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1.
Neurosurg Rev ; 47(1): 618, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39278993

RESUMEN

Electrical stimulation is an important adjuvant therapy for spinal surgery, but whether receiving electrical stimulation can improve the fusion rate after spinal surgery is still controversial. The purpose of this study was to analyse and evaluate the effect of electrical stimulation on the fusion rate after spinal surgery. We systematically searched for related articles published in the PubMed, Embase and Cochrane Library databases on or before September 30, 2023. The odds ratio (OR) with 95% confidence interval (CI) and the fusion rates of the experimental group and the control group were calculated by a random-effects meta-analysis model. The analysis showed that receiving electrical stimulation significantly increased the probability of successful spinal fusion (OR 2.66 [95% CI 1.79-3.97]), and the average fusion rate of the electrical stimulation group (86.8%) was significantly greater than that of the control group (73.7%). The fusion rate in the direct current (DC) stimulation group was 2.33 times greater than that in the control group (OR 2.33 [95% CI 1.37-3.96]), and that in the pulsed electromagnetic field (PEMF) group was 2.60 times greater than that in the control group (OR 2.60 [95% CI 1.29-5.27]). Similarly, the fusion rate in the capacitive coupling (CC) electrical stimulation group was 3.44 times greater than that in the control group (OR 3.44 [95% CI 1.75-6.75]), indicating that regardless of the type of electrical stimulation, the fusion rate after spinal surgery improved to a certain extent. Electrical stimulation as an adjuvant therapy seems to improve the fusion rate after spinal surgery to a certain extent, but the specific effectiveness of this therapy needs to be further studied.


Asunto(s)
Fusión Vertebral , Humanos , Fusión Vertebral/métodos , Terapia por Estimulación Eléctrica/métodos , Estimulación Eléctrica/métodos , Resultado del Tratamiento , Enfermedades de la Columna Vertebral/cirugía
2.
BMC Oral Health ; 24(1): 1096, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285382

RESUMEN

BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease (AIBD). Some reports suggest that it has a drug-related pathogenesis especially anti-hypertensive drug. CASE PRESENTATION: A 67-year-old man with a 7-year history of essential hypertension was prescribed enalapril maleate for 5 months. He presented at our department with pain, ulcers, and blisters on the oral mucosa. We performed clinical, histopathology, and direct immunofluorescence examinations, and findings were consistent with the diagnostic criteria for MMP. Consequently, we consulted with the cardiovascular physician and agreed to discontinue the enalapril maleate replacing it with irbesartan/hydrochlorothiazide tablets and topical corticosteroid therapies instead. The lesions healed without recurrence. CONCLUSIONS: ABID induced by antihypertensive drugs have been reported, and enalapril maleate has been implicated as an antihypertensive agent that may trigger AIBDs, such as MMP. This case highlights the potential relationship between antihypertensive drugs and MMP, of which clinicians should be aware to accurately diagnose and promptly relieve patients' pain.


Asunto(s)
Antihipertensivos , Enalapril , Penfigoide Benigno de la Membrana Mucosa , Humanos , Enalapril/efectos adversos , Enalapril/uso terapéutico , Masculino , Anciano , Antihipertensivos/efectos adversos , Antihipertensivos/uso terapéutico , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológico , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/complicaciones , Irbesartán/uso terapéutico , Hidroclorotiazida/efectos adversos , Hidroclorotiazida/uso terapéutico
3.
Int J Biol Macromol ; 279(Pt 2): 135237, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39218190

RESUMEN

Kuey teow is one of the delicacies of Guangdong, China and is a gluten-free noodle dish made from rice. It has a short storage period and extending the shelf life by quick freezing induces quality deterioration due to temperature fluctuations. To improve its freeze-thaw frozen storage quality, this paper examined the effects of hydroxypropyl corn starch (HCS), guar gum (GG), and compound phosphates (CP) on the quality of quick-frozen kuey teow during freeze-thaw cycles. The mechanism was investigated by identifying changes in the moisture status, aging degree of the starch, and textural and cooking characteristics. The results showed that all three additions improved the toughness, chewiness and steaming characteristics of the kuey teow, with CP significantly enhancing chewiness. XRD and FTIR results revealed that GG more significantly inhibited the decrease of starch crystallinity, while HCS inhibited starch aging. GG, HCS and CP all improved the hydration characteristics and water holding capacity of rice starch. GG enhances the ability of starch to bind more tightly with water, resulting in a more uniform water distribution and a more continuous and tight structure of the kuey teow. This study will provide a theoretical basis for compounding and optimizing the quick-freezing of kuey teow.

