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1.
Biomed Pharmacother ; 175: 116658, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38701562

RESUMEN

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has reached 30 %, with an annual increase. The incidence of NAFLD-induced cirrhosis is rapidly rising and has become the leading indicator for liver transplantation in the US. However, there are currently no US Food and Drug Administration-approved drugs for NAFLD. Increasing evidence underscores the close association between NAFLD and bile acid metabolism disorder, highlighting the feasibility of targeting the bile acid signaling pathway for NAFLD treatment. The farnesoid X receptor (FXR) is an endogenous receptor for bile acids that exhibits favorable effects in ameliorating the metabolic imbalance of bile acids, lipid disorders, and disruption of intestinal homeostasis, all of which are key characteristics of NAFLD, making FXR a promising therapeutic target for NAFLD. The present review provides a comprehensive overview of the diverse mechanisms through which FXR improves NAFLD, with particular emphasis on its involvement in regulating bile acid homeostasis and the recent advancements in drug development targeting FXR for NAFLD treatment.

2.
J Phys Chem A ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691833

RESUMEN

We investigate the reaction pathways of nine important CO2-related reactions using the revDSD-PBEP86-D3(BJ)/jun-cc-pV(T+d)Z level and simultaneously employ an accurate composite method (jun-Cheap) based on coupled-cluster (CC) theory. Subsequently, the Rice-Ramsperger-Kassel-Marcus/master equation (RRKM/ME) is solved to calculate the temperature- and pressure-dependent rate constants. This work investigates reactions involving transition states that have been overlooked in previous literature, including the dissociation of singlet-state C3O2, the triple channel formation of C2O + CO to form C3O2, and the formation of O3 + CO. The results show that CO3 is highly prone to dissociation at high temperatures. Finally, the kinetic data show that over a wide temperature range, our calculations are consistent with previous experimental measurements. The majority of the reaction rate constants studied exhibit significant pressure dependence, while the O3 + CO reaction is pressure-independent at low temperatures. These results are instrumental in the development of detailed kinetic models for the CO2 radiolysis reaction network.

3.
J Hazard Mater ; 472: 134469, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38691995

RESUMEN

The scarcity of selective adsorbents for efficient extraction and removal of microcystins (MCs) from complex samples greatly limits the precise detection and effective control of MCs. Three-dimensional covalent organic frameworks (3D COFs), characterized by their large specific surface areas and highly ordered rigid structure, are promising candidates, but suffer from lack of specific recognition. Herein, we design to engineer molecularly imprinted cavities within 3D COFs via molecularly imprinted technology, creating a novel adsorbent with exceptional selectivity, kinetics and capacity for the efficient extraction and removal of MCs. As proof-of-concept, a new CC bond-containing 3D COF, designated JNU-7, is designed and prepared for copolymerization with methacrylic acid, the pseudo template L-arginine and ethylene dimethacrylate to yield the JNU-7 based molecularly imprinted polymer (JNU-7-MIP). The JNU-7-MIP exhibits a great adsorption capacity (156 mg g-1) for L-arginine. Subsequently, the JNU-7-MIP based solid-phase extraction coupled with high performance liquid chromatography-mass spectrometry achieves low detection limit of 0.008 ng mL-1, wide linear range of 0.025-100 ng mL-1, high enrichment factor of 186, rapid extraction of 10 min, and good recoveries of 92.4%-106.5% for MC-LR. Moreover, the JNU-7-MIP can rapidly remove the MC-LR from 1 mg L-1 to levels (0.26-0.35 µg L-1) lower than the WHO recommended limit for drinking water (1 µg L-1). This work reveals the considerable potential of 3D COF based MIPs as promising adsorbents for the extraction and removal of contaminants in complex real samples.

