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1.
Cancer Immunol Immunother ; 72(7): 2045-2056, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36795124

RESUMO

Immunotherapy based on immune checkpoint inhibitors (ICIs) has provided revolutionary results in treating various cancers. However, its efficacy in colorectal cancer (CRC), especially in microsatellite stability-CRC, is limited. This study aimed to observe the efficacy of personalized neoantigen vaccine in treating MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy. Candidate neoantigens were analyzed from whole-exome and RNA sequencing of tumor tissues. The safety and immune response were assessed through adverse events and ELISpot. The clinical response was evaluated by progression-free survival (PFS), imaging examination, clinical tumor marker detection, circulating tumor DNA (ctDNA) sequencing. Changes in health-related quality of life were measured by the FACT-C scale. A total of six MSS-CRC patients with recurrence or metastasis after surgery and chemotherapy were administered with personalized neoantigen vaccines. Neoantigen-specific immune response was observed in 66.67% of the vaccinated patients. Four patients remained progression-free up to the completion of clinical trial. They also had a significantly longer progression-free survival time than the other two patients without neoantigen-specific immune response (19 vs. 11 months). Changes in health-related quality of life improved for almost all patients after the vaccine treatment. Our results shown that personalized neoantigen vaccine therapy is likely to be a safe, feasible and effective strategy for MSS-CRC patients with postoperative recurrence or metastasis.


Assuntos
Vacinas Anticâncer , Neoplasias Colorretais , Humanos , Antígenos de Neoplasias , Vacinas Anticâncer/uso terapêutico , Neoplasias Colorretais/genética , Imunoterapia/métodos , Imunoterapia Ativa , Repetições de Microssatélites , Qualidade de Vida
2.
Neoplasma ; 69(1): 193-202, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34779642

RESUMO

Pancreatic ductal adenocarcinoma is a complex gastrointestinal tumor with high metastatic potential and poor prognosis. Actin-binding protein Girdin is highly expressed in a variety of tumors and promotes tumorigenesis and progression. However, the mechanisms underlying the involvement of Girdin in pancreatic cancer have not been clarified. In this study, we observed that the expression of Girdin was upregulated in pancreatic cancer cells. The siRNA-mediated gene knockdown experiments showed that reduced expression of Girdin in pancreatic cancer cells inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. Functional assays revealed that c-MYC overexpression in pancreatic cancer cells could significantly increase the cell proliferation ability and rates of cell migration and invasion while decreasing the apoptosis rate. It has been shown that phosphorylation plays a role in the functional regulation of the c-MYC gene. Subsequently, we examined the expression level of c-MYC in cells with manipulated expression of Girdin and identified a positive correlation between Girdin expression and c-MYC expression. Moreover, we found that Girdin knockdown in c-MYC-overexpressing pancreatic cancer cells slowed cell growth, blocked the cell cycle progression, significantly promoted apoptosis, and markedly decreased the cell migration and invasion. This finding indicated that silencing Girdin could mitigate the effect of c-MYC on promoting proliferation and metastasis of pancreatic cancer. Overall, this study provided evidence that Girdin promoted pancreatic cancer development presumably by regulating the c-MYC overexpression.


Assuntos
Genes myc , Neoplasias Pancreáticas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/genética , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
3.
J Surg Res ; 241: 8-14, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31004874

