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1.
Curr Oncol ; 31(3): 1311-1322, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38534932

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) refers to the malignancy of squamous cells in the head and neck region. Ranked as the seventh most common cancer worldwide, HNSCC has a very low survival rate, highlighting the importance of finding therapeutic targets for the disease. Integrins are cell surface receptors that play a crucial role in mediating cellular interactions with the extracellular matrix (ECM). Within this protein family, Integrin αV (ITGAV) has received attention for its important functional role in cancer progression. In this study, we first demonstrated the upregulation of ITGAV expression in HNSCC, with higher ITGAV expression levels correlating with significantly lower overall survival, based on TCGA (the Cancer Genome Atlas) and GEO datasets. Subsequent in vitro analyses revealed an overexpression of ITGAV in highly invasive HNSCC cell lines UM1 and UMSCC-5 in comparison to low invasive HNSCC cell lines UM2 and UMSCC-6. In addition, knockdown of ITGAV significantly inhibited the migration, invasion, viability, and colony formation of HNSCC cells. In addition, chromatin immunoprecipitation (ChIP) assays indicated that SOX11 bound to the promoter of ITGAV gene, and SOX11 knockdown resulted in decreased ITGAV expression in HNSCC cells. In conclusion, our studies suggest that ITGAV promotes the progression of HNSCC cells and may be regulated by SOX11 in HNSCC cells.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello , Integrina alfaV , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral
2.
Mol Med ; 30(1): 40, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38509524

RESUMEN

The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads to endoplasmic reticulum stress (ER stress). As ER stress ensues, the unfolded protein response (UPR), comprising three signaling pathways-inositol-requiring enzyme 1, protein kinase R-like endoplasmic reticulum kinase, and activating transcription factor 6 promptly activates to enhance the ER's protein-folding capacity and restore ER homeostasis. However, prolonged ER stress levels propels the UPR towards cellular demise and the subsequent inflammatory cascade, contributing to the development of human diseases, including cancer, neurodegenerative disorders, and diabetes. Notably, increased expression of all three UPR signaling pathways has been observed in these pathologies, and reduction in signaling molecule expression correlates with decreased proliferation of disease-associated target cells. Consequently, therapeutic strategies targeting ER stress-related interventions have attracted significant research interest. In this review, we elucidate the critical role of ER stress in cancer, metabolic, and neurodegenerative diseases, offering novel therapeutic approaches for these conditions.


Asunto(s)
Neoplasias , Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/terapia , Estrés del Retículo Endoplásmico/genética , Respuesta de Proteína Desplegada , Transducción de Señal , Neoplasias/terapia
3.
Eur J Clin Pharmacol ; 80(3): 335-354, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38197944

RESUMEN

INTRODUCTION: Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. OBJECTIVE: To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. METHODS: Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. RESULTS: A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). CONCLUSION: TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.


Asunto(s)
Antivirales , Hepatitis B Crónica , Humanos , Antivirales/uso terapéutico , LDL-Colesterol , Hepatitis B Crónica/tratamiento farmacológico , Metaanálisis en Red , Tenofovir/uso terapéutico , Resultado del Tratamiento
4.
Hum Exp Toxicol ; 42: 9603271231221567, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38073479

RESUMEN

OBJECTIVE: To explore the differential expression of genes between wild-type chronic compressive injury (CCI) mice (WT-CCI) and interferon regulatory factors 4 (IRF4) knockout CCI mice (KO-CCI) by RNA-seq analysis of the mouse spinal cord. METHODS: RNA-seq analysis of the spinal cord tissue of the chronic sciatic nerve ligation mice and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used. RESULTS: A total of 104 genes were up-regulated and 116 genes were down-regulated in spinal cord of the mice in IRF4 knockout (KO-CCI) group compared with that in the wild-type CCI (WT-CCI) group. There were 1472 differentially expressed genes in the biological process group, 62 differentially expressed genes in the cellular component group, and 163 differentially expressed genes in the molecular function group in KO-CCI mice. A total of 14 genes related to inflammatory reactions were differentially expressed. Real-time PCR results confirmed that Pparg and Grpr mRNA expression was up-regulated and Arg 1 and Ccl11 mRNA expression was down-regulated in the KO-CCI group. CONCLUSION: IRF4 is involved in neuropathic pain in CCI mice, IRF4 may participate in neuropathic pain by regulating Grpr, Mas1, Galr3, Nos2, Arg1, Ccl11, Ptgs2, S100a8, Pparg, Cd40, Has2, Gpr151, Il123a, Capns2, Ankrd1, Ccnb1, and Nppb genes.