4.
J Dent ; 149: 105304, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39159741

RESUMEN

OBJECTIVES: To determine whether tooth loss affects all-cause and cause-specific mortality in a nationally representative sample of adults with diabetes mellitus (DM) in the United States. METHODS: This prospective cohort study involved 8207 participants aged 30 years or older at baseline, all diagnosed with diabetes mellitus and enrolled in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Tooth loss was stratified into 28 teeth (complete), 20-27 teeth (tooth loss), 9-19 teeth (lacking functional), 1-8 teeth (severe tooth loss) and edentulism. To estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for all-cause and specific-cause mortality in diabetes mellitus participants according to tooth loss, multivariate cox proportional hazards regression models were used. Relationships between mortality and quartiles of mean tooth loss levels were analyzed, with the lowest quartile as the baseline for comparisons. RESULTS: During a median of 6.92 years of follow-up, 2317 deaths were documented. After multivariate adjustments, higher tooth loss levels were significantly and non-linearly associated with higher risks of all-cause, CVD-related and DM-related mortality among participants with DM. When compared with the reference group of mean tooth loss levels, the highest quartile showed significantly increased risks: all-cause mortality (HR, 2.11; 95 % CI, 1.53-2.91, P-trend < 0.001), CVD-related mortality (HR, 3.24, 95 % CI, 1.54-6.85, P-trend < 0.001) and DM-related mortality (HR, 2.78, 95 % CI, 1.15-6.68, P-trend < 0.001). CONCLUSIONS: Tooth loss is associated with an increased risk of all-cause, CVD-related and diabetes mellitus mortality among adults with diabetes mellitus in the US. CLINICAL SIGNIFICANCE: This study presents evidence for physicians and dentists that higher tooth loss was significantly associated with increased risk of all-cause, CVD-related and diabetes mellitus mortality in a dose-response manner among adults with diabetes mellitus. Therefore, assessment of survival in individuals with diabetes mellitus could pay attention to the tooth loss.


Asunto(s)
Causas de Muerte , Diabetes Mellitus , Encuestas Nutricionales , Pérdida de Diente , Humanos , Pérdida de Diente/complicaciones , Masculino , Femenino , Estados Unidos/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Adulto , Diabetes Mellitus/mortalidad , Factores de Riesgo , Anciano , Modelos de Riesgos Proporcionales , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/complicaciones , Complicaciones de la Diabetes/complicaciones
5.
Ecotoxicol Environ Saf ; 283: 116799, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39094450

RESUMEN

Acrolein is a ubiquitous gaseous air pollutant and endogenous toxicant, which poses strong risk for oxidative stress-related diseases such as cardiovascular disease. Adenosine has been identified as potential therapeutic agent for age-related cardiovascular disease, while the molecular mechanisms underlying its cardioprotection remain elusive. In the present study, we investigated the myocardial protective effects and the mechanism of adenosine on acrolein-induced toxicity in H9c2 cells and primary neonatal rat cardiomyocytes. We found that acrolein caused apoptosis of cardiomyocytes resulting from oxidative damage, autophagy defect, and mitochondrial dysfunction, as evidenced by loss of mitochondrial membrane potential, impairment of mitochondrial biogenesis, dynamics, and oxidative phosphorylation, decrease of mitochondrial deoxyribonucleic acid (mtDNA) copy number and adenosine 5'-triphosphate (ATP) production. Adenosine pretreatment protected against acrolein-induced cardiotoxicity by maintaining mitochondrial homeostasis, activating the phase II detoxifying enzyme system, promoting autophagic flux, and alleviating mitochondrial-dependent apoptosis. We further demonstrated that the up-regulation of forkhead box protein O1 (FoxO1) mediated by extracellular regulated protein kinases (ERK) activation contributes to the cardioprotection of adenosine. These results expand the application of adenosine in cardioprotection to preventing myocardial damages induced by environmental pollutant acrolein exposure, and uncover the adenosine-ERK-FoxO1 axis as the underlying mechanism mediating the protection of mitochondrial homeostasis, Nrf2-mediated antioxidant defense and autophagic flux, shedding light on the better understanding about the pathological mechanism of cardiovascular disease caused by environmental pollutants and applications of adenosine in cardioprotection.


