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1.
Int J Mol Sci ; 20(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597345

RESUMO

Among the radicals (hydroxyl radical (•OH), hydrogen atom (H•), and solvated electron (esol-)) that are generated via water radiolysis, •OH has been shown to be the main transient species responsible for radiation damage to DNA via the indirect effect. Reactions of these radicals with DNA-model systems (bases, nucleosides, nucleotides, polynucleotides of defined sequences, single stranded (ss) and double stranded (ds) highly polymeric DNA, nucleohistones) were extensively investigated. The timescale of the reactions of these radicals with DNA-models range from nanoseconds (ns) to microseconds (µs) at ambient temperature and are controlled by diffusion or activation. However, those studies carried out in dilute solutions that model radiation damage to DNA via indirect action do not turn out to be valid in dense biological medium, where solute and water molecules are in close contact (e.g., in cellular environment). In that case, the initial species formed from water radiolysis are two radicals that are ultrashort-lived and charged: the water cation radical (H2O•+) and prethermalized electron. These species are captured by target biomolecules (e.g., DNA, proteins, etc.) in competition with their inherent pathways of proton transfer and relaxation occurring in less than 1 picosecond. In addition, the direct-type effects of radiation, i.e., ionization of macromolecule plus excitations proximate to ionizations, become important. The holes (i.e., unpaired spin or cation radical sites) created by ionization undergo fast spin transfer across DNA subunits. The exploration of the above-mentioned ultrafast processes is crucial to elucidate our understanding of the mechanisms that are involved in causing DNA damage via direct-type effects of radiation. Only recently, investigations of these ultrafast processes have been attempted by studying concentrated solutions of nucleosides/tides under ambient conditions. Recent advancements of laser-driven picosecond electron accelerators have provided an opportunity to address some long-term puzzling questions in the context of direct-type and indirect effects of DNA damage. In this review, we have presented key findings that are important to elucidate mechanisms of complex processes including excess electron-mediated bond breakage and hole transfer, occurring at the single nucleoside/tide level.

2.
Org Lett ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580690

RESUMO

Propargylamines are an important class of compounds in organic synthesis and drug discovery, yet the synthesis of chiral ß-keto propargylamines remains underdeveloped. Herein, we describe a streamlined and general enantioselective Mannich reaction of enamides with C-alkynyl N-Boc N,O-acetals, which serve as readily available C-alkynyl imine precursors, to access a broad range of chiral ß-keto N-Boc-propargylamines bearing single stereogenic centers in high yields (up to 98%) and in high enantioselectivities (up to 95% ee).

3.
Artigo em Inglês | MEDLINE | ID: mdl-31582349

RESUMO

BACKGROUND: Physical fitness is strongly associated with health. Despite the extent of the nutritional transition from food scarcity to diets high in fats and refined carbohydrates that has occurred in China, to our knowledge, trends in physical fitness have not been described. We aimed to assess trends in physical fitness and its association with the nutritional transition among Chinese children and adolescents. METHODS: In this retrospective analysis, data from Chinese school students aged 7-18 years were extracted from six successive national surveys undertaken between 1985 and 2014. Six components of physical fitness (forced vital capacity, standing long jump, sit-and-reach, body muscle strength, 50 m dash, and endurance running) were measured repeatedly in each survey and aggregated as a summary physical fitness indicator (PFI). Growth and nutritional status (stunting, thinness, normal weight, overweight, and obesity) were defined by use of WHO definitions, and we combined stunting and thinness as undernutrition and overweight and obesity as overnutrition. Urbanisation levels were obtained from the statistical yearbook of the National and Provincial Bureau of Statistics of China. We used fractional polynomial regression and generalised additive models to assess associations between PFI and nutritional outcomes and between PFI and levels of urbanisation. FINDINGS: Between 1985 and 2014, 1 513 435 students participated in the Chinese National Survey on Students' Constitution and Health, and 1 494 485 were included in our study. We observed a decline of the PFI during 1985-2014 (overall PFI change -0·8), albeit with an increase from 1985 to 1995 (PFI change 1·2), coinciding with a shift in the major nutritional problems from stunting and thinness to overweight and obesity. Both undernourished (PFI -2·44 for thin and -3·42 for stunting) and overnourished (-1·49 for overweight and -3·63 for obese) students had a lower PFI than that of those with normal weight (-0·41) in 2014. Boys had a larger decline in PFI than girls in 1985-2014, especially boys with obesity (PFI change -2·7). We observed the highest PFI in 1995 (1·17), when the proportion of students with normal weight was highest. Advancing urbanisation was accompanied by declines in physical fitness, which occurred in both students in rural settings and those in urban settings in these regions. INTERPRETATION: Our study supports the continuation of policies to improve physical fitness that focus on undernutrition, including economic subsidies, in poorer rural regions. However, for most of China, taxation of unhealthy foods, promotion of physical activity, reduction in academic pressures, promotion of dietary diversity, reduction of sedentary time, and engagement in formal sporting activities should be elements of policies to promote healthy weight status and prevent obesity in school students, which will also support physical fitness. FUNDING: National Natural Science Foundation, Humanities and Social Sciences Planning Fund Project, China Scholarship Council, and Innovation Fund for Outstanding Doctoral Candidates of Peking University Health Science Center.

