bluuebunny/crossref_metadata_2025 huggingface dataset:
Rheumatoid arthritis Fibroblast-like synoviocytes maintain tumor-like biological characteristics through ciRS-7-dependent regulation of miR-7
Authors: Hu Zuoyu , Chen Jingrong , Wang Manli , Weng Weizhen , Chen Ye , Pan Yunfeng
Published: February 2022

BACKGROUND Altered phenotype of Fibroblast-like synoviocyte(FLS) is an important cause of the pathogenesis and progression of rheumatoid arthritis(RA) , but the specific mechanism causing this change has not yet been fully explained. The exact mechanism by which the biological properties of FLS change in RA is still unclear. MiRNAs regulate the biological activity of FLS. Thus, we first used miRNA microarray and WGCNA to confirm the RA-FLS miRNA landscape and establish their biological functions via network analyses at the system level, as well as to provide a platform for modulating the overall phenotypic effects of RA-FLS.METHODS We enrolled a total of 3 patients with RA and 3 healthy participants, constructed a network analysis of via miRNA microarray and RNA-sequencing. Furthermore, the coexpression analyses of miR-7 and ciRS-7 were verified by siRNA transfection, overexpression and qPCR analyses. Finally, we evaluated the effects of adjusting the expression levels of miR-7 and ciRS-7 on RA-FLS, respectively.RESULTS We identified distinct miRNA features in RA-FLS, including miR-7, which was significantly lower expressed. Furthermore, we discovered the negative regulatory relationship between ciRS-7 and miR-7 in RA-FLS. Finally, we overexpressed miR-7 in RA-FLS and discovered that miR-7 inhibited RA-FLS hyperproliferation, migration, invasion, and apoptosis, whereas ciRS-7 overexpression reversed these effects.CONCLUSION Our investigation identified that ciRS-7-miR-7 axis affects the tumor-like biological characters of RA-FLS. These findings could aid in our understanding of essential roles of miR-7 in RA-FLS and will facilitate to development potential intervention target for RA.
HDAC class IIa expression and regulation in human endometrial tissues and stromal cells during the menstrual cycle
Authors: Gujral Palak , Mahajan Vishakha , Ponnampalam Anna P.
Published: February 2022

Background: Histone Deacetylases (HDACs) are a class of enzymes that deacetylate the lysine residues on the protruding histone tails, causing tightening of the chromatin structure and making genes inaccessible to be transcribed. Class I and II HDACs have been involved in cell cycle regulation and progression. Class 1 HDACs have been widely studied in endometrial pathologies and menstrual cycle regulation. Studies have shown that class IIa HDACs (4, 5, 7, and 9) regulate the cell cycle, proliferation, and differentiation. But any potential roles for class IIa HDACs in endometrial biology have not been explored. This study aims to characterise the temporal expression of class IIa HDACs in the endometrium and their regulation by steroid hormones in human endometrial stromal cells (HESCs). Methods: mRNA expression and protein expression of HDAC 4, 5, 7, and 9 were analyzed in endometrial tissue biopsies collected from premenopausal women throughout the menstrual cycle by real-time quantitative PCR and fluorescent western blot analysis, respectively. Effect of hormonal regulation on class IIa HDAC expression was studied in endometrial stromal cell line following treatments with estrogen (E2) and estrogen-progesterone combined (E2+P4) over 24hrs, 48hrs, and 72hrs period. The cells were also treated with HDAC inhibitor Trichostatin A (TSA) combined with the steroid hormones. Results: In endometrial tissue, mRNA expression of class IIa HDACs showed cyclic changes. HDACs 5 and 7 were significantly upregulated during the early secretory phase, while HDAC9 was upregulated during the mid-secretory phase, compared to other cycle stages. In addition, HDAC 5 and 9 proteins were significantly upregulated in the human endometrium during the secretory phase, compared to the proliferative stage. Protein expression levels of class IIa HDACs in HESCs were upregulated in response to the combined estrogen-progesterone treatment for 24 and 48 hrs, in vitro. While TSA mitigated these hormonal effects.. Conclusions: This study shows that class IIa HDACs are expressed in the human endometrium in a cyclic pattern and are influenced by steroid hormones. Suggesting their possible involvement in menstrual cycle regulation and endometrial pathologies.
A comparison of transmissibility of SARS-CoV-2 Variants of Concern
Authors: Manathunga S.S , Abeyagunawardena I. A , Dharmaratne S.D
Published: February 2022

Background

The World Health Organization (WHO) has currently detected five Variants of Concern of SARS-CoV-2 having the WHO labels of ‘Alpha’, ‘Beta’, ‘Gamma’, ‘Delta’ and ‘Omicron’. We aimed to assess and compare the transmissibility of the five VOCs in terms of basic reproduction number, time-varying reproduction number and growth rate.