4.
Surg Innov ; : 15533506241246335, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656291

RESUMEN

BACKGROUND: Accurate recognition of Calot's triangle during cholecystectomy is important in preventing intraoperative and postoperative complications. The use of indocyanine green (ICG) fluorescence imaging has become increasingly prevalent in cholecystectomy procedures. Our study aimed to evaluate the specific effects of ICG-assisted imaging in reducing complications. MATERIALS AND METHODS: A comprehensive search of databases including PubMed, Web of Science, Europe PMC, and WANFANGH DATA was conducted to identify relevant articles up to July 5, 2023. Review Manager 5.3 software was applied to statistical analysis. RESULTS: Our meta-analysis of 14 studies involving 3576 patients compared the ICG group (1351 patients) to the control group (2225 patients). The ICG group had a lower incidence of postoperative complications (4.78% vs 7.25%; RR .71; 95%CI: .54-.95; P = .02). Bile leakage was significantly reduced in the ICG group (.43% vs 2.02%; RR = .27; 95%CI: .12-.62; I2 = 0; P = .002), and they also had a lower bile duct drainage rate (24.8% vs 31.8% RR = .64, 95% CI: .44-.91, P = .01). Intraoperative complexes showed no statistically significant difference between the 2 groups (1.16% vs 9.24%; RR .17; 95%CI .03-1.02), but the incidence of intraoperative bleeding is lower in the ICG group. CONCLUSION: ICG fluorescence imaging-assisted cholecystectomy was associated with a range of benefits, including a lower incidence of postoperative complications, decreased rates of bile leakage, reduced bile duct drainage, fewer intraoperative complications, and reduced intraoperative bleeding.

5.
Funct Integr Genomics ; 24(2): 63, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38517555

RESUMEN

The TRIM family is associated with the membrane, and its involvement in the progression, growth, and development of various cancer types has been researched extensively. However, the role played by the TRIM5 gene within this family has yet to be explored to a great extent in terms of hepatocellular carcinoma (HCC). The data of patients relating to mRNA expression and the survival rate of individuals diagnosed with HCC were extracted from The Cancer Genome Atlas (TCGA) database. UALCAN was employed to examine the potential link between TRIM5 expression and clinicopathological characteristics. In addition, enrichment analysis of differentially expressed genes (DEGs) was conducted as a means of deciphering the function and mechanism of TRIM5 in HCC. The data in the TCGA and TIMER2.0 databases was utilized to explore the correlation between TRIM5 and immune infiltration in HCC. WGCNA was performed as a means of assessing TRIM5-related co-expressed genes. The "OncoPredict" R package was also used for investigating the association between TRIM5 and drug sensitivity. Finally, qRT-PCR, Western blotting (WB) and immunohistochemistry (IHC) were employed for exploring the differential expression of TRIM5 and its clinical relevance in HCC. According to the results that were obtained from the vitro experiments, mRNA and protein levels of TRIM5 demonstrated a significant upregulation in HCC tissues. It is notable that TRIM5 expression levels were found to have a strong association with the infiltration of diverse immune cells and displayed a positive correlation with several immune checkpoint inhibitors. The TRIM5 expression also displayed promising clinical prognostic value for HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Expresión Génica , ARN Mensajero , Biomarcadores , Proteínas de Motivos Tripartitos/genética , Factores de Restricción Antivirales , Ubiquitina-Proteína Ligasas
6.
J Glob Health ; 14: 04010, 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38304974

