bluuebunny/crossref_metadata_2025 huggingface dataset:
Age-varying susceptibility to the Omicron variant (B.1.1.529) of SARS-CoV-2
Authors: Chun June Young , Kim Yongdai , Jeong Hwichang
Published: June 2022

The Omicron variant (B.1.1.529) is estimated to be more transmissible than previous strains of SARS-CoV-2 especially among children, potentially resulting in croup which is characteristic disease in children. However, there have been no reports confirming the relative susceptibility of different age groups to SARS-CoV-2. In this study, we estimated the age-specific susceptibility during the 5th (Omicron driven), 4th (Delta driven), and 3rd (pre-Delta) waves in South Korea, using the age-structured compartmental model. Even after adjusting for contact pattern, vaccination status, and waning of vaccine effectiveness, the susceptibility among age group 0–19 years was approximately 5 times higher during the 5th wave (Omicron driven) than that during the 3rd wave (pre-Delta), and 3 times higher than that during the 4th wave (Delta driven). Here, we found that children are indeed more susceptible to the Omicron variant compared with the previous strains of SARS-CoV-2.
Fusion Classification of Stroke Patients' Biosignals by Weighted Cross-Validation-based Feature Selection (W-CVFS) Method
Authors: Pan Xuejiao , Chen Xiaojuan , Ji Tiecheng , Yu Suli , Sun Yue
Published: June 2022

A multi-source information fusion-based disease class classification of stroke patients was implemented to address the low classification accuracy of pure input motion and electromyographic signals. sEMG sensor MYO arm ring and wearable wireless motion sensor Shimmer were used as data acquisition devices. The Butterworth high-pass filter filtering and envelope thresholding method detected the activity segment. Detection and FIR filtering using the window function method remove interference from the motion signal. A weighted cross-validation-based feature selection (W-CVFS) method is proposed for feature fusion selection. The top 10 features selected by the W-CVFS method and all 18 features are input to the deep neural network for training and testing, and the feature classification result of the W-CVFS method is 79.17%, which is better than the existing mRMR method (66.67%) and ILFS method (62.50%). The classification accuracy of multi-source information fusion was 95.385%, which was higher than that of a single input motion signal or sEMG. The experiments showed that the proposed method can retain the features that have more influence on the classification results and can improve the classification accuracy of the rehabilitation model for stroke patients.
L1-boundedness of rough Fourier integral operators.
Authors: Sindayigaya Joachim
Published: June 2022

In this paper, we study the L1-boundedness of Fourier integral operator T_{\phi,a} with rough symbol a\in L^{\infty}S^{m}_{\rho} and a new class of rough phase \phi. In this class, we extend the L^{\infty}\phi^{2} and non-degeneracy conditions to some generalized derivative estimation and some measure condition respectively. Our main result substantially extends and emproves some known results about L1-boundedness of Fourier integral operator. Moreover, the result in this paper can be used to prove the boundedness of the maximal wave operator.
Petrochemical attributes of glazed architectural elements from Middle- Elamite to Achaemenid excavation sites in Iran
Authors: Raith Michael M. , Abdali Negar , Yule Paul A.
Published: June 2022

Glazed decoration in Iran from the Middle Elamite to the Achaemenid periods includes world art milestones. With the exception of Hasanlu IVB, for most sites comprehensive chemical and mineralogical data are lacking, owing to the generally profound alteration of the vitreous material. To bridge the information gap, and to enable to reconstruct operation production chains in a diachronic fashion, thirty-six glazed artefacts from Qalaichi, Rabat, Hasanlu, Ziwiye, Chogha Zanbil, Susa and Persepolis are studied. The microstructural make-up and alteration phenomena of glazes are characterized by petrographic microscopy, back scattered electron (BSE) imaging, and electron probe microanalysis (WDS-EPMA) on high-quality polished thin sections. Pristine glaze domains at all sites show plant ash soda-lime glass compositions and indicate the use of regionally specific halophyte species for soda production. A distinct feature in the composition of white and turquoise glazes from Qalaichi, Ziwiye and Achaemenid Susa is the employment of sodium-antimonate as white colourant and opacifier. Inter-diffusion and dissolution-precipitation are identified as regionally and temporally contrasting alteration processes.
A creep prediction model for concrete made from pit sand with low silica content
Authors: Pasalli Daud Andang , Tudjono Sri , Nurhuda Ilham
Published: June 2022

Pit sand generally has a lower silica content than sand sourced from rivers or crushed stones. The effect of this sand on the creep of concrete has not yet been fully studied. Understanding the creep on concrete can help to estimate the behaviour of structures in the future. This study aims to investigate the effect of the properties of pit sand with different chemical compositions and grain size distributions on the creep of concrete, and to develop a creep prediction model for concrete made of pit sand with low silica content. This investigation employs laboratory testing to obtain the physical and chemical properties of the sand, as well as its relationship to shrinkage and creep of concrete. The results indicate that shrinkage in concrete is influenced by the water absorption of sand. It is also found that sand with a large Calcium Oxide (CaO) compound has a smaller shrinkage compared to those with small CaO content. This study shows that sand with a high percentage of fine grains and mud content exhibit a higher creep. A concrete creep prediction model is proposed based on the modification of the B3 Model. Modifications are made by proposing a material constant obtained from short creep tests. The creep parameter obtained from the test can be better used to predict the creep of concrete.
Serine/threonine kinase TBK1 promotes Intrahepatic cholangiocarcinoma progression via direct regulation of β-catenin
Authors: Gao Chongqing , Chu Zhenzhen , Xiao Yang , Zhou Xingyan , Wu Junru , Yuan Hui , Jiang Yuchuan , Chen Dong , Zhang Jichun , Yao Nan , Chen Kaiyun , Hong Jian
Published: June 2022

Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy with limited therapeutic options. Metastasis is one of the main contributors to ICC progression and poor prognosis. However, the underlying mechanism of ICC metastasis remains largely unknown. Here, we showed that TANK-binding kinase 1 (TBK1), a serine/threonine-protein kinase, was significantly upregulated in tumor tissues of ICC patients with larger tumor diameter, lymph node metastasis, and advanced TNM stage. Consistently, during the different stages of cholangiocarcinoma (CCA) carcinogenesis (hyperplasia, dysplasia, and CCA), TBK1 showed a dynamic increase in spontaneous rat and mouse models. Functional studies showed that enforced expression of TBK1 promoted metastasis both in vitro and in vivo. Mechanistically, TBK1 directly interacts with β-catenin and stimulates its nuclear translocation, further activating the β-catenin-mediated epithelial-mesenchymal transition (EMT) process. Moreover, we demonstrate that the S172 site of TBK1 kinase domain was essential for the interaction between TBK1 and β-catenin as well as for TBK1 mediated β-catenin activation. In addition, high levels of TBK1 in clinical ICC tissues were correlated with elevated nuclear β-catenin levels and predicted worse overall and disease-free survival. A TBK1 inhibitor GSK-8612 and the liver-specific accumulation of DNA/RNA heteroduplex oligonucleotide (TBK1-HDO) significantly reduced TBK1 expression of ICC and inhibited its intrahepatic metastasis. In summary, our study demonstrated that TBK1 could activate β-catenin via protein-protein interaction, then promote EMT and ICC metastasis, which might serve as a potential therapeutic target for patients with cholangiocarcinoma.
POTENTIAL TRAJECTORIES OF SMART ENERGY DEVELOPMENT IN UKRAINE
Authors: Vakulenko I. , Kolosok S.
Published: June 2022

The Ukrainian energy system requires a radical overhaul. Ukraine's energy infrastructure is significantly worn out and supposes to be modernized according to current market needs, safety standards, flexibility, and other parameters. In addition, the unified energy system of Ukraine faces a large-scale task of changing the trajectory: from historical relations with Russia and Belarus to synchronization with ENTSO-E. Ukraine's involvement in the pan-European energy market opens up opportunities for the export of Ukrainian energy resources and imposes requirements to ensure the stability and interoperability of Ukraine's energy system. Another challenge for Ukraine's energy system is to reduce the level of accidents in energy networks and the loss of energy resources during their transportation and distribution. Unfortunately, these indicators in Ukraine are much higher than the European average. The use of smart energy tools can solve many of these problems.
The possibility of conceptualizing the trajectories of smart energy development is crucial for the successful transformation of Ukraine's energy system. The formation of the basic trajectory of smart energy development should consider the national vision of socio-economic development in the country, the country's energy security strategy, energy sector reform, and the development of primary sectors of the economy. At this stage, it is necessary to conduct a feasibility study of reforms, which should be performed using a set of analysis methods: analysis of big data (on supply and demand of energy resources, technical parameters of networks, state of energy generating, and distribution equipment, etc.). (public, stakeholders, and a specific range of experts), economic assessment (reform costs, tariffs, diversified energy resources), risk analysis, network modeling, etc. The roadmap for reforms and strategic and operational plans should be adhered to develop smart energy while reforming the energy sector. If necessary, changes should be made to regulations, conduct functional supervision of the energy market, enable consumers to connect their applications and microgrids, use smart technologies in energy, etc.
EVALUATION OF INVESTMENT POTENTIAL OF UKRAINE TAKING INTO ACCOUNT INFRASTRUCTURE CHANGES
Authors: Kobushko I. M. , Chukhno R. Yu.
Published: June 2022

This statute is assigned to the day and the estimate of the investment potential of Ukraine for 2017-2019 years. For the correct rationalization of the definition of "investment potential", two terms have been looked at in the fashion: "investment" and "potential", which allowed the sutta to adjust the correctness of the assessment. Bulo is located in the warehouses of the investment potential of the country, as well as a factor in pouring into the country.
Formation and implementation of investment potential by the head official in the process of improving the competitiveness and economic security of the country, and also in the image of the power of the economy of Ukraine in the process of improving the financial stability of the process, making to the establishment of the main viral funds and non-material assets; generating new ideas; development of scientific, informational and educational potential.
Therefore, to assess the level of investment potential of the country, it is necessary to find a new approach, so that even in a few hours the factor will be injected into the capital of investment potential to grow Oleksandrenko IV's model has been stuck in the robot for assessing the investment potential of the bule, but in this case such an indicator, like infrastructure resources, has not been boosted. In our opinion, the power of this indicator will give the ability to more accurately assess the level of investment potential of Ukraine, and also there is a direct availability of the existing infrastructure and economic
The investment potential of Ukraine has been determined on the basis of the integrated indicators of the country's labor safety, financial, financial, natural and infrastructural resources. As we move towards the development of investment potential in Ukraine, there are a number of obvious problems, such as injecting the development of the economy of the country into the country and reducing the level of investment potential. As a matter of fact, until the end of the day, the policy of reducing the country's investment potential has been promoted, and it is important in Ukraine that there is a need to secure the state-level principle in order to start the process of managing the country's investment potential.
Comparative Analysis of Structural Characteristics and Expression of the CPS Gene in Williams Banana Dwarf Mutant and Its Wild-type Parent
Authors: Lin Jiaqi , Xuan Weiyan , Li Yanpei , Xiao Shixiang , Feng Dou
Published: June 2022