Asunto(s)
Acroleína , Adenosina , Antioxidantes , Autofagia , Homeostasis , Mitocondrias , Miocitos Cardíacos , Regulación hacia Arriba , Acroleína/toxicidad , Animales , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Ratas , Autofagia/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Homeostasis/efectos de los fármacos , Cardiotoxicidad , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Proteína Forkhead Box O1/metabolismo , Línea Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo
6.
BMC Biol ; 22(1): 182, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39183297

RESUMEN

BACKGROUND: Accurately identifying drug-target affinity (DTA) plays a pivotal role in drug screening, design, and repurposing in pharmaceutical industry. It not only reduces the time, labor, and economic costs associated with biological experiments but also expedites drug development process. However, achieving the desired level of computational accuracy for DTA identification methods remains a significant challenge. RESULTS: We proposed a novel multi-view-based graph deep model known as MvGraphDTA for DTA prediction. MvGraphDTA employed a graph convolutional network (GCN) to extract the structural features from original graphs of drugs and targets, respectively. It went a step further by constructing line graphs with edges as vertices based on original graphs of drugs and targets. GCN was also used to extract the relationship features within their line graphs. To enhance the complementarity between the extracted features from original graphs and line graphs, MvGraphDTA fused the extracted multi-view features of drugs and targets, respectively. Finally, these fused features were concatenated and passed through a fully connected (FC) network to predict DTA. CONCLUSIONS: During the experiments, we performed data augmentation on all the training sets used. Experimental results showed that MvGraphDTA outperformed the competitive state-of-the-art methods on benchmark datasets for DTA prediction. Additionally, we evaluated the universality and generalization performance of MvGraphDTA on additional datasets. Experimental outcomes revealed that MvGraphDTA exhibited good universality and generalization capability, making it a reliable tool for drug-target interaction prediction.


Asunto(s)
Aprendizaje Profundo , Descubrimiento de Drogas/métodos , Biología Computacional/métodos , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/metabolismo
7.
Anal Methods ; 16(34): 5902-5908, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39158376

RESUMEN

The levels of uric acid (UA) and tyrosine (Tyr) in sweat reflect a person's overall health. However, simultaneously identifying several components in sweat remains challenging. Here, we achieve simultaneous detection of UA and Tyr by synthesizing CoWO4@CNT in a single step using a hydrothermal method. CoWO4's high catalytic efficacy and large CNT reaction area allow the detection of 1-1000 µM UA (LOD = 0.14 µM) and 5-1000 µM Tyr (LOD = 4.2 µM). To increase sweat collection, we developed a polydopamine-polyacrylamide (PDA-PAM) hydrogel with a sweat absorption rate of up to 226%. Finally, by monitoring sweat at various times of day, our sensors can discriminate between UA and Tyr in real sweat, and the results are consistent with the individuals' activity levels. Overall, the effective electrocatalytically active materials and PDA-PAM hydrogel improve the detection of UA and Tyr. The remarkable performance of CoWO4@CNT in real samples shows that it has the potential to improve health detection and real-time sweat analysis.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Hidrogeles , Sudor , Tirosina , Ácido Úrico , Ácido Úrico/análisis , Ácido Úrico/química , Sudor/química , Técnicas Biosensibles/métodos , Tirosina/química , Tirosina/análisis , Humanos , Hidrogeles/química , Técnicas Electroquímicas/métodos , Polímeros/química , Límite de Detección , Indoles/química , Resinas Acrílicas/química
8.
Alzheimers Dement ; 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39129310

RESUMEN

INTRODUCTION: The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive. METHODS: The present study enrolled 54 patients diagnosed with late-onset Alzheimer's disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs). RESULTS: Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells. DISCUSSION: These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy. HIGHLIGHTS: The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer's disease. Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy. The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.