Asunto(s)
Neuralgia , PPAR gamma , Animales , Ratones , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/metabolismo , Ratones Noqueados , Neuralgia/genética , Neuralgia/metabolismo , PPAR gamma/metabolismo , ARN Mensajero , Análisis de Secuencia de ARN
5.
J Biomol Struct Dyn ; : 1-14, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38038388

RESUMEN

Ginsenoside Rg1 (GRg1), a key bioactive component of medicinal herbs, has shown beneficial effects on non-alcoholic fatty liver disease (NAFLD) and numerous other conditions. Nevertheless, the specific targets that are actively involved and the potential mechanisms underlying NAFLD treatment remain unclear. This study aimed to elucidate the therapeutic effects and mechanism of GRg1 in alleviating NAFLD using a combined approach of network pharmacology and molecular biology validation. The analysis yielded 294 targets for GRg1 and 1293 associated with NAFLD, resulting in 89 overlapping targets. Through protein-protein interactions (PPI) network topology analysis, 10 key targets were identified. Upon evaluating the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis, GRg1 may exert therapeutic effects on NAFLD by negatively regulating the apoptotic process, insulin and endocrine resistance, the AGE-RAGE signaling pathway in diabetic complications, and the Estrogen, PI3K/Akt, and MAPK pathways. The three differential gene targets for Akt1, EGFR, and IGF1 were identified through the compound-target network in conjunction with the aforementioned methods. The molecular docking and molecular dynamics (MD) simulations showed that AKT1 and EGFR had a strong binding affinity with GRg1. Overall, our findings point to a novel therapeutic strategy involving NAFLD, with further in vivo and in vitro studies promising to deepen our comprehension and validate its potential advantages.Communicated by Ramaswamy H. Sarma.

6.
Anal Chem ; 95(45): 16733-16743, 2023 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-37922386

RESUMEN

In the era of single-cell biology, spatial proteomics has emerged as an important frontier. However, it still faces several challenges in technology. Formalin-fixed paraffin-embedded (FFPE) tissues are an important material in spatial proteomics, in which fixed tissues are excised using laser capture microdissection (LCM), followed by protein identification with mass spectrometry. For a satisfied spatial proteomics upon FFPE tissues, the excision area is expected to be as small as possible, and the identified proteins are countered upon as much as possible. For a general laboratory for spatial proteomics, a routine workflow is required, not relying on any special device, and is easily operating. In view of these challenges in technology, we initiated a technology evaluation throughout the entire procedure of proteomic analysis with micro-FFPE tissues. In contrast to the protocols reported previously, several innovations in technology were proposed and conducted, such as removal of destaining, decross-linking with "hang-down", solution simplification for peptide generation and balancing to excision area, and capture rate of micro-FFPE tissues. After optimization of all the necessary steps, a routine workflow was established, in which the minimized area for protein identification was 0.002 mm2, while the excision area for a consistent proteomic analysis was 0.05 mm2. Using the developed workflow and collecting the micro-FFPE tissues continuously, for the first time, a spatial proteomic atlas of mouse brain was preliminarily constructed, which exhibited the typical characteristics of spatial-dependent protein abundance and functional enrichment.