RESUMO

BACKGROUND: Recently, we demonstrated that the expression of 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) in breast cancer is associated with shorter recurrence-free survival, and genetic or pharmacologic inhibition of HSD3B1 reduced colony formation and xenograft growth. However, the mechanisms are unclear. METHODS: Triple-negative MDA-MB-231 and BT-20 breast cancer cells underwent HSD3B1 silencing. Microarray and bioinformatic analysis were performed. The interleukin-6 (IL-6) expression and secretion were evaluated using real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Clonogenic ability and cell viability were determined in the absence or presence of recombinant IL-6. RESULTS: Functional and pathway enrichment analyses showed that HSD3B1 silencing modulates the expression of several growth factors and cytokines. Cells transfected with HSD3B1-targeting small interfering RNA or treated with an HSD3B1 inhibitor (trilostane) had decreased IL-6 expression and secretion. HSD3B1 inhibition reduced colony formation, which was partially rescued by IL-6 supplementation. The HSD3B1 knockdown enhanced paclitaxel sensitivity, and IL-6 treatment partially reversed the augmented cytotoxicity. CONCLUSIONS: Our findings suggest that the therapeutic potential of targeting HSD3B1 is in part mediated by IL-6 suppression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/tratamento farmacológico , Interleucina-6/metabolismo , Complexos Multienzimáticos/antagonistas & inibidores , Progesterona Redutase/antagonistas & inibidores , Esteroide Isomerases/antagonistas & inibidores , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Di-Hidrotestosterona/análogos & derivados , Di-Hidrotestosterona/farmacologia , Di-Hidrotestosterona/uso terapêutico , Sinergismo Farmacológico , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Complexos Multienzimáticos/genética , Análise de Sequência com Séries de Oligonucleotídeos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Progesterona Redutase/genética , RNA Interferente Pequeno/metabolismo , Proteínas Recombinantes/metabolismo , Esteroide Isomerases/genética
4.
Ann Surg Oncol ; 24(13): 4033-4041, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28744792

RESUMO

BACKGROUND: Human 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings. METHODS: Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo. RESULTS: The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth. CONCLUSIONS: Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Complexos Multienzimáticos/metabolismo , Progesterona Redutase/metabolismo , Receptores de Estrogênio/metabolismo , Esteroide Isomerases/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/metabolismo , Ciclo Celular , Movimento Celular , Proliferação de Células , Di-Hidrotestosterona/análogos & derivados , Di-Hidrotestosterona/farmacologia , Feminino , Seguimentos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Complexos Multienzimáticos/antagonistas & inibidores , Complexos Multienzimáticos/genética , Progesterona Redutase/antagonistas & inibidores , Progesterona Redutase/genética , Prognóstico , RNA Interferente Pequeno/genética , Esteroide Isomerases/antagonistas & inibidores , Esteroide Isomerases/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Zhongguo Zhong Yao Za Zhi ; 42(14): 2683-2690, 2017 Jul.
Artigo em Zh | MEDLINE | ID: mdl-29098822

RESUMO

This study attempts to evaluate the quality of Chinese formula granules by combined use of multi-component simultaneous quantitative analysis and bioassay. The rhubarb dispensing granules were used as the model drug for demonstrative study. The ultra-high performance liquid chromatography (UPLC) method was adopted for simultaneously quantitative determination of the 10 anthraquinone derivatives (such as aloe emodin-8-O-ß-D-glucoside) in rhubarb dispensing granules; purgative biopotency of different batches of rhubarb dispensing granules was determined based on compound diphenoxylate tablets-induced mouse constipation model; blood activating biopotency of different batches of rhubarb dispensing granules was determined based on in vitro rat antiplatelet aggregation model; SPSS 22.0 statistical software was used for correlation analysis between 10 anthraquinone derivatives and purgative biopotency, blood activating biopotency. The results of multi-components simultaneous quantitative analysisshowed that there was a great difference in chemical characterizationand certain differences inpurgative biopotency and blood activating biopotency among 10 batches of rhubarb dispensing granules. The correlation analysis showed that the intensity of purgative biopotency was significantly correlated with the content of conjugated anthraquinone glycosides (P<0.01), and the intensity of blood activating biopotency was significantly correlated with the content of free anthraquinone (P<0.01). In summary, the combined use of multi-component simultaneous quantitative analysis and bioassay can achieve objective quantification and more comprehensive reflection on overall quality difference among different batches of rhubarb dispensing granules.


