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Objective: To analyze three reconstruction techniques and mid-term clinical outcomes of hip revision for acetabular bone defect after total hip arthroplasty (THA). Methods: This is a retrospective case series study. Included in the study were 109 patients (109 hips) with acetabular bone defect after THA reconstructions in hip revisions from January 2015 to December 2021 in the Senior Department, Forth Medical Center of Chinese People's Liberation Army General Hospital and the Department of Orthopaedics, First Medical Center of Chinese People's Liberation Army General Hospital. According to the preoperative simulated surgeries and different bone defect reconstruction techniques, all patients were divided into a normal cup group, an augment group or a triflange group,respectively. There were 54 patients (54 hips) in the normal cup group, reconstructed with the uncemented porous metal cup (including Jumbo cup), with 23 males and 31 females, aged (59.6±9.9) years (range:32 to 76 years); 44 patients (44 hips) in the augment group, reconstructed with the individualized three-dimensional (3D) printed porous metal augment and uncemented porous metal cup, with 18 males and 26 females, aged (52.8±13.6) years(range:17 to 76 years); 11 patients (11 hips) in the triflange group, reconstructed by the individualized 3D printed porous metal triflange cup, with 5 males and 6 females, aged (59.4±11.2)years (range: 43 to 78 years). Radiographic results, including rotation center height, rotation center offset, and leg length discrepancy (LLD) and clinical results, including Harris hip score (HHS) and visual analogue scale(VAS) were evaluated outpatient at 3, 6, 12 months after the operation and annually thereafter. The last follow-up was completed in March 2024, and all parameters at the last follow-up and before the operation were compared. Paired t test and repeated measurement ANOVA were used for the radiographic and clinical parameters before and after the operation. Results: All hip revisions for patients with acetabular bone defect after THA were completed and followed for more than two years. The follow-up time of the normal cup group was (6.5±1.7) years (range: 2.8 to 9.3 years), and that of the augment group was (6.0±1.3) years (range: 3.5 to 9.0 years). The follow-up time of the triflange group was (2.8±0.6) years (range: 2.0 to 3.8 years). At the last follow-up, the rotation center height, rotation center offset and LLD of 54 hips in the normal cup group were (24.2±5.6)mm, (29.1±5.5) mm and (4.6±3.3)mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips (t=9.671, P<0.01; t=6.073, P<0.01). In the augment group, the rotational center height, the rotation center offset and the LLD of 44 hips were (22.4±9.0) mm, (25.4±5.5) mm and (6.0±4.0) mm, respectively, which were significantly lower than those of the preoperative hips (t=9.071, P<0.01; t=11.345, P<0.01; t=4.927, P<0.01). In the triflange group, the rotational center height, the rotation center offset and LLD of 11 hips were (22.7±6.0) mm,(30.9±8.0) mm and (5.3±2.2) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips (t=2.716, P=0.022; t=6.226, P<0.01). At the last follow-up, fractures occurred in 3 patients and dislocation occurred in 1 patient in the normal cup group, and fracture reduction and closed reduction were administered under anesthesia, respectively. In the augment group, dislocation occurred in 1 patient and open reduction under anesthesia was performed. The HHS and VAS of the three groups improved significantly after surgery and the differences were statistically significant(all P<0.01). There was no complication in the triflange group. The X-ray at the last follow-up showed that all prostheses and augments were in stable positions and no loosening or migration was observed. Conclusions: For patients with acetabular bone defect after THA undergoing hip revisions, preoperative surgical simulation and rehearsal could help surgeons choose convenient and efficient reconstruction techniques. The targeted selection of Jumbo Cup, individualized 3D printed metal augment, and customized triflange cup could achieve satisfactory clinical outcomes.
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Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); the total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , Imunoensaio , SARS-CoV-2/isolamento & purificação , Sensibilidade e EspecificidadeRESUMO
Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3, 2021 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); The total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.
