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1.
Small ; 20(13): e2307333, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37967329

RESUMO

Reducing the dark current of photodetectors is an important strategy for enhancing the detection sensitivity, but hampered by the manufacturing cost due to the need for controlling the complex material composition and processing intricate interface. This study reports a new single-component photochromic semiconductor, [(HDMA)4(Pb3Br10)(PhSQ)2]n (1, HDMA = dimethylamine cation, PhSQ = 1-(4-sulfophenyl)-4,4'-bipyridinium), by introducing a redox-active monosubstituted viologen zwitterion into inorganic semiconducting skeleton. It features yellow to green coloration after UV irradiation with the sharply dropping intrinsic conductivity of 14.6-fold, and the photodetection detection sensitivity gain successfully doubles. The reason of decreasing conductivity originates from the increasing the band gap of the inorganic semiconducting component and formation of Frenkel excitons with strong Coulomb interactions, thereby decreasing the concentration of thermally excited intrinsic carriers.

2.
Acta Pharmacol Sin ; 45(4): 686-703, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38049578

RESUMO

Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancers with mutations predominantly occurring in codon 12. These mutations disrupt the normal function of KRAS by interfering with GTP hydrolysis and nucleotide exchange activity, making it prone to the GTP-bound active state, thus leading to sustained activation of downstream pathways. Despite decades of research, there has been no progress in the KRAS drug discovery until the groundbreaking discovery of covalently targeting the KRASG12C mutation in 2013, which led to revolutionary changes in KRAS-targeted therapy. So far, two small molecule inhibitors sotorasib and adagrasib targeting KRASG12C have received accelerated approval for the treatment of non-small cell lung cancer (NSCLC) harboring KRASG12C mutations. In recent years, rapid progress has been achieved in the KRAS-targeted therapy field, especially the exploration of KRASG12C covalent inhibitors in other KRASG12C-positive malignancies, novel KRAS inhibitors beyond KRASG12C mutation or pan-KRAS inhibitors, and approaches to indirectly targeting KRAS. In this review, we provide a comprehensive overview of the molecular and mutational characteristics of KRAS and summarize the development and current status of covalent inhibitors targeting the KRASG12C mutation. We also discuss emerging promising KRAS-targeted therapeutic strategies, with a focus on mutation-specific and direct pan-KRAS inhibitors and indirect KRAS inhibitors through targeting the RAS activation-associated proteins Src homology-2 domain-containing phosphatase 2 (SHP2) and son of sevenless homolog 1 (SOS1), and shed light on current challenges and opportunities for drug discovery in this field.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Terapia de Alvo Molecular , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Descoberta de Drogas , Guanosina Trifosfato , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/genética , Antineoplásicos/química , Antineoplásicos/uso terapêutico
3.
Phys Rev Lett ; 131(7): 073401, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37656862

RESUMO

Ultracold atoms in optical lattices form a competitive candidate for quantum computation owing to the excellent coherence properties, the highly parallel operations over spins, and the ultralow entropy achieved in qubit arrays. For this, a massive number of parallel entangled atom pairs have been realized in superlattices. However, the more formidable challenge is to scale up and detect multipartite entanglement, the basic resource for quantum computation, due to the lack of manipulations over local atomic spins in retroreflected bichromatic superlattices. In this Letter, we realize the functional building blocks in quantum-gate-based architecture by developing a cross-angle spin-dependent optical superlattice for implementing layers of quantum gates over moderately separated atoms incorporated with a quantum gas microscope for single-atom manipulation and detection. Bell states with a fidelity of 95.6(5)% and a lifetime of 2.20±0.13 s are prepared in parallel, and then connected to multipartite entangled states of one-dimensional ten-atom chains and two-dimensional plaquettes of 2×4 atoms. The multipartite entanglement is further verified with full bipartite nonseparability criteria. This offers a new platform toward scalable quantum computation and simulation.

