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1.
Neural Regen Res ; 20(3): 632-645, 2025 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38886930

RESUMO

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as 'cell polarization.' There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations (microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

2.
Plants (Basel) ; 13(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38931057

RESUMO

This research aimed to explore the diverse phenotypic characteristics of moso bamboo in China and pinpoint essential characteristics of moso bamboo. In this study, 63 grids were selected using the grid method to investigate 28 phenotypic traits of moso bamboo across the entire distribution area of China. The results suggest that the phenotypic traits of moso bamboo exhibit rich diversity, with coefficients of variation ranging from 5.87% to 36.57%. The phenotypic traits of moso bamboo showed varying degrees of correlation. A principal component analysis was used to identify seven main phenotypic trait indicators: diameter at breast height (DBH), leaf area (LA), leaf weight (LW), branch-to-leaf ratio (BLr), leaf moisture content (Lmc), wall-to-cavity ratio (WCr), and node length at breast height (LN), which accounted for 81.64% of the total information. A random forest model was used, which gave good results to validate the results. The average combined phenotypic trait value (D-value) of most germplasm was 0.563. The highest D-value was found in Wuyi 1 moso in Fujian (0.803), while the lowest D-value was observed in Pingle 2 moso in Guangxi (0.317). The clustering analysis of phenotypic traits classified China's moso bamboo germplasm into four groups. Group I had the highest D-value and is an important candidate germplasm for excellent germplasm screening.

3.
Phys Rev Lett ; 132(20): 206401, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829092

RESUMO

Coexisting orders are key features of strongly correlated materials and underlie many intriguing phenomena from unconventional superconductivity to topological orders. Here, we report the coexistence of two interacting charge-density-wave (CDW) orders in EuTe_{4}, a layered crystal that has drawn considerable attention owing to its anomalous thermal hysteresis and a semiconducting CDW state despite the absence of perfect Fermi surface nesting. By accessing unoccupied conduction bands with time- and angle-resolved photoemission measurements, we find that monolayers and bilayers of Te in the unit cell host different CDWs that are associated with distinct energy gaps. The two gaps display dichotomous evolutions following photoexcitation, where the larger bilayer CDW gap exhibits less renormalization and faster recovery. Surprisingly, the CDW in the Te monolayer displays an additional momentum-dependent gap renormalization that cannot be captured by density-functional theory calculations. This phenomenon is attributed to interlayer interactions between the two CDW orders, which account for the semiconducting nature of the equilibrium state. Our findings not only offer microscopic insights into the correlated ground state of EuTe_{4} but also provide a general nonequilibrium approach to understand coexisting, layer-dependent orders in a complex system.

4.
Trends Biochem Sci ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38880687

RESUMO

The dynamics behavior of a protein is essential for its functionality. Here, Doucet et al. demonstrate how the evolutionary analysis of conformational pathways within a protein family serves to identify common core scaffolds that accommodate branch-specific functional regions controlled by flexibility switches, offering a model for evolutionary-dynamics based protein design.

5.
Nat Commun ; 15(1): 4743, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834672

RESUMO

Recent theoretical studies have suggested that transition metal perovskite oxide membranes can enable surface phonon polaritons in the infrared range with low loss and much stronger subwavelength confinement than bulk crystals. Such modes, however, have not been experimentally observed so far. Here, using a combination of far-field Fourier-transform infrared (FTIR) spectroscopy and near-field synchrotron infrared nanospectroscopy (SINS) imaging, we study the phonon polaritons in a 100 nm thick freestanding crystalline membrane of SrTiO3 transferred on metallic and dielectric substrates. We observe a symmetric-antisymmetric mode splitting giving rise to epsilon-near-zero and Berreman modes as well as highly confined (by a factor of 10) propagating phonon polaritons, both of which result from the deep-subwavelength thickness of the membranes. Theoretical modeling based on the analytical finite-dipole model and numerical finite-difference methods fully corroborate the experimental results. Our work reveals the potential of oxide membranes as a promising platform for infrared photonics and polaritonics.

