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BACKGROUND: Atherosclerosis (AS) is the main pathological basis for the development of cardiovascular diseases. Vascular inflammation is an important factor in the formation of AS, and macrophage pyroptosis plays a key role in AS due to its unique inflammatory response. Guizhitongluo Tablet (GZTLT) has shown clinically effective in treating patients with AS, but its mechanism is elusive. PURPOSE: This study was to determine the effects of GZTLT on atherosclerotic vascular inflammation and pyroptosis and to understand its underlying mechanism. MATERIALS AND METHODS: The active constituents of GZTLT were analysed by means of UPLC-HRMS. In vivo experiments were performed using ApoE-/- mice fed a high fat diet for 8 weeks, followed by treatment with varying concentrations of GZTLT orally by gavage and GsMTx4 (GS) intraperitoneally and followed for another 8 weeks. Oil red O, Haematoxylin-eosin (HE) and Masson staining were employed to examine the lipid content, plaque size, and collagen fibre content of the mouse aorta. Immunofluorescence staining was utilised to identify macrophage infiltration, as well as the expression of Piezo1 and NLRP3 proteins in aortic plaques. The levels of aortic inflammatory factors were determined using RT-PCR and ELISA. In vitro, foam cell formation in bone marrow-derived macrophages (BMDMs) was observed using Oil Red O staining. Intracellular Ca2+ measurements were performed to detect the calcium influx in BMDMs, and the expression of NLRP3 and its related proteins were detected by Western blot. RESULTS: The UPLC-HRMS analysis revealed 31 major components of GZTLT. Our data showed that GZTLT inhibited aortic plaque formation in mice and increased plaque collagen fibre content to stabilise plaques. In addition, GZTLT could restrain the expression of serum lipid levels and suppress macrophage foam cell formation. Further studies found that GZTLT inhibited macrophage infiltration in aortic plaques and suppressed the expression of inflammatory factors. It is noteworthy that GZTLT can restrain Piezo1 expression and reduce Ca2+ influx in BMDMs. Additionally, we found that GZTLT could regulate NLRP3 activation and pyroptosis by inhibiting Piezo1. CONCLUSION: The present study suggests that GZTLT inhibits vascular inflammation and macrophage pyroptosis through the Piezo1/NLRP3 signaling pathway, thereby delaying AS development. Our finding provides a potential target for AS treatment and drug discovery.
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A series of novel binuclear PNP ligands based on the cyclohexyldiamine scaffold were synthesized for this study. The experimental results showed that positioning the two PNP sites at the para-positions of the cyclohexyl framework led to a significant enhancement in the catalytic activity for selective tri/tetramerization of ethylene. The PNP/Cr(acac)3/MAO(methylaluminoxane) catalytic system exhibited relatively high catalytic activity (up to 3887.7 kg·g-1·h-1) in selective ethylene oligomerization with a total selectivity of 84.5% for 1-hexene and 1-octene at 40 °C and 50 bar. The relationship between the ligand structure and ethylene oligomerization performance was further explored using density functional theory calculations.
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Polyesters, a highly promising class of circular polymers for achieving a closed-loop sustainable plastic economy, inherently exhibit material stability defects, especially in thermal and hydrolytic instability. Here, we introduce a class of polyesters, P(4R-BL) (R=Ph, Bu), featuring conformationally rigid 1,3-cyclobutane rings in the backbone. These polyesters not only exhibit superior thermostability (Td,5%=376-380 °C) but also demonstrate exceptional hydrolytic resistance with good integrity even after 1 year in basic and acidic aqueous solutions, distinguishing themselves from typical counterparts. Tailoring the flexibility of the side group R enables the controlled thermal and mechanical performance of P(4Ph-BL) and P(4Bu-BL) to rival durable syndiotactic polystyrene (SPS) and low-density polyethylene (LDPE), respectively. Significantly, despite their high stability, both polyesters can be effectively depolymerized into pristine monomers, establishing a circular life cycle.