Assuntos
Antraquinonas/análise , Medicamentos de Ervas Chinesas/administração & dosagem , Rheum/química , Animais , Bioensaio , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/normas , Glucosídeos/análise , Camundongos , Controle de Qualidade , Ratos
6.
Zhongguo Zhong Yao Za Zhi ; 42(23): 4636-4640, 2017 Dec.
Artigo em Zh | MEDLINE | ID: mdl-29376264

RESUMO

Seven compounds(deacetylasperulasidic acid methyl ester, gardenoside, chlorogenic acid, geniposide, crocin-Ⅰ, crocin-Ⅱ, chikusetsu saponin Ⅳa)were determined simultaneously by multiple wavelength HPLC with diode array detector(DAD) in different parts of Gardenia jasminoides. The results showed that these components in different parts of G. jasminoides had a different distribution, and there was a large difference in content of each component. Geniposide was mainly distributed in fruits and leaves; chikusetsu saponin Ⅳa was mainly distributed in roots and stems; crocus glycosides existed mainly in fruits; chlorogenic acid had a higher distribution in leaves and stems; gardenoside had a higher distribution in leaves and roots, while ceacetylasperulasidic acid methyl ester had a higher distribution in roots and stems. Based on the analysis of the chemical composition and content difference in different parts of G. jasminoides, the basis for the comprehensive utilization and quality evaluation of resources of G. jasminoides was provided.


Assuntos
Frutas/química , Gardenia/química , Compostos Fitoquímicos/análise , Folhas de Planta/química , Ácido Clorogênico/análise , Cromatografia Líquida de Alta Pressão , Iridoides/análise
7.
Microb Cell Fact ; 15: 54, 2016 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-27039899

RESUMO

BACKGROUND: Trehalose is related to several types of stress responses, especially freezing response in baker's yeast (Saccharomyces cerevisiae). It is desirable to manipulate trehalose-related genes to create yeast strains that better tolerate freezing-thaw stress with improved fermentation capacity, which are in high demand in the baking industry. RESULTS: The strain overexpressing MAL62 gene showed increased trehalose content and cell viability after prefermention-freezing and long-term frozen. Deletion of NTH1 in combination of MAL62 overexpression further strengthens freezing tolerance and improves the leavening ability after freezing-thaw stress. CONCLUSIONS: The mutants of the industrial baker's yeast with enhanced freezing tolerance and leavening ability in lean dough were developed by genetic engineering. These strains had excellent potential industrial applications.


Assuntos
Aclimatação/genética , Fermentação/genética , Congelamento , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Trealase/genética , alfa-Glucosidases/genética , Temperatura Baixa , Farinha/microbiologia , Deleção de Genes , Regulação Fúngica da Expressão Gênica , Organismos Geneticamente Modificados , Regulação para Cima/genética
8.
Biom J ; 58(6): 1311-1318, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27062639

RESUMO

In randomized trials with noncompliance, causal effects cannot be identified without strong assumptions. Therefore, several authors have considered bounds on the causal effects. Applying an idea of VanderWeele (), Chiba () gave bounds on the average causal effects in randomized trials with noncompliance using the information on the randomized assignment, the treatment received and the outcome under monotonicity assumptions about covariates. But he did not consider any observed covariates. If there are some observed covariates such as age, gender, and race in a trial, we propose new bounds using the observed covariate information under some monotonicity assumptions similar to those of VanderWeele and Chiba. And we compare the three bounds in a real example.


Assuntos
Interpretação Estatística de Dados , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Humanos , Cooperação do Paciente , Projetos de Pesquisa
9.
Anesth Analg ; 118(1): 116-24, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24247230

RESUMO

BACKGROUND: Previous studies have shown that local anesthetics may induce apoptosis in some cell types. In this study, we investigated the apoptotic effects of local anesthetics in human breast tumor cells. METHODS: Human breast cancer (MCF-7) and mammary epithelial (MCF-10A) cell lines were treated with lidocaine and/or bupivacaine. Cell viability, DNA fragmentation, and annexin V immunofluorescence staining were assessed. The effects on apoptosis-related protein expression were investigated by Western blot analysis. The findings were extended to studies in an in vivo xenograft model. RESULTS: Treatment of breast tumor cells with lidocaine and bupivacaine resulted in inhibition of cell viability via induction of apoptosis. The effects were more prominent in MCF-7 cells than in MCF-10A cells. Treatment with local anesthetics induced caspase 7, 8, 9, and poly ADP-ribose polymerase cleavage. The cleavage of caspase 7 and poly ADP-ribose polymerase induced by local anesthetics were effectively blocked by caspase inhibitors. Furthermore, treatment of MCF-7 xenografts with local anesthetics resulted in higher expression of cleaved caspase 7 and an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. CONCLUSION: Lidocaine and bupivacaine induce apoptosis of breast tumor cells at clinically relevant concentrations. Our results reveal previously unrecognized beneficial actions of local anesthetics and call for further studies to assess the oncologic advantages of their use during breast cancer surgery.