4.
BMC Cancer ; 23(1): 1205, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062430

RESUMO

Gastrointestinal (GI) cancers (gastric cancer, oesophageal cancer, liver cancer, colorectal cancer, etc.) are the most common cancers with the highest morbidity and mortality in the world. The therapy for most GI cancers is difficult and is associated with a poor prognosis. In China, upper GI cancers, mainly gastric cancer (GC) and oesophageal cancer (EC), are very common due to Chinese people's characteristics, and more than half of patients are diagnosed with distant metastatic or locally advanced disease. Compared to other solid cancers, such as lung cancer and breast cancer, personalized therapies, especially targeted therapy and immunotherapy, in GC and EC are relatively lacking, leading to poor prognosis. For a long time, most studies were carried out by using in vitro cancer cell lines or in vivo cell line-derived xenograft models, which are unable to reproduce the characteristics of tumours derived from patients, leading to the possible misguidance of subsequent clinical validation. The patient-derived models represented by patient-derived organoid (PDO) and xenograft (PDX) models, known for their high preservation of patient tumour features, have emerged as a very popular platform that has been widely used in numerous studies, especially in the research and development of antitumour drugs and personalized medicine. Herein, based on some of the available published literature, we review the research and application status of PDO and PDX models in GC and EC, as well as detail their future challenges and prospects, to promote their use in basic and translational studies or personalized therapy.


Assuntos
Neoplasias Esofágicas , Neoplasias Gastrointestinais , Neoplasias Gástricas , Animais , Humanos , Modelos Animais de Doenças , Neoplasias Gastrointestinais/tratamento farmacológico , Organoides/patologia , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Opt Express ; 30(25): 44665-44680, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36522887

RESUMO

In this study, we propose a polarization-modulated laser-induced microjet-assisted ablation method for machining microgrooves with controllable cross-sections. A novel mathematical model is presented to accurately predict the cross-sections by considering the combined effects of polarization and secondary ablation. The simulation and experimental results reveal that the effect of secondary ablation becomes more obvious when steeper grooves are ablated with higher repetition frequency and larger pulse energy. The polarization effect and secondary ablation of target material result in asymmetric ablation of linearly polarized laser beam. To avoid the asymmetric ablation, we present the cylindrical vector beams to achieve scanning-path independent laser micromachining with various cross-sections. Based on the prediction model, the cross-sectional characteristics are precisely designed and fabricated by tuning laser processing parameters. Our work provides a reliable approach for the controllable fabrication of microgrooves at the scale of tens of micrometers.

6.
Acta Biochim Biophys Sin (Shanghai) ; 54(4): 504-513, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35462473

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent metabolic disorder all over the world, and lipid metabolic disorders and inflammation are closely associated and contribute to the pathogenesis of NAFLD. Cholesterol 25-hydroxylase (Ch25h) and its product, 25-hydroxycholesterol (25-HC), play important roles in cholesterol homeostasis and inflammation, but whether Ch25h and 25-HC are involved in NAFLD remains uncertain. In this study, we use Ch25h knockout mice, hepatic cells and liver biopsies to explore the role of Ch25h and 25-HC in lipid metabolism and accumulation in liver, determine the molecular mechanism of lipid accumulation and inflammation influenced by Ch25h and 25-HC, and assess the regulatory effects of Ch25h and 25-HC on human NAFLD. Our results indicate that mice lacking Ch25h have normal cholesterol homeostasis with normal diet, but under the condition of high fat diet (HFD), the mice show higher total cholesterol and triglyceride in serum, and prone to hepatic steatosis. Ch25h deficiency reduces the cholesterol efflux regulated by liver X receptor α (LXRα), increases the synthesis of cholesterol mediated by sterol-regulatory element binding protein 2 (SREBP-2), and increases the activation of NLRP3 inflammasome, therefore promotes hepatic steatosis. Collectively, our data suggest that Ch25h and 25-HC play important roles in lipid metabolism and inflammation, thereby exerting anti-NAFLD functions.


Assuntos
Inflamassomos , Hepatopatia Gordurosa não Alcoólica , Camundongos , Humanos , Animais , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Metabolismo dos Lipídeos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado/metabolismo , Inflamação/metabolismo , Dieta Hiperlipídica , Colesterol/metabolismo , Camundongos Knockout , Triglicerídeos/metabolismo
7.
Water Sci Technol ; 85(1): 27-38, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35050863

