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1.
Artigo em Inglês | MEDLINE | ID: mdl-38827080

RESUMO

This study addresses rising incidence of pediatric venous thromboembolism by validating a VTE phenotype and developing a polygenic risk score (PRS) using UK Biobank data. Our findings demonstrate predictive value of the PRS, enhancing VTE risk assessment in clinical settings. Future steps involve integrating the PRS into risk stratification models.

2.
Heliyon ; 10(11): e31487, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38828323

RESUMO

Background: Cervical cancer is one of the most common malignancies in women worldwide. As a RING type ubiquitin ligase, SIAH2 has been reported to promote the progression of a variety of tumors by interacting with and targeting multiple chaperones and substrates. The aim of this study was to further identify the role and the related molecular mechanisms involved of SIAH2 in cervical carcinogenesis. Methods and results: Cellular assays in vitro showed that knockdown of SIAH2 inhibited the proliferation, migration and invasion of human cervical cancer cells C33A and SiHa, induced apoptosis, and increased the sensitivity to cisplatin treatment. Knockdown of SIAH2 also inhibited the epithelial-mesenchymal transition and activation of the Akt/mTOR signaling pathway in cervical cancer cells, which were detected by Western blot. Mechanistically, SIAH2, as a ubiquitin ligase, induced the ubiquitination degradation of GSK3ß degradation by using coIP. The results of complementation experiments further demonstrated that GSK3ß overexpression rescued the increase of cell proliferation and invasion caused by SIAH2 overexpression. Specific expression of SIAH2 appeared in precancerous and cervical cancer tissues compared to inflammatory cervical lesions tissues using immunohistochemical staining. The more SIAH2 was expressed as the degree of cancer progressed. SIAH2 was significantly highly expressed in cervical cancer tissues (44/55, 80 %) compared with precancerous tissues (18/69, 26.1 %). Moreover, the expression level of SIAH2 in cervical cancer tissues was significantly correlated with the degree of cancer differentiation, and cervical cancer tissues with higher SIAH2 expression levels were less differentiated. Conclusion: Targeting SIAH2 may be beneficial to the treatment of cervical cancer.

3.
Sci Rep ; 14(1): 12704, 2024 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830996

RESUMO

To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP-with the osteogenic active zone labelled by RUNX2-tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.


Assuntos
Anquilose , Células-Tronco Mesenquimais , Osteogênese , Transtornos da Articulação Temporomandibular , Animais , Células-Tronco Mesenquimais/metabolismo , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/genética , Anquilose/metabolismo , Anquilose/patologia , Anquilose/genética , Proteínas de Sinalização YAP/metabolismo , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/patologia , Ovinos , Proliferação de Células , Modelos Animais de Doenças , Diferenciação Celular , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Movimento Celular , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética
4.
J Exp Clin Cancer Res ; 43(1): 154, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822363

RESUMO

BACKGROUND: RNA modifications of transfer RNAs (tRNAs) are critical for tRNA function. Growing evidence has revealed that tRNA modifications are related to various disease processes, including malignant tumors. However, the biological functions of methyltransferase-like 1 (METTL1)-regulated m7G tRNA modifications in breast cancer (BC) remain largely obscure. METHODS: The biological role of METTL1 in BC progression were examined by cellular loss- and gain-of-function tests and xenograft models both in vitro and in vivo. To investigate the change of m7G tRNA modification and mRNA translation efficiency in BC, m7G-methylated tRNA immunoprecipitation sequencing (m7G tRNA MeRIP-seq), Ribosome profiling sequencing (Ribo-seq), and polysome-associated mRNA sequencing were performed. Rescue assays were conducted to decipher the underlying molecular mechanisms. RESULTS: The tRNA m7G methyltransferase complex components METTL1 and WD repeat domain 4 (WDR4) were down-regulated in BC tissues at both the mRNA and protein levels. Functionally, METTL1 inhibited BC cell proliferation, and cell cycle progression, relying on its enzymatic activity. Mechanistically, METTL1 increased m7G levels of 19 tRNAs to modulate the translation of growth arrest and DNA damage 45 alpha (GADD45A) and retinoblastoma protein 1 (RB1) in a codon-dependent manner associated with m7G. Furthermore, in vivo experiments showed that overexpression of METTL1 enhanced the anti-tumor effectiveness of abemaciclib, a cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor. CONCLUSION: Our study uncovered the crucial tumor-suppressive role of METTL1-mediated tRNA m7G modification in BC by promoting the translation of GADD45A and RB1 mRNAs, selectively blocking the G2/M phase of the cell cycle. These findings also provided a promising strategy for improving the therapeutic benefits of CDK4/6 inhibitors in the treatment of BC patients.