RESUMEN

Background: Lower socioeconomic status (SES) is a risk factor for poor cognitive function, while a healthy lifestyle is associated with better cognitive function. We examined the complex relationship between SES and a healthy lifestyle and cognitive function among older Chinese adults. Methods: We used a national prospective cohort of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008-18, aged 65 years and older with normal cognition at baseline. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors and the unfavourable group for zero to three factors. SES was classified as higher and lower by assessing the socioeconomic vulnerability index (SEVI) with six components. Cognitive function was measured using the Mini-Mental State Examination (MMSE) scores and the standardised Z-scores. We applied the linear mixed effects and time-dependent Cox regression models to explore associations and further stratified the analysis by healthy lifestyles. Results: A total of 6851 participants were included (the mean age was 80.87, 43.44% had a favourable lifestyle, and 49.29% had higher SES). Over the 10-year follow-up period, SES status and lifestyle profiles significantly affected the decline in the standardised Z-scores (P < 0.05). The higher SES group with favourable lifestyles exhibited a slower cognitive decline than those with lower SES (by 0.031 points per year, P < 0.05). The association was not observed in those in the unfavourable group (0.010 points per year, P > 0.05). During a follow-up, 25.06% of participants developed cognitive impairment (MMSE<18). We also observed a significant interaction between SES and healthy lifestyles (P < 0.05), with the corresponding associations of SES being more pronounced among participants with unfavourable lifestyles (hazard ratio (HR) = 0.821; 95% confidence interval (CI) = 0.701-0.960) than those with favourable lifestyles (HR = 1.006; 95% CI = 0.844-1.200). Conclusions: A healthy lifestyle may attenuate the adverse impacts of lower SES on cognitive function among older adults. This study might provide important information for protecting cognitive function, especially in low- and middle-income countries.


Asunto(s)
Cognición , Estilo de Vida Saludable , Humanos , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Clase Social , China/epidemiología
7.
J Glob Health ; 14: 04034, 2024 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-38214316

RESUMEN

Background: Whether and to what extent multiple healthy lifestyles affect the longevity of people with disabilities, including those in basic activities of daily living, mobility, vision, hearing and cognition, is crucial to policymakers. We aimed to determine the impact of combined lifestyles on life expectancy (LE) lived with and without five disabilities. Methods: We recruited participants (n = 15 121 from the China Longitudinal Healthy Longevity Survey between 2008 and 2018. Healthy lifestyle levels were estimated from six factors: smoking, drinking, physical exercise, diet, cognitive activity, and sleep, which we categorised as favourable and unfavourable using the latent class growth mixture model throughout the follow-up period. We used Multi-state Markov models to assess the different disability stages of LE. Results: Of the total LE at age 65, older adults with a favourable lifestyle spent 59.60% (disability-free LE (DFLE) = 10.24 years) without five disabilities in combination, whereas those with unfavourable lifestyle spent 56.74% (DFLE = 7.28 years). Furthermore, the percentage of DFLE was 64.98 (7.71 years) and 68.38 (9.91 years) in males with unfavourable and favourable lifestyle levels, respectively, and 47.92 (6.62 years) and 55.12 (10.30 years) for females. Compared to older adults with low socioeconomic status (SES) and unfavourable lifestyle level, those with lower SES and favourable lifestyle level had more 3.77 years of DFLE, those with higher SES and unfavourable lifestyle level had more 1.94 years, as well as those with higher SES and favourable lifestyle level had more 5.10 years at age 65. Corresponding associations were found separately for each of the five individual disabilities. Conclusions: A favourable lifestyle level was associated with longer total LE along with a higher proportion of DFLE and may contribute to narrowing socioeconomic health inequalities. Policymakers should develop lifestyle interventions and scale up rehabilitation services in primary care, thereby delaying disabilities to later ages, especially in low- and middle-income countries.


Asunto(s)
Actividades Cotidianas , Personas con Discapacidad , Masculino , Femenino , Humanos , Anciano , Esperanza de Vida , Estilo de Vida Saludable , China
8.
Int J Nanomedicine ; 19: 367-388, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38229706

RESUMEN

Autoimmune diseases are diseases caused by the body's chronic immune responses to self-antigens and attacks on the host's own cells, tissues and organs. The dysfunction of innate immunity and adaptive immunity leads to the destruction of autoimmune tolerance, which is the most basic factor leading to pathogenesis. The optimal strategy for autoimmune diseases is to modify the host immune system to restore tolerance. The ideal effect of therapeutic autoimmune diseases is to eliminate the autoantigen-specific spontaneous immune response without interfering with the immune response against other antigens. Therapeutic nanovaccines that produce immune tolerance conform to this principle. Nanomaterials provide a platform for antigen loading and modification due to their unique physical and chemical properties. Nanovaccines based on nanomaterial technology can simultaneously enable antigens and adjuvants to be absorbed by immune cells and induce rapid and durable immunity. Nanovaccines have the advantages of being able to be designed and loaded and of better protecting antigens from premature degradation. Nanovaccines also have the ability to target specific tissues or cells through optimized design. We review the latest research progress of nanovaccines for autoimmune diseases and the design strategies of nanovaccines to promote the development of more effective nanovaccines for autoimmune diseases.


