A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

Dry Fractionation Approach in Concentrating Tocopherols and Tocotrienols from Palm Fatty Acid Distillate: A Green Pretreatment Process for Vitamin E Extraction

Palm fatty acid distillate (PFAD) is a rich source of vitamin E. As compared to other vegetable oil, PFAD has higher tocotrienol (70–80%) over tocopherol content, which makes it a valuable source for vitamin E extraction. Current vitamin E extraction methods are not sustainable due to the intensive usage of chemical and high operational cost. Hence, the present study investigated for the first time using dry fractionation process as a green and economical pretreatment method for separating solid fraction (stearin) and liquid fraction (olein) in order to concentrate vitamin E from PFAD in olein fraction. We examined the dry fractionation conditions: crystallization ending temperature (36–44 °C), cooling rate (0.3 and 1.5°C min⁻¹), stirring speed (20–125 rpm), and holding time (0–60 min) on the composition of unsaturated and saturated fatty acids as well as vitamin E content in liquid fraction (olein) and solid fraction (stearin) using gas chromatography and high performance liquid chromatography, respectively. In most of these conditions, vitamin E was ultimately higher in olein fraction as compared to stearin fraction, which is correlated with the high degree of unsaturation. Under a cooling rate of 0.3°C min⁻¹, 90 rpm stirring speed, and ending crystallization of 38 °C, the highest vitamin E rich olein fraction was attained with 1479 ± 10.51 ppm in 50 g olein fraction as compared to 1366 ± 7.94 ppm in 500 g of unfractionated PFAD.     

Metformin Preserves β-Cell Compensation in Insulin Secretion and Mass Expansion in Prediabetic Nile Rats

Prediabetes is a high-risk condition for type 2 diabetes (T2D). Pancreatic β-cells adapt to impaired glucose regulation in prediabetes by increasing insulin secretion and β-cell mass expansion. In people with prediabetes, metformin has been shown to prevent prediabetes conversion to diabetes. However, emerging evidence indicates that metformin has negative effects on β-cell function and survival. Our previous study established the Nile rat (NR) as a model for prediabetes, recapitulating characteristics of human β-cell compensation in function and mass expansion. In this study, we investigated the action of metformin on β-cells in vivo and in vitro. A 7-week metformin treatment improved glucose tolerance by reducing hepatic glucose output and enhancing insulin secretion. Although high-dose metformin inhibited β-cell glucose-stimulated insulin secretion in vitro, stimulation of β-cell insulin secretion was preserved in metformin-treated NRs via an indirect mechanism. Moreover, β-cells in NRs receiving metformin exhibited increased endoplasmic reticulum (ER) chaperones and alleviated apoptotic unfold protein response (UPR) without changes in the expression of cell identity genes. Additionally, metformin did not suppress β-cell mass compensation or proliferation. Taken together, despite the conflicting role indicated by in vitro studies, administration of metformin does not exert a negative effect on β-cell function or cell mass and, instead, early metformin treatment may help protect β-cells from exhaustion and decompensation.     

A study on typology of areas densely populated with foreigners in Seoul,South Korea

This study identifies the types of areas in Seoul where foreigners are concentrated by reflecting the characteristics of their region of origin and residence in Seoul. Lack of cultural understanding and uniform policies for various immigrant communities are causing some social issues. Hence, this study aims to prepare the basic data from which the government can predict changes in ethnic areas and prepare policies suitable for each derived type. The 14 most populous immigrant communities in Seoul were investigated, and cluster analysis and ANOVA test were performed. This examination resulted in four immigrant community types. Each type has specific characteristics, which have influenced the creation and change of the built environment. Types 1 and 4 are collectivistic. These types gradually tend to change urban environments to emulate the environment in their region of origin. In addition, they make little effort to improve their degraded environments, and such areas become increasingly backward. In contrast, types 2 and 3 are individualistic and prefer to assimilate into a migrant region. The formation and change of the urban environment for each type can be predicted on the basis of these characteristics. From this information, the government can prepare an appropriate urban architecture policy for each type.     

