen levels before and after TDF treatment. The serum HBV DNA viral load of the TDF-treated group became significantly lower than those of the control group and their own pre-medication levels. Infants showed no significant difference in body growth, including weight, height, head size, and five-min Apgar score. At 7 months after birth, 94.29% of infants in the TDF group and 86.54% of control-group infants had protective HBsAb levels ≥ 10 mIU/ml (p>0.05). The HBV infection rate of infants in the TDF-treated group was lower than that in the non-treated group. In high-HBV-DNA-load pregnant women, TDF administered from 28 weeks gestational age to delivery was associated with a lower risk of mother-to-infant transmission of HBV.


Assuntos
Antivirais , Hepatite B , Transmissão Vertical de Doenças Infecciosas , Complicações Infecciosas na Gravidez , Tenofovir , Carga Viral , Humanos , Feminino , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Tenofovir/uso terapêutico , Adulto , Hepatite B/transmissão , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Recém-Nascido , Carga Viral/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , DNA Viral/sangue
11.
Nat Commun ; 15(1): 3301, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671004

RESUMO

Diphthamide is a modified histidine residue unique for eukaryotic translation elongation factor 2 (eEF2), a key ribosomal protein. Loss of this evolutionarily conserved modification causes developmental defects through unknown mechanisms. In a patient with compound heterozygous mutations in Diphthamide Biosynthesis 1 (DPH1) and impaired eEF2 diphthamide modification, we observe multiple defects in neural crest (NC)-derived tissues. Knockin mice harboring the patient's mutations and Xenopus embryos with Dph1 depleted also display NC defects, which can be attributed to reduced proliferation in the neuroepithelium. DPH1 depletion facilitates dissociation of eEF2 from ribosomes and association with p53 to promote transcription of the cell cycle inhibitor p21, resulting in inhibited proliferation. Knockout of one p21 allele rescues the NC phenotypes in the knockin mice carrying the patient's mutations. These findings uncover an unexpected role for eEF2 as a transcriptional coactivator for p53 to induce p21 expression and NC defects, which is regulated by diphthamide modification.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21 , Histidina , Histidina/análogos & derivados , Antígenos de Histocompatibilidade Menor , Crista Neural , Fator 2 de Elongação de Peptídeos , Proteína Supressora de Tumor p53 , Proteínas Supressoras de Tumor , Animais , Crista Neural/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Humanos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Camundongos , Fator 2 de Elongação de Peptídeos/metabolismo , Fator 2 de Elongação de Peptídeos/genética , Histidina/metabolismo , Ribossomos/metabolismo , Mutação , Proliferação de Células , Xenopus laevis , Feminino , Técnicas de Introdução de Genes , Xenopus , Masculino , Camundongos Knockout
12.
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
13.
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.

14.
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.

15.
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
16.
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
17.
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.

18.
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
19.
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.

20.
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
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