Assuntos
Neoplasias da Mama , Metiltransferases , RNA de Transferência , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Camundongos , Animais , Metiltransferases/metabolismo , Metiltransferases/genética , RNA de Transferência/genética , RNA de Transferência/metabolismo , Metilação , Linhagem Celular Tumoral , Proliferação de Células , Carcinogênese/genética , Pontos de Checagem do Ciclo Celular , Biossíntese de Proteínas , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus
5.
Front Immunol ; 15: 1402250, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855107

RESUMO

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters. Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% (P < 0.05). Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status.


Assuntos
Angioplastia com Balão , Biomarcadores , Hipertensão Pulmonar , Embolia Pulmonar , Humanos , Masculino , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Feminino , Biomarcadores/sangue , Pessoa de Meia-Idade , Embolia Pulmonar/sangue , Embolia Pulmonar/terapia , Idoso , Proteômica/métodos , Doença Crônica
6.
J Transl Med ; 22(1): 535, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840216

RESUMO

BACKGROUND: Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated. METHODS: We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS. RESULTS: We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation. CONCLUSIONS: S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS.


Assuntos
Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Mitocôndrias , NF-kappa B , Fosforilação Oxidativa , Síndrome do Desconforto Respiratório , Receptores de Esfingosina-1-Fosfato , Animais , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/metabolismo , Síndrome do Desconforto Respiratório/patologia , Receptores de Esfingosina-1-Fosfato/metabolismo , Receptores de Esfingosina-1-Fosfato/antagonistas & inibidores , NF-kappa B/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Fosforilação Oxidativa/efeitos dos fármacos , Masculino , Receptores de Lisoesfingolipídeo/metabolismo , Receptores de Lisoesfingolipídeo/antagonistas & inibidores , Humanos , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Camundongos , Inflamação/patologia , Células Endoteliais/metabolismo , Células Endoteliais/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Citocinas/metabolismo
7.
Heliyon ; 10(11): e31303, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38845938

RESUMO

Background: Patients with type 2 diabetes mellitus (T2DM) experience a decline in cardiac function, resulting in poor prognosis. Therefore, restoration of cardiac function and improvement of myocardial fibrosis is an important treatment goal for patients with T2DM. Material and methods: The chemical structure of oleanolic acid(OA) was downloaded from PubChem and uploaded to PharmMapper. GeneCards and OMIM databases were searched for genes related to OA and disease and plotted into a Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R software. Then, a mouse model of diabetes mellitus was established, and ELISA, echocardiographic analysis of cardiac function, TUNEL assay, and reactive oxygen species assay were performed. Results: Network pharmacology analysis identified the related targets and potential molecular mechanisms underlying the effects of OA in T2DM. ELISA, echocardiographic analysis of cardiac function, and TUNEL assay results showed that OA inhibits apoptosis and improves apoptotic indexes in mice with T2DM-induced myocardial injury. Conclusion: The results demonstrate the myocardial protective effect of OA in this mouse model.