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With the continuous development of society, people's life pressure is constantly increasing, and the mental health problems of college students are becoming increasingly prominent, bringing many challenges to their education and management. Universities should not only cultivate students' theoretical and professional knowledge and practical skills, but also attach importance to their mental health and effectively implement psychological education. Therefore, it is very necessary to develop and design a simple and effective student psychological evaluation system. As a new form of ideological and political transformation in universities in the era of big data, online ideological and political work has potential development space. It is necessary to carry out mental health education in universities, fully utilize online education forms, and improve ability of universities to repair mental health problems. Based on this, this system designs and implements software for typical image resolution based recognition and artificial intelligence. The use of B/S architecture in the development and use of. net technology and web server technology will enable more students to connect and use different terminals. In addition, an algorithm for image super-resolution recognition was proposed, which uses clustering convolution to improve residual blocks, improves modeling ability by extracting features on a larger scale, reduces the number of parameters to improve model calculation efficiency, and enables mental health educators and managers to work better. This article combines image super-resolution recognition technology with artificial intelligence technology to apply it to the process of psychological education in universities, thereby promoting the development of problem repair applications.
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Inteligencia Artificial , Estudiantes , Humanos , Escolaridad , Educación en Salud , Algoritmos , UniversidadesRESUMEN
The coexistence of conservation and degradation is a challenge for protected areas, and unequal political and social power is the mechanism underlying this conservation paradox. The World Heritage site of the Honghe Hani Rice Terraces (HHRT) has important natural and cultural value, but despite the enormous investment in protecting the site, the rice terraces continue to degrade, and much of the degradation has been unexpected. This study attempts to reveal the mechanism of these unintended protection outputs from the perspective of power relations. After reviewing the literature on the political ecology of protected areas, this study further considers the conceptual framework of power in view of the ambiguity of the concept and integrates the themes from research on protected areas into the power analysis framework of political ecology. Three aspects of the power process and environmental impact of heritage sites are analyzed: the actor network, conservation discourse and natural reconstruction. The results reveal that power among actors in the HHRT has changed over the course of continuous interaction, power has been produced and re-established in different relational networks, and the exercise of power has changed and reshaped the natural environment of the heritage site through a series of spatial planning decisions. Conservation discourse related to heritage is an important way for actors to establish and exercise power. However, due to spatial differences in the allocation of power, local development opportunities are unbalanced. In this unbalanced relationship, in order to maintain or strive for development opportunities and achieve economic development, residents of the HHRT have reshaped the natural environment by changing their farming methods and traditional planting methods, posing a potential threat to the sustainable development of the heritage site.
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Oryza , Ambiente , Ecología , Agricultura , Granjas , Conservación de los Recursos NaturalesRESUMEN
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Although significant advances have been achieved in the treatment of NSCLC during the past two decades, the 5-year survival rate of patients with NSCLC remains <20%. Thus, there is an urgent requirement to further understand the molecular mechanisms that promote NSCLC development and to identify novel therapeutic targets. In the present study, the gene expression profiles of patients with NSCLC from The Cancer Genome Atlas database were carefully analyzed and SPINK1 was identified as a tumor-inducing factor. SPINK1 expression level was found to be increased in both NSCLC tissues and cell lines. Moreover, SPINK1 promoted cell proliferation in A549 and H1299 cells. Knockdown of SPINK1 could activate cell autophagy and apoptosis. Mechanistically, SPINK1 was demonstrated to induce the proliferation of NSCLC via activating the MEK/ERK signaling pathway. In conclusion, these findings suggested that SPINK1 may serve as a potential biomarker in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Inhibidores de Proteasas , Serina/metabolismo , Inhibidor de Tripsina Pancreática de Kazal/genética , Inhibidor de Tripsina Pancreática de Kazal/metabolismoRESUMEN
Aim: To assess the contribution of polymicrobial disruption of host homeostasis to periodontitis progression in orthodontic wire ligation murine model. Methods: Orthodontic wire rings were inserted between the first and second molars of mice for 18 days for the orthodontic wire ligation mouse model, and Pg injection model and Pg-LPS injection model were used as controls. Alveolar bone loss and periodontal inflammation were analyzed by micro-CT, histological staining and qRT-PCR. Further, pyrosequencing of 16S rRNA gene amplicon was used to analyze the development of oral microorganism dysbiosis in the mice. Results: Micro-CT, TRAP staining and qRT-PCR showed that orthodontic wire ligation model led to more severe alveolar bone loss than Pg and Pg-LPS models.H&E staining and qRT-PCR demonstrated that stronger inflammatory response was induced by the orthodontic wire treatment compared to the other models. In addition, pyrosequencing of 16S rRNA gene amplicons revealed that the composition of oral microbiota presented a transition as the disease progressed and significant differences emerged in oral microbiota communities between orthodontic ligature mice and healthy controls. Furthermore, antibiotic treatment decreased both inflammation and alveolar bone loss in response to microbial community dysbiosis. However, no significant difference in bacterial community composition was observed in Pg and Pg-LPS models. Conclusions: Orthodontic wire ligation drove oral microbial community transitions that mimicked polymicrobial communities characterized by polymicrobial synergy and dysbiosis. Our improved model is suitable for further study of pathogenesis of periodontitis and exploration of corresponding treatment strategies.