Asunto(s)
Formaldehído , Proteómica , Ratones , Animales , Fijación del Tejido/métodos , Formaldehído/química , Proteómica/métodos , Adhesión en Parafina/métodos , Flujo de Trabajo , Proteínas/análisis
7.
Front Immunol ; 14: 1204338, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680641

RESUMEN

Background: Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored. Methods: Based on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied. Results: Different subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells. Conclusion: We developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Pronóstico , Bioensayo , Glucólisis/genética , Microambiente Tumoral/genética , Transportador 1 de Anión Orgánico Específico del Hígado
8.
Methods Mol Biol ; 2689: 169-177, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37430054

RESUMEN

Droplet digital polymerase chain reaction (ddPCR) is a new quantitative PCR method based on water-oil emulsion droplet technology. ddPCR enables highly sensitive and accurate quantification of nucleic acid molecules, especially when their copy numbers are low. In ddPCR, a sample is fractionated into ~20,000 droplets, and every nanoliter-sized droplet undergoes PCR amplification of the target molecule. The fluorescence signals of droplets are then recorded by an automated droplet reader. Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitously expressed in animals and plants. CircRNAs are promising as biomarkers for cancer diagnosis and prognosis and as therapeutic targets or agents to inhibit oncogenic microRNAs or proteins (Kristensen LS, Jakobsen T, Hager H, Kjems J, Nat Rev Clin Oncol 19:188-206, 2022). In this chapter, the procedures for the quantitation of a circRNA in single pancreatic cancer cells using ddPCR are described.


Asunto(s)
Biomarcadores de Tumor , Reacción en Cadena de la Polimerasa , ARN Circular , Análisis de la Célula Individual , Análisis de la Célula Individual/instrumentación , Análisis de la Célula Individual/métodos , ARN Circular/análisis , ARN Circular/genética , Reacción en Cadena de la Polimerasa/instrumentación , Reacción en Cadena de la Polimerasa/métodos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Línea Celular Tumoral , Biomarcadores de Tumor/análisis , Humanos
9.
Hum Exp Toxicol ; 42: 9603271231173382, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37125703

RESUMEN

Peripheral neurotoxicity injury caused by local anesthetics is a common complication of clinical anesthesia. The study of its mechanism is helpful to prevent and treat the neurotoxic injury of local anesthetics. Previous studies on peripheral neurotoxicity injury caused by local anesthetics have mainly focused on in vitro cell experiments. Due to the lack of an animal model of peripheral neurotoxicity damage caused by local anesthetics, there are few in vivo experimental studies regarding this topic. Herein, 1% ropivacaine hydrochloride was injected into the sciatic nerve by direct incision and exposure of the sciatic nerve to create a local anesthetic neurotoxic injury model. The results showed that 1% ropivacaine hydrochloride could reduce the lower limb motor score and mechanical paw withdrawal threshold in mice 48 hours after injection. Pathological sections showed that 48 hours after treatment with 1% ropivacaine hydrochloride, the sciatic nerve showed increased axonal edema and degeneration, edema between nerve fiber bundles, increased degeneration of axon and myelin sheath vacuoles, edema of nerve bundle membrane and local degeneration and necrosis, and a large number of inflammatory cells around the nerve adventitia were soaked. The above results show that under open vision, 1% ropivacaine hydrochloride can cause injury to the sciatic nerve after 48 h of treatment, which can simulate the neurotoxic damage of local anesthetics. This animal model provides a research tool for studying the mechanism of neurotoxic injury caused by local anesthetics.


Asunto(s)
Anestésicos Locales , Modelos Animales , Síndromes de Neurotoxicidad , Animales , Ratones , Anestésicos Locales/efectos adversos , Anestésicos Locales/toxicidad , Edema , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/patología , Ropivacaína/toxicidad , Nervio Ciático/patología
10.
Transl Lung Cancer Res ; 12(3): 547-565, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-37057123