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Aspergillus section Aspergillus (formerly the genus Eurotium) includes xerophilic species with uniseriate conidiophores, globose to subglobose vesicles, green conidia and yellow, thin walled eurotium-like ascomata with hyaline, lenticular ascospores. In the present study, a polyphasic approach using morphological characters, extrolites, physiological characters and phylogeny was applied to investigate the taxonomy of this section. Over 500 strains from various culture collections and new isolates obtained from indoor environments and a wide range of substrates all over the world were identified using calmodulin gene sequencing. Of these, 163 isolates were subjected to molecular phylogenetic analyses using sequences of ITS rDNA, partial ß-tubulin (BenA), calmodulin (CaM) and RNA polymerase II second largest subunit (RPB2) genes. Colony characteristics were documented on eight cultivation media, growth parameters at three incubation temperatures were recorded and micromorphology was examined using light microscopy as well as scanning electron microscopy to illustrate and characterize each species. Many specific extrolites were extracted and identified from cultures, including echinulins, epiheveadrides, auroglaucins and anthraquinone bisanthrons, and to be consistent in strains of nearly all species. Other extrolites are species-specific, and thus valuable for identification. Several extrolites show antioxidant effects, which may be nutritionally beneficial in food and beverages. Important mycotoxins in the strict sense, such as sterigmatocystin, aflatoxins, ochratoxins, citrinin were not detected despite previous reports on their production in this section. Adopting a polyphasic approach, 31 species are recognized, including nine new species. ITS is highly conserved in this section and does not distinguish species. All species can be differentiated using CaM or RPB2 sequences. For BenA, Aspergillus brunneus and A. niveoglaucus share identical sequences. Ascospores and conidia morphology, growth rates at different temperatures are most useful characters for phenotypic species identification.
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Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a crucial adaptor molecule of the interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily, which can trigger downstream signaling cascades involved in innate immunity. The function of TRAF6 has been clarified in mammals but is poorly understood in chicken. In our study, we investigated TRAF6 function in birds, particularly in chicken innate immune responses, by cloning and characterizing chicken TRAF6 (chTRAF6). The full-length coding sequence of chTRAF6 comprised 1638 bp and encoded a 545-amino acid protein, which shares high sequence similarity with TRAF6 of other species and consists of four structurally conserved domains. Quantitative real-time polymerase chain reaction revealed that chTRAF6 was widely expressed in all tested tissues and its expression was induced in chicken embryo fibroblast cells treated with poly(I:C) and poly(dA:dT). Increased expression of chTRAF6 was observed both in vitro and in vivo following infection with Newcastle disease virus in chickens. Taken together, these results suggest that chTRAF6 plays a vital role in host defense against viral infection in chicken.
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Proteínas Aviárias/genética , Galinhas/genética , Fator 6 Associado a Receptor de TNF/genética , Animais , Proteínas Aviárias/química , Proteínas Aviárias/metabolismo , Galinhas/imunologia , Galinhas/metabolismo , Resistência à Doença/genética , Resistência à Doença/imunologia , Expressão Gênica , Imunidade Inata/genética , Domínios e Motivos de Interação entre Proteínas , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/química , Fator 6 Associado a Receptor de TNF/metabolismoRESUMO
Objective: To investigate the methods and short-time clinical results of reconstruction of Paprosky type â ¢ acetabulum bone defects by using tantalum augments. Methods: A total of 17 patients (17 hips) with Paprosky type â ¢ acetabulum bone defects, treated with tantalum augments in revision of total hip arthroplasty at Department of Orthopedics Surgery in General Hospital of Chinese People's Liberation Army were retrospectively analyzed from March 2014 to May 2016.There were 6 males and 11 females aged from 23 to 74 years with an average of (50.2±16.3) years. Tantalum augments or TM-Cup augment (the cup-on-cup technique) were used to reconstruct the defects.The TM-Cup augment was the tantalum revision cup which was removed titanium ring. The cup-on-cup technique combined TM-Cup augment and biological acetabulum cup. Augments were served as the nonresorptive structural allograft in revision of total hip arthroplasty. Harris hip score was used to evaluate clinical effects. The vertical position of the rotation center was measured and analyzed. Radiographic assessments of the acetabular components were performed by DeLee-Charnley and the Anderson criteria and recorded postoperative complications. Results: All the patients were followed up from 3 to 29 months with an average of (16.2±5.4) months, tantalum augments and biological acetabulum cup were used in 13 patients, the TM-Cup augment and biological acetabulum cup were used in 4 patients. At the time of the latest follow-up, the mean Harris hip score increased compared to preoperatively (86.8±8.3 vs. 30.0±12.0) (t=12.78, P<0.01), the average vertical location of the center of rotation was decreased ((25.3±9.8) mm vs.(47.6±10.5)) mm (t=4.95, P<0.01). All the tantalum augments and biological acetabulum cups were stable, there were no infection, dislocation and other complications. Conclusions: The use of tantalum augments could be considered as an effective management of Paprosky type â ¢ defects providing good clinical and radiographic outcomes in the short term.The cup-on-cup technique which was used in reconstruction of severe superior-invagination acetabular bone defects and restoration relatively normal center of rotation had special application value.