Banana (Musa sp.) is one of the world’s most important crops, and a source of extreme economic importance in many countries around the world. However, the height of banana plant poses a significant challenge in both harvesting fruit and their tolerance to extreme weather. Gibberellin (GA) is one of the important endogenous hormones affecting plant height. Copalyl diphosphate synthase (CPS) is the first key enzyme in the GA biosynthesis pathway. In this paper, two full-length coding sequences of CPS genes were cloned from ‘William B6’ dwarf mutant banana and its wild-type parent (Musa AAA group), named CPS-A and CPS-G, respectively. The full-length complementary DNA (cDNA) sequences of CPS-G and CPS-A were both 2163 base pairs (bp), and encoded 720 amino acid residues. There were eight differences between the two speculative amino acid sequences in the alignment analysis. The molecular weights of CPS-G and CPS-A were 82,359.00 and 82,412.15 Da, respectively, and their isoelectric points were 6.17 and 6.03, respectively; there were no signal peptides and transmembrane structures. The banana CPS was mainly located in the cytoplasm by subcellular localization prediction. The results of reverse quantitative real-time polymerase chain reaction showed that CPS gene expression levels in the leaves and false stems of dwarf banana were lower than those of wild banana except for the developmental stage of the 10th leaf. Its expression level in the dwarf banana stem was significantly lower than that of the wild type at the 15th, 20th, and 25th-leaf age, respectively. The results showed that the dwarfism of the ‘Williams B6’ dwarf mutant might be related to the mutation of the CPS sequence and the difference of expression level. This study laid a foundation for further research on functional verification and the genetic regulation mechanism of the CPS gene.
Multi-market demand response from pump-controlled open canal systems: an economic MPC approach to pump-scheduling
Authors: van der Heijden Ties , Lugt Dorien , van Nooijen Ronald , Palensky Peter , Abraham Edo
Published: June 2022

Participation in demand response (DR) has been explored for many large energy-using assets based on day ahead electricity markets. In this manuscript, we propose the use of multiple electricity spot markets to enable price-based DR for open canal systems in the Netherlands, where many large pumping stations are used for flood mitigation and control of groundwater levels. In the new strategy for pump-scheduling, we combine the day ahead and intraday electricity markets to be used in a hierarchical receding horizon economic Model Predictive Control (MPC). We formulate the decision problem as a Mixed-Integer Quadratic Problem (MIQP), to be solved to near global optimality. A cost-potential analysis was performed for multiple market strategies and the automatic Frequency Restoration Reserves (aFRRs), using actual market and water system data. We show new insights into the trade-off between CO2 emissions and operating cost, the difference between the German and Dutch markets, and temporal changes in market conditions due to renewable energy integration. We observe that the German energy market is rewarding DR more than the Dutch equivalent, due to the higher renewable energy market penetration. The proposed multi-market strategy leads to a cost decrease of 10 and 16% in the Netherlands in 2017 and 2019, respectively. When applying German market scenarios, we found a cost-saving potential of 56 and 50% in 2017 and 2019, respectively. The cost-saving potential for the aFRR market was found to be up to 12% in the Netherlands and 28% in Germany, through a conservative analysis. The results suggest that the proposed control system, optimising costs over the day ahead, intraday and possibly the aFRR markets, is profitable compared to the current strategy in both the current and future electricity market.
Beyond scarcity and its management: Sociocultural dimensions of the water crisis in the Atacama Desert
Authors: Cantillana Raphael , Iniesta-Arandia Irene
Published: June 2022

The depletion of freshwater sources by indiscriminate industrial actions is one of the direct causes of the current water crisis. One of the emblematic cases of this problem is the Atacama Desert, a unique hyper-arid zone in which an extensive copper industry depletes its scarce freshwater reserves. This territory, occupied for millennia by indigenous groups, is experiencing a water crisis that threatens its very subsistence. This paper uses the ethnographic method and the Water Justice framework to approach the everyday and often invisible issues of this crisis within the Mamiña community. This Quechua community holds an ambivalent position in front of the copper mine project because of its control of the water rights, the economic interests of some of their members, and the role of the Aymara minority. We suggest that researchers in this field pay more attention to the communities’ internal diversity and its relations with the copper industry to understand how the water crisis is detached from its biophysical conceptions to be socioculturally constructed.
Preparation and photocatalytic performance of UIO-66/La-MOF composite
Authors: Tong Haixia , Ji Yu , He Tenghui , He Ruidong , Chen Maolong , Zeng Julan , Wu Daoxin
Published: June 2022

