Downregulation of CYP39A1 Serves as a Novel Biomarker in Hepatocellular Carcinoma with Worse Clinical Outcome

Background. CYP39A1 is a poorly characterized metabolic enzyme that has been investigated in a few tumors. However, the role of CYP39A1 in hepatocellular carcinoma (HCC) has not yet been clarified. In this study, the expression and clinical significance of CYP39A1 in HCC were explored. Methods. CYP39A1 protein expression was detected in Akt/c-Met-induced HCC mice and 14 paired fresh HCC samples as well as another 159 HCC and matched noncancerous tissues. Meanwhile, the mRNA expression was analyzed by GEO and TCGA analysis and validated in 14 paired fresh HCC tissues. Furthermore, the relationships between CYP39A1 expression and clinicopathologic features as well as prognosis were analyzed. HCC cell growth changes were analyzed by cell viability assays after CYP39A1 overexpression and then validated after CYP39A1 knockout by DepMap database analysis. Results. CYP39A1 protein expression was lower expressed in HCC mouse models, and its mRNA and protein expression were also downregulated in HCC compared with noncancerous liver tissues. Higher CYP39A1 expression was associated with well differentiation. Moreover, survival analysis indicated that lower CYP39A1 expression was associated with poorer overall survival. In addition, HepG2 and SMMC-7721 cell viability were inhibited after CYP39A1 overexpression. Genome-wide CRISPR/Cas9 proliferation screening indicated that knockout of CYP39A1 could promote HCC cell growth. Likewise, p-NF-κB and Nrf2 were suppressed after CYP39A1 overexpression. It is worth mentioning that total bile acid, total bilirubin, and direct bilirubin were significantly increased in the patients with low CYP39A1 expression. Conclusions. Downregulation of CYP39A1 is associated with HCC carcinogenesis, tumor differentiation, and poor overall survival, suggesting that CYP39A1 may serve as a tumor suppressor gene and novel biomarker for HCC patients.

Genetic Architecture of Multiphasic Growth Covariation as Revealed by a Nonlinear Mixed Mapping Framework

Trait covariation during multiphasic growth is of crucial significance to optimal survival and reproduction during the entire life cycle. However, current analyses are mainly focused on the study of individual traits, but exploring how genes determine trait interdependence spanning multiphasic growth processes remains challenging. In this study, we constructed a nonlinear mixed mapping framework to explore the genetic mechanisms that regulate multiphasic growth changes between two complex traits and used this framework to study stem diameter and stem height in forest trees. The multiphasic nonlinear mixed mapping framework was implemented in system mapping, by which several key quantitative trait loci were found to interpret the process and pattern of stem wood growth by regulating the ecological interactions of stem apical and lateral growth. We quantified the timing and pattern of the vegetative phase transition between independently regulated, temporally coordinated processes. Furthermore, we visualized the genetic machinery of significant loci, including genetic effects, genetic contribution analysis, and the regulatory relationship between these markers in the network structure. We validated the utility of the new mapping framework experimentally via computer simulations. The results may improve our understanding of the evolution of development in changing environments.

STRATEGY TO ACHIEVE MACROECONOMIC STABILITY IN UKRAINE

The comprehensive analysis of domestic economy and it’s actual state undoubtedly confirms its steady transformation into a small, resource-based economy. Its also proves the absence of positive trends related to key factors for ensuring financial sustainability and attaining national security. Special attention is paid to factors in the fiscal sector (an increase in budget revenues based on economic growth as the result of changes in the volume of domestic and foreign trade, due to improvement in the financial results of enterprises and an increase in wages, as well as due to changes in direct tax receipts, and a decrease in the budget deficit); it is also analysed the debt sector (management of Ukraine’s sovereign debt); the detailed attention is given to banking sector (overcoming crisis phenomena in the banking system). Revealing the institutional problems, inefficiency of the public administration system we are justifying the implementation the number of measures in the areas of economic growth recovery, development of the internal market as the basis for sustainable growth, changes in the structure and activation of export policy. The expansion of small farming can be a trigger of the Ukrainian economy’s development. A significant part of the world’s natural resources is located in Ukraine. There is a significant increase in the number of populations worldwide, as well as an increase in soil deficiency suitable for agriculture. Since Ukraine is an agricultural country and most of its lands are suitable for the production of agricultural products – it gives it significant advantages for both self-sufficiency and economic development. Ukraine has always been and remains an agrarian country. Most of its’ lands are suitable for the growing of agricultural products and it gives Ukraine the significant self-sustaining advantages for both exponential growth and supporting of country’s economy. Small farming stays the main factor of the agrarian sector’s development, it supports the economy and helps to sustain the natural resources of Ukraine.