4.
J Org Chem ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31591886

RESUMO

N-aryl amides are an important class of compounds in pharmaceutical and agrochemical chemistry. Rapid and low-cost synthesis of N-aryl amides remains in high demand. Herein, we disclose an operationally simple process to access N-aryl amides directly from readily available nitroarenes and carboxylic acids as coupling substrates. This method involves the in-situ activation of carboxylic acids to acyloxyphosphonium salt for one-pot amidation, without the need for isolation of the corresponding synthetic intermediates. Furthermore, the ease of preparation and workup allows the quick and efficient synthesis of a wide range of N-aryl amides, including several amide-based druglike and agrochemical molecules.

5.
J Hazard Mater ; 384: 121264, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31590082

RESUMO

Promotional effect of Mn(II)/K2FeO4 [Fe(VI)] applying onto Se(IV) removal was determined for the first time, with description of reaction mechanisms. Four different combinations of water treatment agents [K2FeO4 alone, K2FeO4 with Al(III) ions, K2FeO4 with Fe(III) ions, and K2FeO4 with Mn(II) ions] were used for Se removal in spiked deionized water, and K2FeO4 in combination with Mn(II) ions showed great removal efficiency. Over 90% of Se(IV) (200 µg/L) was removed within 2 min by using 1 mg/L of K2FeO4 and 9 mg/L of Mn(II) ions (pH 7.0, 23 °C). XPS analysis identified that in the reaction process, Se(0) formed on the settlement. It was speculated that Se(IV) was oxidized to Se(VI) by K2FeO4, and the Se(VI) species was reduced to insoluble Se(0) by γ-Fe2O3-Mn(II) nanocomplex. Insoluble Se(0) adsorbed on the surface of Fe-Mn particle and coprecipitated, thus removed from aqueous solution. As solution pH varied from 4.0 to 8.0, Se(IV) removal ratio ranged from 89% to 98% in the system. Co-existing ions such as Na+, Ca2+ and SO42- had no intense effect on Se removal, while PO43- and humic acid (HA) inhibited Se removal in Mn(II)/K2FeO4 system. Mn(II)/K2FeO4 was an effective and convenient way for Se(IV) removal from polluted water.