Asunto(s)
Enfermedades Autoinmunes , Nanovacunas , Humanos , Enfermedades Autoinmunes/terapia , Sistema Inmunológico , Antígenos , Tolerancia Inmunológica
9.
Front Microbiol ; 14: 1273024, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38033598

RESUMEN

Background: Previous studies have suggested an association between gut microbiota and primary biliary cholangitis (PBC). Nonetheless, the causal relationship between gut microbiota and PBC risk remains unclear. Methods: A bidirectional two-sample Mendelian Randomization (MR) study was employed using summary statistical data for gut microbiota and PBC from the MiBioGen consortium and Genome-Wide Association Studies (GWAS) database to investigate causal relationships between 211 gut microbiota and PBC risk. Inverse variance weighted (IVW) method was the primary analytical approach to assess causality, and the pleiotropy and heterogeneity tests were employed to verify the robustness of the findings. Additionally, we performed reverse MR analyses to investigate the possibility of the reverse causal association. Results: The IVW method identified five gut microbiota that demonstrated associations with the risk of PBC. Order Selenomonadales [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.10-4.14, p = 0.03], Order Bifidobacteriales (OR 1.58, 95% CI 1.07-2.33, p = 0.02), and Genus Lachnospiraceae_UCG_004 (OR 1.64, 95%CI 1.06-2.55, p = 0.03) were correlated with a higher risk of PBC, while Family Peptostreptococcaceae (OR 0.65, 95%CI 0.43-0.98, p = 0.04) and Family Ruminococcaceae (OR 0.33, 95%CI 0.15-0.72, p = 0.01) had a protective effect on PBC. The reverse MR analysis demonstrated no statistically significant relationship between PBC and these five specific gut microbial taxa. Conclusion: This study revealed that there was a causal relationship between specific gut microbiota taxa and PBC, which may provide novel perspectives and a theoretical basis for the clinical prevention, diagnosis, and treatment of PBC.

10.
BMC Geriatr ; 23(1): 569, 2023 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-37716958

RESUMEN

BACKGROUND: It remains unclear whether plant-based or animal-based dietary patterns are more beneficial for older adults more in maintaining muscle mass. Using a prospective cohort with nationwide sample of China older adults in this study, we aimed to examine the relationship between adhering to plant-based diet patterns or animal-based diet patterns and muscle loss. METHODS: We included 2771 older adults (≥ 65 years) from the Chinese Longitudinal Health Longevity Survey (CLHLS) with normal muscle mass at baseline (2011 and 2014 waves), which followed up into 2018. Plant-based dietary pattern scores and preference subgroups were constructed using 16 common animal-based and plant-based food frequencies. We used the corrected appendicular skeletal muscle mass (ASM) prediction formula to assess muscle mass. We applied the Cox proportional hazard risk regression to explore associations between dietary patterns and low muscle mass (LMM). RESULTS: During a mean of 4.1 years follow-up, 234 (8.4%) participants with normal muscle mass at baseline showed LMM. The plant-based dietary pattern reduced the risk of LMM by 5% (Hazard Ratios [HR]: 0.95, 95% confidence intervals [95%CI]: 0.92-0.97). In addition, a high plant-based food company with a high animal-based food intake pattern reduced the risk of LMM by 60% (HR: 0.40, 95% CI: 0.240-0.661) and 73% (HR: 0.27, 95% CI: 0.11-0.61) in the BADL disability and IADL disability population compared with a low plant-based food and high animal-based food intake, whereas a high plant-based food and low animal-based food intake was more beneficial in reducing the risk of LMM in the normal BADL functioning (HR: 0.57, 95% CI: 0.35-0.90) and IADL functioning (HR: 0.51, 95% CI: 0.28-0.91) population. CONCLUSIONS: When it comes to maintaining muscle mass in older Chinese people with functional independence, a plant-based diet pattern is more beneficial and effective than the animal-based one. People with functional dependence may profit from a combination of plant-based and animal-based diets to minimize muscle loss.