9.
Int J Biol Macromol ; 278(Pt 1): 134469, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39102911

RESUMEN

In this study, pectin extracted from pomelo peel was investigated using three different combination methods of pulsed electric field (PEF) and cellulase. Three action sequences were performed, including PEF treatment followed by enzymatic hydrolysis, enzymatic hydrolysis followed by PEF treatment, and enzymatic hydrolysis simultaneously treated by PEF. The three corresponding pectins were namely PEP, EPP and SP. The physiochemical, molecular structural and functional properties of the three pectins were determined. The results showed that PEP had excellent physiochemical properties, with the highest yield (12.08 %), total sugar (80.17 %) and total phenol content (38.20 %). The monosaccharide composition and FT-IR analysis indicated that the three pectins were similar. The molecular weights of PEP, EPP and SP were 51.13, 88.51 and 40.00 kDa, respectively. PEP showed the best gel properties, emulsification stability and antioxidant capacity among the three products, due to its high galacturonic acid and total phenol content, appropriate protein and low molecular weight. The mechanism of PEF-assisted cellulase hydrolysis of pomelo peel was also revealed by SEM analysis. These results suggested that PEF pretreatment was the best method, which not only improved the efficiency of enzymatic extraction, but also reduced resource waste and increased financial benefits.


Asunto(s)
Celulasa , Citrus , Peso Molecular , Pectinas , Hidrólisis , Celulasa/metabolismo , Celulasa/química , Pectinas/química , Citrus/química , Antioxidantes/química , Antioxidantes/farmacología , Electricidad , Fenómenos Químicos , Fenoles/química , Frutas/química , Espectroscopía Infrarroja por Transformada de Fourier , Monosacáridos/análisis
10.
Sci Total Environ ; 951: 175694, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39173765

RESUMEN

There is no evidence on the associations between persistent organic pollutants (POPs) and the incidence of chronic kidney disease (CKD) in the Chinese rural population. We aimed to investigate the individual and mixed effects of 22 POPs on the prevalence and incidence of CKD, and the joint effects of POPs and abnormal glucose metabolism as well as the modification effects of healthy lifestyle on these associations. A total of 2775 subjects, including 925 subjects with normal plasma glucose (NPG) and 925 subjects with prediabetes (PDM) and type 2 diabetes mellitus (T2DM), were enrolled from the Henan Rural Cohort Study. Logistic regression and quantile g-computation were performed to assess the individual and mixed effects of POPs on the risk of CKD. Joint effects of POPs and abnormal glucose metabolism status, as well as the modification effects of lifestyle on CKD were assessed. After 3-year follow-up, an increment of ln-o,p'-DDT was related to an elevated risk of CKD prevalence. Positive associations of p,p'-DDE and ß-BHC with CKD incidence were observed (P < 0.05). In addition, participants with high levels of ∑POPs were associated elevated incidence risk of CKD (OR: 1.217, 95%CI: 1.008-1.469). One quartile increase in POPs mixture was associated with the increased incidence of CKD among T2DM patients (P < 0.05). Further, a higher risk of CKD was observed among PDM and T2DM patients with high levels of o,p'-DDT, p,p'-DDE, ß-BHC, and ∑POPs than NPG subjects with low levels of pollutants. In addition, interactive effects of ∑POPs and lifestyle score on CKD incidence were found. Individual and mixed exposure to POPs increased the prevalence and incidence of CKD, and glucose metabolic status exacerbated the risk of CKD resulting from such exposures. Further, the modifying effects of lifestyle were observed, highlighting the importance of precision prevention for high-risk CKD population and healthy lifestyle intervention measures.


Asunto(s)
Diabetes Mellitus Tipo 2 , Exposición a Riesgos Ambientales , Estilo de Vida , Contaminantes Orgánicos Persistentes , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/epidemiología , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Estudios Prospectivos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Diabetes Mellitus Tipo 2/epidemiología , Incidencia , Adulto , Glucemia , Estado Prediabético/epidemiología , Prevalencia , Glucosa/metabolismo , Población Rural/estadística & datos numéricos
11.
Int J Biol Macromol ; 279(Pt 3): 135186, 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39216569

RESUMEN

The chelation reaction of soluble soybean polysaccharide (SSPS) with zinc was investigated. Using response surface methodology, the optimum parameters for SSPS-Zn synthesis were obtained: pH 5.3, SSPS-ZnCl2 mass ratio of 9.44:1, reaction temperature 50.44 °C, and reaction time 1.5 h, with the highest zinc content of 24.73 %. Compared with SSPS, SSPS-Zn increased in rhamnogalacturonan content and decreased in that of neutral monosaccharides (Fuc, Ara, Gal, Glu and Xyl). UV-vis spectra indicated that SSPS-Zn was lower than SSPS in protein content. FTIR spectra indicated that CO group of SSPS was bonded to Zn2+. X-ray diffraction spectra demonstrated that SSPS-Zn had higher crystallinity. Congo red reactions showed that SSPS possessed a triple-helix conformation while SSPS-Zn formed an irregular free-coiled conformation. EDX confirmed SSPS-Zn synthesis successfully. TGA curves exhibited that SSPS-Zn required higher temperature to undergo degradation. AFM revealed that SSPS-Zn was clustered while SSPS was filamentous. SEM micrographs showed the cracked fragments on the surface of SSPS-Zn. By in vitro simulation of gastrointestinal digestion, Zn2+ release reached 68.87 % after 2 h digestion. Consequently, the chelation of SSPS with zinc could change structure and provide a basis for research and application of novel zinc supplements.