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Acetábulo/cirurgia , Artroplastia de Quadril , Prótese de Quadril , Adulto , Idoso , Feminino , Humanos , Luxações Articulares , Masculino , Metais , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Falha de Prótese , Reoperação , Estudos Retrospectivos , Rotação , Tantálio , Transplante HomólogoRESUMO
Talaromyces contains both asexual and sexually reproducing species. This genus is divided in seven sections and currently has 105 accepted species. In this study we investigated the Talaromyces isolates that were obtained during a study of indoor air collected in Beijing, China. These indoor Talaromyces strains are resolved in four sections, seven of them are identified as T. islandicus, T. aurantiacus, T. siamensis and T. albobiverticillius according to BenA sequences, while 14 isolates have divergent sequences and are described here as nine new species. The new species are placed in four sections, namely sections Helici, Islandici, Talaromyces and Trachyspermi. They are described based on sequence data (ITS, BenA, CaM and RPB2) in combination with phenotypic and extrolite characters. Morphological descriptions and notes for distinguishing similar species are provided for each new species. The recently described T. rubrifaciens is synonymised with T. albobiverticillius based on presented phylogenetic results.
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Objective: To estimate the longitudinal association between serum lipid biomarkers and the development of cardiometabolic multimorbidity (CMM) in middle-aged and old adults (≥45) in China, while examining effect differences among degree of dyslipidemia aggregation and various dyslipidemia combination patterns. Methods: Based on data from the China Health and Retirement Longitudinal Study (2011-2018), logistic regression analysis was used to evaluate the associations of TC, LDL-C, HDL-C, TG (4 forms of dyslipidemias), degree and pattern of dyslipidemia combination with CMM. We also used restricted cubic splines to show the dose-response associations between 4 lipid biomarkers and CMM development. Results: Of the 6 522 participants included, 590 (9.05%) developed CMM. After adjusting for covariates, all 4 forms of dyslipidemias were positively associated with CMM development (high TC: OR=1.33, 95%CI: 1.03-1.71; high LDL-C: OR=1.35, 95%CI: 1.05-1.75; low HDL-C: OR=1.45, 95%CI: 1.19-1.77; high TG: OR=1.50, 95%CI: 1.20-1.88). The U-shaped dose-response relationship between LDL-C and CMM development was observed (P for non-linear =0.022). The odds of CMM increased with the increase of dyslipidemias forms, which was highest in those with ≥3 forms of dyslipidemias (OR=2.02, 95%CI: 1.33-3.06). In various dyslipidemia form combinations, the possibility of CMM development was highest in those with high TC, high LDL-C and low HDL-C (OR=3.54, 95%CI: 1.40-8.67). High TC and high LDL-C were significantly associated with CMM development in people without cardiometabolic diseases. Low HDL-C was positively associated with diabetes and CMM development in participants without cardiometabolic diseases, cardiovascular disease (CVD) followed by diabetes, and diabetes followed by CVD. High TG was positively associated with diabetes and CMM in participants without cardiometabolic diseases, and diabetes followed by CVD. Conclusions: A total of 4 forms of dyslipidemia were all independently associated with CMM development in middle-aged and old adults in China. The dose-response relationship between LDL-C level and CMM development was U-shaped. The aggregation of 4 forms of dyslipidemia were associated with the development of CMM. Low HDL-C and high TG were significantly associated with multiple patterns of cardiometabolic diseases development.