Asunto(s)
Dieta Vegetariana , Pueblos del Este de Asia , Músculo Esquelético , Atrofia Muscular , Humanos , Dieta/efectos adversos , Dieta/métodos , Estudios Prospectivos , Dieta Vegetariana/efectos adversos , Dieta Vegetariana/métodos , Anciano , Atrofia Muscular/dietoterapia , Atrofia Muscular/prevención & control , Estado Funcional , Músculo Esquelético/fisiología , Músculo Esquelético/fisiopatología , Dieta Rica en Proteínas/métodos
11.
Cell Commun Signal ; 21(1): 224, 2023 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-37626338

RESUMEN

BACKGROUND: The role of the membrane-associated RING-CH (MARCH) family in carcinogenesis has been widely studied, but the member of this family, RNF173, has not yet been thoroughly explored in the context of hepatocellular carcinoma (HCC). METHODS: With the use of an HCC tissue microarray and IHC staining, we aim to determine the differential expression of RNF173 in HCC patients and its clinical significance. The biological role of RNF173 is investigated through in vitro and in vivo experiments. RNA sequencing, mass spectrometry, and immunoprecipitation are performed to uncover the underlying mechanism of RNF173's impact on the development of HCC. RESULTS: The mRNA and protein levels of RNF173 were significantly lower in HCC tissues than in normal tissues. HCC patients with low RNF173 expression had shorter overall survival and recurrence-free survival, and RNF173 was significantly correlated with tumor number, tumor capsule, tumor differentiation, and BCLC stage. In addition, in vitro and in vivo experiments showed that RNF173 downregulation exacerbated tumor progression, including migration, invasion, and proliferation. GRB2 is a key molecule in the RAF/MEK/ERK pathway. RNF173 inhibits the RAF/MEK/ERK signaling by ubiquitinating and degrading GRB2, thereby suppressing HCC cell proliferation, invasion and migration. Combining clinical samples, we found that HCC patients with high RNF173 and low GRB2 expression had the best prognosis. CONCLUSION: RNF173 inhibits the invasion and metastasis of HCC by ubiquitinating and degrading GRB2, thereby suppressing the RAF/MEK/ERK signaling pathway. RNF173 is an independent risk factor for the survival and recurrence of HCC patients. RNF173 may serve as a novel prognostic molecule and potential therapeutic target for HCC. Video Abstract Graphical abstract Model of RNF173 on RAF/MEK/ERK signaling. RNF173 knockdown resulted in impaired ubiquitination and degradation of GRB2, leading to the activation of the RAF/MEK/ERK signaling pathway and promotion of invasion and metastasis in HCC cells.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Proteína Adaptadora GRB2 , Sistema de Señalización de MAP Quinasas , Quinasas de Proteína Quinasa Activadas por Mitógenos , Transducción de Señal
12.
J Hepatocell Carcinoma ; 10: 765-781, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37250505

