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Patients with gastric cancer exhibit considerable genetic and phenotypic heterogeneity, necessitating the establishment of a model for personalized medicine screening. Here, we successfully established three-dimensional cell spheroids (3D cell spheroids) from fresh gastric cancer tissues (n = 30) as in vitro models for further therapeutic screening. Hematoxylin-eosin and immunohistochemical staining of whole spheroids and parental tumor tissues revealed that the 3D cell spheroids recapitulated the parental tissue structure and maintained the histological characteristics of the parental tumor tissue during long-term expansion in vitro. Further, transcriptome sequencing verified that the cell spheroids could recapitulate the gene expression profile characteristics of the parental tumor tissue. Drug susceptibility testing of the 3D cell spheroids demonstrated that these cell spheroids can be used as a reliable model for drug prediction.

The main manifestation of obesity is persistent low-level inflammation and insulin resistance, which is an important factor inducing or promoting other obesity-related diseases. As a proinflammatory programmed cell death, pyroptosis plays an important role, especially in the activation and regulation of the NLRP3 inflammasome pathway. Pyroptosis is associated with the pathogenesis of many chronic inflammatory diseases and is characterized by the formation of micropores in the plasma membrane and the release of a large number of proinflammatory cytokines. This article mainly introduces the main pathways and key molecules of pyroptosis and focuses on the phenomenon of pyroptosis in obesity. It is suggested that the regulation of pyroptosis-related targets may become a new potential therapy for the prevention and treatment of systemic inflammatory response caused by obesity, and we summarize the potential molecular substances that may be beneficial to obesity-related inflammatory diseases through target pyroptosis.

三元相图是研究羊毛角蛋白再生过程热力学行为的有效工具。通过浊度测试和Boom经验方程构建离子液体(IL)/羊毛纤维/凝固剂浊点线性关系(LCP)曲线和三元相图，进一步系统地研究了凝固剂种类、再生温度和离子液体结构对羊毛角蛋白再生性能的影响规律。结果表明，羊毛角蛋白最优再生体系是1-乙基-3-甲基咪唑磷酸二乙酯([Emim]Dep)/羊毛纤维/水(25℃)。对羊毛纤维原料和不同再生条件获得的再生羊毛角蛋白进行FT-IR和XRD表征，结果表明再生羊毛角蛋白的结构和羊毛纤维原料基本保持一致，但相对结晶度有所下降。实验温度为25℃时，以水为凝固剂制备的再生羊毛角蛋白相对结晶度最高。 Keratin is one of the natural polymers with abundant reserves, wool fiber consists 95wt% of keratin, which is an important source of natural keratin and has excellent mechanical and biological properties. However, due to the numerous complex inter- and intra-molecular hydrogen bonds, disulfide bonds and other chemical bonds, wool fiber is insoluble in water and common organic solvents. As an emerging green solvent, ionic liquid (IL) shows outstanding performance in dissolving natural polymers such as wool fiber, cellulose, chitin, etc. due to their tunable structure, non-volatile, thermal stability, as well as high solubility for biopolymer. According to the reports, the current researches of ionic liquids on wool fiber are mainly focused on the solubility properties of wool fiber. The studies on the regeneration properties of wool keratin are still limited. There are three components involved in the regeneration process of wool fiber, and thus the thermodynamic behavior of polymer regeneration can be investigated by the ternary phase diagram. In this study, the linearized cloud point (LCP) correlation and ternary phase diagram of IL/wool fiber/coagulator (T) system were constructed by the turbidity method. The effects of coagulator types, coagulation temperatures, and structures of ILs on the properties of wool keratin regeneration were investigated systematically. The regenerated wool keratin was obtained using [Emim]Dep as the solvent with the coagulation temperature of 25℃. In different coagulator systems, the order of wool keratin regeneration capacity is water>ethanol>iso-propanol. The regenerated wool keratin was obtained using [Emim]Dep as the solvent, and water as the coagulator. In different coagulation temperature systems, as the coagulation temperature increased, the regeneration capacity of wool keratin gradually decreased. The regenerated wool keratin was obtained using water as the coagulator with a coagulation temperature of 25℃. In different IL structure systems, the order of wool keratin regeneration capacity was [Emim]Dep>[DBNE]Dep>[DBNH]OAc. The characterization of raw wool fiber and regenerated wool keratin under different regeneration conditions were obtained by FT-IR and XRD, the characterization of the structures and properties showed that the main structure of the regenerated wool keratin basically agreed with the raw wool fiber, and the crystallinity of the regenerated wool keratin had decreased than raw wool keratin. The highest crystallinity of the regenerated wool keratin was obtained from the system of [Emim]Dep/wool fiber/water system at the coagulation temperature of 25℃. Godkänd;2021;Nivå 0;2021-04-09 (alebob)