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Biomarcadores , HDL-Colesterol , Dislipidemias , Multimorbidade , Humanos , China/epidemiologia , Dislipidemias/epidemiologia , Dislipidemias/sangue , Pessoa de Meia-Idade , Idoso , Biomarcadores/sangue , Estudos Longitudinais , HDL-Colesterol/sangue , Masculino , LDL-Colesterol/sangue , Feminino , Triglicerídeos/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/sangue , Lipídeos/sangue , Fatores de Risco , Modelos LogísticosRESUMO
Grain yield is the most important and complex trait in maize. In this study, a total of 258 F(9) recombinant inbred lines (RIL), derived from a cross between dent corn inbred Dan232 and popcorn inbred N04, were evaluated for eight grain yield components under four environments. Quantitative trait loci (QTL) and their epistatic interactions were detected for all traits under each environment and in combined analysis. Meta-analysis was used to integrate genetic maps and detected QTL across three generations (RIL, F(2:3) and BC(2)F(2)) derived from the same cross. In total, 103 QTL, 42 pairs of epistatic interactions and 16 meta-QTL (mQTL) were detected. Twelve out of 13 QTL with contributions (R(2)) over 15% were consistently detected in 3-4 environments (or in combined analysis) and integrated in mQTL. Only q100GW-7-1 was detected in all four environments and in combined analysis. 100qGW-1-1 had the largest R(2) (19.3-24.6%) in three environments and in combined analysis. In contrast, 35 QTL for 6 grain yield components were detected in the BC(2)F(2) and F(2:3) generations, no common QTL across three generations were located in the same marker intervals. Only 100 grain weight (100GW) QTL on chromosome 5 were located in adjacent marker intervals. Four common QTL were detected across the RIL and F(2:3) generations, and two between the RIL and BC(2)F(2) generations. Each of five important mQTL (mQTL7-1, mQTL10-2, mQTL4-1, mQTL5-1 and mQTL1-3) included 7-12 QTL associated with 2-6 traits. In conclusion, we found evidence of strong influence of genetic structure and environment on QTL detection, high consistency of major QTL across environments and generations, and remarkable QTL co-location for grain yield components. Fine mapping for five major QTL (q100GW-1-1, q100GW-7-1, qGWP-4-1, qERN-4-1 and qKR-4-1) and construction of single chromosome segment lines for genetic regions of five mQTL merit further studies and could be put into use in marker-assisted breeding.
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Metanálise como Assunto , Locos de Características Quantitativas/genética , Sementes/crescimento & desenvolvimento , Sementes/genética , Zea mays/crescimento & desenvolvimento , Zea mays/genética , Biomassa , Epistasia Genética , Endogamia , Padrões de Herança/genética , Característica Quantitativa Herdável , Recombinação Genética/genéticaRESUMO
Using density functional theory, we consider the adsorption of C on graphene, which gives rise to many interesting phenomena. A single-C at the bridge site shows a clearly covalent-bond feature with graphene, in which the metallic state occurs and a magnetic moment of 0.36 µ(B) was determined. For both-sided adsorption, the magnetic moment is remarkably larger than that in one-sided adsorption, and increases with concentration up to a coverage of 12.5%. High spin polarization obtained at the Fermi level indicates a high degree of passage of preferred spin, which is important for developing spin filters.
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Using density functional calculations, we investigate the geometries, electronic structures and magnetic properties of hexagonal BN sheets with 3d transition metal (TM) and nonmetal atoms embedded in three types of vacancies: V(B), V(N), and V(B+N). We show that some embedded configurations, except TM atoms in V(N) vacancy, are stable in BN sheets and yield interesting phenomena. For instance, the band gaps and magnetic moments of BN sheets can be tuned depending on the embedded dopant species and vacancy type. In particular, embedment such as Cr in V(B+N), Co in V(B), and Ni in V(B) leads to half-metallic BN sheets interesting for spin filter applications. From the investigation of Mn-chain (C(Mn)) embedments, a regular 1D structure can be formed in BN sheets as an electron waveguide, a metal nanometre wire with a single atom thickness.
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The electronic and magnetic properties of a BN sheet doped with 3d transition metals (Fe, Co and Ni) have been investigated using ab initio calculations. Our calculations show many interesting physical properties in a metal-doped BN sheet. A Fe-doped BN sheet is a half-metal with the magnetic moment of 2.0 micro(B), and Co-doped BN sheet becomes a narrow-gap semiconductor with a magnetic moment of 1.0 micro(B). However, no magnetic moment is induced on a Ni-doped BN sheet, which has the same band gap as a pristine BN sheet. Furthermore, Fe atom easily forms an isolated particle on the BN sheet, while Ni and Co atoms are likely to form a sheet-supported metal nanotemplate. These results are useful for spintronics application and could help in the development of magnetic nanotructures and metallic nanotemplate at room temperature.