Facile preparation and strong adhesive strength of honeycomb polyurethane films with small pore diameter

With the continuous development of bionics, such as, geckos and virginia creeper with both superhydrophobic and super-adhesive, the surface wetting and super-adhesive properties of various porous materials have attracted extensive attention of the scientific and medical communities. Here, the honeycomb polyurethane (PU) porous films with strong adhesion were successfully prepared by microphase separation method and the effects of growth parameters on their microstructure and adhesive strength to ice were investigated. It was found that a high relative humidity (e.g., 100%) and a low solution concentration (e.g., 2%) facilitated the formation of ordered honeycomb PU porous films, and as-prepared PU pores with average pore diameter as small as 5 μm are better ordered and more uniform than these in related documents. Although the contact angle of water droplets on the surface of PU porous films increased from the premodification value of 85–130° to more than 160° after surface modification with polydopamine (PDA), the corresponding rolling angle remained approximately constant (180°), indicating that the surface of PU porous films has strong adhesion similar to geckos and virginia creeper. Furthermore, at lower temperature, the PU porous films exhibited the high adhesive strength of 142.13 kPa on ice, which was strongly dependent on the porous microstructures and surface compositions. The improved adhesive behavior to ice of honeycomb PU porous films modified with PDA provides new strategies for surface modification of materials and potential applications in medical domain.     

Antimicrobial and Anticancer Properties of Synthetic Peptides Derived from the Wasp Parachartergus fraternus

Agelaia-MPI and protonectin are antimicrobial peptides isolated from the wasp Parachartergus fraternus that show antimicrobial and neuroactive activities. Previously, two analogues of these peptides, neuroVAL and protonectin-F, were designed to reduce nonspecific toxicity and improve potency. Here, the three-dimensional structures of neuroVAL, protonectin and protonectin-F were determined by using circular dichroism and NMR spectroscopy. Antibacterial, antifungal, cytotoxic and hemolytic activities were tested for the parent peptides and analogues. All peptides showed moderate antimicrobial activity against Gram-positive bacteria, with agelaia-MPI being the most active. Protonectin and protonectin-F were found to be toxic to cancerous and noncancerous cell lines. Internalization experiments revealed that these peptides accumulate inside both cell types. By contrast, neuroVAL was nontoxic to all tested cells and was able to enter cells without accumulating. In summary, neuroVAL has potential as a nontoxic cell-penetrating peptide, while protonectin-F needs further modification to realize its potential as an antitumor peptide.     

An energy-efficient cloud system with novel dynamic resource allocation methods

The Journal of Supercomputing - In the last decade, cloud computing has brought enormous changes to people’s lives. Cloud computing gives a client-driven computational model. In this case,...     

丁香酚和三卡因甲磺酸盐在大口黑鲈中代谢残留的比较

为了确定大口黑鲈成鱼适合的麻醉方式和麻醉剂量,研究了不同浓度的丁香酚和MS-222对大口黑鲈的静水麻醉效果。在最适麻醉质量浓度下模拟运输24 h,记录24 h存活率并测定麻醉0.5、4、8、16和24 h后的血清生化指标、水质p H、氨氮以及麻醉剂的残留量。结果表明:随着丁香酚和MS-222浓度增加,入麻时间缩短,复苏时间延长;丁香酚和MS-222的最适质量浓度分别为18~20 mg/L、50~60 mg/L时,两麻醉组模拟运输和复苏24 h后的成活率为100%,显著高于无麻醉运输组的80%和90%(p<0.05);随着麻醉时间延长,丁香酚和MS-222组血清中的皮质醇(COR)分别从336.83pg/m L下降到291.41pg/m L,从286.11上升到367.05pg/m L(p<0.05),丁香酚组血清中的COR显著低于对照组;葡萄糖分别从14.36、7.48 mg/dL下降到7.36、3.11 mg/dL(p<0.05),而丁香酚组中乳酸脱氢酶(LDH)、碱性磷酸酶(AKP)、谷草转氨酶(GOT)、尿素氮(BUN)的浓度显著低于MS-222组(p<0.05);残留检测结果表明在麻醉0.5h时,鱼肉中丁香酚含量达到最大值5.14mg/kg,在清水中复苏1d时丁香酚残留量为0.45mg/kg;而MS-222组在8 h残留量达到最大值为36.24 mg/kg,复苏4 d时基本消除完全。结果显示,丁香酚剂量小,代谢快,在诱发氧化应激和组织损伤时有较少的副作用。     

Brief Review of Precipitated Iron-Based Catalysts for Low-Temperature Fischer–Tropsch Synthesis

Topics in Catalysis - Fischer–Tropsch synthesis (FTS) is a promising way to produce clean liquid fuels and high value-added chemicals from low-value carbon-containing resources such as coal,...