Assuntos
Anestésicos Locais/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama , Anestésicos Locais/uso terapêutico , Animais , Apoptose/fisiologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Transformada , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Feminino , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
10.
Materials (Basel) ; 17(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38591375

RESUMO

The hydrolysis mechanism of americium was calculated using density functional theory, and the detailed microscopic reaction mechanism was obtained. The results show that americium reacts with water along the octet state to produce oxides and H2, and that this reaction is exothermic. The interaction between Am and O atoms gradually changes from initially electrostatic interaction to covalent interaction, and continues to strengthen. During the reaction process, Am atoms always lose electrons, the 5f orbital is obviously involved, and there is df orbital hybridization. This study provides the necessary theoretical data support for the theoretical and experimental study of the actinide system.

11.
Chem Biodivers ; 10(11): 2032-41, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24243612

RESUMO

The essential oil obtained by hydrodistillation from the aerial parts of Aristolochia delavayi Franch. (Aristolochiaceae), a unique edible aromatic plant consumed by the Nakhi (Naxi) people in Yunnan, China, was investigated using GC/MS analysis. In total, 95 components, representing more than 95% of the oil composition, were identified, and the main constituents found were (E)-dec-2-enal (52.0%), (E)-dodec-2-enal (6.8%), dodecanal (3.35%), heptanal (2.88%), and decanal (2.63%). The essential oil showed strong inhibitory activity (96% reduction) of the production of bacterial volatile sulfide compounds (VSC) by Klebsiella pneumoniae, an effect that was comparable with that of the reference compound citral (91% reduction). Moreover, the antimicrobial activity of the essential oil and the isolated major compound against eight bacterial and six fungal strains were evaluated. The essential oil showed significant antibacterial activity against Providencia stuartii and Escherichia coli, with minimal inhibitory concentrations (MIC) ranging from 3.9 to 62.5 µg/ml. The oil also showed strong inhibitory activity against the fungal strains Trichophyton ajelloi, Trichophyton terrestre, Candida glabrata, Candida guilliermondii, and Cryptococcus neoformans, with MIC values ranging from 3.9 to 31.25 µg/ml, while (E)-dec-2-enal presented a lower antifungal activity than the essential oil.


Assuntos
Anti-Infecciosos/análise , Anti-Infecciosos/farmacologia , Aristolochia/química , Óleos Voláteis/análise , Óleos Voláteis/farmacologia , Anti-Infecciosos/isolamento & purificação , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Fungos/efeitos dos fármacos , Humanos , Micoses/tratamento farmacológico , Óleos Voláteis/isolamento & purificação , Plantas Comestíveis/química
12.
PLoS One ; 18(1): e0279918, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649269

RESUMO

One of the main concerns in multidimensional item response theory (MIRT) is to detect the relationship between observed items and latent traits, which is typically addressed by the exploratory analysis and factor rotation techniques. Recently, an EM-based L1-penalized log-likelihood method (EML1) is proposed as a vital alternative to factor rotation. Based on the observed test response data, EML1 can yield a sparse and interpretable estimate of the loading matrix. However, EML1 suffers from high computational burden. In this paper, we consider the coordinate descent algorithm to optimize a new weighted log-likelihood, and consequently propose an improved EML1 (IEML1) which is more than 30 times faster than EML1. The performance of IEML1 is evaluated through simulation studies and an application on a real data set related to the Eysenck Personality Questionnaire is used to demonstrate our methodologies.