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BACKGROUND: Accelerating wound healing is always accompanied by excessive scar formation. The focus in chronic wounds has been promoting the proliferation of tissue repair cells while decreasing collagen deposition. Smad3 null mice display more rapid wound closure and reduced scar formation. We hypothesized that c-Ski, acting as a co-repressor of transforming growth factor-beta1/Smad3 in epithelial cells and as a complicated regulator of embryo fibroblast proliferation, may play such a role through modulation of skin fibroblast function. AIM: To investigate the effect of c-Ski on skin fibroblast proliferation, cell-cycle progression, type I collagen secretion and myofibroblast differentiation. The potential involvement of Smad3 was also investigated. METHODS: Cultured rat skin fibroblasts were used. Immunocytochemistry and reverse transcription (RT)-PCR was used to examine the localization and expression of c-Ski. Plasmid transfection technology was used to produce c-Ski or/and Smad3 overexpression. Cell proliferation was analysed by 5-bromo-2-deoxyuridine incorporation; cell cycle by fluorescence-activated cell sorting; type I collagen expression by immunocytochemistry, RT-PCR and western blotting; and myofibroblast differentiation by western blotting. RESULTS: c-Ski was expressed in cultured skin fibroblasts. Overexpression of c-Ski was able to promote skin fibroblast proliferation and accelerate cell-cycle progression through inhibiting Smad3 activity. It also decreased type I collagen protein and mRNA expression through inhibiting Smad3 activity. It did not affect fibroblast-myofibroblast differentiation. CONCLUSIONS: Because of the important role of fibroblast proliferation and collagen secretion in tissue repair and scar formation, we speculate that c-Ski may be a new candidate molecule for accelerating wound healing and decreasing scar formation.
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Cicatriz/patologia , Colágeno Tipo I/biossíntese , Proteínas Proto-Oncogênicas/fisiologia , Pele/patologia , Cicatrização/fisiologia , Animais , Ciclo Celular/fisiologia , Diferenciação Celular/fisiologia , Células Cultivadas , Cicatriz/metabolismo , Colágeno Tipo I/genética , Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação da Expressão Gênica/fisiologia , Masculino , RNA Mensageiro/genética , Ratos , Ratos Wistar , Pele/metabolismo , Proteína Smad3/metabolismoRESUMO
OBJECTIVE: To explore the expression, function, and regulation mechanism of the long non-coding ribonucleic acid (lncRNA) tubulin alpha 4b (TUBA4B) in colorectal cancer (CRC) tissues and cells. PATIENTS AND METHODS: Cancer and adjacent tissues were collected from 60 CRC patients. CRC cell lines SW480, SW620, HCT116, Caco-2, DLD-1 and HT29, and colonic epithelial cell line CCD841 were also enrolled. Then, the expression of TUBA4B in CRC tissues and cell lines was detected via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). In vitro assays [cell counting kit-8 (CCK-8) assay, clone formation assay, and flow cytometry] were performed to study the biological function of TUBA4B in CRC. Additionally, the downstream regulatory targets of TUBA4B were investigated through Western blotting analysis and qRT-PCR assay. RESULTS: The results of qRT-PCR revealed that compared with adjacent tissues, the expression of TUBA4B was down-regulated in 47/60 CRC tissues (47/60, 78.3%). According to in vitro assays (CCK-8 assay, clone formation assay, and flow cytometry), over-expression of TUBA4B inhibited the proliferation and promoted the apoptosis of CRC cells. TUBA4B remarkably regulated mRNA and protein levels of p15 and p16. CONCLUSIONS: LncRNA TUBA4B is down-regulated expression in CRC tissues and cells, which facilitates CRC cell proliferation and suppresses apoptosis by regulating the expressions of p15 and p16.