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OBJECTIVE: To explore the role of Marginal Zone B and B-1 Cell-Specific Protein (MZB1), a novel molecule associated with periodontitis, in migration of human periodontal ligament cells (hPDLCs) and alveolar bone orchestration. BACKGROUND: MZB1 is an ER-localized protein and its upregulation has been found to be associated with a variety of human diseases. However, few studies have investigated the effect and mechanism of MZB1 on hPDLCs in periodontitis. METHODS: Gene expression profiles in human gingival tissues were acquired from the Gene Expression Omnibus (GEO) database, and candidate molecules were then selected through bioinformatic analysis. Subsequently, we identified the localization and expression of MZB1 in human gingival tissues, mice, and hPDLCs by immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was applied to assess the binding of miR-185-5p to MZB1. Furthermore, the effects of MZB1 on cell migration, proliferation, and apoptosis in vitro were investigated by wound-healing assay, transwell assay, CCK-8 assay, and flow cytometry analysis. Finally, Micro-CT analysis and H&E staining were performed to examine the effects of MZB1 on alveolar bone loss in vivo. RESULTS: Bioinformatic analysis discovered that MZB1 was one of the most significantly increased genes in periodontitis patients. MZB1 was markedly increased in the gingival tissues of periodontitis patients, in the mouse models, and in the hPDLCs treated with lipopolysaccharide of Porphyromonas gingivalis (LPS-PG). Furthermore, in vitro experiments showed that MZB1, as a target gene of miR-185-5p, inhibited migration of hPDLCs. Overexpression of MZB1 specifically upregulated the phosphorylation of p65, while pretreatment of MZB1-overexpressed hPDLCs with PDTC (NF-κB inhibitor) notably reduced the p-p65 level and promoted cell migration. In addition, the mRNA expression levels of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx2) were inhibited in MZB1-overexpressed hPDLCs and miR-185-5p inhibitor treated hPDLCs, respectively. In vivo experiments showed that knockdown of MZB1 alleviated the loss of alveolar bone. CONCLUSION: As a target gene of miR-185-5p, MZB1 plays a crucial role in inhibiting the migration of hPDLCs through NF-κB signaling pathway and deteriorating alveolar bone loss.
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Proteínas Adaptadoras Transductoras de Señales , Pérdida de Hueso Alveolar , MicroARNs , Periodontitis , Proteínas Adaptadoras Transductoras de Señales/genética , Pérdida de Hueso Alveolar/genética , Pérdida de Hueso Alveolar/metabolismo , Animales , Células Cultivadas , Humanos , Ratones , MicroARNs/genética , FN-kappa B/metabolismo , Osteogénesis , Ligamento Periodontal/metabolismo , Periodontitis/genética , Periodontitis/metabolismo , Transducción de Señal/genéticaRESUMEN
Gastric cancer (GC) is an aggressive malignancy with high incidence and mortality. Radiotherapy is a common treatment for patients with advanced GC. Many long noncoding RNAs (lncRNAs) have been verified to affect the radiosensitivity of multiple cancers in previous studies. Nevertheless, whether lncRNA opioid growth factor receptor pseudogene 1 (OGFRP1) affects the radiosensitivity of GC has not been determined. We hypothesized that OGFRP1 might affect cellular processes in GC development. The present study aims to explore the role of OGFRP1 in GC development. First, high expression of OGFRP1 in GC tissues and cells was determined through RT-qPCR. Subsequently, functional assays including colony formation assays, 5-Ethynyl-2'-deoxyuridine assays and flow cytometry analyses were performed to probe the biological functions of OGFRP1 in GC. Specifically, the effect of OGFRP1 on the radiosensitivity of GC cells was detected. Subsequently, with the help of the starBase tool, we found that miR-149-5p might bind to OGFRP1, which was confirmed through a luciferase reporter assay. Furthermore, we identified that MAP3K3 was targeted by miR-149-5p in GC cells. Finally, the results from rescue experiments validated that enhanced MAP3K3 expression counteracted the effect of OGFRP1 silencing on GC cell proliferation, apoptosis and radiosensitivity. Overall, OGFRP1 was determined to promote GC cell proliferation while suppressing cell apoptosis and radiosensitivity by regulating the miR-149-5p/MAP3K3 axis.