To improve the photocatalytic degradation efficiency of photocatalytic materials UIO-66 and La-MOFs under visible-light irradiation, a series of photocatalytic materials with La and Zr as metal centers and terephthalic acid (H2BDC) and 2-amino terephthalic acid (H2ATA) as organic ligands were prepared by solvothermal method. The photocatalytic materials were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), UV-visible (UV-vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, and Mott-Schottky test. The photocatalytic degradation performance to Rhodamine B of the catalysts was fully investigated. Results show that the H2ATA series had stronger visible-light absorption capacity and better photocatalytic performance. The 0.35 La/Zr-H2ATA composite showed the best photocatalytic degradation. The quenching experiments confirmed that the active species in the photocatalytic degradation were the holes and superoxide radicals. The possible mechanisms of the carrier migration paths in the energy level matching for La/Zr-H2BDC and La/Zr-H2ATA were also discussed in detail.
Observatórios de Turismo e COVID-19:
Authors: Kuss Ana , Gardolinski Stella , Ambrosio Nayla , Kauling Julia , Medaglia Juliana
Published: June 2022

Nos últimos anos a atividade turística presenciou um crescimento acelerado. Entretanto, com a chegada do COVID-19, o setor demonstrou uma queda, ocasionando diversos impactos que levarão um tempo ainda não determinado para recuperação. Assim, é necessário entender os impactos causados pela pandemia para acompanhar o retorno e a evolução das atividades do mercado turístico. Foram utilizadas pesquisas de Sondagem Empresarial dos impactos da COVID-19 no setor de turismo, realizadas por Observatórios de Turismo em parceria com a Rede Brasileira de Observatórios de Turismo - RBOT. Outrossim, o artigo tem como objetivo reconhecer alguns dos impactos da pandemia no turismo, a partir da comparação dos resultados de pesquisas dos Observatórios de Turismo dos Estados do Paraná e do Mato Grosso do Sul. Para tanto, a pesquisa caracteriza-se como descritiva, a partir de uma abordagem quantitativa. No período de realização da sondagem de ambas pesquisas, notou-se que a pandemia ainda não havia causado forte impacto econômico e social, bem como, observou-se que os preços dos produtos / serviços não sofreram alteração nos dois estados. Com isso, percebe-se que as empresas entrevistadas possuem similaridades quanto ao perfil, porte, impactos causados pela pandemia e medidas adotadas em relação aos produtos e serviços. Dessa forma, concluiu-se que a comparação entre ambos estados possibilitou visualizar os impactos causados pela pandemia do COVID-19, bem como o papel dos Observatórios de Turismo, que sustentam a ideia de que as informações e conhecimento são capazes de contribuir para o entendimento do panorama de desenvolvimento e recuperação econômica das empresas.
Information Support of Statistic Research of Budget Investments’ Impact on Socio-Ecological and Economic Development of the Russian Federation regions
Authors: Kovalenko N. N.
Published: June 2022

Purpose of the study is to estimate the information support on budget investments and analyze the sources of their formation from the standpoint of completeness and reliability of information for their use as an information base for a statistical study of the impact of budget investments on the social, environmental and economic development of the regions of the Russian Federation. The main directions for assessing the information security of the research are: studying the requirements and basic standards for information; specifics and structures of formed information flows; analysis of information resources, including their parameters and characteristics describing their properties and purpose; determination of units of main information elements, their grouping by formation sources, by main users, by formation system.

Materials and methods. The research used the theoretical methods: analysis, synthesis, grouping of sources of information on budget investments.

Results. The conducted research allowed making a conclusion on a high degree of information security of a rather extensive, multidimensional set of information sources and resources on budget investments. This paper is the basis for the formation of a categorical instrument of statistical research on budget investments. The information array of data on budget investments is aimed at analytical procedures that can be carried out by types, sorts, forms of implementation, budget levels and budget investments realization stages including regional sectioning.

Conclusion. The conducted research has a high degree of practical value due to its aim at direction on elaboration of tools for state management of budget investments. Rapid development of forms and resource chances of the formed information flows on budget investments determined by realization of requirements to the publication of data by state bodies and local self-government bodies which have become more often placed on the Internet as data arrays in the format ensuring their automatic processing to be reused in terms of free use.
Establishment of a High Throughput Screening System for GABAA1
Modulators in Living Cells
Authors: Wang Chen , Li Liqin , Zhang Yi , Shi Tong , Chen Xuejun , Zhang Ruihua , Shi Jingjing , Jin Qian , Xu Jianfu
Published: June 2022

Background:

The incidence of sleep disorders is more than 27% in the worldwide, and
the development of novel sleep drugs that target GABAA receptors is of great interest. Traditional
drug screening methods restrict the discovery of lead compounds, the high-throughput screening
system is a powerful means for the lead compounds discovery of sleep drug.

Methods:

The GABAA1-CHO cell line stably expressing α1β2γ2L was constituted by cotransfection
of α1, β2 and γ2L subunits into CHO-T-Rex cells. The high-throughput screening
method of membrane potential targeting GABAAR was established and optimized. The optimized
method was used to screen the compound library, and the compounds with high activity were obtained.
The active compounds were confirmed in vitro by electrophysiological detection technique, and the
sleep effects of compounds in vivo were detected by pentobarbital sodium sleep model in mice.