RESUMO

The non-point source (NPS) pollution has become an important limitation to the sustainable development of the Three Gorges Reservoir Area (TGRA) water resources. NPS load estimation research has theoretical and realistic significance for water environment security and water pollution control. Therefore, the TGRA was chosen to be the study area, and the export coefficients of different land-use type were calculated through literature consultation method combined with improved observation experiment. The load of total nitrogen (TN) and total phosphorus (TP) of NPS from different pollution sources including farmland, decentralized livestock and poultry breeding and domestic pollution sources were estimated. The results are shown as follows: the order of TN load of different sources in the TGRA from high to low was land use, livestock and poultry breeding, rural life; the TN from land use was 372% higher than that of rural; the order of TP load of different sources in the TGRA from high to low was livestock and poultry breeding, rural life, land use; the TP from livestock and poultry breeding was 114.5% higher than that of land use. Therefore, control of livestock and poultry sewage discharges was the key practice to limit the TP loss, while the optimization of agricultural management was the key practice to control the loss of TN.


Assuntos
Poluição Difusa , Poluentes Químicos da Água , Monitoramento Ambiental , Fósforo/análise , Rios , Poluentes Químicos da Água/análise
8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(3): 466-473, 2022 May.
Artigo em Zh | MEDLINE | ID: mdl-35642156

RESUMO

Objective: To study the status quo of the readmission of senile dementia patients in Chengdu, and to analyze the primary diagnosis, the economic burden and the influencing factors of readmission. Methods: Dementia inpatients aged 60 and above in Chengdu were the subjects of this study. The subjects were diagnosed with dementia between 2013 and 2017. Their heath insurance coverage was either the basic medical insurance for urban employees in Chengdu or the basic medical insurance for urban and rural residents of Chengdu. The rank sum test and the chi-square test were conducted to analyze the differences in readmission rate and the economic burden of hospitalization among subjects with different characteristics. Logistic regression was done to analyze the factors affecting readmission. Results: The total number of dementia inpatients over the 5-year period was 27881 patients (78820 admissions). The 30-day readmission rate was 25.14% (7011/27881) and the 5-year readmission rate was 45.79% (12767/27881). The primary diagnoses of 12767 readmitted patients mainly included dementia (28.57%), circulatory system diseases (24.26%), and respiratory system diseases (23.71%). The economic burden of hospitalization was higher for readmitted patients than that of patients who were not readmitted ( Z=33.777, P<0.001). The occurrence of readmission was correlated to the following factors, advanced age (compared to that of the 60-65 yr. group, the 70-75 yr. group: odds ratio [ OR]=1.123, 95% confidence interval [ CI]: 1.019-1.237, and the 75-80 yr. group: OR=1.123, 95% CI: 1.108-1.218), participation in the basic medical insurance for urban employees ( OR=1.674, 95% CI: 1.578-1.775), types of dementia (compared to unspecified dementia, Alzheimer's dementia group: OR=1.256, 95% CI: 1.163-1.357, Parkinson's disease dementia group: OR=1.774, 95% CI: 1.658-1.898, and mixed-type dementia group: OR=1.750, 95% CI: 1.457-2.103), disease condition (compared with patients with only dementia, those who have other diseases: OR=0.536,95% CI :0.493-0.583), length of hospital stay ( OR=1.593, 95% CI: 1.552-1.635), and staying at a lower level hospital (compared to that of tertiary hospitals, secondary hospitals: OR=1.319, 95% CI: 1.248-1.395, primary hospitals: OR=1.744, 95% CI: 1.608-1.891, and other hospitals: OR=1.465, 95% CI: 1.311-1.537). Conclusion: Senile dementia patients have a high 30-day readmission rate, and the readmission entails heavy economic burdens on the patients. For the populations covered by medical insurance, the following features are correlated to the occurrence of readmission: advanced age, coverage by the basic medical insurance for urban employees, Alzheimer's dementia, Parkinson's disease dementia, mixed-type dementia, dementia patients without other comorbidities, extended length of stay, and hospitalization at a lower level hospital. However, further research is needed for better understanding of the specific mechanisms so that readmission of senile dementia patients can be reduced and the economic burden of the disease can be minimized.