Background: Chemoresistance is an important cause of malignant progression of esophageal squamous cell carcinomas (ESCCs). miR-378d is sharply reduced in paclitaxel (PTX)-resistance esophageal cancer cells by gene-expression profile analysis (RNA-Seq), but the mechanism of miR-378d-mediated tumor progression is unclear. Patients and methods: Herein, we detected miR-378d expression in 596 ESCC patients by in situ hybridization. Results showed that low miR-378d expression was associated with poor prognosis of ESCC patients, and that miR-378d absence enhanced carcinogenesis by promoting chemoresistance, colony formation, EMT, invasion, and metastasis. Results: Furthermore, miR-378d can target downregulated AKT1 expression by binding to the AKT1 mRNA 3′UTR, inactivating the AKT-β-catenin signaling pathway, and reducing the epithelial–mesenchymal transition marker Vimentin and the cancer stem cell marker ALDH1A1. miR-378d silencing in ESCC cells also promoted polyploidy formation in vitro and in vivo, and miR-378d inhibition suppressed the Hippo-p53 signaling pathway. Consequnetly, YAP and TAZ protein accumulated in nuclei and p53 expression decreased, which may promote the formation of ploidy tumor cells. Conclusions: Therefore, low miR-378d expression is a poor prognostic factor of ESCC patients and promotes polyploidy and cancer progression by activating AKT-β-catenin and suppressing the Hippo-p53 signaling pathway.

Background and purpose Gut microbiota plays an important role in type 2 diabetes mellitus (T2DM) progression. From our previous work N-(4-Hydroxyphenethyl)-3-mercapto-2-methylpropanamide (HMPA) is a potential T2DM drug. We evaluated the effect of HMPA on gut microbiota and studied the molecular mechanism underlying HMPA's regulation of gut microbiota. Experimental approach The pseudo germ-free (PGF) T2DM model and faecal microbiota transplantation method were used to study whether gut microbiota mediates the actions of HMPA. The composition of gut microbiota was detected by using 16S rRNA sequence. Short-chain fatty acids (SCFAs) content was detected by gas chromatography. The HMPA probe was synthesised for finding and identifying the target protein of HMPA. The effect of HMPA on the utilisation of carbon sources in Bifidobacterium was evaluated. Key results HMPA has a slight effect on the PGF T2DM model. The gut microbiota changed by HMPA can also alleviate the symptoms of T2DM. HMPA can regulate gut microbiota structure, increase SCFAs production and reduce nitrate content in the intestinal tissues. The thickness of the mucus on colon tissues increases after HMPA treatment. The target protein of HMPA in gut microbiota is the nitrogen metabolism global transcriptional regulator (GlnR). HMPA promotes the utilisation of less preferred carbon source in the gut microbiota and increases the fermentation product of SCFAs. Conclusion and implications HMPA plays a hypoglycaemic role through the gut microbiota. HMPA improves the carbon catabolite repression effect of gut microbiota and increases SCFAs production by targeting GlnR. GlnR may be a target for gut microbiota regulation.