12.
Brain Behav Immun ; 122: 527-546, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39182588

RESUMEN

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder caused by the interaction of multiple pathogenic factors. Epidemiological studies and animal experiments indicate that maternal immune activation (MIA) is closely related to the development of ASD in offspring. A large number of pro-inflammatory cytokines are transferred from the placenta to the fetal brain during MIA, which impedes fetal neurodevelopment and is accompanied by activation of immune cells and microglia. Programmed cell death protein 1 (PD-1) can be highly expressed on the surface of various activated immune cells, when combined with programmed cell death-ligand 1 (PD-L1), it can activate the PD-1/PD-L1 pathway and exert powerful immunosuppressive effects, suggesting that this immune checkpoint may have the potential to treat MIA-induced ASD. This study combined bioinformatics analysis and experimental validation to explore the efficacy of Fc-fused PD-L1 (PD-L1-Fc) in treating MIA-induced ASD. Bioinformatics analysis results showed that in human placental inflammation, IL-6 was upregulated, T cells proliferated significantly, and the PD-1/PD-L1 pathway was significantly enriched. The experimental results showed that intraperitoneal injection of poly(I:C) induced MIA in pregnant mice resulted in significant expression of IL-6 in their serum, placenta, and fetal brain. At the same time, the expression of PD-1 and PD-L1 in the placenta and fetal brain increased, CD4+ T cells in the spleen were significantly activated, and PD-1 expression increased. Their offspring mice exhibited typical ASD-like behaviors. In vitro experiments on primary microglia of offspring mice have confirmed that the expression of IL-6, PD-1, and PD-L1 is significantly increased, and PD-L1-Fc effectively reduced their expression levels. In the prefrontal cortex of MIA offspring mice, there was an increase in the expression of IL-6, PD-1, and PD-L1; activation of microglial cells, and colocalization with PD-1. Then we administered brain stereotaxic injections of PD-L1-Fc to MIA offspring mice and intraperitoneal injections to MIA pregnant mice. The results indicated that PD-L1-Fc effectively suppressed neuroinflammation in the frontal cortex of offspring mice and partially ameliorated ASD-like behaviors; MIA in pregnant mice was significantly alleviated, and the offspring mice they produced did not exhibit neuroinflammation or ASD-like behaviors. In summary, we have demonstrated the therapeutic ability of PD-L1-Fc for MIA-induced ASD, aiming to provide new strategies and insights for the treatment of ASD.


Asunto(s)
Trastorno del Espectro Autista , Antígeno B7-H1 , Placenta , Receptor de Muerte Celular Programada 1 , Animales , Femenino , Antígeno B7-H1/metabolismo , Embarazo , Receptor de Muerte Celular Programada 1/metabolismo , Ratones , Masculino , Trastorno del Espectro Autista/metabolismo , Trastorno del Espectro Autista/prevención & control , Humanos , Placenta/metabolismo , Modelos Animales de Enfermedad , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Conducta Animal , Ratones Endogámicos C57BL , Trastorno Autístico/metabolismo , Trastorno Autístico/inmunología , Inflamación/metabolismo , Interleucina-6/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos
13.
Front Genet ; 15: 1444459, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184348

RESUMEN

The detection of enhancer-promoter interactions (EPIs) is crucial for understanding gene expression regulation, disease mechanisms, and more. In this study, we developed TF-EPI, a deep learning model based on Transformer designed to detect these interactions solely from DNA sequences. The performance of TF-EPI surpassed that of other state-of-the-art methods on multiple benchmark datasets. Importantly, by utilizing the attention mechanism of the Transformer, we identified distinct cell type-specific motifs and sequences in enhancers and promoters, which were validated against databases such as JASPAR and UniBind, highlighting the potential of our method in discovering new biological insights. Moreover, our analysis of the transcription factors (TFs) corresponding to these motifs and short sequence pairs revealed the heterogeneity and commonality of gene regulatory mechanisms and demonstrated the ability to identify TFs relevant to the source information of the cell line. Finally, the introduction of transfer learning can mitigate the challenges posed by cell type-specific gene regulation, yielding enhanced accuracy in cross-cell line EPI detection. Overall, our work unveils important sequence information for the investigation of enhancer-promoter pairs based on the attention mechanism of the Transformer, providing an important milestone in the investigation of cis-regulatory grammar.