Assuntos
Modelos Estatísticos , Motivação , Modelos Logísticos , Algoritmos , Simulação por Computador
13.
Expert Rev Hematol ; 16(12): 1135-1142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37883026

RESUMO

OBJECTIVE: Currently, immune checkpoint inhibitors (ICIs) therapy is one of the main methods of treatment in non-small cell lung cancer (NSCLC). This study aimed to explore the risk factors of VTE and evaluate the effect of ICIs on VTE in patients with NSCLC. RESEARCH DESIGN AND METHODS: We retrospectively studied patients with NSCLC who were divided into VTE group and without VTE (Non-VTE) group. We identified the risk factors of VTE in NSCLC patients and evaluated the effect of ICIs on VTE in NSCLC patients. RESULTS: We found that clinical stage III-IV (P = 0.015) and Khorana score (KS) ≥ 2 (P = 0.047) were independent risk factors for the occurrence of VTE in NSCLC, and treatment with ICIs reduced the risk of VTE occurrence (P = 0.028). There were no differences of survival rates in the 12-month (P = 0.449), 24-month (P = 0.412), or 36-month (P = 0.315) between the VTE and non-VTE groups. History of anti-angiogenic therapy (P = 0.033) and chronic obstructive pulmonary disease (COPD) (P = 0.046) were independent risk factors for VTE in NSCLC patients who were treated with ICIs. CONCLUSION: This study suggests that we should strengthen anticoagulant therapy when using ICIs for NSCLC patients with a history of anti-angiogenic therapy and COPD.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Doença Pulmonar Obstrutiva Crônica , Tromboembolia Venosa , Humanos , Carcinoma Pulmonar de Células não Pequenas/complicações , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Estudos Retrospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
14.
In Vivo ; 37(1): 262-269, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36593004

RESUMO

BACKGROUND/AIM: A recent study suggested that solute carrier family 35 member A2 (SLC35A2) is related to poor prognosis in patients with breast cancer. SLC35A2 transports uridine diphosphate-galactose from the cytosol to the lumen of the endoplasmic reticulum and Golgi. MATERIALS AND METHODS: Immunohistochemical expression of SLC35A2 was evaluated using tissue microarrays. Cell growth, migration, and invasion of breast cancer cells were examined following loss- and gain-of-expression of SLC35A2. RESULTS: Normal breast tissue exhibited SLC35A2 immunoreactivity in the nucleus. A progressive increase in cytoplasmic expression from in situ carcinoma to invasive carcinoma was observed. There was a correlation between cytoplasmic SLC35A2 expression and breast cancer stage (p<0.001). MDA-MB-468 and MCF-7 cells transfected with SLC35A2 shRNA had unchanged cell viability but significantly reduced cell migration and invasion. In contrast, MDA-MB-231 and HCC1806 cells transfected with the SLC35A2 expression vector showed increased migration. CONCLUSION: Breast cancer progression is accompanied by differential expression patterns of SLC35A2. The migratory or invasive capacity of breast cancer cells is associated with SLC35A2 expression.


Assuntos
Neoplasias da Mama , Carcinoma , Humanos , Feminino , Neoplasias da Mama/patologia , Mama/patologia , Células MCF-7 , Invasividade Neoplásica/genética , Carcinoma/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
15.
Front Cardiovasc Med ; 10: 1224795, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37736023

RESUMO

Background: Hypertension is a major public health problem, and its resulting other cardiovascular diseases are the leading cause of death worldwide. In this study, we constructed a convenient and high-performance hypertension risk prediction model to assist in clinical diagnosis and explore other important influencing factors. Methods: We included 8,073 people from NHANES (2017-March 2020), using their 120 features to form the original dataset. After data pre-processing, we removed several redundant features through LASSO regression and correlation analysis. Thirteen commonly used machine learning methods were used to construct prediction models, and then, the methods with better performance were coupled with recursive feature elimination to determine the optimal feature subset. After data balancing through SMOTE, we integrated these better-performing learners to construct a fusion model based for predicting hypertension risk on stacking strategy. In addition, to explore the relationship between serum ferritin and the risk of hypertension, we performed a univariate analysis and divided it into four level groups (Q1 to Q4) by quartiles, with the lowest level group (Q1) as the reference, and performed multiple logistic regression analysis and trend analysis. Results: The optimal feature subsets were: age, BMI, waist, SBP, DBP, Cre, UACR, serum ferritin, HbA1C, and doctors recommend reducing salt intake. Compared to other machine learning models, the constructed fusion model showed better predictive performance with precision, accuracy, recall, F1 value and AUC of 0.871, 0.873, 0.871, 0.869 and 0.966, respectively. For the analysis of the relationship between serum ferritin and hypertension, after controlling for all co-variates, OR and 95% CI from Q2 to Q4, compared to Q1, were 1.396 (1.176-1.658), 1.499 (1.254-1.791), and 1.645 (1.360-1.989), respectively, with P < 0.01 and P for trend <0.001. Conclusion: The hypertension risk prediction model developed in this study is efficient in predicting hypertension with only 10 low-cost and easily accessible features, which is cost-effective in assisting clinical diagnosis. We also found a trend correlation between serum ferritin levels and the risk of hypertension.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 282: 121679, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-35917619