Results:

A stable cell line expressing human GABAA1 receptor in CHO-T-Rex cells was generated
and used to establish a functional high-throughput screening assay based on the measurement of
membrane potential changes in living cells by fluorometric imaging plate reader (FLIPR). The assay
was further used to detect the dose-effect relationships of tool compounds, the EC50 values of
agonist GABA (137.42 ± 26.31 nM), positive allosteric modulator diazepam (3.22 ± 0.73 μM), and
antagonist gabazine (0.16 ± 0.04 μM), blocking agents bicuculine (0.47 ± 0.06 μM) and PTX (6.39
± 1.17 μM). In the meanwhile, the compounds were screened from a compound library (10000) by
the membrane potential dye assay. Selected 4 active compounds were further identified for their
EC50 values in vitro by electrophysiological method, the EC50 values of 4 compounds were further
determined as 1.37 ± 0.43 μM, 0.69 ± 0.17 μM, 0.77 ± 0.16 μM, and 1.62 ± 0.29 μM. Furthermore,
the pentobarbital sleep rate and the sleep time of mice pretreated with 4 active compounds by oral
administration were significantly increased compared with mice pretreated with a negative control
in vivo experiment.

Conclusion:

We successfully generated a stable CHO cell line expressing human GABAA1 by induced
expression strategy which decreased cytotoxicity. Then, developed an efficient membrane
potential detection method for high-throughput screening, the assay based on the stable cell line
could distinguish different types of GABAA1 modulators, which would be an effective in vitro system
to screen the GABAAR-targeted compounds. Compared with the patch clamp electrophysiological
detection method, the membrane potential detection method has higher detection flux for
compounds and higher detection sensitivity for active compounds.
Vitamin D Metabolism Gene Polymorphisms and Their Associated Disorders: A
Literature Review
Authors: Abouzid Mohamed , Główka Franciszek , Kagan Leonid , Karaźniewicz-Łada Marta
Published: June 2022

Background:

Vitamin D is a fat-soluble vitamin, and it is a potential key factor to maintain a healthy status. Various observational studies have reported the association between vitamin D deficiency and an elevated risk of osteoporosis, cardiovascular disease, diabetes mellitus, and certain types of cancers. The number of studies that investigated the genetic determinants of vitamin D hydroxy metabolism has been growing, still, its association with the genetic variants remains unclear, particularly those genes related to vitamin D metabolism.

Aim:

This work is a comprehensive review of available evidence of the effect of genetic variants on vitamin D metabolism and their impact on vitamin D status in the human body, disorders including coronavirus disease 2019 infection, and its importance for clinical investigators and public health.

Results:

Genome-wide association studies and candidate gene studies show that circulating levels of vitamin D are being influenced by genetic factors. These genetic changes are implicated in various pathways of vitamin D, such as metabolism and transport. It is also involved in the formation of the ternary complex (vitamin D receptor - retinoid receptor - transcription factor II B).

Conclusion:

Linkage studies may fail to identify replicated genetic architecture of vitD metabolism, Genome-wide association studies and the candidate gene approach have shown reproducible influences of gene control on vitD status.
The Combination of Baicalin with Knockdown of mir148a Gene
Suppresses Cell Viability and Proliferation and Induces the Apoptosis and
Autophagy of Human Glioblastoma Multiforme T98G and U87MG Cells
Authors: Paul-Samojedny Monika , Liduk Emilia , Kowalczyk Małgorzata , Borkowska Paulina , Zielińska Aleksandra , Suchanek-Raif Renata , Kowalski Jan
Published: June 2022

Background:

Glioblastoma multiforme (GBM) is a heterogeneous and highly vascularized
brain tumor that avoids apoptosis due to P-glycoprotein (P-gp) mediated multidrug resistance.
Therefore, the development of new therapeutic strategies that induce apoptosis and inhibit proliferation
is urgently warranted.

Objectives:

We examined the efficacy of the combination of baicalin (BAI) and knockdown of
miR-148a gene in human glioblastoma T98G and U87MG cell lines.

Methods:

T98G and U87MG cells were transfected with miR148a siRNA. The influence of miR-
148a siRNA in combination with BAI on T98G and U87MG cell viability, proliferation, apoptosis,
and autophagy was evaluated as well. Alterations in the mRNA expression of autophagy-related
genes were analyzed using RT-qPCR.

Results:

The transfection of T98G and U87MG cells with miR148a specific siRNA and exposition
on baicalin led to a significant reduction in cell viability and proliferation, the accumulation of sub
G1-phase cells and a reduced population of cells in the S and G2/M phases (only in U87MG cell
line), increased population of cells in the S phase in T98G cell line and apoptosis or necrosis induction
and induction of autophagy for both cell lines.