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MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Línea Celular Tumoral , Proliferación Celular/genética , Humanos , MAP Quinasa Quinasa Quinasa 3 , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Tolerancia a Radiación/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/radioterapiaRESUMEN
Lung cancer is one of the most malignant type of tumors worldwide. Nonsmall cell lung cancer (NSCLC), which is the most common type of lung cancer, is defined as a distinct disease that exhibits both genetic and cellular heterogeneity. Although in the past two decades significant advances in the treatment of NSCLC have besen performed, the 5year survival rate of patients with NSCLC remains <20%. Thus, there is an urgent requirement to gain an indepth understanding of the molecular mechanisms that promote NSCLC development and to identify novel therapeutic targets. In the present study, the gene expression profiles of patients with NSCLC from The Cancer Genome Atlas database were analyzed to determine potential therapeutic targets, and transmembrane protein 100 (TMEM100) was identified as a candidate tumor suppressor. TMEM100 expression level was discovered to be decreased in both NSCLC tissues and cell lines, and it was observed to be negatively associated with the TNM stage and positively associated with prognosis. Moreover, TMEM100 inhibited tumor growth and promoted cell apoptosis in A549 and H460 cells. Mechanistically, TMEM100 was demonstrated to induce autophagy in A549 cells via inhibiting the PI3K/AKT signaling pathway, whereas inhibiting autophagy using bafilomycin A1 significantly enhanced TMEM100induced apoptosis to compensate for the cell death. In conclusion, these findings suggested that TMEM100 may serve as a tumor suppressor in NSCLC and promote autophagy via inhibiting the PI3K/AKT signaling pathway.
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Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de la Membrana/biosíntesis , Células A549 , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/patología , Animales , Apoptosis/fisiología , Autofagia/fisiología , Western Blotting , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Casos y Controles , Línea Celular Tumoral , Femenino , Xenoinjertos , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de SeñalRESUMEN
Objective: Streptococcus pneumoniae (S.pn) is a common respiratory pathogen and a frequent cause of acute otitis media (AOM) in children. However, little is known about the immunometabolism during AOM. This study was to assess the presence of glucose metabolic reprogramming during AOM and its underlying mechanism affecting inflammatory response and middle ear injury. Methods: The levels of glycolytic metabolism were evaluated by measuring the expression of glycolysis-related genes and the production of metabolites. HE stain, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to measure the effect of glucose metabolic reprogramming on inflammatory response, pneumococcal clearance, hypoxia-inducible factor 1 alpha (HIF-1α) expression and cytokine secretion during AOM, respectively. Results: The analysis of microarray revealed an increase of the expression of glycolysis-related genes during S.pn-induced AOM, which was verified by real-time PCR. Increased glycolysis promoted the production of IL-1ß and TNF-α and facilitated the clearance of S.pn by enhancing phagocytosis and killing capability of neutrophils, but also aggravated the middle ear injury. Furthermore, these pathogenic effects could be reversed after glycolytic inhibitor 2DG treatment. Additionally, HIF-1α was observed to involve in glycolytic metabolism during AOM. Conclusion: S.pn infection induced increased glycolysis conversion during AOM, which promoted inflammatory responses and bacterial clearance, but also aggravated tissue damage.