14.
J Comput Chem ; 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39189298

RESUMEN

Schistosomiasis is a tropical disease that poses a significant risk to hundreds of millions of people, yet often goes unnoticed. While praziquantel, a widely used anti-schistosome drug, has a low cost and a high cure rate, it has several drawbacks. These include ineffectiveness against schistosome larvae, reduced efficacy in young children, and emerging drug resistance. Discovering new and active anti-schistosome small molecules is therefore critical, but this process presents the challenge of low accuracy in computer-aided methods. To address this issue, we proposed GNN-DDAS, a novel deep learning framework based on graph neural networks (GNN), designed for drug discovery to identify active anti-schistosome (DDAS) small molecules. Initially, a multi-layer perceptron was used to derive sequence features from various representations of small molecule SMILES. Next, GNN was employed to extract structural features from molecular graphs. Finally, the extracted sequence and structural features were then concatenated and fed into a fully connected network to predict active anti-schistosome small molecules. Experimental results showed that GNN-DDAS exhibited superior performance compared to the benchmark methods on both benchmark and real-world application datasets. Additionally, the use of GNNExplainer model allowed us to analyze the key substructure features of small molecules, providing insight into the effectiveness of GNN-DDAS. Overall, GNN-DDAS provided a promising solution for discovering new and active anti-schistosome small molecules.

15.
J Craniofac Surg ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39207141

RESUMEN

This study enrolled 60 patients aged 28 to 76 years who were oral malignancy undergoing radical surgery for more than 3 hours to assess the disinfection effect of povidone-iodine in oral and maxillofacial surgery which is a clean-contaminated wound. The authors collected and compared the sample from oral mucosa and counted the colony-forming units before disinfection, after disinfection for 10 minutes, 1, 2, 3, and 4 hours. The results showed that the oral bacterial colony-forming units significantly decreased after disinfecting with povidone-iodine and the effect existed for 2 hours and the colony-forming units of 3 hours after disinfection showed statistically significant increase. In oral and maxillofacial surgery, povidone-iodine can effectively disinfect the mouth and maintain a certain period of time. Therefore, to reduce the number of oral mucosa microorganisms, it is recommended to disinfect the oral cavity again after 3 hours.

16.
Int J Biol Macromol ; 279(Pt 1): 135142, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39208901

RESUMEN

Bio-refining lignocellulosic resource offers a renewable and sustainable approach for producing biofuels and biochemicals. However, the conversion efficiency of lignocellulosic resource is still challenging due to the intrinsic inefficiency in co-utilization of xylose and glucose. In this study, the industrial bacterium Bacillus licheniformis was engineered for biorefining lignocellulosic resource to produce acetoin. First, adaptive evolution was conducted to improve acetoin tolerance, leading to a 19.6 % increase in acetoin production. Then, ARTP mutagenesis and 60Co-γ irradiation was carried out to enhance the production of acetoin, obtaining 73.0 g/L acetoin from glucose. Further, xylose uptake and xylose utilization pathway were rewired to facilitate the co-utilization of xylose and glucose, enabling the production of 60.6 g/L acetoin from glucose and xylose mixtures. Finally, this efficient cell factory was utilized for acetoin production from lignocellulosic hydrolysates with the highest titer of 68.3 g/L in fed-batch fermentation. This strategy described here holds great applied potential in the biorefinery of lignocellulose for the efficient synthesis of high-value chemicals.

17.
World J Gastroenterol ; 30(28): 3403-3417, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39091717

RESUMEN

BACKGROUND: There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs). AIM: To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort. METHODS: Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed. RESULTS: A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods. CONCLUSION: The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.