6.
PLoS Biol ; 17(10): e3000461, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31600191

RESUMO

Dendritic spine development is crucial for the establishment of excitatory synaptic connectivity and functional neural circuits. Alterations in spine morphology and density have been associated with multiple neurological disorders. Autism candidate gene disconnected-interacting protein homolog 2 A (DIP2A) is known to be involved in acetylated coenzyme A (Ac-CoA) synthesis and is primarily expressed in the brain regions with abundant pyramidal neurons. However, the role of DIP2A in the brain remains largely unknown. In this study, we found that deletion of Dip2a in mice induced defects in spine morphogenesis along with thin postsynaptic density (PSD), and reduced synaptic transmission of pyramidal neurons. We further identified that DIP2A interacted with cortactin, an activity-dependent spine remodeling protein. The binding activity of DIP2A-PXXP motifs (P, proline; X, any residue) with the cortactin-Src homology 3 (SH3) domain was critical for maintaining the level of acetylated cortactin. Furthermore, Dip2a knockout (KO) mice exhibited autism-like behaviors, including excessive repetitive behaviors and defects in social novelty. Importantly, acetylation mimetic cortactin restored the impaired synaptic transmission and ameliorated repetitive behaviors in these mice. Altogether, our findings establish an initial link between DIP2A gene variations in autism spectrum disorder (ASD) and highlight the contribution of synaptic protein acetylation to synaptic processing.

7.
Water Res ; 167: 115111, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31574347

RESUMO

The novel H2O2-MnO2 system was developed to achieve highly efficient membrane cleaning for both fouled PVDF and PES membranes in this study. Compared with conventional chemical cleaning process in which the whole membrane module had to be soaked in highly concentrated solution of chemical reagent for long period of time, the H2O2-MnO2 cleaning process conducting for only 5 min in 0.5 wt% H2O2 solution could achieve more than 95% recovery of permeate flux and almost total removal of the irreversible foulants. More importantly, the permeate flux and filtration efficiency of the membrane could be still kept stable after 6 runs of consecutive fouling and cleaning. Based on the systematic microscopic analyses, Electron Spin Resonance (ESR), Fourier Transform Infrared Spectroscopy (FTIR), as well as the quenching experiments with different free radical scavengers, the outstanding performance of H2O2-MnO2 system was attributed to the generation of both free radicals and abundant oxygen simultaneously, leading to the physico-chemical membrane cleaning. Conclusively, the newly developed H2O2-MnO2 system demonstrated noteworthy advantages on efficient membrane cleaning, and exhibited highly potential for the wide application in practical water treatment process.

8.
Sci Signal ; 12(602)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31594855

RESUMO

CARD9 is an immune adaptor protein in myeloid cells that is involved in C-type lectin signaling and antifungal immunity. CARD9 is implicated in autoimmune and inflammatory-related diseases, such as rheumatoid arthritis, IgA nephropathy, ankylosing spondylitis, and inflammatory bowel disease (IBD). Given that Lyn-deficient (Lyn-/-) mice are susceptible to both autoimmunity and IBD, we investigated the immunological role of CARD9 in the development of these diseases using the Lyn-/- mouse model. We found that genetic deletion of CARD9 was sufficient to reduce the development of both spontaneous autoimmune disease as well as DSS- or IL-10 deficiency-associated colitis in Lyn-/- mice. Mechanistically, CARD9 was a vital component of the Lyn-mediated regulation of Toll-like receptor (TLR2 and TLR4) signaling in dendritic cells, but not in macrophages. In the absence of Lyn, signaling through a CD11b-Syk-PKCδ-CARD9 pathway was amplified, leading to increased TLR-induced production of inflammatory cytokines. Dendritic cell-specific deletion of CARD9 reversed the development of autoimmune and experimental colitis observed in dendritic cell-specific, Lyn-deficient mice. These findings suggest that targeting CARD9 may suppress the development of colitis and autoimmunity by reducing dendritic cell-driven inflammation.

9.
Anal Chem ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31599567

RESUMO

In clinical diagnosis, accurate and reliable measurement technologies for the detection of disease biomarkers at ultralow concentrations can provide guidance for the initiation of treatment and potentially improve survival for patients. Here, we demonstrate an optical microfiber reader for enhanced analytical sensitivity in enzyme-linked immunosorbent assays (ELISA) that enables the detection of tiny changes of refractive index (RI) induced by the catalyzed oxidation of substrate owing to its strong interaction between evanescent field and surrounding medium. By employing the microfiber reader for the C-reaction protein (CRP) and interleukin-6 (IL-6) assays after the enzymatic signal amplification in ELISA, we experimentally investigate the bio-sensing capacity of the device. As a result, log-linear relations of CRP and IL-6 detection in PBS and human serum between the concentration and spectral response was obtained at both nanogram and picogram levels respectively, and Anti-CRP/HRP detection as low as 9.75 pg/mL was achieved that was undetectable by the conventional spectrophotometry. With a stable, accurate and color-free detection capacity, this optical microfiber reader has a promising prospect in early disease diagnosis and clinical treatment.