8.
Artigo em Inglês | MEDLINE | ID: mdl-38850301

RESUMO

The dosing of fluconazole for young infants remains empirical because of the limited pharmacokinetic (PK) data. We aimed to establish a population PK model and assess the systematic exposure-response of commonly used regimens of fluconazole in Chinese infants. We included infants with a postnatal age of less than 120 days and received intravenous fluconazole. Both scheduled and scavenged plasma samples were collected, and fluconzaole concentration was determined by a validated ultra-performance liquid chromatography-tandem mass spectrometry assay. Population PK analysis was conducted using Phoenix NLME, and then Monte Carlo simulation was conducted to predict the probability of target attainment (PTA) of empirically used regimens of both prophylactic and therapeutic purposes. Based on 304 plasma samples from 183 young infants, fluconazole concentration data was best described by a one-compartment model with first-order elimination. Gestational Age (GA), postnatal age (PNA), and body weight (BW) were included in the final model as CL = 0.02*(GA/214)2.77*(PNA/13)0.24*exp(nCL); V = 1.56*(BW/1435)0.90*exp(nV). Model validation revealed the final model had qualified stability and acceptable predictive properties. Monte Carlo simulation indicated that under the same minimum inhibitory concentration (MIC) value and administration regimen, PTA decreased with GA and PNA. The commonly used prophylactic regimens can meet the clinical need, while higher doses might be needed for treatment of invasive candidiasis. This population PK model of fluconazole discriminated the impact of GA and PNA on CL and BW on V. Dosing adjustment was needed according to the GA and PNA of infants to achieve targeted exposures.

10.
J Chem Phys ; 160(17)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38748014

RESUMO

Fatty acids from cooking fumes and hypochlorous acid (HOCl) released from indoor cleaning adversely affect respiratory health, but the molecular-level mechanism remains unclear. Here, the effect of cooking oil fumes [palmitic acid (PA), oleic acid (OA), and linoleic acid (LA)] on lung model phospholipid (POPG) hydrochlorination mediated by HOCl at the air-water interface of the hanged droplets was investigated. Interfacial hydrochlorination of POPG was impeded by OA and LA, while that of POPG was facilitated by PA. The effect on POPG hydrochlorination increased with the decrease in oil fume concentration. A potential mechanism with respect to the chain length of these oil fumes, regardless of their saturation, was proposed. PA with a short carbon chain looses the POPG packing and leads to the exposure of the C=C double bonds of POPG, whereas OA and LA with a long carbon chain hinder HOCl from reaching the C=C bonds of POPG. These results for short chain and low concentration dependence suggest that the decay of oil fumes or the conversion of short-chain species by indoor interfacial chemistry might be adverse to lung health. These results provide insights into the relationship between indoor multicomponent pollutants and the respiratory system.


Assuntos
Poluição do Ar em Ambientes Fechados , Ácidos Graxos , Ácidos Graxos/química , Ácido Hipocloroso/química , Culinária , Fosfolipídeos/química
11.
Nat Struct Mol Biol ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769389

RESUMO

NADH/NAD+ redox balance is pivotal for cellular metabolism. Systematic identification of NAD(H) redox regulators, although currently lacking, would help uncover unknown effectors critically implicated in the coordination of growth metabolism. In this study, we performed a genome-scale RNA interference (RNAi) screen to globally survey the genes involved in redox modulation and identified the HES family bHLH transcription factor HES4 as a negative regulator of NADH/NAD+ ratio. Functionally, HES4 is shown to be crucial for maintaining mitochondrial electron transport chain (ETC) activity and pyrimidine synthesis. More specifically, HES4 directly represses transcription of SLC44A2 and SDS, thereby inhibiting mitochondrial choline oxidation and cytosolic serine deamination, respectively, which, in turn, ensures coenzyme Q reduction capacity for DHODH-mediated UMP synthesis and serine-derived dTMP production. Accordingly, inhibition of choline oxidation preserves mitochondrial serine catabolism and ETC-coupled redox balance. Furthermore, HES4 protein stability is enhanced under EGFR activation, and increased HES4 levels facilitate EGFR-driven tumor growth and predict poor prognosis of lung adenocarcinoma. These findings illustrate an unidentified mechanism, underlying pyrimidine biosynthesis in the intersection between serine and choline catabolism, and underscore the physiological importance of HES4 in tumor metabolism.