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Oído Medio/metabolismo , Glucólisis , Otitis Media/metabolismo , Infecciones Neumocócicas/metabolismo , Streptococcus pneumoniae/patogenicidad , Animales , Modelos Animales de Enfermedad , Oído Medio/inmunología , Oído Medio/microbiología , Oído Medio/patología , Regulación Enzimológica de la Expresión Génica , Interacciones Huésped-Patógeno , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Mediadores de Inflamación/metabolismo , Interleucina-1beta/metabolismo , Ratones Endogámicos C57BL , Neutrófilos/inmunología , Neutrófilos/metabolismo , Neutrófilos/microbiología , Otitis Media/inmunología , Otitis Media/microbiología , Otitis Media/patología , Fagocitosis , Infecciones Neumocócicas/inmunología , Infecciones Neumocócicas/microbiología , Infecciones Neumocócicas/patología , Streptococcus pneumoniae/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
A Ru(ii)-catalyzed coupling of various α-carbonyl phosphoniums with sulfoxonium ylides has been realized for the facile synthesis of 1-naphthols in good to excellent yields. This oxidant-free transformation proceeds through Ru-catalyzed C-H activation of phosphoniums, Ru-carbene insertion, and intramolecular Wittig reaction processes.
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BACKGROUND: Otitis media (OM), a prevalent pediatric infectious disease, is mainly caused by Streptococcus pneumoniae (S.pn). Neutrophil extracellular traps (NETs), a novel antimicrobial strategy, were reported in 2004. We found that NETs formed in the middle ear with acute otitis media (AOM) induced by S.pn. However, the mechanisms of NETs formation are not entirely clear. METHODS: We stimulated neutrophils isolated from mouse bone marrow with S.pn clinical stain 19F in vitro, and established mouse model of AOM via transbullar injection with S.pn. NETs formation, reactive oxygen species (ROS) production, autophagy activation and bacterial load were analyzed in TLR4-/- and wild-type neutrophils stimulated in vitro with S.pn and in vivo during AOM. RESULTS: We found that autophagy and ROS were required for S.pn-induced NETs formation. Moreover, TLR4 partly mediated NETs formation in response to S.pn in vitro and in vivo during AOM. We also showed that attenuated NETs formation in TLR4-/- neutrophils correlated with an impaired ROS production and autophagy activation in vitro and in vivo. In addition, both the in vivo and in vitro-produced NETs were able to engulf and kill S.pn. CONCLUSIONS: TLR4 regulates ROS and autophagy to control NETs formation against S.pn in the course of AOM. IMPACT: S.pn can induce NETs formation in vitro and in vivo; TLR4 regulates NETs formation by ROS and autophagy; NETs contribute to the clearance of bacteria in acute otitis media. In this study, we firstly found that autophagy and ROS were required for S.pn-induced NETs formation in the model of acute otitis media (AOM). And to some extent, TLR4 mediated NETs formation during AOM. Our research might provide a potential strategy for the treatment of otitis media.
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Trampas Extracelulares , Otitis Media/metabolismo , Especies Reactivas de Oxígeno , Streptococcus pneumoniae/metabolismo , Receptor Toll-Like 4/metabolismo , Enfermedad Aguda , Animales , Autofagia , Médula Ósea/microbiología , Células de la Médula Ósea/metabolismo , Modelos Animales de Enfermedad , Ratones , Neutrófilos/microbiologíaRESUMEN
An efficient method for the construction of various pyrazolo[5,1-a]isoquinolines has been achieved via Ru(ii)-catalyzed α-carbonyl sulfoxonium ylide annulations with aryl substituted pyrazoles. This oxidant-free transformation occurred through pyrazole-directed C-H activation, Ru-carbene insertion, and acid-promoted carbonyl condensation processes, enabling dual C-C and C-N bond formation. A broad substrate scope with respect to both coupling components worked efficiently with high yields.