6.
Food Chem ; 457: 140102, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38905823

RESUMO

Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been widely used for microbial analysis. However, due to the impenetrable shell of fungi the direct identification of fungi remains challenges. Targeting on this problem, the yeast Saccharomyces cerevisiae (S. cerevisiae) was selected as a model fungus, and a new fungal cell membrane disruption reagent C18-G1 was used before MALDI-MS detection. As a result, much more intensive peaks which distributed in wider m/z range of S. cerevisiae have been identified in comparison with the use of traditional fungal pretreatment methods. Furthermore, a differential peak at m/z 4993 between two subspecies of S. cerevisiae has been identified. The corresponding protein with exclusive sequence of the specific peak was obtained based on MS/MS fragments and database searching. In addition, the method was successfully applied for the discrimination of four commercial yeasts.

7.
Front Cardiovasc Med ; 11: 1358066, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38720918

RESUMO

Background: The prevalence of Type 2 Diabetes Mellitus (T2D) and its significant role in increasing Coronary Heart Disease (CHD) risk highlights the urgent need for effective CHD screening within this population. Despite current advancements in T2D management, the complexity of cardiovascular complications persists. Our study aims to develop a comprehensive CHD screening model for T2D patients, employing multimodal data to improve early detection and management, addressing a critical gap in clinical practice. Methods: We analyzed data from 699 patients, including 471 with CHD (221 of these also had T2D) and a control group of 228 without CHD. Employing strict diagnostic criteria, we conducted significance testing and multivariate analysis to identify key indicators for T2D-CHD diagnosis. This led to the creation of a neural network model using 21 indicators and a logistic regression model based on an 8-indicator subset. External validation was performed with an independent dataset from an additional 212 patients to confirm the models' generalizability. Results: The neural network model achieved an accuracy of 90.7%, recall of 90.78%, precision of 90.83%, and an F-1 score of 0.908. The logistic regression model demonstrated an accuracy of 90.13%, recall of 90.1%, precision of 90.22%, and an F-1 score of 0.9016. External validation reinforced the models' reliability and effectiveness in broader clinical settings. Conclusion: Our AI-driven diagnostic models significantly enhance early CHD detection and management in T2D patients, offering a novel, efficient approach to addressing the complex interplay between these conditions. By leveraging advanced analytics and comprehensive patient data, we present a scalable solution for improving clinical outcomes in this high-risk population, potentially setting a new standard in personalized care and preventative medicine.

8.
Org Lett ; 26(20): 4218-4223, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38747898

RESUMO

Enamides and their derivatives are prominent bioactive pharmacophores found in various bioactive molecules. Herein we report a palladium-catalyzed oxidative N-α,ß-dehydrogenation of amides to produce a range of enamides with high yields and excellent tolerance toward different functional groups. Mechanistic studies indicate that the reaction involves allylic C(sp3)-H activation followed by ß-H elimination. The effectiveness of this approach is demonstrated through late-stage functionalization of bioactive molecules and the synthesis of valuable compounds through product elaboration.

9.
Environ Pollut ; 351: 124099, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38703980

RESUMO

Rivers play a significant role in the global nitrous oxide (N2O) budget. However, the microbial sources and sinks of N2O in river systems are not well understood or quantified, resulting in the prolonged neglect of nitrification. This study investigated the isotopic signatures of N2O, thereby quantifying the microbial source of N2O production and the degree of N2O reduction in the Yellow River. Although denitrification has long been considered to be the dominant pathway of N2O production in rivers, our findings indicated that denitrification only accounted for 18.3% (8.2%-43.0%) of the total contribution to N2O production in the Yellow River, with 50.2%-80.2% being concurrently reduced. The denitrification contribution to N2O production (R2 = 0.44, p < 0.01) and N2O reduction degree (R2 = 0.70, p < 0.01) were positively related to the dissolved organic carbon (DOC) content. Similar to urban rivers and eutrophic lakes, denitrification was the primary process responsible for N2O production (43.0%) in certain reaches with high organic content (DOC = 5.29 mg/L). Nevertheless, the denitrification activity was generally constrained by the availability of electron donors (average DOC = 2.51 mg/L) throughout the Yellow River basin. Consequently, nitrification emerged as the primary contributor in the well-oxygenated Yellow River. Additionally, our findings further distinguished the respective contribution of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to N2O emissions. Although AOB dominated the N2O production in the Yellow River, the AOA specie abundance (AOA/(AOA + AOB)) contributed up to 32.6%, which resulted in 25.6% of the total nitrifier-produced N2O, suggesting a significant occurrence of AOA in the oligotrophic Yellow River. Overall, this study provided a non-invasive approach for quantifying the microbial sources and sinks to N2O emissions, and demonstrated the substantial role of nitrification in the large oligotrophic rivers.