In this work, 502 experimental data for CO2 solubilities and 132 for Henry’s constantsof CO2 in DESs were comprehensively summarized from literatures and used for furtherverification and development of COSMO-RS. Large systematic deviations of 62.2, 59.6,63.0, and 59.1% for the logarithmic CO2 solubilities in the DESs (1:2, 1:3, 1:4, 1:5),respectively, were observed for the prediction with the original COSMO-RS, while thepredicted Henry’s constants of CO2 in the DESs (1:1.5, 1:2, 1:3, 1:4, 1:5) at temperaturesranging of 293.15–333.15 K are more accurate than the predicted CO2 solubility withthe original COSMO-RS. To improve the performance of COSMO-RS, 502 data pointsof CO2 solubility in the DESs (1:2, 1:3, 1:4, 1:5) were used for correcting COSMO-RSwith a temperature-pressure dependent parameter, and the CO2 solubility in the DES(1:6) was predicted to further verify the performance of the corrected model. The resultsindicate that the corrected COSMO-RS can significantly improve the model performancewith the ARDs decreasing down to 6.5, 4.8, 6.5, and 4.5% for the DESs (1:2, 1:3, 1:4, and 1:5), respectively, and the corrected COSMO-RS with the universal parameters can beused to predict the CO2 solubility in DESs with different mole ratios, for example, for theDES (1:6), the corrected COSMO-RS significantly improves the prediction with an ARD of10.3% that is much lower than 78.2% provided by the original COSMO-RS. Additionally,the result from COSMO-RS shows that the σ-profiles can reflect the strength of molecularinteractions between an HBA (or HBD) and CO2, determining the CO2 solubility, and thedominant interactions for CO2 capture in DESs are the H-bond and Van der Waals force,followed by the misfit based on the analysis of the predicted excess enthalpies. Validerad;2020;Nivå 2;2020-02-24 (johcin)