RESUMEN

Introduction: Immune checkpoint therapy (ICIs) effectively improves the prognosis of advanced (stage III/IV) hepatocellular carcinoma (HCC) patients. However, its objective response rate (ORR) is below 20%, significantly limiting ICI use in advanced HCC patients. The level of tumour immune infiltration influences ICI response rate. Recent studies have found ubiquitinase to be an important factor that regulates tumour immune infiltration. Therefore, the aim of this study is to explore the key ubiquitination genes that regulate immune infiltration in advanced HCC and further validate them. Methods: A biotechnological process was performed as a means of classifying 90 advanced HCC patients into three immune subtypes and identifying associations with immune infiltration in the co-expressed modules. Ubiquitination-related genes were then screened with WGCNA. Gene enrichment analysis was performed for the target module and 30 hub genes were screened out by protein-protein interaction network (PPI). ssGSEA, single-gene sequencing and the MCP counter were used for exploring immune infiltration. TIDE score was applied for predicting drug efficacy and GSEA was used for exploring potential pathways. Finally, GRB2 expression in HCC tissue was validated by in vitro experiments. Results: GRB2 expression was found to have a significant correlation with the pathological stage and prognosis of HCC patients and a positive correlation with immune infiltration and tumour mutation burden (TMB). In addition, significant correlations with the efficacy of ICIs, sorafenib and transarterial chemoembolization (TACE) were identified. GRB2 was found to be most significantly associated with the JAK-STAT signalling pathway and cytosolic DNA sensing pathway. Finally, it was found that GRB2 expression is closely related to the prognosis, tumour size and TMN stage. Conclusion: A significant association was observed between the ubiquitinated gene GRB2 and the prognosis and immune infiltration of advanced HCC patients and it may potentially be used for predicting therapy efficacy in advanced HCC patients in the future.

13.
Front Med (Lausanne) ; 9: 1051113, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36438052

RESUMEN

Hepatocellular carcinoma (HCC) remains a major challenge to clinicians due to its unacceptably high mortality and morbidity. The etiology of HCC is multi-faceted, including viral infection, alcoholism and non-alcoholic fatty liver disease. Dysregulated host immunity contributes to tumorigenesis among these susceptible individuals with pre-existing condition(s). IL-32 and IL-34 are key cytokines driving the development of chronic inflammatory conditions such as rheumatoid arthritis, systemic lupus erythematosus, as well as chronic liver diseases. IL-32 and IL-34 play an important role augmenting the development of HCC, due to their direct influence over host inflammation, however, new roles for these cytokines in HCC are emerging. Here we comprehensively review the latest research for IL-32 and IL-34 in HCC, identifying a subset of potential therapeutic targets for use in precision medicine.

14.
Front Immunol ; 13: 997265, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36263042

RESUMEN

The membrane-associated RING-CH (MARCH) family, a member of the E3 ubiquitin ligases, has been confirmed by a growing number of studies to be associated with immune function and has been highlighted as a potential immunotherapy target. In our research, hepatocellular carcinoma (HCC) patients were divided into C1 and C2 MARCH ligase-related patterns by the non-negative matrix factorization (NMF) algorithm. Multiple analyses revealed that the MARCH ligase-related cluster was related to prognosis, clinicopathological characteristics, and the tumor immune microenvironment (TIME). Next, the signature (risk score) of the MARCH prognosis was constructed, including eight genes associated with the MARCH ligase (CYP2C9, G6PD, SLC1A5, SPP1, ANXA10, CDC20, PON1, and FTCD). The risk score showed accuracy and stability. We found that the correlations between risk score and TIME, tumor mutation burden (TMB), prognosis, and clinicopathological characteristics were significant. Additionally, the risk score also had important guiding significance for HCC treatment, including chemotherapy, immunotherapy, and transarterial chemoembolization (TACE).


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/genética , Citocromo P-450 CYP2C9 , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinas , Microambiente Tumoral , Antígenos de Histocompatibilidad Menor , Sistema de Transporte de Aminoácidos ASC , Arildialquilfosfatasa
15.
J Gastrointest Oncol ; 13(4): 1942-1958, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36092338