10.
Org Lett ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513413

RESUMO

We report a general and efficient approach to construct achiral and chiral gem-difluoroallylic amines from a masked difluorodiazo reagent (PhSO2CF2CHN2) and readily available imines. This facile protocol takes advantage of the phenylsulfonyl and diazo moieties as efficient activating and directing groups to assist difluoroalkyl incorporation and facilitate the chemodivergent and stereoselective formation of gem-difluoroallylic amines.

11.
Math Biosci Eng ; 16(5): 5788-5803, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31499738

RESUMO

In this study, the radial basis function (RBF) which has good performance for nonlinear problem is introduced to approximate the implicit relationships between EDM parameters and performance responses for 304 steel. The fitting precision of RBF is compared with the second order polynomial response surface (PRS), support vector regression (SVR) and Kriging model (KRG) using the multiple correlation coefficient (R2) based cross validation error method. Then the RBF model is called to conduct multi-objective optimization using non-dominated sorting genetic algorithm II (NSGA-II) method. The energy consumption index unit energy consumption (UEC) and the air-pollution indices PM2.5 and PM10 are considered in proposed multi-objective optimization model. UEC is considered as the objective function to reduce the machining cost and the PM indices are termed as the constraints to protect the operators' health. The pulse current, time period and duty cycle are considered as the main factors affecting the EDM responses. According to the Pareto plots of multi-objective optimization model, conclusion can be drawn that SR and PM10 play significant roles in multi-optimization and PM2.5 has less influence on optimization results. The results of the present study reveal that using maximum material removal rate (MRR) and minimum UEC as objective and using surface roughness (SR), PM2.5 and PM10 as constraints can be an effective method to provide appropriate process parameters reference for EDM machining.

12.
Food Chem ; 305: 125447, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31499289

RESUMO

A novel α-amylase gene (RmAmyA) from Rhizomucor miehei was cloned and expressed in Pichia pastoris. RmAmyA showed 70% amino acid identity with the α-amylase from Rhizomucor pusillus. A high α-amylase activity of 29,794.2 U/mL was found through high cell density fermentation. The molecular mass of RmAmyA was determined to be 49.9 kDa via SDS-PAGE. RmAmyA was optimally active at 75 °C and pH 6.0, and it did not require Ca2+ to improve its activity. It exhibited broad substrate specificity towards amylose, amylopectin, soluble starch, pullulan, and cyclodextrins. High level of maltose (54%, w/w) was produced after liquefied starch was hydrolysed with RmAmyA for 16 h. Moreover, the addition of RmAmyA into Chinese steamed bread resulted in 7.7% increment in the specific volume, and 17.2% and 11.5% reduction in the chewiness and hardness, respectively. These results indicate that RmAmyA might be a potential candidate for applications in the food industry.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31552197

RESUMO

There have been several previous reports showing that PA-X and PB1-F2 proteins can regulate innate immune responses and may play roles in the adaptation of influenza viruses to new hosts. In this research, we investigated, for the first time, the combined effects of PA-X and PB1-F2 proteins on viral virulence in mice. Based on the 2009 pH1N1 A/Guangdong/1057/2010 virus backbone, four viruses encoding different combinations of full-length or truncated PA-X and PB1-F2 proteins were rescued by a reverse genetic engineering system. We analyzed viral replication, host-shutoff activity, in vitro viral pathogenicity and in vivo host immune response. We found that simultaneously expressing the full-length PA-X and PB1-F2 proteins enhanced viral replication in vitro through increasing the accumulation of the RNP complex protein and enhanced viral pathogenicity in mice during the early stage of infection. Furthermore, PA-X and PB1-F2 simultaneously regulated the host innate response, and different forms of PB1-F2 proteins may have impacts on the host shutoff activity induced by the PA-X protein. Our results provide a better understanding of the mechanisms of PA-X and PB1-F2 proteins during viral replication, pathogenicity and host immune response.