Evaluation of an automated superimposition method based on multiple landmarks for growing patients

ABSTRACT Objectives To determine if an automated superimposition method using six landmarks (Sella, Nasion, Porion, Orbitale, Basion, and Pterygoid) would be more suitable than the traditional Sella-Nasion (SN) method to evaluate growth changes. Materials and Methods Serial lateral cephalograms at an average interval of 2.7 years were taken on 268 growing children who had not undergone orthodontic treatment. The T1 and T2 lateral images were manually traced. Three different superimposition methods: Björk's structural method, conventional SN, and the multiple landmark (ML) superimposition methods were applied. Bjork's structural method was used as the gold standard. Comparisons among the superimposition methods were carried out by measuring the linear distances between Anterior Nasal Spine, point A, point B, and Pogonion using each superimposition method. Multiple linear regression analysis was performed to identify factors that could affect the accuracy of the superimpositions. Results The ML superimposition method demonstrated smaller differences from Björk's method than the conventional SN method did. Greater differences among the cephalometric landmarks tested resulted when: the designated point was farther from the cranial base, the T1 age was older, and the more time elapsed between T1 and T2. Conclusions From the results of this study in growing patients, the ML superimposition method seems to be more similar to Björk's structural method than the SN superimposition method. A major advantage of the ML method is likely to be that it can be applied automatically and may be just as reliable as manual superimposition methods.

Correlations between temporary teeth and functional treatment in mixed dentition – case presentation

Objectives. Orthodontic treatment intends to create a harmony between dental, muscular and osseous components. The purpose of this case presentation was to emphasize consequences of early loss of temporary teeth on dental-maxillary complex development. Material and methods. 10 years old patient with dental movements following the early extraction of temporary teeth. The patient has habitual oral breathing associated with lower lip interposition. Results. The functional treatment with twin-block appliance was chosen, taking into account the age-specific growth potential. Discussions. Premature extraction of temporary teeth engenders lee-way-space loss, significant shortening and transverse constriction of the dental arch, elements aggravated by dysfunctions and parafunctions. Conclusion. The early extractions performed during the growth period, through the associated dental migrations, determine growth changes with consequences on the functionality of the dento-maxillary apparatus.

Haematological and histopathological examinations of African mud catfish (Clarias gariepinus) exposed to petroleum wastewater

Effects of petroleum refinery wastewater on Clarias gariepinus juvenile were investigated. Commercially obtained C. gariepinus fingerlings were acclimatized in a plastic tank (100 L capacity) of de-chlorinated tap water at 25±2°C for 14 days and fed with commercial feed pellet at 2% body weight of the fingerlings. Bioassay tests were carried out in four transparent plastics tank with nominal concentrations of 100 ml, 200 ml, 300 ml of the wastewater added to 40L of de-chlorinated tap water and only de-chlorinated tap water as control. Each tank contains twenty fish samples, while the assay was replicated three times concurrently. Following standard procedures, behavioural response, growth changes, haematological and histopathological tests were carried out on the samples. Significant reduction in the weight was observed in the fingerlings cultured with the wastewaters, while no significant difference occurred in the control fish. Highest values of Packed Cell Volume (PCV) (22), Haemoglobin (HB) (7.0), Red Blood Cell (RBC) (1.62) and endocochlear potential (EP) (5) were recorded for the control fish than exposed fish. On the other hand, Haptoglobin (HP), Mean Corpuscular Volume (MCV) and Mean Corpuscular Haemoglobin (MCH) were higher in the blood of exposed fish than in control. Histopathologically, exposed fishes showed no visible lesion in gills except from the thickening of the lamellae as the concentration of wastewater increases, indicating an increase in tissue disintegration. Similarly, gross tissue disintegration was observed in those fish exposed to 200ml wastewater as evidenced by the presence of large open spaces (hepatocytes) in the liver.

Characterization of structural changes in modern and archaeological burnt bone: Implications for differential preservation bias

Structural and thermodynamic factors which may influence burnt bone survivorship in archaeological contexts have not been fully described. A highly controlled experimental reference collection of fresh, modern bone burned in temperature increments 100–1200˚C is presented here to document the changes to bone tissue relevant to preservation using Fourier transform infrared spectroscopy and X-ray diffraction. Specific parameters investigated here include the rate of organic loss, amount of bone mineral recrystallization, and average growth in bone mineral crystallite size. An archaeological faunal assemblage ca. 30,000 years ago from Tolbor-17 (Mongolia) is additionally considered to confirm visibility of changes seen in the modern reference sample and to relate structural changes to commonly used zooarchaeological scales of burning intensity. The timing of our results indicates that the loss of organic components in both modern and archaeological bone burnt to temperatures up to 700˚C are not accompanied by growth changes in the average crystallite size of bone mineral bioapatite, leaving the small and reactive bioapatite crystals of charred and carbonized bone exposed to diagenetic agents in depositional contexts. For bones burnt to temperatures of 700˚C and above, two major increases in average crystallite size are noted which effectively decrease the available surface area of bone mineral crystals, decreasing reactivity and offering greater thermodynamic stability despite the mechanical fragility of calcined bone. We discuss the archaeological implications of these observations within the context of Tolbor-17 and the challenges of identifying anthropogenic fire.