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Apoptose , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proliferação de Células , Células Cultivadas , Neoplasias Colorretais/metabolismo , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , HumanosRESUMO
Searching for a metallic material that possesses intrinsic and high catalytic activity is interesting for the hydrogen evolution reaction (HER) in the electrochemical reduction of water. In this work, via density functional theory, we identified a promising two-dimensional (2D) catalyst material, namely TiC (1 0 0) sheet, which is composed of two atomic layers. Phonon spectrum calculation shows that all vibrational modes of the TiC (1 0 0) sheet are real. Even at 1200 K, the geometrical structure of TiC (1 0 0) sheet is still well kept. Interestingly, TiC (1 0 0) sheet is metallic, which means that TiC (1 0 0) sheet can possess high conductivity. Moreover, the Gibbs free energy ([Formula: see text]) of hydrogen on TiC (1 0 0) sheet at a low coverage is about 0.13 eV, which can be further optimized to an ideal value of 0 eV by introducing a strain. Besides, the effect of thickness on its catalytic activity is also assessed. We observed that TiC (1 0 0) sheet with a large thickness is also metallic. Calculated values of [Formula: see text] for four-layered and six-layered TiC (1 0 0) sheets at a moderate coverage can be about -0.06 and -0.04 eV, respectively. Our results highlight a new promising 2D catalyst material for the HER in the electrochemical reduction of water.
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Effectively modulating the electronic and magnetic properties of a two-dimensional system is critical for the application of it in nanoscale devices. In this work, we explore the effect of nanohole on arsenene on the basis of density functional theory calculations. Our calculations show that, except slight distortion at the corner of nanoholes, geometries of both un-hydrogenated nanohole-embedded arsenene (As-NH) structure and hydrogenated nanohole-embedded arsenene (H-As-NH) structure are well maintained after optimization. Interestingly, the As-NH structure can be magnetized so that it can represent ferromagnetic, ferrimagnetic or antiferromagnetic behavior depending on the shape of the nanoholes. Furthermore, As-NH structure with triangle nanoholes is expected to exhibit remarkable magnetism. Besides, owning to the induction of flat defect levels by the nanoholes, As-NH structure can represent a relatively small band gap. In contrast, the H-As-NH structure is shown to lack the magnetism due to the saturation of unpaired As atoms. In this case, the H-As-NH structure exhibits a relatively large band gap due to the quantum confinement effect. These results indicate an opportunity for the design of arsenene-based nanoscale devices with potential applications in spintronic and optical fields.
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Tau is a microtubule-associated protein, and the oligomeric and hyperphosphorylated forms of tau are increased significantly after neurotrauma and considered important factors in mediating cognitive dysfunction. Blockade of adenosine A2A receptors, either by caffeine or gene knockout (KO), alleviates cognitive dysfunction after traumatic brain injury (TBI). We postulated that A2AR activation exacerbates cognitive impairment via promoting tau hyperphosphorylation. Using a mouse model of moderate controlled cortical impact, we showed that TBI induced hyperphosphorylated tau (p-tau) in the hippocampal dentate gyrus and spatial memory deficiency in the Morris water maze test at 7 days and 4 weeks after TBI. Importantly, pharmacological blockade (A2AR antagonist ZM241385 or non-selective adenosine receptor antagonist caffeine) or genetic inactivation of A2ARs reduced the level of tau phosphorylation at Ser404 and alleviated spatial memory dysfunction. The A2AR control of p-tau is further supported by the observations that a KO of A2AR decreased the activity of the tau phosphorylation kinases, glycogen synthase kinase-3ß (GSK-3ß) and protein kinase A (PKA) after TBI, and by that CGS21680 (A2AR agonist) exacerbated okadaic acid-induced tau hyperphosphorylation in cultured primary hippocampal neurons. Lastly, CGS21680-induced neuronal tau hyperphosphorylation and axonal injury were effectively alleviated by individual treatments with ZM241385 (A2AR antagonist), H89 (PKA antagonist) and SB216763 (GSK-3ß antagonist), or by the combined treatment with H89 and SB216763. Our findings suggest a novel mechanism whereby A2AR activation triggers cognitive dysfunction by increasing the phosphorylation level of tau protein after TBI and suggest a promising therapeutic and prophylactic strategy by targeting aberrant A2AR signaling via tau phosphorylation.