RESUMEN

Background: Lung adenocarcinoma (LUAD) is the most common form of lung cancer and is often accompanied by brain metastasis (BM). The heterogeneity of the tumor renders all current conventional treatments less effective. This study aims to dissect tumor cell heterogeneity and identify potential therapeutic targets. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) in 8 patients with treatment-naïve LUAD BM and included scRNA-seq data of 10 primary LUAD samples and their matched adjacent normal tissue from GSE131907 to determine the tumor cell heterogeneity. Results: Our analyses revealed tumor cells derived from brain metastases were more heterogeneous. Tumor cells from BM harbored significantly more copy number variants (CNVs), and cells of magnoid subtype were the critical source of malignant cells both in BM and the primary lung tumor. Pseudo-time trajectory analysis revealed that malignant cells had upregulated genes enriched for cell cycle and cell division. Integrated analysis of tumor cells revealed 2 distinct malignant cell clusters (cluster 4 and cluster 6) and their marker genes. The signatures identified in the single-cell profile had prognostic value in the bulk tumor profiles. Moreover, the signature of cluster 4 had significant prognostic value in predicting patients surviving longer than 3.5 years, while the signature of cluster 6 showed better predictive ability within 1 year. Magnoid-type cells are most likely to develop into the riskiest cell type and potentially promote tumor progression. Conclusions: scRNA profiling that integrates LUAD BM and primary LUAD can provide information on those malignant cells with BM potential, offering additional prognostic information at cellular level, and may serve as a foundational resource for further tumor cell dissection and therapeutic target exploration.

11.
Phys Chem Chem Phys ; 25(13): 9273-9281, 2023 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-36919713

RESUMEN

In many of the existing refractive index (RI) sensing works, only the shape and size of plasmonic structures are usually taken into account, while the parameters of spacer layers are ignored. In this publication, we explored the long-range surface plasmon resonance (LRSPR) and Fabry-Pérot resonance coupling effects of our proposed gold nanoring cavity array/spacer layer/Au mirror/glass substrate. Both the RI sensitivity and full width at half-maximum (FWHM) values were superior than those of conventional surface plasmon resonance substrates. We discussed the tunability of the RI sensitivity through changing the RI and thickness of the spacer layer. Then, under the optimized parameter conditions of the spacer layer, the geometry parameters (including size, gap and periodicity) of gold nanoring cavity arrays were tuned to optimize the best RI sensitivity. Finally, we broke the structural symmetry of a nanoring cavity to introduce Fano resonances into our system, and a high RI sensitivity and figure-of-merit (FOM) of 695 nm per RIU (refractive index unit) and 96.5, respectively, were achieved when the breaking angle θ was 30°. This study opens up many possibilities for boosting the FOM of RI sensing by taking into account the hybridization effects of localized surface plasmon resonance, LRSPR, and Fabry-Pérot and Fano resonances.

12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(2): 386-392, 2023 Mar.
Artículo en Chino | MEDLINE | ID: mdl-36949703

RESUMEN

Objective: To explore the impact of socioeconomic status and productive aging on the frailty index of urban elderly population in China, and to provide reference for improving their health level. Methods: We obtained data from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS) and included 1890 urban elderly people aged 60 and over in the study. Multiple linear regression model was used to analyze the influencing factors of the productive aging and the frailty index of the urban elderly population in China. A structural equation model was constructed to explore the relationship between socioeconomic status, productive aging, and frailty index. Results: Elderly people with high socioeconomic status ( ß=0.082, P<0.001) had higher level of productive aging. Elderly people with high socioeconomic status ( ß=-0.091, P<0.001) and high level of productive aging ( ß=-0.330, P<0.001) had lower frailty index. Productive aging played an intermediary role ( ß=-0.259, 95% CI: -0.380--0.181) between socioeconomic status and frailty index. Conclusion: The socioeconomic status and productive aging of the elderly people are important predictors of their frailty index. The government should exert its leadership functions to encourage the elderly, especially those with low education and income levels, to actively learn knowledge and skills, and to provide support for the elderly to participate in productive activities.