RESUMEN

Background: The tripartite motif (TRIM) family are important members of the Gene-finger-containing E3 ubiquitin-conjugating enzyme and are involved in the progression of hepatocellular carcinoma (HCC). Previous studies have largely focused on gene expression and molecular pathways, while the underlying role of the TRIM family in the tumor immune microenvironment (TIME) remains poorly understood. Methods: We systematically explored the correlations of prominent TRIM genes with immune checkpoints and immune infiltrates in 231 HCC samples [International Cancer Genome Consortium (ICGC) cohort (n=231); The Cancer Genome Atlas (TCGA) cohort (n=370)]. A prognostic risk model was constructed using the least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression analysis in the ICGC cohort. Kaplan-Meier curves based on the overall survival (OS) were used to assess differences in survival between clusters. We utilized gene set variation analysis (GSVA) to characterize the differences in biological functions. Based on univariate and multivariate Cox progression analysis, we developed a risk score signature and verified its reliability and validity. The Tumor Immune Single-cell Hub (TISCH) single-cell database was employed to evaluate the correlation of TRIM genes with the tumor microenvironment. Results: Cluster 1 was preferentially associated with a favorable prognosis (P<0.001). The amino acid, fatty acid, and drug metabolism pathways were significantly enriched in cluster 2. A prognosis risk score project was established and evaluated based on the 9 independent prognostic genes (all P<0.05). The immune score and stromal scores of patients with low-risk scores were greater than those of patients with high-risk scores (all P<0.001). However, patients with a high-risk score exhibited lower responses to immune check-point inhibitors (ICIs), sorafenib, and transarterial chemoembolization (TACE) treatment (all P<0.05). Consistently, TRIM genes showed the same influence in the external TCGA cohort. TRIM gene-based signatures were implicated in TIME and their copy-number alterations dynamically impacted the abundance of tumor-infiltrating immune cells. Conclusions: Our findings revealed that MID1, TRIM5, TRIM22, TRIM28, TRIM 31, TRIM37, TRIM38, TRIM47, and TRIM74 could serve as efficient prognostic biomarkers and therapeutic targets in HCC. The identified TRIM gene-based signatures could serve as important TIME mediators in HCC, potentially increasing immune treatment efficacy.

16.
Front Psychol ; 13: 895266, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35814156

RESUMEN

The purpose of this paper is to investigate how supervisor's mental state and behavior choice affect the relationship between employees' strong growth need (GNS) and their innovation performance. Using 210 sets of supervisor-subordinate dyads data from two-wave survey, this research reveals that GNS has a significant positive effect on innovation performance, and leader-member exchange (LMX) mediates the effect of GNS on innovation performance. Supervisor perceived status threat moderates the relationship between GNS and LMX, such that this relationship gets weaker for supervisors with higher perceived status threat. Furthermore, supervisor perceived status threat moderates the relationship between GNS and innovation performance, such that this relationship becomes weaker for supervisors with higher perceived status threat. The study concludes with theoretical and practical implications, as well as future research avenues.

17.
Bull Environ Contam Toxicol ; 108(6): 1153-1158, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35061049

RESUMEN

In this study, silver-ytterbium-modified biochar (MBC) was prepared to adsorb ciprofloxacin hydrochloride. It was compared with biochar (BC) and alkali-modified biochar (NBC). The results show that the MBC had more functional groups and a larger specific surface area than the BC and NBC. The saturated adsorption capacity of the MBC (312.500 mg g-1) was 3 and 19 times higher than that of the NBC and BC, respectively. The adsorption data were consistent with the pseudo-second-order kinetics model and the Langmuir isotherm model. In addition, the mechanism of CIP adsorption onto NBC and MBC may be dominated by π-π electron donor-accepter interactions. C-O, C=O and -NH2 play important roles in adsorption, and Ag-O and Yb-O groups participate in the adsorption of CIP onto MBC.


Asunto(s)
Ciprofloxacina , Contaminantes Químicos del Agua , Adsorción , Carbón Orgánico/química , Ciprofloxacina/química , Hongos , Cinética , Contaminantes Químicos del Agua/química
18.
J Hum Genet ; 67(5): 247-252, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-34815525