12.
Talanta ; 276: 126278, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38776776

RESUMO

Perfluoroalkyl substances (PFASs) are ubiquitous in the environment and even accumulate in the human body associated with their excellent stability and persistence. However, the effect and reaction mechanism at the molecular level on the cell phospholipid peroxidation remained unclear. In this work, the interfacial reaction of model phospholipids (POPG) intervened by per- and polyfluoroalkyl substances (PFASs) at the air-water interface of a hanged droplet exposed to ozone (O3) was investigated. Perfluorinated carboxylates and sulfonates were evaluated. Four-carbon PFASs promoted interfacial ozonolysis, but PFASs with longer carbon skeletons impeded this chemistry. A model concerning POPG packing was proposed and it was concluded that the interfacial chemistry was mediated by chain length rather than their functional groups. Four-carbon PFASs could couple into POPG ozonolysis by mainly reacting with aldehyde products along with minor Criegee intermediates, but this was not observed for longer PFASs. This is different from that condensed-phase Criegee intermediates preferred to reacting with per-fluoroalkyl carboxylic acids. These results provide insight into the adverse health of PFASs on cell peroxidation.

13.
BMC Genomics ; 25(1): 456, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730418

RESUMO

In this study, we investigated the codon bias of twelve mitochondrial core protein coding genes (PCGs) in eight Pleurotus strains, two of which are from the same species. The results revealed that the codons of all Pleurotus strains had a preference for ending in A/T. Furthermore, the correlation between codon base compositions and codon adaptation index (CAI), codon bias index (CBI) and frequency of optimal codons (FOP) indices was also detected, implying the influence of base composition on codon bias. The two P. ostreatus species were found to have differences in various base bias indicators. The average effective number of codons (ENC) of mitochondrial core PCGs of Pleurotus was found to be less than 35, indicating strong codon preference of mitochondrial core PCGs of Pleurotus. The neutrality plot analysis and PR2-Bias plot analysis further suggested that natural selection plays an important role in Pleurotus codon bias. Additionally, six to ten optimal codons (ΔRSCU > 0.08 and RSCU > 1) were identified in eight Pleurotus strains, with UGU and ACU being the most widely used optimal codons in Pleurotus. Finally, based on the combined mitochondrial sequence and RSCU value, the genetic relationship between different Pleurotus strains was deduced, showing large variations between them. This research has improved our understanding of synonymous codon usage characteristics and evolution of this important fungal group.


Assuntos
Uso do Códon , Genoma Mitocondrial , Pleurotus , Pleurotus/genética , Códon/genética , Composição de Bases , Especificidade da Espécie , Seleção Genética , Evolução Molecular , Variação Genética
14.
Urol Oncol ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38806387

RESUMO

Prostate cancer (PCa) is one of the most common tumors affecting men all over the world. PCa has brought a huge health burden to men around the world, especially for elderly men, but its pathogenesis is unclear. In prostate cancer, epigenetic inheritance plays an important role in the development, progression, and metastasis of the disease. An important role in cancer invasion and metastasis is played by matrix metalloproteinases (MMPs), zinc-dependent proteases that break down extracellular matrix. We review two important forms of epigenetic modification and the role of matrix metalloproteinases in tumor regulation, both of which may be of significant value as novel biomarkers for early diagnosis and prognosis monitoring. The author considers that both mechanisms have promising therapeutic applications for therapeutic agent research in prostate cancer, but that efforts should be made to mitigate or eliminate the side effects of drug therapy in order to maximize quality of life of patients. The understanding of epigenetic modification, MMPs, and their inhibitors in the functional regulation of prostate cancer is gradually advancing, it will provide a new technical means for the prevention of prostate cancer, early diagnosis, androgen-independent prostate cancer treatment, and drug research.

15.
Nat Commun ; 15(1): 4328, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773155

RESUMO

Parental experiences can affect the phenotypic plasticity of offspring. In locusts, the population density that adults experience regulates the number and hatching synchrony of their eggs, contributing to locust outbreaks. However, the pathway of signal transmission from parents to offspring remains unclear. Here, we find that transcription factor Forkhead box protein N1 (FOXN1) responds to high population density and activates the polypyrimidine tract-binding protein 1 (Ptbp1) in locusts. FOXN1-PTBP1 serves as an upstream regulator of miR-276, a miRNA to control egg-hatching synchrony. PTBP1 boosts the nucleo-cytoplasmic transport of pre-miR-276 in a "CU motif"-dependent manner, by collaborating with the primary exportin protein exportin 5 (XPO5). Enhanced nuclear export of pre-miR-276 elevates miR-276 expression in terminal oocytes, where FOXN1 activates Ptbp1 and leads to egg-hatching synchrony in response to high population density. Additionally, PTBP1-prompted nuclear export of pre-miR-276 is conserved in insects, implying a ubiquitous mechanism to mediate transgenerational effects.


