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We previously found allelic deletions on chromosomes 17 in primary gastric cancers (GC) using microsatellite markers for loss of heterozygosity (LOH). OVCA1 lies in one of these regions (17q21.33). The association between single nucleotide polymorphism (SNP) of OVCA1 gene and risk of gastric cancer is not yet clear. In this study, the peripheral blood of 505 gastric cancer patients and 544 healthy controls were genotyped for six SNPs (rs2273981, rs1131600, rs3752963, rs3803806, rs2236375, and rs1051322) of OVCA1, to evaluate the association of these SNPs with the risk of gastric cancer in the Han population in northeast China. The effect of rs2273981 located in the promoter region of OVCA1 on the transcription activity was determined using dual luciferase reporter assay. We found that the association between the AA + AG genotype of rs2273981 and the risk of gastric cancer was significant in smokers (AA + AG vs. GG, OR = 2.47, 95% CI = 1.04 - 5.87, P less then 0.05). Stratified analysis of the clinicopathological parameters revealed that rs1131600 AG + GG genotype were significantly associated with increased gastric tumor volume (AG + GG vs. AA, OR = 1.81, 95% CI = 1.00 - 3.29, P less then 0.05). The rs2236375 CT + TT genotype was also significantly associated with increased gastric tumor volume (CT + TT vs. CC, OR = 2.65, 95% CI = 1.38 - 5.10, P less then 0.05). Additionally, by interacting with the transcription factor AP2A, the GG genotype the rs2273981 increased the transcription activity of OVCA1 compared with AA genotype, thus involved in gastric cancer development.Sclerosing epithelioid fibrosarcoma (SEF), typically arising in middle-aged and older adults, is a rare malignant fibroblastic neoplasm characterized by epithelioid fibroblasts embedded in sclerotic hyalinized stroma. This tumor frequently harbors translocation between EWSR1 and CREB3 subfamily members. Here, we describe four cases of SEF with unique genetic characteristics in children. All tumors were located in the deep soft tissue of the trunk and celom. Histopathologically, the tumors were featured by prominent hyalinized sclerotic collagenous stroma within which relatively bland and monomorphic epithelioid cells were arranged in cords, nests, or sheets. Low-grade fibromyxoid sarcoma-like zones varied among cases. MUC4 was strong and diffuse. CD99 was positive. Transmission electron microscopy demonstrated spindle or polyhedral neoplastic cells with a collagen fiber-rich stroma. Interphase fluorescence in situ hybridization (FISH) revealed local amplification of the EWSR1 locus. Whole-genome sequencing indicated translocation between EWSR1 and CREB3L1 together with low-level amplification of the fusion parts. RT-PCR and Sanger sequencing confirmed the fusion transcript. Single nucleotide polymorphism and FISH analyses demonstrated co-deletion of 11p and 22q. The consistent genetic features indicated the presence of a unique molecular variant of SEF. DATA AVAILABILITY STATEMENT The data used to support the findings of this study are available from the corresponding author upon request.With the acceleration of China's urbanization and industrialization, air pollution has become a major environmental problem. Retrospective data analysis of 6564 patients who underwent IVF-ET in the center for reproductive medicine of the First Affiliated Hospital of Zhengzhou University from 2015 to 2020. Different stages were selected from 90 days before oocyte retrieval to 35 days after transfer and divided into five exposure periods. Multivariate logistic regression was used to analyze the relationship between six ambient air pollutants (PM2.5, PM10, NO2, SO2, CO and O3) and the IVF-ET pregnancy outcome. The results showed that air pollutants can significantly affect the IVF pregnancy outcome. The harmful effects of ambient air pollutants are more obvious in the patients aged less then 35 years, single embryo transfer and cleavage stage embryo transfer.
Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine.
To compare global differences in ease of access to biologics.
In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access.
Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/μL) and exacerbations were key requirements for found in the current study present a challenge to implementing precision medicine across the world.Polypharmacology is a concept where a molecule can interact with two or more targets simultaneously. It offers many advantages as compared to the conventional single-targeting molecules. A multi-targeting drug is much more efficacious due to its cumulative efficacy at all of its individual targets making it much more effective in complex and multifactorial diseases like cancer, where multiple proteins and pathways are involved in the onset and development of the disease. For a molecule to be polypharmacologic in nature, it needs to possess promiscuity which is the ability to interact with multiple targets; and at the same time avoid binding to antitargets which would otherwise result in off-target adverse effects. There are certain structural features and physicochemical properties which when present would help researchers to predict if the designed molecule would possess promiscuity or not. Promiscuity can also be identified via advanced state-of-the-art computational methods. In this review, we also elaborate on the methods by which one can intentionally incorporate promiscuity in their molecules and make them polypharmacologic. The polypharmacology paradigm of "one drug-multiple targets" has numerous applications especially in drug repurposing where an already established drug is redeveloped for a new indication. Though designing a polypharmacological drug is much more difficult than designing a single-targeting drug, with the current technologies and information regarding different diseases and chemical functional groups, it is plausible for researchers to intentionally design a polypharmacological drug and unlock its advantages.The effects of combined 4-chlorophenol (4-CP) and Cu2+ on microbial community structures, functional genes for nitrogen and phosphorus removal, and heavy metal resistance genes (HMRGs) were explored in wastewater treatment using sequencing batch bioreactors (SBRs). Compared to influent 4-CP (2.3-4.5 mg/L), the removal of pollutants including chemical oxygen demands (COD), NH4+-N, PO43--P, and 4-CP was inhibited under Cu2+ stress (5 mg/L). The effects of Cu2+ on microbial community structures were more significant than those of 4-CP with respect to operational time, while the dominant function from gene information was not affected with or without influent 4-CP and Cu2+ via sequencing analysis. The influent 4-CP and Cu2+ largely influenced the dynamic changes of functional genes and HMRGs, and the abundance of partial HMRGs was correlated to the functional genes and dominant genera. This study provides insights into the treatment of combined chlorophenols and Cu2+ in wastewater.Novel cell-disruption combinations (autolytic incubation and hypotonic osmotic shock combined with HPH or pH12) were used to investigate the fundamental mass transfer of lipids and proteins from Nannochloropsis slurries (140 mg biomass/g slurry). Since neutral lipids exist as cytosolic globules, their mass transfer was directly dependent on disintegration of cell walls. Complete recovery was obtained with complete physical disruption. HPH combinations exerted more physical disruption and led to higher yields than pH12. In contrast, proteins exist as both cytosolic water-soluble fractions and cell-wall/membrane structural fractions and have a complex extraction behaviour. Mass transfer of cytosolic proteins was dependent on cell-wall disintegration, while that of structural proteins was governed by cell-wall disintegration and severance of protein linkage from the wall/membrane. HPH combinations exerted only physical disruption and were limited to releasing soluble proteins. pH12 combinations hydrolysed chemical linkages in addition to exerting physical disruption, releasing both soluble and structural proteins.Efficient removal of nitrate under low temperature is challenging because of the reduction of the microbial activity. This study successfully explored the promotion on the performance of denitrification utilizing the immobilized biochar in biofilters under low temperature (6 ± 2 °C). The results showed that the immobilized biochar increased the denitrification rate by 76.8% and decreased the nitrous oxide emissions by 82.5%. Mechanistic studies revealed that the immobilized biochar increased the activities of the denitrifying enzymes and three enzymes involved in glycolysis. Furthermore, the immobilized biochar elevated the activity of the electron transport system by 31.8%. Finally, structural equation model explained that the increase of nitrate reductase activity was a crucial factor to enhance the total nitrogen removal efficiency in biofilters with immobilized biochar. Overall, the use of immobilized biochar can be a novel strategy to enhance nitrogen removal and reduce greenhouse gas emissions in biofilters under low temperature.Removal of nutrients from swine wastewater digester effluent (SWDE) by microalgae Coelastrella sp. and production of Coelastrella sp. were investigated at the presence of oxytetracycline (OTC) and Zn(II). selleck compound Mechanisms of stress of OTC and Zn(II) on microalgae were discussed via analyzing the removal performance of SWDE and biochemical characteristics of microalgae. Results showed that removal efficiency of ammonia nitrogen and biomass yield of microalgae at the presence of 5000 μg/L of OTC decreased by 13.1% - 50.1% and 28.2% -71.5%, respectively, when Zn concentration was increased from 0.50 mg/L to 5.0 mg/L. The presence of 5.0 mg/L Zn(II) promoted the accumulation of lipids in microalgae, and the presence of 50 μg/L OTC increased unsaturation of fatty acid methyl ester. Content of glutathione and activity of both glutamine synthetase and superoxide dismutase decreased with the increase of OTC concentration, while content of adenosine triphosphatase increased when Zn(II) concentration was also increased.The purpose of this study was to evaluate the bioremediation potential of the microalga Scenedesmus quadricauda in removing hexavalent chromium (Cr (VI)) from synthetic wastewater, under autotrophic and heterotrophic conditions and different inoculum concentrations. In both cultivation modes, the highest inoculum density of 0.8 g L-1 led to the highest Cr (VI) removal efficiency. In addition, Cr (VI) stress was more severe in 10 ppm compared to 5 ppm, while heavy metal effects were alleviated under heterotrophic conditions. Concurrently, Cr (VI) stress affected biomass quality, resulting in an increase in lipid and carbohydrate production and decreased proteins. Furthermore, under higher Cr (VI) concentration more saturated and monounsaturated fatty acids were produced, while monounsaturated fatty acids content was also greater under heterotrophic conditions. In total, the findings of this study highlight the advantages of heterotrophic cultivation of microalgae for concomitant industrial wastewater treatment and biofuel production.
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