Asunto(s)
Fragilidad , Humanos , Anciano , Persona de Mediana Edad , Envejecimiento , Clase Social , Estado de Salud , China/epidemiología , Factores Socioeconómicos
13.
Acta Neuropathol Commun ; 11(1): 24, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36750863

RESUMEN

BACKGROUND: Gonadotrophic pituitary adenoma is a major subtype of pituitary adenoma in the sellar region, but it is rarely involved in the hypersecretion of hormones into blood; thus, it is commonly regarded as "non-functioning." Its tumorigenic mechanisms remain unknown. The aim of this study was to identify human gonadotrophic pituitary adenoma stem cells (hPASCs) and explore the underlying gene expression profiles. In addition, the potential candidate genes involved in the invasive properties of pituitary adenoma were examined. METHODS: The hPASCs from 14 human gonadotrophic pituitary adenoma clinical samples were cultured and verified via immunohistochemistry. Genetic profiling of hPASCs and the matched tumor cells was performed through RNA-sequencing and subjected to enrichment analysis. By aligning the results with public databases, the candidate genes were screened and examined in invasive and non-invasive gonadotrophic pituitary adenomas using Real-time polymerase chain reaction. RESULTS: The hPASCs were successfully isolated and cultured from gonadotrophic pituitary adenoma in vitro, which were identified as positive for generic stem cell markers (Sox2, Oct4, Nestin and CD133) via immunohistochemical staining. The hPASCs could differentiate into the tumor cells expressing follicle-stimulating hormone in the presence of fetal bovine serum in the culture medium. Through RNA-sequencing, 1352 differentially expressed genes were screened and identified significantly enriched in various gene ontologies and important pathways. The expression levels of ANXA2, PMAIP1, SPRY2, C2CD4A, APOD, FGF14 and FKBP10 were significantly upregulated while FNDC5 and MAP3K4 were downregulated in the invasive gonadotrophic pituitary adenomas compared to the non-invasive ones. CONCLUSION: Genetic profiling of hPASCs may explain the tumorigenesis and invasiveness of gonadotrophic pituitary adenoma. ANXA2 may serve as a potential therapeutic target for the treatment of gonadotrophic pituitary adenoma.


Asunto(s)
Adenoma , Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/metabolismo , Perfilación de la Expresión Génica , Análisis por Micromatrices , Adenoma/genética , Células Madre/metabolismo , ARN , Proteínas de la Membrana/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Fibronectinas
14.
Materials (Basel) ; 16(4)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36837293

RESUMEN

Seepage is a main cause of dam failure, and its stability analysis is the focus of a dam's design, construction, and management. Because a geological survey can only determine the range of a dam foundation's hydraulic conductivity, hydraulic conductivity inversion is crucial in engineering. However, current inversion methods of dam hydraulic conductivity are either not accurate enough or too complex to be directly used in engineering. Therefore, this paper proposes a new method for the inversion of hydraulic conductivity with high application value in hydraulic engineering using an improved genetic algorithm coupled with an unsaturated equivalent continuum model (IGA-UECM). This method is implemented by a new code that fully considers engineering applicability. In addition to overcoming the premature convergence shortcomings of traditional genetic algorithms, it converges faster than Bayesian optimization and tree-structured Parzen estimator inversion algorithms. This method is verified by comparing the water head from drilling exploration and inversion. The results of the inversion are used to study the influence of a cement grouting curtain layout scheme on the seepage field of the Hami concrete-face rockfill dam in China, which is used as an engineering application case of the IGA-UECM. The law of the seepage field is reasonable, which verifies the validity of the IGA-UECM. The new inversion method of hydraulic conductivity and the proposed cement grouting curtain layout in this study offer possible strategies for the design, construction, and management of concrete-face rockfill dams.