Assuntos
Transporte Ativo do Núcleo Celular , Gafanhotos , MicroRNAs , Proteína de Ligação a Regiões Ricas em Polipirimidinas , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Gafanhotos/genética , Gafanhotos/metabolismo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Fatores de Transcrição Forkhead/genética , Óvulo/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Núcleo Celular/metabolismo , Oócitos/metabolismo
16.
J Oral Microbiol ; 16(1): 2345942, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38756148

RESUMO

Objective: To investigate the associations of the oral microbiome status with diabetes characteristics in elderly patients with type 2 diabetes mellitus. Methods: A questionnaire was used to assess age, sex, smoking status, drinking status, flossing frequency, T2DM duration and complications, and a blood test was used to determine the glycated haemoglobin (HbA1c) level. Sequencing of the V3-V4 region of the 16S rRNA gene from saliva samples was used to analyze the oral microbiome. Results: Differential analysis revealed that Streptococcus and Weissella were significantly enriched in the late-stage group, and Capnocytophaga was significantly enriched in the early-stage group. Correlation analysis revealed that diabetes duration was positively correlated with the abundance of Streptococcus (r= 0.369, p= 0.007) and negatively correlated with the abundance of Cardiobacterium (r= -0.337, p= 0.014), and the level of HbA1c was not significantly correlated with the oral microbiome. Network analysis suggested that the poor control group had a more complex microbial network than the control group, a pattern that was similar for diabetes duration. In addition, Streptococcus has a low correlation with other microorganisms. Conclusion: In elderly individuals, Streptococcus emerges as a potential biomarker linked to diabetes, exhibiting elevated abundance in diabetic patients influenced by disease exposure and limited bacterial interactions.

17.
Sci Total Environ ; 932: 173038, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38719055

RESUMO

Despite global concerns about metal(loid)s in atmospheric particulate matter (PM), the presence of metal(loid) resistance genes (MRGs) in PM remains unknown. Therefore, we conducted a comprehensive investigation of the metal(loid)s and associated MRGs in PMs in two seasons (summer and winter) in Xiamen, China. According to the geoaccumulation index (Igeo), most metal(loid)s, except for V and Mn, exhibited enrichment in PM, suggesting potential anthropogenic sources. By employing Positive Matrix Factorization (PMF) model, utilizing a dataset encompassing both total and bioaccessible metal(loid)s, along with backward trajectory simulations, traffic emissions were determined to be the primary potential contributor of metal(loid)s in summer, whereas coal combustion was observed to have a dominant contribution in winter. The major contributor to the carcinogenic risk of metal(loid)s in both summer and winter was predominantly attributed to coal combustion, which serves as the main source of bioaccessible Cr. Bacterial communities within PMs showed lower diversity and network complexity in summer than in winter, with Pseudomonadales being the dominant order. Abundant MRGs, including the As(III) S-adenosylmethionine methyltransferase gene (arsM), Cu(I)-translocating P-type ATPase gene (copA), Zn(II)/Cd(II)/Pb(II)-translocating P-type ATPase gene (zntA), and Zn(II)-translocating P-type ATPase gene (ziaA), were detected within the PMs. Seasonal variations were observed for the metal(loid) concentration, bacterial community structure, and MRG abundance. The bacterial community composition and MRG abundance within PMs were primarily influenced by temperature, rather than metal(loid)s. This research offers novel perspectives on the occurrence of metal(loid)s and MRGs in PMs, thereby contributing to the control of air pollution.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Material Particulado , Material Particulado/análise , Poluentes Atmosféricos/análise , China , Metais/análise , Estações do Ano , Atmosfera/química
18.
Angew Chem Int Ed Engl ; : e202401707, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38700007