Conclusion:

The siRNA-induced miR-148a mRNA knockdown in combination with baicalin may
offer a novel therapeutic strategy to more effectively control the growth of human GBM cells.
Thus, knockdown of this gene in combination with baicalin inhibits proliferation (cell cycle arrest
in the S phase in T98G but not in U87MG cells), induces apoptosis, and regulates autophagy in
T98G and U87MG cells. However, further studies are urgently needed to confirm a positive phenomenon
for the treatment of GBM.
The MAP2K2 Gene as Potential Diagnostic Marker in Monitoring
Adalimumab Therapy of Psoriatic Arthritis
Authors: Strzałka-Mrozik Barbara , Krawczyk Agata , Juszczyk Karol , Kimsa-Dudek Magdalena , Wcisło-Dziadecka Dominika , Gola Joanna
Published: June 2022

Background:

MAP kinases are some of the cascades that are specialized in the cell’s
response to external stimuli. Their impaired functioning can be observed during the course of psoriatic
arthritis. Currently, the best-known class of biological drugs is the inhibitors of the proinflammatory
cytokine TNF-α, including adalimumab.

Objective:

The aim of this study was to assess changes in the expression of MAP kinase genes in
patients with psoriatic arthritis treated with adalimumab, as well as to determine which of the analyzed
transcripts could be used as a diagnostic or therapeutic target.

Methods:

An analysis was performed on the total RNA extracted from PBMCs of patients with
psoriatic arthritis before and after three months of adalimumab therapy as well as from a control
group. Changes in the expression of the mitogen-activated protein kinase genes were assessed
using the HG-U133A 2.0 oligonucleotide microarray method, while the obtained results were validated
using the real-time RT-qPCR method.

Results:

Using the oligonucleotide microarray method, 14 genes coded for proteins from the
MAPK group were identified with at least a two-fold change of expression in the control group
and during adalimumab therapy. Validation of the results confirmed a statistically significant decrease
in the transcriptional activity of the MAP2K2 gene in the group of patients three months
after the administration of adalimumab relative to the control group.

Conclusion:

Adalimumab therapy alters the expression of MAPK-coding genes. The assessment
of the number of MAP2K2 mRNA molecules can potentially be used in diagnostic analyses or in
monitoring adalimumab therapy.
Integrated Bioinformatics Analysis for the Screening of Hub Genes and
Therapeutic Drugs in Hepatocellular Carcinoma
Authors: Su Qiuming , Li Wang , Zhang Xibing , Wu Ruichao , Zheng Kepu , Zhou Tao , Dong Yun , He Yutao , Wang Duo , Ran Jianghua
Published: June 2022

Background:

Liver cancer is a major medical problem because of its high morbidity
and mortality. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Currently,
the mechanism of HCC is unclear, and the prognosis is poor with limited treatment.

Objective:

The purpose of this study is to identify hub genes and potential therapeutic drugs for
HCC.

Methods:

We used the GEO2R algorithm to analyze the differential expression of each gene in 4
gene expression profiles (GSE101685, GSE62232, GSE46408, and GSE45627) between HCC
and normal hepatic tissues. Next, we screened out the differentially expressed genes (DEGs) by
corresponding calculation data according to adjusted P-value < 0.05 and | log fold change (FC) | >
1.0. Subsequently, we used the DAVID software to analyze the DEGs by GO and KEGG enrichment
analysis. Then, we carried out the protein-protein interaction (PPI) network analysis of
DEGs using the STRING tool, and the PPI network was constructed by Cytoscape software.
MCODE plugin was used for module analysis, and the hub genes were screened out by the Cyto-
Hubba plugin. Meanwhile, we used The Kaplan-Meier plotter, GEPIA2 and HPA databases to
exert survival analysis and verify the expression alternation of hub genes. Furthermore, we used
ENCORI, TargetScan, miRDB and miRWalk database to predict the upstream regulated miRNA
of hub genes and construct a miRNA-hub genes network by Cytoscape software. Finally, we selected
potential therapeutic drugs for HCC through DGIdb databases.

Results:

A total of 415 DEGs were screened in HCC, including 196 up-regulated DEGs and 219
down-regulated DEGs. The results of KEGG pathway analysis suggested that the up-regulated
DEGs can regulate the cell cycle, and DNA replication signal pathway, while the down-regulated
DEGs were associated with metabolic pathways. In this study, we identified 11 hub genes
(AURKA, BUB1B, TOP2A, MAD2L1, CCNA2, CCNB1, BUB1, KIF11, CDK1, CCNB2 and
TPX2), which were independent risk factors of HCCand all up-regulated DEGs. We verified the
expression difference of hub genes through the GEPIA2 and HPA database, which was consistent
with the results of GEO data. We found that those hub genes were mutations in HCC according to
the cBioPortal database. Finally, we used the DGIdb database to select 32 potential therapeutic
targeting drugs for hub genes.