RESUMO

We theoretically investigate the possibility of laser cooling 87Sr35Cl molecule in accordance with vibrational and hyperfine spectroscopy. The potential energy curves and dipole moment of the X2Σ+1/2, A2Π1/2,3/2 and B2Σ+ states are calculated using ab initio method and the spectroscopic parameters are in good agreement with the experimental data. On account of the accurate potential energy curves and the transition dipole moment, the Franck - Condon factors and radiative lifetimes are predicted. Comparing the conditions of laser cooling candidate molecules, the A2Π 1/2 â†” X2Σ+1/2 transition is selected as the laser cooling cycle system. In order to obtain an approximately closed cooling cycle system, we employed matrix element algorithm to calculated the hyperfine spectroscopy and branching ratios of the 87Sr35Cl molecule. Furthermore, an electro-optical modulator (EOM) is designed including six hyperfine levels of the ground state X2Σ+1/2 (v = 0, N = 1).

17.
Br J Math Stat Psychol ; 75(2): 363-394, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34918834

RESUMO

The aim of latent variable selection in multidimensional item response theory (MIRT) models is to identify latent traits probed by test items of a multidimensional test. In this paper the expectation model selection (EMS) algorithm proposed by Jiang et al. (2015) is applied to minimize the Bayesian information criterion (BIC) for latent variable selection in MIRT models with a known number of latent traits. Under mild assumptions, we prove the numerical convergence of the EMS algorithm for model selection by minimizing the BIC of observed data in the presence of missing data. For the identification of MIRT models, we assume that the variances of all latent traits are unity and each latent trait has an item that is only related to it. Under this identifiability assumption, the convergence of the EMS algorithm for latent variable selection in the multidimensional two-parameter logistic (M2PL) models can be verified. We give an efficient implementation of the EMS for the M2PL models. Simulation studies show that the EMS outperforms the EM-based L1 regularization in terms of correctly selected latent variables and computation time. The EMS algorithm is applied to a real data set related to the Eysenck Personality Questionnaire.


Assuntos
Algoritmos , Motivação , Teorema de Bayes , Simulação por Computador
18.
Brain Behav ; 12(4): e2545, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35315239

RESUMO

BACKGROUND: Direct moxibustion (DM) is reported to be useful for cervical spondylotic radiculopathy (CSR), but the analgesic mechanism remains unknown. Autophagy plays a protective role in neuronal apoptosis, Act A/Smads signaling pathway has been confirmed to be associated with the activation of autophagy. The study aimed to explore the effect of DM on autophagy in rats with CSR and the involvement of Act A/Smads signaling pathway. METHODS: Rats were randomly divided into Sham, CSR, CSR + DM, CSR + DM + 3-MA (PI3K inhibitor), and CSR + DM + SB (Act A inhibitor) group. Three days after establishment of CSR model with a fish line inserted under the axilla of the nerve roots, DM at Dazhui (GV14) was performed six times once for seven consecutive days. Western blot and immunofluorescence staining were used to observe the expression of the neuronal autophagy molecule LC3II/I, Atg7, and Act A/Smads signaling molecule Act A, p-Smad2, and p-Smad3. Bcl-2/Bax mRNA expression was measured by real time PCR. RESULTS: DM improved the pain threshold and motor function of CSR rats and promoted the expression of Act A, p-Smad2, p-Smad3, LC3II/I, and Atg7 in the entrapped-nerve root spinal dorsal horn. DM reduced the expression of Bax mRNA and decreased the number of apoptotic neurons. 3-MA and Act A inhibitor SB suppressed the expression of above-mentioned proteins and reduced the protective effect of DM on apoptotic neurons. CONCLUSION: DM exerts analgesic effects by regulating the autophagy to reduce cell apoptosis and repair nerve injury, and this feature may be related to the Act A/Smads signaling pathway.