The overall hypotheses underlying this PhD work were that: a) It is possible to produce conductive carbon nano-tube-cellulose based fibers with improved strength using ionic liquids (ILs) and enzymes in the spinning process. b) It is possible to predict the cellulose solubilisation properties of ILs via thermodynamic modeling of the cellulose and IL properties using COSMO-RS. c) Freeze crystallization of water is an energy saving way to separate IL+H2O mixtures for ILs recycling in cellulose spinning processes as compared to separation by evaporation. In turn, the main work objectives were: (1) Identify the best ILs for dissolving cellulose. (2) Assess energy-use via freeze crystallization for recycling of the ILs to reduce the cost. (3) Prepare conductive fibers based on spinning of cellulose and carbon nano-tubes using ILs for dissolution and assess enzymatic improvement of fiber tensile strength by use of laccase. Due to strong the hydrogen bonds (H-bonds) in its supra-molecular structure, cellulose is insoluble in water and in most organic solvents. Traditional cellulose spinning processes (e.g. fortextile manufacture) therefore often involve use of strong acid or alkali, which in turn poses an environmental burden. As outlined above, this study was based on that ionic liquids might be useful for cellulose dissolution. For this, the following research parts were completed: First, 375 ILs candidates were screened by COSMO-RS modelling for cellulose dissolution properties. As a part of this, a comparison of cellulose models in COSMORS was performed, identifying the mid-monomer in cellotriose as best, and enthalpy calculations of cellulose dissolution in 7 relevant, selected ILs was accomplished, and the cellulose dissolution experimentally verified. COSMO-RS excess enthalpy predictions indicated that the cellulose dissolution process is mostly anion dependent and the main forces in the cellulose dissolution in ILs are H-bonds: Ac−, Cl−, DEP−, and Br−were the most promising anions for cellulose dissolution. Cations with ethyl, allyl, 2-hydroxylethyl, 2-methoxyethyl and acryl-oyloxypropyl functional groups exhibited particularly good properties for cellulose dissolution.Second, recycling ILs from water mixtures by freeze crystallization was conducted. Six ILs, EmimAc, EmimDep, AmimCl, HOEtpyBr, HOEtmimBr, and EtOMmimCl, which had been found to have high cellulose solubility in phase one, were selected for freezing point measurements alone and in ILs+H2O mixtures. The results illustrated that the ILs exhibit similar features as inorganic salts of MgCl2 and MgSO4 in depressing the freezing point of water. Ice starts forming when the IL aqueous solutions are cooled to their freezing points in the dilute region. At higher IL concentrations, the solid phases formed were presumed to be solid IL or hydrates of the form IL·nH2O. The HOEtpyBr+H2O and HOEtmimBr+H2O systems formed simple eutectic systems and the freeing points of these two system were higher than those of the other four ILs. This result indicated that these two bromide ILs could be separated from water directly byfreeze crystallization of the water. From the experimental results it was moreover determined that the freezing points of IL+H2O systems were affected by the nature of both the cations and the anions of the ILs. Third, separation of IL+H2O by freeze crystallization was applied to recycling EmimAc and EmimDep, respectively, in the cellulose spinning process, and themethodology was named as the freeze crystallization method. The energy requirement for EmimAc and EmimDep recycling after cellulose spinning by the freeze crystallization method followed by evaporation was calculated and compared to the energy use in a traditional (patented) evaporation method. It was found that to fabricate 1 kg dry cellulose fiber using freeze crystallization+evaporation rather than evaporation, 21.5 MJ can be saved for EmimAc and 37.3 MJ for EmimDep recycling. It was also shown that significantly less H2O is required in the cellulose spinning process with ILs than with N-methylmorpholine oxide. Finally, the production of multiwall carbon nanotubes (MWCNTs)-cellulose conductive fibers using a selected IL with good cellulose dissolution properties, namely EmimDep, was studied: The material used was cotton pulp and MWCNTs. The work verified that EmimDep can dissolve cellulose and disperse MWCNTs. The fiber electrical conductivity increased with increasing mass ratio of MWCNTs relative to the cellulose. The highest electrical conductivity measured was 760 S/m at a spinning extrusion flow of 1 mL/min, spinneret diameter of 0.46 mm and a ratio of 5:1 of MWCNTs versus cellulose. Thermogravimetric analysis and surface area results gaveevidence that the fiber was more stable at the spinneret diameter of 0.46 mm than at 0.98 mm. The surface area of the conductive fiber reached 188 m2/g. The SEM data also revealed pore structures in the fiber surface and hinted that the alignment of MWCNTs in the fiber decreases the fiber electrical conductivity. Tensile strength measurements showed that the fiber tensile strength could be increased by laccase enzyme treatment, provided that phenols were added to the spun cotton pulp-CNTs fiber bath solution. The data obtained verified the hypotheses formulated for the PhD work and provided new knowledge of: ILs cellulose solubility properties, COSMO-RS modelling of cellulose, freezing points and freeze thermodynamics properties of ILs and ILs+H2O mixtures, energy saving for ILs recycling by freeze crystallization, and finally indicated the promising potential of using ILs and enzymes in the production ofconductive CNT-cellulose based fibers.

Epidemiologic data suggested that there was an obvious predominance of young adult patients with a slight female proneness in severe acute respiratory syndrome (SARS). The angiotensin-converting enzyme 2 (ACE2) was very recently identified as a functional receptor for SARS virus and is therefore a prime target for pathogenesis and pharmacological intervention. Rats of both genders at three distinct ages (young-adult, 3 months; middle-aged, 12 months; old, 24 months) were evaluated to determine the characteristic of ACE2 expression in lung and the effect of aging and gender on its expression. ACE2 was predominantly expressed in alveolar epithelium, bronchiolar epithelium, endothelium and smooth muscle cells of pulmonary vessels with similar content, whereas no obvious signal was detected in the bronchiolar smooth muscle cells. ACE2 expression is dramatically reduced with aging in both genders: young-adult vs. old P

This document explains and demonstrates how to use the VRML / X3D to build an on-line virtual furniture store, which includes EXTERNPROTO technology, the script language support technology, and user interface support technology. Study the Modeling, the texture, the scene interaction technology of VRML / X3D. Research a model of the relationship between VRML / X3D and the database.