Assuntos
Desnitrificação , Monitoramento Ambiental , Nitrificação , Óxido Nitroso , Rios , Óxido Nitroso/análise , Rios/química , China , Poluentes Atmosféricos/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/metabolismo , Bactérias/metabolismo
10.
Mol Neurobiol ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38743209

RESUMO

Intracerebral hemorrhage (ICH) is a subtype of stroke with the highest fatality and disability rate. Up to now, commonly used first-line therapies have limited value in improving prognosis. Angiogenesis is essential to neurological recovery after ICH. Recent studies have shown that microRNA-451(miR-451) plays an important role in angiogenesis by regulating the function of vascular endothelial cells. We found miR-451 was significantly decreased in the peripheral blood of ICH patients in the acute stage. Based on the clinical findings, we conducted this study to investigate the potential regulatory effect of miR-451 on angiogenesis after ICH. The expression of miR-451 in ICH mouse model and in a hemin toxicity model of human brain microvascular endothelial cells (hBMECs) was decreased the same as in ICH patients. MiR-451 negatively regulated the proliferation, migration, and tube formation of hBMECs in vitro. MiR-451 negatively regulated the microvessel density in the perihematoma tissue and affected neural functional recovery of ICH mouse model. Knockdown of miR-451 could recovered tight junction and protect the integrity of blood-brain barrier after ICH. Based on bioinformatic programs, macrophage migration inhibitory factor (MIF) was predicted to be the target gene and identified to be regulated by miR-451 inhibiting the protein translation. And p-AKT and p-ERK were verified to be downstream of MIF in angiogenesis. These results all suggest that miR-451 will be a potential target for regulating angiogenesis in ICH.

11.
J Exp Clin Cancer Res ; 43(1): 143, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745179

RESUMO

BACKGROUND: Sorafenib is a standard first-line treatment for advanced hepatocellular carcinoma (HCC), yet its effectiveness is often constrained. Emerging studies reveal that sorafenib triggers ferroptosis, an iron-dependent regulated cell death (RCD) mechanism characterized by lipid peroxidation. Our findings isolate the principal target responsible for ferroptosis in HCC cells and outline an approach to potentially augment sorafenib's therapeutic impact on HCC. METHODS: We investigated the gene expression alterations following sgRNA-mediated knockdown induced by erastin and sorafenib in HCC cells using CRISPR screening-based bioinformatics analysis. Gene set enrichment analysis (GSEA) and the "GDCRNATools" package facilitated the correlation studies. We employed tissue microarrays and cDNA microarrays for validation. Ubiquitination assay, Chromatin immunoprecipitation (ChIP) assay, RNA immunoprecipitation (RIP) assay, and dual-luciferase reporter assay were utilized to delineate the specific mechanisms underlying ferroptosis in HCC cells. RESULTS: Our study has revealed that pleiomorphic adenoma gene 1 (PLAG1), a gene implicated in pleomorphic adenoma, confers resistance to ferroptosis in HCC cells treated with sorafenib. Sorafenib leads to the opposite trend of protein and mRNA levels of PLAG1, which is not caused by affecting the stability or ubiquitination of PLAG1 protein, but by the regulation of PLAG1 at the transcriptional level by its upstream competitive endogenous long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1). Data from 139 HCC patients showed a significant positive correlation between PLAG1 and GPX4 levels in tumor samples, and PLAG1 is instrumental in redox homeostasis by driving the expression of glutathione peroxidase 4 (GPX4), the enzyme that reduces lipid peroxides (LPOs), which further leads to ferroptosis inhibition. CONCLUSIONS: Ferroptosis is a promising target for cancer therapy, especially for patients resistant to standard chemotherapy or immunotherapy. Our findings indicate that PLAG1 holds therapeutic promise and may enhance the efficacy of sorafenib in treating HCC.