14.
Cancer Med ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31560840

RESUMO

BACKGROUND: To identify thyroid dose-volume thresholds for radiotherapy (RT)-related hypothyroidism (HT) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated RT (IMRT). In this way, we desired to guide the design of treatment plans and, finally, lower HT prevalence. METHODS: In total, 345 NPC patients treated with IMRT were evaluated retrospectively during a median follow-up of 45.2 (range, 11.3-64.9) months. Serum-based assessments of thyroid function before and after IMRT were monitored periodically. Thyroid dose-volume parameters were analyzed for their association with HT risk. RESULTS: In total, 44.1% of patients (152/345) developed primary HT. Analyses of thyroid dose-volume parameters identified a stringent dose-volume histogram (DVH) threshold defined by V25Gy (the percentage thyroid volume that receives >25 Gy, not the absolute volume) ≤60%, V35Gy  ≤ 55%, and V45Gy  ≤ 45%. Patients whose thyroid DVHs satisfied these constraints had a lower prevalence of 2-year HT compared with the overall prevalence (13.2% vs 25.8%, P < .001). Another DVH was defined by V25Gy  > 95%, V35Gy  > 90%, and V45Gy  > 75%, and patients whose thyroid DVHs satisfied with these constraints had a higher prevalence of 2-year HT than the overall incidence (36.0% vs 25.8%, P < .001). CONCLUSION: We recommend V25Gy  ≤ 60%, V35Gy  ≤ 55%, and V45Gy  ≤ 45% as the "stringent" DVH line, and V25Gy  > 95%, V35Gy  > 90%, and V45Gy  > 75% as the "inhibition" DVH line, under the precondition of not compromising the target coverage. These findings could help in the design of individual treatment plans and, eventually, to lowering of HT prevalence.

15.
ACS Appl Mater Interfaces ; 11(38): 35501-35508, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31482699

RESUMO

Novel multifunctional core-shell nanoparticles (Fe3O4@PSBMA NPs) with magnetic and zwitterionic properties were first synthesized and efficiently incorporated into the poly(vinylidene fluoride) (PVDF) membranes via magnetically controlled surface segregation toward the better water-energy-food nexus. The combination of zwitterionic polymers poly(sulfobetaine methacrylate) (PSBMA) and Fe3O4 particles can improve the compatibility of additives with the PVDF matrix and significantly improve the migration of Fe3O4@PSBMA NPs onto membrane surfaces under magnetic fields during nonsolvent-induced phase separations. The modified membrane with surface-enriched multifunctional zwitterionic NPs had an enhanced water flux (168%, ∼630.5 L m-2 h-1), excellent fouling resistance (∼93.8%), and increased rejection to bovine serum albumin (94.1%). Most importantly, the PVDF/M-Fe3O4@PSBMA membrane had excellent stability under the long-term filtration test for practical water-treatment applications.