Conclusions:

In summary, our study provided a new perspective for researching the molecular
mechanism of HCC. Hub genes, miRNAs, and candidate drugs provide a new direction for the
early diagnosis and treatment of HCC.
Targeting and Modulation of the Natriuretic Peptide System in Covid-19: A Single or Double-Edged Effect?
Authors: Alexiou Athanasios , Batiha Gaber El-Saber , Al-kuraishy Hayder M. , Al-Gareeb Ali I.
Published: June 2022

Natriuretic peptide system [NPS] is a group of peptide hormones or paracrine factors, including atrial natriuretic peptide [ANP], brain natriuretic peptide [BNP], and natriuretic peptide precursor C [NPC], that are structurally related. The physiological effects of NPS include natriuresis, increased glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological effects, as it is also produced locally from immune cells; it regulates innate and adaptive immune responses. Metabolism and degradation of ANP are achieved by neutral endopeptidase [NEP], also known as neprilysin. Coronavirus disease 2019 [Covid-19] pandemic may lead to acute lung injury [ALI] and/or respiratory distress syndrome [ARDS]. The underlying causes of inflammatory and immunological disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent release of a pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs, which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin inhibitors like sacubitril increase endogenous NPs may reduce the risk of ALI in Covid-19 due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by neprilysin. In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of neprilysin inhibitors in the management of Covid-19.
A Comprehensive Comparative Review of Protein Sequence-Based Computational
Prediction Models of Lysine Succinylation Sites
Authors: Mollah Md. Nurul Haque , Tasmia Samme Amena , Kibria Md. Kaderi , Islam Md. Ariful , Khatun Mst Shamima
Published: June 2022

Lysine succinylation is a post-translational modification (PTM) of protein in which a succinyl
group (-CO-CH2-CH2-CO2H) is added to a lysine residue of protein that reverses lysine's positive
charge to a negative charge and leads to the significant changes in protein structure and function. It occurs
on a wide range of proteins and plays an important role in various cellular and biological processes
in both eukaryotes and prokaryotes. Beyond experimentally identified succinylation sites, there have
been a lot of studies for developing sequence-based prediction using machine learning approaches, because
it has the promise of being extremely time-saving, accurate, robust, and cost-effective. Despite
these benefits for computational prediction of lysine succinylation sites for different species, there are a
number of issues that need to be addressed in the design and development of succinylation site predictors.
In spite of the fact that many studies used different statistical and machine learning computational
tools, only a few studies have focused on these bioinformatics issues in depth. Therefore, in this comprehensive
comparative review, an attempt is made to present the latest advances in the prediction models,
datasets, and online resources, as well as the obstacles and limits, to provide an advantageous guideline
for developing more suitable and effective succinylation site prediction tools.
Phytochemical based Modulation of Endoplasmic Reticulum Stress in
Alzheimer's Disease
Authors: Dsouza Venzil Lavie , Shivakumar Apoorva Bettagere , Kulal Nikshitha , Gangadharan Gireesh , Kumar Dileep , Kabekkodu Shama Prasada
Published: June 2022

Alzheimer's disease (AD) is a severe progressive neurodegenerative condition that shows misfolding and aggregation of proteins contributing to a decline in cognitive function involving multiple behavioral, neuropsychological, and cognitive domains. Multiple epi (genetic) changes and environmental agents have been shown to play an active role in ER stress induction. Neurodegener-ation due to endoplasmic reticulum (ER) stress is considered one of the major underlying causes of AD. ER stress may affect essential cellular functions related to biosynthesis, assembly, folding, and post-translational modification of proteins leading to neuronal inflammation to promote AD pathol-ogy. Treatment with phytochemicals has been shown to delay the onset and disease progression and improve the well-being of patients by targeting multiple signaling pathways in AD. Phytochemical's protective effect against neuronal damage in AD pathology may be associated with the reversal of ER stress and unfolding protein response by enhancing the antioxidant and anti-inflammatory prop-erties of the neuronal cells. Hence, pharmacological interventions using phytochemicals can be a potential strategy to reverse ER stress and improve AD management. Towards this, the present re-view discusses the role of phytochemicals in preventing ER stress in the pathology of AD.
Protective Effect of Artemisia absinthium Extract Against Glutamate-
Induced Toxicity in PC12 Cells
Authors: Rashidi Roghayeh , Akaberi Maryam , Mobasheri Leila , Sadeghi Mahmood , Mousavi Seyed Hadi , Forouzanfar Fatemeh
Published: June 2022

Objectives:

Glutamatergic dysfunction has been implicated in the pathogenesis of numerous
central nervous system disorders. Artemisia absinthium (A. absinthium), has been reported to have neuro protective and antioxidant activities. The current study examined the effect of A. absinthium extract on
glutamate-induced cytotoxicity using PC12 cells.

Methods:

PC12 cells were pretreated with A. absinthium extract (70% ethanol) at concentration ranges of
6.25-25 µg/ml for 2 h, followed by exposure to glutamate (8 mM) for 24 hr. The cells viability, reactive
oxygen species (ROS) accumulation, and lipid peroxidation were measured. Moreover, a propidium iodide flow cytometry assay was performed for the assessment of apoptosis.

Results:

Pretreatment with A. absinthium extract markedly attenuated the loss of cell viability, ROS gen-eration, lipid peroxidation, and cell apoptosis in glutamate-injured PC-12 cells.