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Lesões Encefálicas Traumáticas/complicações , Disfunção Cognitiva/complicações , Fosforilação/efeitos dos fármacos , Receptor A2A de Adenosina/genética , Proteínas tau/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacologia , Agonistas do Receptor A2 de Adenosina/farmacologia , Adulto , Idoso , Animais , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Quinases da Glicogênio Sintase/antagonistas & inibidores , Hipocampo/metabolismo , Humanos , Indóis/farmacologia , Isoquinolinas/farmacologia , Masculino , Maleimidas/farmacologia , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Neurônios/metabolismo , Fenetilaminas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Receptor A2A de Adenosina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfonamidas/farmacologia , Triazinas/farmacologia , Triazóis/farmacologiaRESUMO
No-carrier-added (NCA)[11C](+/-)-ketamine (2a) and its enantiomers (+)-2b and (-)-2c were synthesized by methylation of the corresponding norketamine (1a-c) with [11C]H3I in an overall radiochemical yield of 20% (EOB) with specific activities of 0.35-0.45 Ci/mumol at EOB in a synthesis time of 40 min from EOB. Compound 2a was metabolized rapidly in mouse brain and labeled metabolites appeared in baboon plasma. PET studies of compounds 2a-c in a baboon showed that influx of compounds 2a-c into the brain was high for the first few min but radioactivity then declined rapidly. Although the retention of radioactivity in the baboon striatum was not significantly different for 2a-c 20 min post-injection, graphical analysis of time-activity data for each enantiomer and for the racemate in baboon striatum suggested that (+)-ketamine may interact with receptors slightly more effectively than its (-)-enantiomer or racemate. However, due to its rapid metabolism in the brain and a similar uptake in the striatum and cerebellum, [11C]ketamine may not be an ideal tracer for studying NMDA receptor with PET.
Assuntos
Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono/farmacocinética , Ketamina/farmacocinética , Tomografia Computadorizada de Emissão/métodos , Animais , Transporte Biológico , Biotransformação , Encéfalo/metabolismo , Radioisótopos de Carbono/sangue , Feminino , Marcação por Isótopo/métodos , Ketamina/sangue , Camundongos , Camundongos Endogâmicos , Papio , Distribuição TecidualRESUMO
Alterations in responsiveness to stimulation of G protein-coupled receptors in the cardiovascular system have been noted during aging and may be due to changes in the G proteins. The levels of G protein alpha subunits (Gs alpha, G(o) alpha and Gi alpha) and their mRNAs (Gs alpha, G(o) alpha, Gi2 alpha and Gi3 alpha) were examined in the aorta, heart, and brain of 6 and 24 month old fischer 344 rats by Western blot analysis, quantitative RNA dot blot hybridization and Northern Blot analysis. There were four bands (52, 45, 42 and 38 kD) in the aorta for Gs alpha. The 42 kD band decreased significantly in 24 month old rats (69.2 +/- 0.2%, P < 0.05), while the other bands did not change. The Go alpha and the Gi alpha contain respectively only a band of 39 kD and of 41 kD which decreased significantly in the 24 month rats by 71.8 +/- 10.7% and 63.1 +/- 10.4%; There were no significant changes in the level of G alpha mRNA between 6 and 24 month old rats. In the heart anti-Gs alpha antiserum could detect 3 bands (52, 45 and 42 kD) which did not change during aging; the levels of Gi alpha and G(o) alpha also did not change, but the mRNAs for Gi2 alpha and Gi3 alpha were significantly increased respectively to 120.8 +/- 8.4% and 136.4 +/- 14.2%. The above results indicated that the decrease of levels of Gi alpha G(o) alpha expression may be the molecular basis for the alterations in signal transduction and biological response of aging aorta and heart.
Assuntos
Envelhecimento/metabolismo , Aorta/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Miocárdio/metabolismo , Animais , Western Blotting , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos F344 , Transdução de SinaisRESUMO
Clinical data (n = 275) collected from 52 patients with respiratory tract infection receiving amikacin (AMK) by intravenous infusion were analysed with NONMEM, a computer program designed for estimating population pharmacokinetic parameters. Concentrations of AMK in serum were determined by fluorescence polarization immunoassay (FPIA). A two compartment open model was used for analysing AMK population pharmacokinetics. The influence of body weight (BW), creatinine clearance (CC), administration history (HIS) and state of pathology (chronic obstructional pulmonary disease, COPD) on pharmacokinetics was investigated. The pharmacokinetic parameters of AMK were shown to be influenced by creatinine clearance (CC) and COPD.