15.
Lipids Health Dis ; 22(1): 22, 2023 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-36759837

RESUMEN

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is one of the most frequent liver diseases at present, and there is no radical treatment. The consequences of a variety of ginsenoside compounds on this situation have before been reported, however, the specific effect on the monomeric ginsenoside Rg1 (Rg1) and its associated underlying molecular mechanism stay unknown. MATERIAL AND METHODS: In vitro, the cell models were constructed by exposing free fatty acids (FFAs) to HepG2 cells. A methionine and choline deficiency (MCD)-induced NASH mouse model was also established over 5-6 weeks of treatment. Rg1 is a traditional Chinese medicine monomer. These NASH models were treated with Rg1 and analyzed by qRT-PCR, Western Blot, sequencing, Oil red O staining, immunofluorescence, enzyme activity, HE staining, ELISA, double luciferase reporter assay, and immunohistochemistry. RESULTS: Overexpression of ATG2B, an autophagy-related protein, attenuated lipid droplet accumulation and reduces ALT, AST, inflammatory cytokines, hydrogen peroxide, and pyroptosis in established mouse and cellular models of NASH and increased levels of ATP and autophagy. The binding sites of miR-375-3p and ATG2B were verified by bioinformatic prediction and a dual-luciferase reporter gene. Knockdown of miR-375-3p promoted autophagy and inhibited pyroptosis. ATG2B knockdown substantially attenuated the impact of miR-375-3p on NASH. Rg1 appears to regulate the occurrence and development of NASH inflammation through miR-375-3p and ATG2B in vitro and in vivo, and is regulated by PTEN-AKT pathway. CONCLUSIONS: This study showed that Rg1 participates in autophagy and pyroptosis through the miR-375-3p/ATG2B/PTEN-AKT pathway, thereby alleviating the occurrence and development of NASH, for that reason revealing Rg1 as a candidate drug for NASH.


Asunto(s)
Ginsenósidos , MicroARNs , Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Piroptosis , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ginsenósidos/farmacología , Proteínas Proto-Oncogénicas c-akt/genética , MicroARNs/genética , MicroARNs/metabolismo , Autofagia/genética
16.
PLoS Negl Trop Dis ; 17(2): e0011092, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36800375

RESUMEN

BACKGROUND: Leprosy, caused by Mycobacterium leprae infection, mainly affects skin and peripheral nerves and may further lead to disability and deformity if not treated timely. The new case detection rate of leprosy in children reflects the active transmission of leprosy infection. This study aims to present the epidemiology and clinical characteristics of new leprosy cases in children in China from 2011 to 2020. METHODOLOGY/PRINCIPAL FINDINGS: All data from leprosy patients younger than 15 years old were extracted from the Leprosy Management Information System in China (LEPMIS). Statistical Package for the Social Sciences (SPSS) version 12.0 was used for descriptive and analytical statistics of the epidemiological and clinical indicators by the Mann-Whitney test, Kruskal-Wallis test, and Fisher's exact test. And geographical distribution was analyzed by ArcGIS 10.5. A total of 152 pediatric new cases of leprosy were found over the last decade. The new case detection rate of pediatric leprosy cases decreased from 0.13 to 0.02 per 1,000,000 population over the last ten years. New pediatric cases had a higher new case detection rate in Guizhou, Sichuan, and Yunnan Provinces. All but 7 provinces in China achieved zero new child case for consecutive five years. The onset of leprosy peaked between 10 and 14 years of age, and the male to female ratio was 1.71:1. Pediatric patients were predominantly infected from symptomatic household adult contacts HHCs. Multibacillary leprosy (MB) was the most common. However, a low proportion of patients developed leprosy reaction and grade 2 disability. CONCLUSIONS/SIGNIFICANCE: The new case detection rate of pediatric leprosy cases has decreased over the past ten years in China. Spatial analysis indicated clusters in high-endemic areas. Leprosy transmission has stopped in the majority of provinces in China. However, sporadic cases may continue to exist for a long time. Active surveillance especially contact tracing should be focused on in future plan for management of leprosy, and interventions in leprosy clusters should be prioritized.