Conclusion:

Our results indicate that A. absinthium extract protects PC12 cells against glutamate-induced
injury, possibly by reducing oxidative stress and apoptosis.
Heavy Metal Pollution and Male Fertility: An Overview on Adverse Biological Effects and Socio-Economic Implications
Authors: Ballini Andrea , Arrigoni Roberto , Crocetto Felice , Risolo Rossella , Colapietro Rita , Bellavita Rosa , Barone Biagio , Francesco Caputo Vincenzo , Luca Giovanni , Grieco Paolo , Santini Giunio , Brancorsini Stefano
Published: June 2022

Trace metals can be divided into two subgroups considering their pathophysiological effects: the first consists of microelements essential for life (arsenic, cobalt, chromium, copper, fluorine, iron, iodine, manganese, molybdenum, nickel, selenium, silicon, tin, vanadium and zinc), implicated in important metabolic processes; the second includes toxic microelements, such as cadmium (Cd), mercury (Hg), chromium (Cr), and lead (Pb) for living organisms, even at low concentrations. These metals contribute to serious consequences for human health, including male infertility. Studies performed in several in vitro and in vivo models revealed that environmental exposure to toxic pollutants, as heavy metals, negatively affects human male fertility. Stem cells, due to their ability to self-renew and differentiate in several cell types, have been proposed as a useful tool in assisted reproductive technology, permitting the spermatogenesis recovery in patients with irreversible infertility. Considering the effects of heavy metals on male fertility and, from a demographic point of view, the decreased fertility ratio, further strategies are required to maintain a sustainable turn-over of 2 children for woman. We discuss here the findings on the biological effects of heavy metal pollution in the male fertility and underline the related socioeconomic impact on population demography.
Synthesis, Characterization, and Antitubercular Evaluation of Tetrahydrotetrazolo
Quinazoline Derivatives
Authors: Babu N. Raghavendra , Raju R. Subhakar , Alavala Rajasekhar Reddy , Rao G.S.N. Koteswara , Desu Prasanna Kumar , Namratha J. Risy , Muralidharan V.
Published: June 2022

Background:

Tuberculosis is a highly contagious disease that is one of the major
causes of mortality worldwide and the leading infectious organism-related cause of death.
Various tetrazole and quinazoline compounds have been successfully developed in the past
for tuberculosis treatment. In this case, we planned to design the hybrid moieties by combining
both tetrazole and quinazoline nuclei to create novel compounds with increased activity.

Methods:

6, 6-dimethyl-5, 6, 7, 9–tetrahydrotetrazolo [5, 1-b] Quinazolin-8(4H) -one derivatives
were synthesized, characterized by using spectral data. The antitubercular activity
of the synthesized compounds was tested against the H37RV strain of Mycobacterium tuberculosis.
In order to identify the interactions with the target protein Mtb Pks13 Thioesterase
domain in complex with an inhibitor, docking analysis of the final compounds was performed
(Protein data bank ID: 5V41). To verify their drug-like potential, the synthesized
compounds were subjected to Pharmacokinetic prediction experiments. Zebrafish larvae
had been used to test the teratogenicity of the synthesized compounds.

Results:

At 6.25 μg/mL, compounds F4 and F7 exhibited good efficacy against Mycobacterium
tuberculosis strains. Docking studies aided in determining the most likely binding mode
within the binding cavity of the concerned target protein.

Conclusion:

Compounds containing p-fluorophenyl and p-nitrophenyl groups as substituents
were found to have excellent anti-tubercular activity.
Os jardins da cidade um olhar sociológico sobre o mapeamento do comportamento humano dos utilizadores do Jardim da Corujeira
Authors: Vidal Diogo Guedes , Fernandes Cláudia Oliveira , Dias Ricardo Cunha , Seixas Paulo Castro , Barros Nelson , Vilaça Helena , Maia Rui Leandro
Published: June 2022

This article presents a sociological readingat Corujeiragarden,located in the city of Porto, applying the technique of mapping human behaviour to its users. To this end, social, environmental, and spatial variables were combined to identify regularities of social behaviour that, on the one hand, reflects the relationship between users and the space and, on the other hand, show clues for future interventions in the garden. These results show the potential of mapping human behaviour for a sociological reading of the city's gardens as spaces that reproduce inequalities and struggles for environmental justice and urban socio-spatial justice
Empréstimos do italiano em nomes empresariais em Portugal
Authors: Lídia Coimbra Rosa , De Castro Moutinho Lurdes
Published: June 2022

Juntamente com os movimentos dos povos, as línguas também viajam, deixando e/ou transportando marcas evidentes desse movimento pelos espaços geográficos por onde transitam. De entre as marcas linguísticas mais visíveis, destaca-se o campo do léxico. A entrada de italianismos no português, diretamente ou via outras línguas românicas, como o espanhol e o francês, tem sido situada principalmente na época do Renascimento, período em que a Itália era vista como uma referência cultural importante na Europa. No estudo que aqui nos propomos apresentar, referiremos a presença de marcas lexicais italianas no português atual, sob uma perspetiva sincrónica. Com este objetivo, partimos de um corpus de 151 italianismos, já dicionarizados e compilados, que fazem parte do nome de 1087 empresas em Portugal. O corpus foi obtido num diretório de empresas online, tendo as buscas sido efetuadas por palavra-chave com os referidos italianismos. O corpus obtido foi analisado em categorias formais (nomes, adjetivos) e semânticas (música, arquitetura, artes, gastronomia). Foram, assim, apurados dados relativos a estes nomes, bem como ao ramo de atividade a que se referem e sua localização geográfica. O cruzamento dos dados e os gráficos obtidos permitirão uma leitura objetiva da sua utilização em denominações de empresas sediadas em Portugal