Assuntos
Doença de Alzheimer , Demência , Seguro , Doença de Parkinson , Demência/epidemiologia , Humanos , Readmissão do Paciente , Estudos Retrospectivos , Fatores de Risco
9.
Cancer Cell Int ; 20: 510, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33088218

RESUMO

BACKGROUND: Due to the high morbidity and poor clinical outcomes, early predictive and prognostic biomarker identification is desiderated in colorectal cancer (CRC). As a homologue of the Deleted in Colorectal Cancer (DCC) gene, the role of Neogenin-1 (NEO1) in CRC remained unveiled. This study was designed to probe into the effects and potential function of NEO1 in CRC. METHODS: Online databases, Gene Set Enrichment Analysis (GSEA), quantitative real-time PCR and western blotting were used to evaluate NEO1 expression in colorectal cancer tissues. Survival analysis was performed to predict the prognosis of CRC patients based on NEO1 expression level. Then, cell proliferation was detected by colony formation and Cell Counting Kit 8 (CCK-8) assays. CRC cell migration and invasion were examined by transwell assays. Finally, we utilized the Gene Set Variation Analysis (GSVA) and GSEA to dig the potential mechanisms of NEO1 in CRC. RESULTS: Oncomine database and The Cancer Genome Atlas (TCGA) database showed that NEO1 was down-regulated in CRC. Further results validated that NEO1 mRNA and protein expression were both significantly lower in CRC tumor tissues than in the adjacent tissues in our clinical samples. NEO1 expression was decreased with the progression of CRC. Survival and other clinical characteristic analyses exhibited that low NEO1 expression was related with poor prognosis. A gain-of-function study showed that overexpression of NEO1 restrained proliferation, migration and invasion of CRC cells while a loss-of-function showed the opposite effects. Finally, functional pathway enrichment analysis revealed that NEO1 low expression samples were enriched in inflammation-related signaling pathways, EMT and angiogenesis. CONCLUSION: A tumor suppressor gene NEO1 was identified and verified to be correlated with the prognosis and progression of CRC, which could serve as a prognostic biomarker for CRC patients.

10.
J Cell Mol Med ; 23(9): 5970-5980, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31270932

RESUMO

Obesity is considered a chronic inflammatory disease, the inflammatory factors, such as interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) and small inducible cytokine A5 (RANTES), are elevated in obese individuals. Pituitary adenylate cyclase-activating polypeptide (PACAP) suppresses anti-inflammatory cytokines and ameliorates glucose and lipid metabolism. Our previous study showed that Fas apoptosis inhibitory molecule (FAIM) is a new mediator of Akt2 signalling, increases the insulin signalling pathway and lipid metabolism. In this study, we found that PACAP promoted the expression of FAIM protein in a human hepatocyte cell line (L02). Overexpression of FAIM with lentivirus suppressed the expression of the inflammatory factor interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) and tumour necrosis factor alpha (TNF-α). Following treatment of obese mice with FAIM or PACAP for 2 weeks, inflammation was alleviated and the bodyweight and blood glucose levels were decreased. Overexpression of FAIM down-regulated the expression of adipogenesis proteins, including SREBP1, SCD1, FAS, SREBP2 and HMGCR, and up-regulated glycogen synthesis proteins, including Akt2 (Ser474) phosphorylation, GLUT2 and GSK-3ß, in the liver of obese mice. However, down-regulation of FAIM with shRNA promotes obesity. Altogether, our data identified that FAIM mediates the function of PACAP in anti-inflammation, glucose regulation and lipid metabolism in obese liver.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Glucose/metabolismo , Metabolismo dos Lipídeos/fisiologia , Obesidade/patologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Animais , Proteínas Reguladoras de Apoptose/genética , Glicemia/efeitos dos fármacos , Linhagem Celular , Quimiocina CCL2/metabolismo , Fígado Gorduroso/patologia , Hepatócitos/metabolismo , Humanos , Inflamação/patologia , Interleucina-6/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Interferência de RNA , RNA Interferente Pequeno/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
FASEB J ; : fj201800377R, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-30161002