RESUMEN

Vitiligo is characterized by the progressive disappearance of melanocytes, resulting in depigmentation. Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that play an essential role in the regulation of inflammation and immunity. Published reports on the expression profile of lncRNAs in vitiligo cases and the potential biological function of lncRNAs in vitiligo are lacking. We performed RNA-Seq to identify the functions of lncRNAs in vitiligo. In total, 32 upregulated lncRNAs and 78 downregulated lncRNAs were identified in skin lesions with vitiligo. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis demonstrated that mRNAs regulated by abnormally expressed lncRNAs are most relevant to melanocyte function and melanogenesis. We identified 14 aberrantly expressed lncRNAs through the co-expression pattern that regulate the melanogenesis-related genes DCT, TYR, and TYRP1. Therefore, we speculate that these hub genes may be involved in pathological mechanisms in melanocytes in vitiligo. These genes are closely related to melanogenesis in vitiligo. Abnormally expressed lncRNAs directly or indirectly act on these target genes to regulate melanogenesis. Identifying lncRNAs and clarifying the regulatory roles of the lncRNA-mRNA network may be helpful to develop novel diagnoses or treatment targets for vitiligo.


Asunto(s)
ARN Largo no Codificante , Vitíligo , Perfilación de la Expresión Génica/métodos , Ontología de Genes , Redes Reguladoras de Genes , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Vitíligo/genética
19.
G3 (Bethesda) ; 12(2)2022 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-34897452

RESUMEN

Triticale, a hybrid species between wheat and rye, is one of the newest additions to the plant kingdom with a very short history of improvement. It has very limited genomic resources because of its large and complex genome. Objectives of this study were to generate dense marker data, understand genetic diversity, population structure, linkage disequilibrium (LD), and estimate accuracies of commonly used genomic selection (GS) models on forage yield of triticale. Genotyping-by-sequencing (GBS), using PstI and MspI restriction enzymes for reducing genome complexity, was performed on a triticale diversity panel (n = 289). After filtering for biallelic loci with more than 70% genome coverage, and minor allele frequency (MAF) > 0.05, de novo variant calling identified 16,378 single nucleotide polymorphism (SNP) markers. Sequences of these variants were mapped to wheat and rye reference genomes to infer their homologous groups and chromosome positions. About 45% (7430), and 58% (9500) of the de novo identified SNPs were mapped to the wheat and rye reference genomes, respectively. Interestingly, 28.9% (2151) of the 7430 SNPs were mapped to the D genome of hexaploid wheat, indicating substantial substitution of the R genome with D genome in cultivated triticale. About 27% of marker pairs were in significant LD with an average r2 > 0.18 (P < 0.05). Genome-wide LD declined rapidly to r2 < 0.1 beyond 10 kb physical distance. The three sub-genomes (A, B, and R) showed comparable LD decay patterns. Genetic diversity and population structure analyses identified five distinct clusters. Genotype grouping did not follow prior winter vs spring-type classification. However, one of the clusters was largely dominated by winter triticale. GS accuracies were estimated for forage yield using three commonly used models with different training population sizes and marker densities. GS accuracy increased with increasing training population size while gain in accuracy tended to plateau with marker densities of 2000 SNPs or more. Average GS accuracy was about 0.52, indicating the potential of using GS in triticale forage yield improvement.


Asunto(s)
Triticale , Genoma , Genoma de Planta , Genómica , Genotipo , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple , Triticale/genética
20.
Comput Intell Neurosci ; 2021: 6049195, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34824579

RESUMEN

Scientific risk assessment is an important guarantee for the healthy development of an enterprise. With the continuous development and maturity of machine learning technology, it has played an important role in the field of data prediction and risk assessment. This paper conducts research on the application of machine learning technology in enterprise risk assessment. According to the existing literature, this paper uses three machine learning algorithms, i.e., random forest (RF), support vector machine (SVM), and AdaBoost, to evaluate enterprise risk. In the specific implementation, the enterprise's risk assessment indexes are first established, which comprehensively describe the various risks faced by the enterprise through a number of parameters. Then, the three types of machine learning algorithms are trained based on historical data to build a risk assessment model. Finally, for a set of risk indicators obtained under current conditions, the risk index is output through the risk assessment model. In the experiment, some actual data are used to analyze and verify the method, and the results show that the proposed three types of machine learning algorithms can effectively evaluate enterprise risks.


Asunto(s)
Aprendizaje Automático , Máquina de Vectores de Soporte , Algoritmos , Medición de Riesgo
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