Assuntos
Carcinoma Hepatocelular , Proteínas de Ligação a DNA , Ferroptose , Neoplasias Hepáticas , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Sorafenibe , Humanos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Ferroptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Camundongos , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Masculino
12.
Biomed Pharmacother ; 176: 116807, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38795644

RESUMO

Metabolic syndrome (MetS) is a widespread and multifactorial disorder, and the study of its pathogenesis and treatment remains challenging. Autophagy, an intracellular degradation system that maintains cellular renewal and homeostasis, is essential for maintaining antimicrobial defense, preserving epithelial barrier integrity, promoting mucosal immune response, maintaining intestinal homeostasis, and regulating gut microbiota and microbial metabolites. Dysfunctional autophagy is implicated in the pathological mechanisms of MetS, involving insulin resistance (IR), chronic inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, with IR being a predominant feature. The study of autophagy represents a valuable field of research with significant clinical implications for identifying autophagy-related signals, pathways, mechanisms, and treatment options for MetS. Given the multifactorial etiology and various potential risk factors, it is imperative to explore the interplay between autophagy and gut microbiota in MetS more thoroughly. This will facilitate the elucidation of new mechanisms underlying the crosstalk among autophagy, gut microbiota, and MetS, thereby providing new insights into the diagnosis and treatment of MetS.


Assuntos
Autofagia , Microbioma Gastrointestinal , Resistência à Insulina , Síndrome Metabólica , Autofagia/fisiologia , Microbioma Gastrointestinal/fisiologia , Síndrome Metabólica/microbiologia , Síndrome Metabólica/metabolismo , Humanos , Resistência à Insulina/fisiologia , Animais , Transdução de Sinais
13.
Heart Lung ; 66: 86-93, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38593678

RESUMO

BACKGROUND: Previous observational studies have suggested associations between Coronary Heart Disease (CHD) and Mental Health Disorders (MHD). However, the causal nature of these relationships has remained elusive. OBJECTIVE: The purpose of this study is to elucidate the causal relationships between eight distinct types of CHD and six types of MHD using Mendelian randomization (MR) analysis. METHODS: The MR analysis employed a suite of methods including inverse variance-weighted (IVW), MR-Egger, weighted mode, weighted median, and simple mode techniques. To assess heterogeneity, IVW and MR-Egger tests were utilized. MR-Egger regression also served to investigate potential pleiotropy. The stability of IVW results was verified by leave-one-out sensitivity analysis. RESULTS: We analyzed data from over 2,473,005 CHD and 803,801 MHD patients, informed by instrumental variables from large-scale genomic studies on European populations. The analysis revealed a causal increase in the risk of Major Depressive Disorder and Mania associated with Coronary Artery Disease and Myocardial Infarction. Heart Failure was found to causally increase the risk for Bipolar Disorder and Schizophrenia. Atrial Fibrillation and Ischemic Heart Diseases were positively linked to Generalized Anxiety Disorder and Mania, respectively. There was no significant evidence of an association between Hypertensive Heart Disease, Hypertrophic Cardiomyopathy, Pulmonary Heart Disease, and MHD. Reverse MR analysis indicated that MHD do not serve as risk factors for CHD. CONCLUSIONS: The findings suggest that specific types of CHD may act as risk factors for certain MHDs. Consequently, incorporating psychological assessments into the management of patients with CHD could be advantageous.


Assuntos
Doença das Coronárias , Análise da Randomização Mendeliana , Transtornos Mentais , Humanos , Análise da Randomização Mendeliana/métodos , Doença das Coronárias/psicologia , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Doença das Coronárias/complicações , Fatores de Risco , Transtornos Mentais/epidemiologia , Transtornos Mentais/genética , Masculino , Feminino
14.
Inorg Chem ; 63(18): 8171-8179, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38655575