RESUMO

Prostate cancer is the second-most common malignancy of the male genitourinary system. TNF-α has attracted intense attention as a potential therapeutic agent against various cancers. However, its therapeutic application is restricted by short half life and severe toxic side-effects. In this study, we constructed a stable nanodrug, called TNF-α-derived polypeptide (P16)-conjugated, chitosan (CTS)-modified selenium nanoparticle (SC; SCP), which is composed of SC as a slow-release carrier conjugated to P16. SCP had significant inhibitory effects on multiple types of tumor cells, especially DU145 prostate cancer cells, but not on RWPE-1 normal human prostate epithelial cells. SCP could induce G0/G1 cell-cycle arrest and apoptosis in DU145 cells more effectively than could P16 and TNF-α. In DU145 xenograft tumor models, SCP exerted much stronger antitumor effects than P16 or estramustine (the clinical drug for prostate cancer) but caused fewer toxic side-effects. In addition, SCP significantly inhibited proliferation and accelerated apoptosis in DU145 xenograft tumors. Further mechanistic studies revealed that SCP exerted antitumor effects via activation of the p38 MAPK/JNK pathway, thus inducing G0/G1 cell-cycle arrest and caspase-dependent apoptosis. These findings suggest that SCP may represent a potential long-lasting therapeutic agent for human prostate cancer with fewer side effects.-Yan, Q., Chen, X., Gong, H., Qiu, P., Xiao, X., Dang, S., Hong, A., Ma, Y. Delivery of a TNF-α-derived peptide by nanoparticles enhances its antitumor activity by inducing cell-cycle arrest and caspase-dependent apoptosis.

12.
Inorg Chem ; 58(12): 7667-7671, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31135139

RESUMO

An anionic microporous metal-organic framework (1), featuring a combination of mononuclear and tetranuclear zinc clusters and a mix-and-match strategy of two different types of organic ligands, has been successfully constructed via a solvothermal reaction. Its luminescence can be exclusively quenched by acetone. In situ single-crystal X-ray diffraction studies reveal the specific acetone binding sites and the existence of multiple hydrogen bonds between acetone and the framework. Together with its chemical and thermal stability, 1 has been demonstrated to be a potential luminescence probe for the rapid detection of acetone with a remarkable anti-interference and a low detection limit (1.85 ppm).

13.
Bioorg Chem ; 88: 102973, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31077912

RESUMO

Four new polyketides, including an unusual naphthoquinone derivative (1), two azaphilone analogous (2, 7) and an α-pyrone (12), were isolated from the gorgonian-derived fungus Penicillium sclerotiorum CHNSCLM-0013 together with nine known compounds. Their structures were identified based on the 1D, 2D NMR, HRESIMS, single crystal X-ray diffraction and the absolute configurations were determined by comparing the 1H NMR chemical shift and optical rotations with those reported in literature. In the bioassay, compounds 2, 6, 7, 10 and 12 exhibited significant inhibitory activities against the nitric oxide (NO) production in the LPS-induced macrophage RAW 264.7 with the IC50 values in the range of 2.5-18.0 µM. Compounds 2, 6 and 7 exhibited the possible mechanism of downregulating the expression of iNOS and COX-2 in mRNA level. The primary structure-activity relationship was also discussed based on the molecular-modeling. This study will make a contribution to the chemical diversities of polyketides especially the azaphilone derivatives and the discovery of potential anti-inflammatory agent from marine fungi.


Assuntos
Penicillium/química , Policetídeos/farmacologia , Animais , Antozoários , Anti-Inflamatórios não Esteroides , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Policetídeos/química , Policetídeos/isolamento & purificação , Células RAW 264.7 , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Relação Estrutura-Atividade
14.
Mar Drugs ; 17(8)2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31434338

RESUMO

Four new metabolites, asperchalasine I (1), dibefurin B (2) and two epicoccine derivatives (3 and 4), together with seven known compounds (5-11) were isolated from a mangrove fungus Mycosphaerella sp. SYSU-DZG01. The structures of compounds 1-4 were established from extensive spectroscopic data and HRESIMS analysis. The absolute configuration of 1 was deduced by comparison of ECD data with that of a known structure. The stereostructures of 2-4 were further confirmed by single-crystal X-ray diffraction. Compounds 1, 8 and 9 exhibited significant α-glucosidase inhibitory activity with IC50 values of 17.1, 26.7 and 15.7 µM, respectively. Compounds 1, 4, 6 and 8 showed antioxidant activity by scavenging DPPH· with EC50 values ranging from 16.3 to 85.8 µM.