A unified blockchain-based platform for global e-waste management

Purpose The rapid technological growth, changes in consumer demands, products’ built-in obsolescence, presence of more non-repairable parts, shorter lifespan, etc., lead to the generation of e-waste at an unprecedented rate. Although a number of research proposals and business products to manage e-waste exist in the literature, they lack in many aspects such as incomplete coverage of product’s life cycle, access control, payment channels (in few cases), incentive mechanisms, scalability issues, and missing experimental validation. The purpose of this paper is to introduce a novel blockchain-based e-waste management system aiming to mitigate the above-mentioned downsides and limitations of the existing proposals. Design/methodology/approach This paper proposes a robust and reliable e-waste management system by leveraging the power of blockchain technology, which captures the complete life cycle of e-products commencing from their manufacturing as new products to their disposal as e-waste and their recycling back into raw materials. Findings While the use of blockchain technology increases accountability, transparency and trust in the system, the proposal overcomes various challenges and limitations of the existing systems by providing seamless interactions among various agencies. Originality/value This paper presents a prototype implementation of the system as a proof-of-concept using solidity on the Ethereum platform and this paper performs experimental evaluations to demonstrate its feasibility and effective performance in terms of execution gas cost and transaction throughput.

Bioavailable Nickel and Zinc in Polluted Soil Alter the Growth of Non-pioneer Trees in the Brazilian Atlantic Forest

Background and aimsThe Brazilian Atlantic forest has been affected by the deposition of Ni and Zn, among other heavy metals adsorbed from atmospheric particles, which can be incorporated into the soil. If available in the soil, they can be absorbed by plant roots. The study aimed at testing experimentally the hypotheses: 1) Ni and Zn depositions increase their bioavailable fractions in the soil; 2) pioneer tree species demonstrate a greater potential to absorb Ni and Zn from the soil and less growth changes than non-pioneer species.MethodsThe experiment was carried out with six pioneer and non-pioneer species native to the Atlantic Forest, grown for 90 days in soil from an urban fragment of the Atlantic Forest, according to the treatments: soil with balanced fertilization (control) and soil enriched with Ni, Zn and Ni+Zn. At the end, the concentrations of Ni and Zn were determined in four soil fractions (F1: soluble; F2: linked oxides/hydroxides; F3: organic matter: F4: residual metals) and in leaves, stems/branches and roots. Mobility factors in soil, concentration ratios between treatments and respective controls, translocation index and relative growth rate in height, leaf number and total biomass were also calculated.ResultsThe results showed that Ni and Zn concentrations increased significantly in the bioavailable soil fractions (F1, F2). The absolute content of Ni and Zn in the plants directly reflected the soil level in the available forms.ConclusionsThe metal accumulation in the species occurred regardless of the successional group to which they belonged. Non-pioneer species showed greater susceptibility to the metals.

Porphyromonas somerae Invasion of Endometrial Cancer Cells

Recent evidence suggests an association between endometrial cancer and the understudied bacterial species Porphyromonas somerae. This association was demonstrated in previous work that indicated a significantly enriched abundance of P. somerae in the uterine microbiome of endometrial cancer patients. Given the known associations of the Porphyromonas genus and oral cancer, we hypothesized that P. somerae may play a similar pathogenic role in endometrial cancer via intracellular activity. Before testing our hypothesis, we first characterized P. somerae biology, as current background data is limited. These novel characterizations include growth curves in liquid medium and susceptibility tests to antibiotics. We tested our hypothesis by examining growth changes in response to 17β-estradiol, a known risk factor for endometrial cancer, followed by metabolomic profiling in the presence and absence of 17β-estradiol. We found that P. somerae exhibits increased growth in the presence of 17β-estradiol of various concentrations. However, we did not find significant changes in metabolite levels in response to 17β-estradiol. To study direct host-microbe interactions, we used in vitro invasion assays under hypoxic conditions and found evidence for intracellular invasion of P. somerae in endometrial adenocarcinoma cells. We also examined these interactions in the presence of 17β-estradiol but did not observe changes in invasion frequency. Invasion was shown using three lines of evidence including visualization via differential staining and brightfield microscopy, increased frequency of bacterial recovery after co-culturing, and in silico methods to detail relevant genomic and transcriptomic components. These results underscore potential intracellular phenotypes of P. somerae within the uterine microbiome. Furthermore, these results raise new questions pertaining to the role of P. somerae in the progression of endometrial cancer.