RESUMO

The pursuit of high efficacy C-C coupling during the electrochemical CO2 reduction reaction remains a tremendous challenge owing to the high energy barrier of CO2 activation and insufficient coverage of the desired intermediates on catalytic sites. Inspired by the concept of capture-coupled CO2 activation, we fabricated quinone-grafted carbon nanofibers via an in situ oxidative carbonylation strategy. The quinone functionality of carbon nanofibers promotes the capture of CO2 followed by activation. At a current density of 400 mA cm-2, the Faradaic efficiency of ethylene reached 62.9 %, and a partial current density of 295 mA cm-2 was achieved on the quinone-rich carbon nanofibers. The results of in situ spectroscopy and theoretical calculations indicated that the remarkable selectivity enhancement in ethylene originates from the quinone structure, rather than the electronic properties of Cu particles. The interaction of quinone with CO2 increases the local *CO coverage and simultaneously hinders the co-adsorption of *H on Cu sites, which greatly reduces the energy barrier for C-C coupling and restrains subsequent *CO protonation. The modulation strategy involving specific oxygenated structure, as an independent degree of freedom, guides the design of functionalized carbon materials for tailoring the selectivity of desired products during the CO2 capture and reduction.

19.
Asia Pac J Ophthalmol (Phila) ; 13(3): 100072, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38789041

RESUMO

Retinoblastoma (RB), originating from the developing retina, is an aggressive intraocular malignant neoplasm in childhood. Biallelic loss of RB1 is conventionally considered a prerequisite for initiating RB development in most RB cases. Additional genetic mutations arising from genome instability following RB1 mutations are proposed to be required to promote RB development. Recent advancements in high throughput sequencing technologies allow a deeper and more comprehensive understanding of the etiology of RB that additional genetic alterations following RB1 biallelic loss are rare, yet epigenetic changes driven by RB1 loss emerge as a critical contributor promoting RB tumorigenesis. Multiple epigenetic regulators have been found to be dysregulated and to contribute to RB development, including noncoding RNAs, DNA methylations, RNA modifications, chromatin conformations, and histone modifications. A full understanding of the roles of genetic and epigenetic alterations in RB formation is crucial in facilitating the translation of these findings into effective treatment strategies for RB. In this review, we summarize current knowledge concerning genetic defects and epigenetic dysregulations in RB, aiming to help understand their links and roles in RB tumorigenesis.


Assuntos
Epigênese Genética , Neoplasias da Retina , Retinoblastoma , Retinoblastoma/genética , Humanos , Neoplasias da Retina/genética , Epigênese Genética/genética , Mutação , Metilação de DNA/genética , Proteínas de Ligação a Retinoblastoma/genética , Ubiquitina-Proteína Ligases
20.
Int Immunopharmacol ; 135: 112274, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38772301

RESUMO

OBJECTIVE: The current treatment and mechanism of Sjogren's syndrome (SS) are unclear. The purpose of the present study was to potential molecular mechanisms of SS. METHODS: Immunohistochemical and immunofluorescence techniques reveal the targets and therapeutic approaches of SS. RESULTS: We found through molecular biology techniques such as immunoblotting and immunoprecipitation that USP5 is a novel regulator of NLRP3 involvement in the pathological process of SS. USP5 was significantly downregulated in submandibular gland tissue of SS. Meanwhile, it was found that USP5 is a negative regulator of NLRP3 via ubiquitination NLRP3. In addition, SalvianolicacidB (SaB), a natural USP5 agonist, can alleviate ss by regulating the USP5/NLRP3 signaling pathway. CONCLUSION: Therefore, this study provides a new mechanism for SS and also provides new therapeutic targets for treating SS.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Síndrome de Sjogren , Síndrome de Sjogren/metabolismo , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Humanos , Inflamassomos/metabolismo , Feminino , Glândula Submandibular/patologia , Glândula Submandibular/metabolismo , Ubiquitinação , Transdução de Sinais , Camundongos , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Camundongos Endogâmicos C57BL , Masculino
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