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In recent years, industrial contaminants and especially organic pollutions have been threatening both environmental safety and human health. Particularly, dibutyl phthalate (DBP) has been considered as one of the major hazardous contaminants due to its widespread production and ecological toxicities. Consequently, reliable methods toward the efficient and environmentally benign degradation of DBP in wastewater would be very desirable. To this end, a novel magnetically separable porous TiO2/Ag composite photocatalyst with magnetic Fe3O4 particles as the core was developed and successfully introduced to the photocatalytic degradation of DBP under visible irradiation with a fluorescent lamp. The presented work describes the grafting of Ag co-doped TiO2 composite on the silica-modified porous Fe3O4 magnetic particles with a simple and inexpensive chemical co-precipitation method. Through the investigation of the influencing factors including photocatalyst dosage, initial concentration of DBP, solution pH, and H2O2 content, we found that the degradation efficiency could reach 74%. The photodegradation recovery experiment showed that the degradation efficiency of this photocatalyst remained almost the same after five times of reuse. In addition, a plausible degradation process was also proposed involving the attack of active hydroxyl radicals generated from this photocatalysis system and production of the corresponding intermediates of butyl phthalate, diethyl phthalate, dipropyl phthalate, methyl benzoate, and benzoic acid.
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Dibutil Ftalato , Dióxido de Silicio , Catálisis , Peróxido de Hidrógeno , Fotólisis , Plata , TitanioRESUMEN
BACKGROUND AND OBJECTIVE: Accumulating findings revealed that long noncoding RNAs (lncRNAs) are crucial regulator molecules in the progression of periodontitis. This study aimed to investigate the biological roles and mechanisms of lncRNA-01126 in the progression of periodontitis. MATERIALS AND METHODS: RT-qPCR was used to detect the levels of lncRNA-01126 in gingival tissues and human periodontal ligament cells (hPDLCs). Cell transfection experiments were performed to knock down or overexpress the level of lncRNA-01126 in hPDLCs. Cell Counting Kit-8, wound-healing assay, transwell assay, and flow cytometric analysis were used to evaluate the function of lncRNA-01126 in the progression of periodontitis. Finally, the signaling pathway was assessed by western blot. RESULTS: LncRNA microarray discovered that lncRNA-01126 was the most significantly increased lncRNA in periodontitis patients. LncRNA-01126 markedly increased in the gingival tissues of periodontitis mice and in the hPDLCs treated with lipopolysaccharide of Porphyromonas Gingivalis (LPS-PG). Furthermore, in vitro experiments showed that lncRNA-01126 dramatically suppressed the migration of hPDLCs through MEK/ERK signaling pathway. CONCLUSION: LncRNA-01126 plays a crucial role in inhibiting the migration of hPDLCs through MEK/ERK signaling pathway.
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Ligamento Periodontal , ARN Largo no Codificante , Animales , Células Cultivadas , Humanos , Sistema de Señalización de MAP Quinasas/genética , Ratones , Ligamento Periodontal/citología , ARN Largo no Codificante/genética , Transducción de SeñalRESUMEN
OBJECTIVE: To compare the prevalence of HIV and associated factors for participating HIV voluntary counseling and testing (VCT) among older clients of female sex workers (CFSWs) in Liuzhou City and Fuyang City in China. METHODS: A cross-sectional study was conducted and the study employed 978 male CFSWs, aged 50 years and above from October 2016 to December 2017. All participants were required to complete a questionnaire and provide blood samples for HIV testing. Multivariate logistic regression analysis was used to analyze the influential factors of using VCT program and tested for HIV. RESULTS: The HIV infection prevalence rate was 1.2% and 0.5%, while 52.3% and 54.6% participants had ever utilized VCT service and tested for HIV in Liuzhou City and Fuyang City, respectively. The older CFSWs who ever heard of VCT program were more likely to uptake VCT program in both cities (ORLiuzhou = 2.224, ORFuyang = 2.421). Participants, whose marital status was married or cohabiting (ORLiuzhou = 0.548, ORFuyang = 0.495), who have stigma against individuals who are living with HIV/AIDS (ORLiuzhou = 0.273, ORFuyang = 0.371), whose monthly income is more than 500 yuan (ORLiuzhou = 0.622, ORFuyang = 0.600), and whose age is more than 60 years old (ORLiuzhou = 0.639, ORFuyang = 0.554), were less likely to visit VCT clinics. Those who are worried about HIV-infected participants were more likely to utilize VCT services in Fuyang City (AOR = 1.838, 95%CI : 1.146-2.948). CONCLUSION: Combine strategy will be needed to promote the utilization of VCT service, based on the socioeconomic characteristics of older male CFSWs in different cities of China.