RESUMO

Although 1,10-phenanthroline has been proven to hold a strong complexing capacity for f-block elements and their derivatives have been applied in many fields, research on more highly or completely rigid phenanthroline ligands is still rare due to the challenging syntheses. Here, we reported three tetradentate ligands 2,9-di(pyridin-2-yl)-1,10-phenanthroline (L1), 12-(pyridin-2-yl)-5,6-dihydroquinolino[8,7b][1,10]phenanthroline (L2), and 5,6,11,12-tetrahydrobenzo[2,1-b:3,4-b']bis([1,10]phenanthroline) (L3) with increasing preorganization on the side chain; among which, L3 is fully preorganized. Their complexation reactions with Eu(III) were systematically investigated by electrospray ionization mass spectrometry (ESI-MS), UV-vis titrations, and single-crystal structures. It is found that all three ligands form only 1:1 M/L complexes with Eu(III). The single-crystal structures revealed that the three ligands hold similar coordination modes, while their stability constants determined by UV-vis titrations were L3 (4.80 ± 0.01) > L2 (4.38 ± 0.01) > L1 (3.88 ± 0.01). This trend is supported not only by the thermodynamic stability of rigid ligands compared to free ligands but also by the conclusion that rigid ligands exhibit faster reaction rates (lower energy barrier) than free ligands kinetically. This work is helpful in providing theoretical guidance for the subsequent development of highly preorganized chelating ligands with strong coordination ability and high selectivity for f-block elements.

15.
Ren Fail ; 46(1): 2344655, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38685582

RESUMO

The association between blood flow rate (BFR) and clinical outcomes in patients undergoing maintenance hemodialysis (MHD) is inconclusive. This retrospective study included 175 patients undergoing MHD treatment between July 2015 and March 2022, divided into two groups based on time-averaged effective blood flow rate (eBFR) median value. We investigated arteriovenous fistula (AVF) outcomes and the association of eBFR with all-cause mortality and new major adverse cardiovascular events (MACE). Mean ± SD and median time-averaged eBFR values were 276 ± 24 and 275 mL/min, respectively. After adjusting for relevant factors including age, sex, vintage, diabetes, CVD, receiving hemodiafiltration (HDF) treatment and spKt/V, Cox models indicated a low time-averaged eBFR (≤ 275 ml/min) was associated with increased risks of all-cause mortality (hazard ratio [HR] 14.18; 95% confidence interval [CI], 3.14-64.1) and new MACE (HR 3.76; 95% CI, 1.91-7.40) in MHD patients. Continuous Cox models demonstrated each 20 ml/min increase in eBFR linked to a 63% decrease in the risk of all-cause mortality (HR: 0.37, 95% CI: 0.23-0.59) and a 38% decrease in the occurrence of new MACE (HR: 0.62, 95% CI: 0.46-0.84). There was no significant difference in AVF outcomes between the two groups. Our study noted higher eBFR (>275 mL/min) is associated with lower risks of both all-cause mortality and new MACE compared with low eBFR (≤275 mL/min). Increased eBFR is not associated with a higher risk of AVF failure.


Assuntos
Falência Renal Crônica , Diálise Renal , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Velocidade do Fluxo Sanguíneo , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Modelos de Riscos Proporcionais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Resultado do Tratamento , Hemodiafiltração/métodos , Hemodiafiltração/efeitos adversos
16.
Environ Sci Pollut Res Int ; 31(20): 28939-28949, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38564128

RESUMO

Encouraging the recycling of plastic packaging materials in express delivery is a necessary step toward environmentally friendly industrial development. In this study, we present a framework for analyzing the flow of materials in express plastic packaging, from production and manufacturing to consumption and recycling. In examining the use of recycled materials in post-consumer express plastic packaging and the destination of consumer packaging waste in 2020 and 2021, we found that 44.4% (1613.6 Gg) of the studied express plastic packaging was incinerated. Additionally, approximately 1296.6 Gg of express plastic packaging flowed into rural areas. Our calculations showed that the ΔRSE in 2020 was 15.1%, and on the condition that 25% separated collection with 80% recycling, ΔRSE would be - 0.5%. Results verified that separated collection is an important step in the recycling strategy for packaging materials. Survey data from universities in Beijing indicate that currently, 26% of college students are participating in the separate collection of packaging.


Assuntos
Entropia , Plásticos , Embalagem de Produtos , Reciclagem , China
17.
Nat Genet ; 56(5): 846-860, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38641644

RESUMO

Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.