Asunto(s)
Estadificación de Neoplasias , Tumores Neuroendocrinos , Nomogramas , Neoplasias del Recto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias del Recto/mortalidad , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Tumores Neuroendocrinos/mortalidad , Tumores Neuroendocrinos/patología , Tumores Neuroendocrinos/terapia , Tumores Neuroendocrinos/diagnóstico , Estudios Retrospectivos , China/epidemiología , Pronóstico , Anciano , Factores de Riesgo , Adulto , Curva ROC , Supervivencia sin Progresión , Clasificación del Tumor , Medición de Riesgo/métodos , Modelos de Riesgos Proporcionales , Valor Predictivo de las Pruebas , Evaluación Nutricional , Pueblos del Este de Asia
18.
Org Lett ; 26(32): 6809-6813, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39102516

RESUMEN

Represented herein is the first 1,3-difunctionalization of alkenes via photocatalysis. A single cobaloxime is used to carry out two catalytic cycles in which cobaloxime is used not only as a photocatalyst to initiate the reaction but also as a metal catalyst for the ß-H elimination process. Electron-deficient alkenes, electron-rich alkenes, and unactivated alkenes could be directly converted to 1,3-bisphosphorylated products, even unsymmetric 1,3-bisphosphorylated products, with only H2 as a byproduct under extremely mild reaction conditions.

19.
Mol Biomed ; 5(1): 27, 2024 07 16.
Artículo en Inglés | MEDLINE | ID: mdl-39009906

RESUMEN

miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3. Consequently, this interaction accelerates the metastasis of HNSCC. Notably, clinical observations indicate a correlation between high expression of miR-151-5p and low levels of LYPD3 in clinical settings are correlated with poor prognosis of HNSCC patients. Furthermore, our investigation demonstrates that glycosylation of LYPD3 modulates its subcellular localization and reinforces its role in suppressing HNSCC metastasis. Additionally, we uncover a potential regulatory mechanism involving the facilitation of miR-151-5p maturation and accumulation through N6-methyladenosine (m6A) modification. This process is orchestrated by methyltransferase-like 3 (METTL3) and mediated by a newly identified reader, heterogeneous nuclear ribonucleoprotein U (hnRNP U). These findings collectively underscore the significance of the METTL3/miR-151-5p/LYPD3 axis serves as a prominent driver in the malignant progression of HNSCC.


Asunto(s)
Adenosina , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello , MicroARNs , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Regiones no Traducidas 3'/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo
20.
J Gastroenterol ; 59(9): 788-797, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39028343

RESUMEN

BACKGROUND: The regulatory role of gut microbiota and gut-derived metabolites through the gut-liver axis in the development of cirrhotic portal hypertension (PH) has received increasing attention. METHODS: The review summarized a series of investigations on effects of metabolites derived from microbiota and medicines targeting microbiome including rifaximin, VSL#3, statins, propranolol, FXR agonists as well as drugs derived from bile acids (BAs) on PH progression. RESULTS: Patients with PH exhibit alterations in gut microbial richness and differential overall microbiota community, and several results clearly displayed the correlation of PH with enrichment of Veillonella dispar or depletion of Clostridiales, Peptostreptococcaceae, Alistipes putredinis, Roseburia faecis and Clostridium cluster IV. The gut-derived metabolites including hydrogen sulfide, tryptophan metabolites, butyric acid, secondary BAs and phenylacetic acid (PAA) participate in a range of pathophysiology process of PH through modulating intrahepatic vascular resistance and portal blood flow associated with the formation and progression of PH. Established and emerging drugs targeting on bacterial translocation and intestinal eubiosis are gradually identified as potential strategies for treatments of liver cirrhosis and PH by modulating intestinal inflammation, splanchnic arterial vasodilation and endothelial dysfunction. CONCLUSIONS: Future explorations should further characterize the alteration of the fecal microbiome and metabolite profiles in PH and elucidate the regulatory mechanism of the intestinal microbiome, gut-derived metabolites and gut microbiota targeted pharmaceutical treatments involved in PH.


Asunto(s)
Microbioma Gastrointestinal , Hipertensión Portal , Cirrosis Hepática , Hipertensión Portal/tratamiento farmacológico , Hipertensión Portal/metabolismo , Hipertensión Portal/microbiología , Humanos , Microbioma Gastrointestinal/fisiología , Cirrosis Hepática/microbiología , Cirrosis Hepática/complicaciones , Cirrosis Hepática/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Ácidos y Sales Biliares/metabolismo , Rifaximina/uso terapéutico , Hígado/metabolismo , Progresión de la Enfermedad
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