Asunto(s)
Personas con Discapacidad , Lepra , Adulto , Humanos , Masculino , Niño , Femenino , Adolescente , China/epidemiología , Lepra/diagnóstico , Lepra/epidemiología , Lepra/microbiología , Trazado de Contacto , Composición Familiar , Mycobacterium leprae
17.
Front Public Health ; 10: 1038211, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36518582

RESUMEN

Background: Carcinosarcoma is a rare biphasic tumor composed of both carcinoma and sarcoma elements, which occurs at various sites. Most studies are case reports or small population-based studies for a single disease site, so comprehensive evaluations of epidemiology and prognostic factors for carcinosarcoma are needed. Methods: Surveillance, Epidemiology, and End Results (SEER)-8 (1975-2019) provided data for the epidemiological analysis. SEER-17 (2000-2019) provided data on the primary tumor sites, initial treatment, construction, and validation of the nomogram. Results: The age-adjusted incidence per 100,000 persons of carcinosarcoma increased significantly from 0.46 to 0.91 [1975-2019; average annual percent change (AAPC): 1.3%, P = 0.006], with localized stage increasing from 0.14 to 0.26 [2005-2015; annual percent change (APC): 4.2%]. The 20-year limited-duration prevalence per 100,000 increased from 0.47 to 3.36 (1999-2018). The mortality per 100,000 increased significantly from 0.16 to 0.51 (1975-2019; AAPC: 1.9%, P < 0.001). The 5-year relative survival was 32.8%. The greatest number of carcinosarcomas were from the uterus (68.7%), ovary (17.8%), lung and bronchus (2.3%). The main treatment is comprehensive treatment based on surgery; however, surgery alone is preferred in older patients. In multivariate analysis (N = 11,424), age, sex, race, year of diagnosis, disease stage, tumor site, and treatment were associated with survival. A nomogram was established to predict 1-, 3-, and 5-year survival, and the C-indexes were 0.732 and 0.748 for the training and testing sets, respectively. The receiver operating characteristic curve demonstrated that the nomogram provided a comprehensive and accurate prediction [1-year area under the curve (AUC): 0.782 vs. 0.796; 3-year AUC: 0.771 vs. 0.798; 5-year AUC: 0.777 vs. 0.810]. Conclusions: In this study, the incidence, prevalence, and mortality of carcinosarcoma have increased over the past decades. There was a rapid rise in the incidence of localized stage in recent years, which reflected improved early detection. The prognosis of carcinosarcoma remains poor, signifying the urgency of exploring targeted cancer control treatments. Explicating distribution and gender disparities of carcinosarcoma may facilitate disease screening and medical surveillance. The nomogram demonstrated good predictive capacity and facilitated clinical decision-making.


Asunto(s)
Carcinosarcoma , Pacientes , Femenino , Estados Unidos/epidemiología , Humanos , Anciano , Carcinosarcoma/epidemiología , Nomogramas , Curva ROC , Análisis Multivariante
18.
BMC Psychiatry ; 22(1): 685, 2022 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-36333717

RESUMEN

BACKGROUND: At present, the empty nest phenomenon is becoming more and more serious in the world, especially in China, and its health problems deserve attention. Therefore, the purpose of this study is to explore the impact of community social capital on the health-related quality of life of empty-nest elderly. METHODS: The study used data collected from a survey study conducted between 2018 and 2019 in Sichuan province, China, with 638 empty-nest elderly meeting our criteria. SF-12 scale and self-made social capital scale were used to evaluate the health-related quality of life and community social capital of empty-nest elderly. Through descriptive statistical analysis, bivariate analysis and hierarchical multiple regression model, this study analyzes the relationship between community social capital and health-related quality of life of empty-nest elderly. Considering the role of living arrangements, this study further uses the simple effect analysis method to explore the moderating role of living arrangements. RESULTS: After controlling the relevant variables, the cognitive social capital (CSC) of empty-nest elderly had a positive relationship with the physical health summary (PCS) (ß = 0.188, p<0.001) and mental health summary (MCS) (ß = 0.205, p<0.001). No effect of structural social capital on quality of life was found as a result. Living arrangements played a moderation effect on the relationship between CSC and MCS (ß=-2.018, p<0.05). The MCS score of high CSC group (55.516 ± 0.757) was significantly higher than that of low CSC group (49.383 ± 0.722). CONCLUSION: The results suggest empty-nest elderly has poorer physical health and weaker structural social capital, while the cognitive social capital has a greater positive impact on their quality of life. Targeted interventions to enhance community social capital may be beneficial to improve health status of this vulnerable population.