Assuntos
Antioxidantes/química , Ascomicetos/química , Ascomicetos/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Cristalografia por Raios X , Estrutura Molecular , alfa-Glucosidases/metabolismo
15.
J Cell Biochem ; 119(4): 3519-3527, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29144017

RESUMO

It was found that the expression level of miR-147a was significantly increased and the pathway of PI3K/AKT was dramatically inhibited after radiation. In view of the relationship between miRNA and target genes, we put forward the question, what is the relationship between PI3K/AKT and miR-147a? In order to find the answer to the question, we used bioinformatics techniques to analyze the relationship between miR-147 (a or b) and PI3K/AKT signaling pathway. miR-147a overexpression plasmid and PDPK1 3'UTR luciferase reporter gene plasmid were constructed. Dual luciferase reporter gene system validation experiments were carried out on miR-147a and PDPK1 relationship. The verification experiments were also carried out. Bioinformatics analysis showed that there is a miR-147a binding site in the non-coding region (3'UTR) of PDPK1. In the experimental groups transfected with wild type PDPK1 gene of 3'UTR plasmid, the luciferase activity decreased (or increased) significantly in miR-147a (or inhibitor) group compared with miR-NC (or anti-miR-NC); There was no significant difference between the miR-147a group (or inhibitor) and the miR-NC group (or anti-miR-NC) in the transfection of PDPK1-3'UTR-Mut gene vector. PDPK1 was a target gene for direct regulation of miR-147a downstream. Verifying test results showed that the expression of PDPK1 mRNA and protein was reduced after overexpression of miR-147a, which was up-regulated after silencing miR-147a in TC, and V79 cells. These results suggest that miR-147a could be involved in the regulation of PDPK1 transcription by binding to the target site in PDPK1 mRNA 3'UTR, and then regulated AKT.


Assuntos
Proteínas Quinases Dependentes de 3-Fosfoinositídeo/genética , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Regiões 3' não Traduzidas/genética , Animais , Células Cultivadas , Biologia Computacional , Cricetinae , Células HEK293 , Humanos , Immunoblotting , Camundongos , Ligação Proteica/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos
16.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(5): 759-764, 2018 Sep.
Artigo em Zh | MEDLINE | ID: mdl-30378340

RESUMO

OBJECTIVE: To determine the prevalence and associated factors of cognitive impairments in the community-dwelling elderly aged 60 years or older in Chengdu of Sichuan province. METHODS: A random cluster sampling strategy was adopted to select 621 community-dwelling elderly. Face-to-face interviews were conducted to assess the cognitive status of the participants. 2 tests and logistic regression analyses were performed to identify factors associated with cognitive impairments. RESULTS: About 40.9% of the participants had cognitive impairments. Those attended primary schools had a lower risk of cognitive impairments [odds ratio OR)=0.369, P<0.001] compared with the illiterate ones. Older age OR=1.505 for 70-79 years, P=0.042; OR=3.069 for ≥80 years, P<0.001), cerebrovascular disease OR=2.159, P=0.003) and smoking OR=2.388, P<0.001) were risk factors of cognitive impairments. Men had lower risk OR=0.489, P=0.005) of cognitive impairments than women. CONCLUSION: The prevalence of cognitive impairments in community-dwelling elderly in Chengdu is high in comparison with those in other cities. Illiteracy, older age (over 70 years), women, smoking, and cerebrovascular disease are risk factors of cognitive impairments.


Assuntos
Disfunção Cognitiva/epidemiologia , Idoso , Transtornos Cerebrovasculares , China/epidemiologia , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Fumar
17.
Org Biomol Chem ; 15(48): 10276-10280, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29184955

RESUMO

A pair of novel enantiomeric polyketide dimers, (+)- and (-)-ascomlactone A (1a and 1b), were obtained from a mangrove endophytic fungus Ascomycota sp. SK2YWS-L. The structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and electronic circular dichroism (ECD) calculations. Ascomlactone A possessed an unprecedented polymerization system, which constructed an unusual nine-membered lactone ring between the monomers. A possible biogenetic pathway was proposed. Both 1a and 1b exhibited significant inhibitory effects against α-glucosidase with IC50 values of 63.7 and 27.9 µM, respectively. A further docking study provided an inside perspective of the action in α-glucosidase.