Assuntos
Metilação de DNA , População do Leste Asiático , Locos de Características Quantitativas , Feminino , Humanos , Masculino , População do Leste Asiático/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Herança Multifatorial , Polimorfismo de Nucleotídeo Único
18.
Aging Dis ; 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38607739

RESUMO

End-stage liver disease (ESLD), stemming from a spectrum of chronic liver pathologies including chronic liver failure, acute cirrhosis decompensation and hepatocellular carcinoma, imposes a significant global healthcare burden. Liver transplantation (LT) remains the only treatment for ESLD. However, the escalating mortality on transplant waitlists has prompted the utilization of marginal liver grafts in LT procedures. These grafts primarily encompass elderly livers, steatotic livers, livers from donation after circulatory death, split livers and those infected with the hepatitis virus. While the expansion of the donor pool offers promise, it also introduces concomitant risks. These encompass graft failure, biliary and cardiovascular complications, the recurrence of liver disease and reduced patient and graft survival. Consequently, various established strategies, ranging from improved donor-recipient matching to surgical interventions, have emerged to mitigate these risks. This article undertakes a comprehensive assessment of the current landscape, evaluating the viability of diverse marginal liver grafts. Additionally, it synthesizes approaches aimed at enhancing the quality of such marginal liver grafts. The overarching objective is to augment the donor pool and ameliorate the risk factors associated with the shortage of liver grafts.

19.
iScience ; 27(5): 109682, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38660403

RESUMO

The aryl hydrocarbon receptor (AhR) pathway may play an important role in the regulation of osteoclasts, but there are still conflicting studies on this aspect, and the specific mechanism of action has not been fully elucidated. Therefore, we conducted this study to find a drug to treat osteoporosis that targets AhR. We found that StemRegenin 1 inhibited RANKL-induced osteoclastogenesis in a concentration-dependent and time-dependent manner. Through further experiments, we found that SR1 can inhibit nuclear transcription of AhR and inhibit c-src phosphorylation, and ultimately regulates the activation of the NF-κB and p-ERK/mitogen-activated protein kinase pathways. Therefore, for the first time, we discovered the way in which the AhR-c-src-NF-κB/p-ERK MAPK-NFATc1 signaling pathway regulates the expression of osteoclast differentiation-associated proteins. Finally, SR1 was shown to successfully reverse bone loss in OVX mice. These studies provide us with ideas for finding new way to treat osteoporosis.

20.
Am J Transl Res ; 16(3): 864-872, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38586099

RESUMO

OBJECTIVE: To analyze the efficacy of arthroscopic treatment for patients with rotator cuff injuries and frozen shoulder combined with rotator cuff injuries and assess the factors influencing patient prognosis. METHODS: A retrospective analysis was performed on 85 patients who underwent arthroscopic surgery at Hanzhong Central Hospital between October 2016 and October 2021, including 42 patients treated for rotator cuff injuries alone (Group A), and 43 patients for frozen shoulder combined with rotator cuff injuries (Group B). Both groups underwent general anesthesia with controlled hypotension during surgery. Treatment outcomes, including shoulder joint functional scores, pain scores, shoulder joint range of motion, and muscle strength were assessed and compared between the two groups before treatment, as well as at 2 weeks and 2 months post-treatment. Quality of life was also evaluated and compared at 2 months post-treatment. Patients were categorized into good and poor prognosis groups based on their outcome, and factors influencing patient prognosis were analyzed. RESULTS: Before treatment, both groups exhibited relatively low shoulder joint function scores and external rotation angles, coupled with higher pain scores; however, these differences were not significant between groups (all P>0.05). The surgery duration for Group B was notably longer than that of Group A (P<0.05). Nevertheless, there was no significant variance in intraoperative blood loss between the two groups (P>0.05). After a 2-week treatment duration, both groups demonstrated a significant improvement in shoulder joint function score, pain score, and shoulder joint range of motion compared to baseline, but with no statistically significant intergroup differences. However, two months after the treatment, patients in Group A exhibited marked improvements in shoulder joint function score, pain score, shoulder joint range of motion, and overall quality of life compared to Group B (all P<0.05). Furthermore, the therapeutic efficacy in Group A was superior to that in Group B at the 2-month follow-up (P<0.05). Age, comorbid diabetes, metabolic disorders such as thyroid dysfunction, and the extent of shoulder cuff injury were identified as independent risk factors influencing prognosis. CONCLUSION: Arthroscopic treatment is effective for both frozen shoulder combined with rotator cuff injury and rotator cuff injury alone, with better outcomes observed in patients with rotator cuff injury only. This technique warrants further promotion.

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