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Consejo/estadística & datos numéricos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Tamizaje Masivo/estadística & datos numéricos , Trabajadores Sexuales/estadística & datos numéricos , Programas Voluntarios/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , China , Ciudades , Estudios Transversales , Composición Familiar , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Persona de Mediana Edad , Aceptación de la Atención de Salud/estadística & datos numéricos , Prevalencia , Estigma Social , Encuestas y CuestionariosRESUMEN
BACKGROUND: Endoscopic nasobiliary drainage (ENBD) was often used for preoperative biliary drainage in cases like cholangiocarcinoma or acute obstructive suppurative cholangitis, reports on endoscopic nasobiliary drainage (ENBD) over primary closure of the common bile duct (CBD) are limited. This study compares outcomes of laparoscopic cholecystectomy (LC) + laparoscopic CBD exploration (LCBDE) + intraoperative ENBD + primary closure of CBD with equivalent patients who underwent preoperative endoscopic retrograde cholangiopancreatography (ERCP) and subsequent LC. METHODS: From January 2013 to December 2015, 829 consecutive patients with choledocholithiasis combined with cholecystolithiasis underwent surgery in our department. 211 patients underwent LC + LCBDE + intraoperative ENBD + primary closure of CBD (group A) and 117 preoperative ERCP + subsequent LC (group B). A total of 501 patients (355 who underwent T-tube drainage and 146 who underwent transcystic exploration) were excluded from the analysis. Clinical records, operative findings, and postoperative follow-up were analyzed. RESULTS: Age and sex distribution, comorbidity, presentations, CBD diameter, and size and number of stones were similar in the two groups, and there was no postoperative mortality. Duration of surgery in group A was shorter (83 vs. 104 min, P < 0.01), as was postoperative hospital stay (6 vs. 9 days, P < 0.01). Average operative expenditure in group A was less than that of group B ($ 3816 vs. $ 4015, P < 0.01). The success rate in group A was higher (100 vs. 91%, P < 0.01). Ten patients in group B converted to LCBDE. The postoperative complication rate was higher in group B but without significant difference (1.9 vs. 4.2%, P = 0.29). Median follow-up time was 24 (3-28) months (n = 302 patients). Two patients in group B reported residual stones. CONCLUSION: LC + LCBDE + intraoperative ENBD + primary closure of CBD should have priority over preoperative ERCP + subsequent LC for choledocholithiasis combined with cholecystolithiasis.
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Colangiopancreatografia Retrógrada Endoscópica/métodos , Colecistolitiasis/cirugía , Coledocolitiasis/cirugía , Endoscopía/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colecistolitiasis/complicaciones , Coledocolitiasis/complicaciones , Estudios de Cohortes , Conducto Colédoco/cirugía , Drenaje , Femenino , Humanos , Periodo Intraoperatorio , Tiempo de Internación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Resultado del Tratamiento , Adulto JovenRESUMEN
Iridoid synthase (IS), as a vegetal enzyme belonging to the short-chain dehydrogenase/reductase (SDR) superfamily, produces the ring skeletons for downstream alkaloids with various pharmaceutical activities, including the commercially available antineoplastic agents, vinblastine and vincristine. Here, we present the crystal structures of IS in apo state and in complex with NADP(+)/8-oxogeranial, exhibiting an active center that lacks the classical Tyr/Lys/Ser triad spatially conserved in SDRs, with only the catalytically critical function of triad tyrosine remained in Tyr178. In consistent, mutation of Tyr178 to a phenylalanine residue significantly abolished the catalytic activity of IS. Within the substrate binding pocket, the linear-shaped 8-oxogeranial adopts an entirely extended conformation with its two aldehyde ends hydrogen-bonded to Tyr178-OH and Ser349-OH, respectively. In addition, the intermediate carbon chain of bound substrate is harbored by a well-ordered hydrophobic scaffold, involving residues Ile145, Phe149, Leu203, Met213, Phe342, Ile345 and Leu352. Mutagenesis studies showed that both Ser349 and the hydrophobic residues around are determinant to the substrate specificity and, consequently, the catalytic activity of IS. In contrast, the Gly150-Pro160 loop previously proposed as a factor involved in substrate binding might have very limited contribution, because the deletion of residues Ile151-His161 has only slight influence on the catalytic activity. We believe that the present work will help to elucidate the substrate specificity of IS and to integrate its detailed catalytic mechanism.