Assuntos
Moxibustão , Radiculopatia , Espondilose , Animais , Autofagia , Fosfatidilinositol 3-Quinases , RNA Mensageiro , Radiculopatia/genética , Radiculopatia/terapia , Ratos , Transdução de Sinais , Proteína X Associada a bcl-2
19.
Sci Rep ; 12(1): 17201, 2022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-36229645

RESUMO

Lung cancer is the leading cause of cancer-related death worldwide. MicroRNAs (miRNAs) in circulating small extracellular vesicles (sEVs) have been suggested to be potential biomarkers for cancer diagnosis. The present study was designed to explore whether plasma-derived sEV miRNAs could be utilized as diagnostic biomarkers for differentiating between early-stage small cell lung cancer (SCLC) and early-stage non-small cell lung cancer (NSCLC). We compared the miRNA profiles of plasma-derived sEVs from healthy individuals, patients with early-stage SCLC and patients with early-stage NSCLC. Next-generation sequencing was used to screen for differentially expressed miRNAs (DEMs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict the potential functions of these DEMs. Weighted gene coexpression network analysis (WGCNA) was used to identify the different pathology-related miRNA modules. We found that 22 DEMs were significantly different among healthy individuals, patients with early-stage SCLC, and patients with early-stage NSCLC. We selected six representative DEMs for validation by qRT‒PCR, which confirmed that miRNA-483-3p derived from plasma sEVs could be used as a potential biomarker for the diagnosis of early-stage SCLC, miRNA-152-3p and miRNA-1277-5p could be used for the diagnosis of early-stage NSCLC respectively.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , MicroRNA Circulante , Vesículas Extracelulares , Neoplasias Pulmonares , MicroRNAs , Carcinoma de Pequenas Células do Pulmão , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Vesículas Extracelulares/genética , Vesículas Extracelulares/patologia , Perfilação da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Carcinoma de Pequenas Células do Pulmão/genética
20.
Front Plant Sci ; 13: 1023739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36388474

RESUMO

Auxin response factors (ARFs) are transcription factors that play important roles in plants. ARF2 is a member of the ARF family and participates in many plant growth and developmental processes. However, the role of ARF2 in strawberry fruit quality remains unclear. In this study, FveARF2 was isolated from the woodland strawberry 'Ruegen' using reverse transcription-polymerase chain reaction (RT-PCR), which showed that FveARF2 expression levels were higher in the stem than in other organs of the 'Ruegen' strawberry. Moreover, FaARF2 was higher in the white fruit stage of cultivated strawberry fruit than in other stage. Subcellular localization analysis showed that FveARF2 is located in the nucleus, while transcriptional activation assays showed that FveARF2 inhibited transcription in yeast. Silencing FveARF2 in cultivated strawberry fruit revealed earlier coloration and higher soluble solid, sugar, and anthocyanin content in the transgenic fruit than in the control fruit, overexpression of FveARF2 in strawberry fruit delayed ripening and lower soluble solid, sugar, and anthocyanin content compared to the control fruit. Gene expression analysis indicated that the transcription levels of the fruit ripening genes FaSUT1, FaOMT, and FaCHS increased in FveARF2-RNAi fruit and decreased in FveARF2-OE fruit, when compared with the control. Furthermore, yeast one-hybrid (Y1H) and GUS activity experiments showed that FveARF2 can directly bind to the AuxRE (TGTCTC) element in the FaSUT1, FaOMT, and FaCHS promoters in vitro and in vivo. Potassium ion supplementation improved the quality of strawberry fruit, while silencing FveARF2 increased potassium ion content in transgenic fruit. The Y1H and GUS activity experiments also confirmed that FveARF2 could directly bind to the promoter of FveKT12, a potassium transporter gene, and inhibited its expression. Taken together, we found that FveARF2 can negatively regulate strawberry fruit ripening and quality, which provides new insight for further study of the molecular mechanism of strawberry fruit ripening.

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