16.
BMJ ; 366: l5016, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511230

RESUMO

OBJECTIVE: To assess the effects of Helicobacter pylori treatment, vitamin supplementation, and garlic supplementation in the prevention of gastric cancer. DESIGN: Blinded randomized placebo controlled trial. SETTING: Linqu County, Shandong province, China. PARTICIPANTS: 3365 residents of a high risk region for gastric cancer. 2258 participants seropositive for antibodies to H pylori were randomly assigned to H pylori treatment, vitamin supplementation, garlic supplementation, or their placebos in a 2×2×2 factorial design, and 1107 H pylori seronegative participants were randomly assigned to vitamin supplementation, garlic supplementation, or their placebos in a 2×2 factorial design. INTERVENTIONS: H pylori treatment with amoxicillin and omeprazole for two weeks; vitamin (C, E, and selenium) and garlic (extract and oil) supplementation for 7.3 years (1995-2003). MAIN OUTCOME MEASURES: Primary outcomes were cumulative incidence of gastric cancer identified through scheduled gastroscopies and active clinical follow-up through 2017, and deaths due to gastric cancer ascertained from death certificates and hospital records. Secondary outcomes were associations with other cause specific deaths, including cancers or cardiovascular disease. RESULTS: 151 incident cases of gastric cancer and 94 deaths from gastric cancer were identified during 1995-2017. A protective effect of H pylori treatment on gastric cancer incidence persisted 22 years post-intervention (odds ratio 0.48, 95% confidence interval 0.32 to 0.71). Incidence decreased significantly with vitamin supplementation but not with garlic supplementation (0.64, 0.46 to 0.91 and 0.81, 0.57 to 1.13, respectively). All three interventions showed significant reductions in gastric cancer mortality: fully adjusted hazard ratio for H pylori treatment was 0.62 (95% confidence interval 0.39 to 0.99), for vitamin supplementation was 0.48 (0.31 to 0.75), and for garlic supplementation was 0.66 (0.43 to 1.00). Effects of H pylori treatment on both gastric cancer incidence and mortality and of vitamin supplementation on gastric cancer mortality appeared early, but the effects of vitamin supplementation on gastric cancer incidence and of garlic supplementation only appeared later. No statistically significant associations were found between interventions and other cancers or cardiovascular disease. CONCLUSIONS: H pylori treatment for two weeks and vitamin or garlic supplementation for seven years were associated with a statistically significant reduced risk of death due to gastric cancer for more than 22 years. H pylori treatment and vitamin supplementation were also associated with a statistically significantly reduced incidence of gastric cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00339768.


Assuntos
Infecções por Helicobacter/terapia , Lesões Pré-Cancerosas/terapia , Neoplasias Gástricas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiulcerosos/administração & dosagem , Biópsia , China/epidemiologia , Suplementos Nutricionais , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Alho/química , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Gastroscopia , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/administração & dosagem , Lesões Pré-Cancerosas/microbiologia , Lesões Pré-Cancerosas/patologia , Inibidores da Bomba de Prótons/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/prevenção & controle , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
17.
Sci Rep ; 9(1): 13868, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31554914

RESUMO

Identification of primary targets associated with phenotypes can facilitate exploration of the underlying molecular mechanisms of compounds and optimization of the structures of promising drugs. However, the literature reports limited effort to identify the target major isoform of a single known target gene. The majority of genes generate multiple transcripts that are translated into proteins that may carry out distinct and even opposing biological functions through alternative splicing. In addition, isoform expression is dynamic and varies depending on the developmental stage and cell type. To identify target major isoforms, we integrated a breast cancer type-specific isoform coexpression network with gene perturbation signatures in the MCF7 cell line in the Connectivity Map database using the 'shortest path' drug target prioritization method. We used a leukemia cancer network and differential expression data for drugs in the HL-60 cell line to test the robustness of the detection algorithm for target major isoforms. We further analyzed the properties of target major isoforms for each multi-isoform gene using pharmacogenomic datasets, proteomic data and the principal isoforms defined by the APPRIS and STRING datasets. Then, we tested our predictions for the most promising target major protein isoforms of DNMT1, MGEA5 and P4HB4 based on expression data and topological features in the coexpression network. Interestingly, these isoforms are not annotated as principal isoforms in APPRIS. Lastly, we tested the affinity of the target major isoform of MGEA5 for streptozocin through in silico docking. Our findings will pave the way for more effective and targeted therapies via studies of drug targets at the isoform level.