Assuntos
Ascomicetos/química , Policetídeos/química , Modelos Moleculares , Conformação Molecular , Policetídeos/isolamento & purificação , Teoria Quântica , Estereoisomerismo
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(3): 389-93, 2016 May.
Artigo em Zh | MEDLINE | ID: mdl-27468486

RESUMO

OBJECTIVE: To determine the prevalence of cognitive impairment and its influencing factors in rural elderly in Sichuan Province. METHODS: A multi-stage random sampling method was adopted to select participants in six towns and eighteen administrative villages in Fushun and Lizhou. The cognitive functions of 1 065 rural elderly were assessed. Factors associated with cognitive impairments of the rural elderly were identified. RESULTS: About 39. 9% of the rural elderly had cognitive impairments. Gender, age, marital status, educational attainment, regular physical activities, quality of life and social support were associated with cognitive impairments. CONCLUSION: The prevalence of cognitive impairments in rural elderly in Sichuan is high in comparison with national and international averages. Targeted interventions are needed based on the identified influencing factors.


Assuntos
Transtornos Cognitivos/epidemiologia , População Rural , Idoso , China , Humanos , Prevalência , Qualidade de Vida , Apoio Social
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(5): 768-771, 2016 Sep.
Artigo em Zh | MEDLINE | ID: mdl-28598096

RESUMO

OBJECTIVES: To estimate catastrophic health expenditure (CHE) of rural families in Zigong, and to determine the main influencing factors of CHE. METHODS: CHE was estimated using indicators such as occurrence and average deviations. The influencing factors of CHE were identified through binary logistic regression. RESULTS: We found 6.37% catastrophic health payment headcount, 1.13% mean catastrophic payment gap, and 17.80% mean positive gap after compensations. Compensations from the new rural cooperative medical scheme (NCMS) led to a reduction of 74.81% catastrophic health payment headcount for hospitalization costs and 48.00% catastrophic health payment headcount for outpatient costs, respectively. The numbers of hospitalizations in a family, presence of patients with chronic diseases, per capita household income, and numbers of family members with a job were found to be predictors of CHE. CONCLUSIONS: Rural families that have patients with chronic diseases are vulnerable to CHE.The government should develop policies to ease the financial burdens of the families with a high accumulated health expenditure over time.


Assuntos
Doença Catastrófica/economia , Gastos em Saúde , População Rural , China , Doença Crônica/economia , Humanos , Seguro Saúde , Modelos Logísticos
20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 47(3): 443-9, 2015 Jun 18.
Artigo em Zh | MEDLINE | ID: mdl-26080873

RESUMO

OBJECTIVE: To examine factors that may have impact on the Mini-Mental State Examination (MMSE) screening validity, which could lead to further establishing the general model of the MMSE score in Chinese health elderly and to improve the screening accuracy of the existing MMSE reference. METHODS: Based on the data of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), the MMSE scores of 19,117 normal elderly and 137 dementia patients who met the inclusion criteria were used for the analysis. The area under the curve (AUC) and validity indexes were used to compare the screening accuracy of various criteria. Multiple linear regression was used to identify factors that had impact on the MMSE score for both the normal and dementia elderly. Descriptive analysis was performed for differences in the MMSE scores by age trends and gender between the normal and dementia elderly. RESULTS: The AUC of MMSE was ≥0.75(P<0.05). The MMSE score of the normal elderly declined nonlinearly as the age grew older(male: R2=0.924, P<0.05; female: R2=0.951, P<0.05), and increased nonlinearly as the education level rose(male: R2=0.948, P<0.05; female: R2=0.859, P< 0.05). The females had significantly lower MMSE scores than the males, with a faster decline trend with age than the males (95%CI of female partial regression coefficient was not overlapped with 95%CI of male partial regression coefficient). The dementia elderly showed a much lower MMSE score (male: difference of Z score:-1.573, P<0.05; female: difference of Z score:-1.222, P<0.05) and tended to with a faster decline speed than that of the normal elderly (95%CI of dementia partial regression coefficient included 95%CI of normal partial regression coefficient). CONCLUSION: The screening validity of MMSE in CLHLS is not affected by educational level. The analysis of factors that may impact on the MMSE screening validity are gender, age, vision and residence which with validity identification. These four factors can be used as assist tool of MMSE in the screening of dementia to improve the screening accuracy.


Assuntos
Demência/diagnóstico , Testes Neuropsicológicos , Idoso , Povo Asiático , Feminino , Humanos , Masculino
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