Asunto(s)
Calidad de Vida , Capital Social , Humanos , Anciano , China/epidemiología , Encuestas y Cuestionarios , Estado de Salud
19.
Materials (Basel) ; 15(17)2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-36079550

RESUMEN

Particle shape is one of the critical parameter factors that affect gravel's pore structure and permeability. However, few studies have considered its effects on engineering applications due to the difficulty of conducting laboratory tests. To overcome these difficulties, new methods of estimating the gravel pack shape that involve manual work and measuring the surface area of particles and pores based on support vector machine segmentation and the reconstruction of X-ray diffraction computed tomography (CT) images were proposed. Under the same conditions, CT tests were carried out on gravel packs and two other regular-shaped particle packs to investigate the influence of particle shape on the fractal dimension of gravel's pore-particle interface and the specific surface area of the pore network. Additionally, permeability tests were performed to study the effect of particle shape on gravel's hydraulic conductivity. The results showed that a gravel pack with a larger aspect ratio and a smaller roundness had a larger specific pore network surface area and a more complex pore structure, leading to lower permeability. This kind of gravel had a more significant length, quantity, and tortuosity of the seepage path when seepage occurred in a two-dimensional seepage field simulation. Therefore, we suggest that the filter materials of hydraulic projects should preferably use blasting gravel with a larger aspect ratio and smaller roundness to achieve better anti-seepage properties. In addition, projects can increase pores' specific surface area using our method as a control factor in filter construction.

20.
Curr Microbiol ; 79(9): 255, 2022 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-35834049

RESUMEN

With the aim of isolating clopyralid-degrading bacterial species for potential bioremediation, a pale-yellow, Gram-negative, rod-shaped, and non-motile designated as Clo-40T was isolated from soil which was about 10 years use of clopyralid in Zaozhuang city, Shandong province. Growth occurred within the ranges from 10 to 40 °C and 0-2.5% (w/v) NaCl. Strain could completely degrade 50 mg/L clopyralid within 2 days after induction and formed 3, 6-hydroxypicolinic acid, a major clopyralid metabolite, hydrolyze esculin, and reduce nitrates to nitrites, but could not hydrolyze gelatin. Based on phylogenetic analysis, strain clustered within the genus Xinfangfangia clade and branched with Xinfangfangia humi IMT-291T (97.6%) and Xinfangfangia soli ZQBWT (96.9%). Genome sequencing revealed a genome size of 4.41 Mbp and G + C content of 67.3%. The average nucleotide ANI values of strain with respect to X. humi IMT-291T and X. soli ZQBWT were 77.5% and 76.9%, respectively. The DDH estimated values between strain Clo-40T and X. humi IMT-291T and X. soli ZQBWT were 20.5% and 20.0%, respectively. The predominant fatty acids (> 5% of the total fatty acids) were C18:1 w7c (42.9%), C16:0 (28.8%), C17:0 cyclo (13.0%), and C14:0 (7.0%). The major polar lipids were identified as phosphatidylethanolamine, phosphatidylglycerol, unidentified phospholipid, unidentified glycolipid, and unidentified lipids. The predominant respiratory quinone was Q-10. Based on data from phenotypic, chemotaxonomic, and genotypic analyses in this study, strain Clo-40T represent a novel species in the genus of Xinfangfangia, for which the name Xinfangfangia pollutisoli sp. nov. is proposed. The type strain is Clo-40T (= KCTC 92089T = GDMCC 1.2845T).


Asunto(s)
Fosfolípidos , Microbiología del Suelo , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Ácidos Grasos/análisis , Fosfolípidos/análisis , Filogenia , Ácidos Picolínicos , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Suelo
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