18.
J Neurooncol ; 145(1): 75-83, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471790

RESUMO

INTRODUCTION: There has been a resurgence of interest in brachytherapy as a treatment for glioblastoma, with several currently ongoing clinical trials. To provide a foundation for the analysis of these trials, we analyze the Surveillance, Epidemiology, and End Results (SEER) database to determine whether receipt of brachytherapy conveys a survival benefit independent of traditional prognostic factors. MATERIALS AND METHODS: We identified 60,456 glioblastoma patients, of whom 362 underwent brachytherapy. We grouped patients based on receipt of brachytherapy and compared clinical and demographic variables between groups using Student's t-test and Pearson's chi-squared test. We assessed survival using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Median overall survival was 16 months in patients who received brachytherapy compared to 9 months in those who did not (log-rank p < 0.001). Patients who underwent brachytherapy tended to be younger (p < 0.001), suffered from smaller tumors (< 4 cm, p < 0.001), and were more likely to have undergone gross total resection (GTR, p < 0.001). In univariable Cox models, these variables were independently associated with improved overall survival. Additionally, improved survival was associated with known receipt of chemotherapy (HR 0.459, p < 0.001), external beam radiation (HR 0.447, p < 0.001), and brachytherapy (HR 0.637, p < 0.001). The association between brachytherapy and improved survival remained robust (HR 0.859, p = 0.031) in a multivariable model that adjusted for patient age, tumor size, tumor location, GTR, receipt of chemotherapy, and receipt of external beam radiation. CONCLUSION: Our SEER analysis indicates that brachytherapy is associated with improved survival in glioblastoma after controlling for age, tumor size/location, extent of resection, chemotherapy, and external beam radiation.

19.
BMC Musculoskelet Disord ; 20(1): 402, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31481049

RESUMO

BACKGROUND: The lower limb joints, including hip and knee, are the most commonly involved joints in haemophilic arthropathy. With a higher risk of transfusion, total hip and knee arthroplasty (THA and TKA) are still the first choice after failure of conservative treatment. In the present study, we aimed to analyze clinical outcomes and complications rate after total joint arthroplasty of the lower limbs using tranexamic acid (TXA) or not. METHODS: Thirty-four patients with haemophilia A undergoing 24 TKA and 18 THA were evaluated in this retrospective study (No. 201302009). Based on using TXA or not, they were divided into either TXA (12 knees and 10 hips) or Non-TXA groups (12 knees and 8 hips). Total blood loss, intraoperative blood loss, total amount of FVIII usage, range of motion, inflammatory biomarkers, joint function, pain status, complication rate and patient satisfaction were assessed and compared at a mean follow-up of 68 months. RESULTS: Usage of TXA can decrease not only the perioperative blood loss (p = 0.001), transfusion rate (p = 0.017) and supplemental amount of FVIII (p < 0.001) but also swelling ratio, surgical joint pain. Moreover, compared with non-TXA group, the patients in TXA group had a lower level of inflammatory biomarkers and better joint function. CONCLUSION: The hemophiliacs treated with TXA had less perioperative blood loss, hidden blood loss, transfusion rate, a lower ratio of postoperative knee swelling, less postoperative joint pain, lower levels of inflammatory biomarkers and better joint function. Further studies need performing to assess the long-term effects of TXA in these patients.

20.
Opt Express ; 27(14): 19768-19777, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31503732

RESUMO

The recent development of liquid-phase chemical analyses, drug delivery, and flow cytometry requires precise sensing and control of the liquid flow in a microfluidic chip environment. The channel in microfluidic chips is getting narrower to cope with complex liquid controls on a single chip, where small-footprint sensors and actuators are in urgent demand for accurate flow management. In this study, a unique microscopic bubble-on-fiber (BoF) device that can be readily integrated to current microfluidic chips was proposed and demonstrated for in situ sensing and control of microfluidic flow rate. The single microbubble was optically generated on the gold-deposited facet of an optical fiber by the local heating due to optical absorption. The BoF is a microscopic Fabry-Perot cavity, which serves as a thermal flow sensor precisely detecting the flow-induced temperature changes in the optical frequency domain. Experimentally we achieved the minimum detectable flow rate of ~0.06 mm/s in a single microfluidic channel, which is equivalent to a volume flow rate of 22 nL/s, and a response time of ~6 s. We also demonstrated that the BoF functioned as a microfluidic valve to regulate the flow rate in a Y-shape microfluidic chip by optically varying the bubble diameter. In addition to advantages of highly integrated functionalities and microscopic form factor, the proposed BoF can obviate the usage of chemical tracer such as dyes and can provide a high sensitivity over repeated flow cycles in a highly consistent manner. The BoF is promising for the timely development of high-density lab-on-a-chip devices using its efficient liquid flow management capability.

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