Methods

Publicly available data on the number of analyzed sequences over two-week windows for each country were extracted from covariants.org and GISAID initiative database. The ten countries which reported the highest number of analyzed sequences for each of the five variants were included in the final dataset and was analyzed using R language. The epidemic curves for each variant were estimated utilizing the two-weekly discretized incidence data using local regression (LOESS) models. The basic reproduction number was estimated with the exponential growth rate method. The time-varying reproduction number was calculated for the estimated epidemic curves by the ratio of the number of new infections generated at time step t to the total infectiousness of infected individuals at time t, using the EpiEstim package.

Results

The highest R0 for the variants Alpha (1.22), Beta (1.19), Gamma (1.21), Delta (1.38) and Omicron (1.90) were reported from Japan, Belgium, the United States, France and South Africa, respectively. Nine out of ten epidemic curves with the highest estimated growth rates and reproduction numbers were due to the Omicron variant indicating the highest transmissibility.

Conclusions

The transmissibility was highest in the omicron variant followed by Delta, Alpha, Gamma and Beta respectively.
Substrate Effect on Hydrogen Evolution Reaction in Two-Dimensional Mo2C Monolayers
Authors: Lee Sujin , Min Byungjoon , Bang Junhyeok
Published: February 2022

The physical and chemical properties of atomically thin two-dimensional (2D) materials can be modified by the substrates. In this study, the substrate effect on the electrocatalytic hydrogen evolution reaction (HER) in 2D Mo2C monolayers was investigated using first principles calculations. The isolated Mo2C monolayer shows large variation in HER activity depending on hydrogen coverage: it has relatively low activity at low hydrogen coverage but high activity at high hydrogen coverage. Among Ag, Au, Cu, and graphene substrates, the HRE activity is improved on the Ag and Cu substrates especially at low hydrogen coverage, while the effects of the Au and graphene substrates on the HER activity are insignificant. The improvement is caused by the charge redistribution in the Mo2C layer on the substrate, and therefore the HER activity becomes high for any hydrogen coverage on the Ag and Cu substrates. Our results suggest that, in two-dimensional electrocatalysis, the substrate has a degree of freedom to tune the catalytic activity.
Digitale Collagen als Medium ästhetischer Interaktion
Authors: Hallmann Kerstin , Hofmann Fabian , Knauer Jessica , Lembcke-Thiel Astrid , Preuß Kristine , Roßkopf Claudia , Schmidt-Wetzel Miriam
Published: February 2022

Dieser Beitrag dokumentiert Eindrücke, Beobachtungen und Ergebnisse aus einem Online-Workshop des Forschungsclusters «Interaktion und Partizipation in der Kulturellen Bildung», der die Vorstellung von Themen, Arbeitsweisen und Prinzipien des Forschungsclusters zum Ziel hatte. Dabei lag es nahe, die Auseinandersetzung selbst interaktiv und partizipativ sowie entlang der Thematik der rahmenden Tagung zu konzipieren. Ein Grossteil der Kommunikation wird hierfür parallel zur Videokonferenz auf ein digitales Whiteboard verlagert, auf dem alle Teilnehmenden individuell und gemeinsam agieren können. Als Material liegen zentrale Fragmente aus einem Text des Clusters bereit, in dem die Begriffe Interaktion und Partizipation in einem gemeinsamen Selbstversuch und geleitet vom Prinzip der Collage verhandelt werden. Dieses Textprinzip wird zum Handlungsprinzip des Workshops: Die Teilnehmenden werden dem Versuch ausgesetzt, in kleinen Gruppen auf dem digitalen Whiteboard sowohl mit dem bereitgestellten als auch mit eigenem Material selbst Collagen zu erstellen. In dem experimentellen Format des Workshops konturiert sich performativ ein ästhetisch-digitaler Möglichkeits- und Erfahrungsraum, in dem die individuellen Positionen und Perspektiven aller Beteiligten über Text, Bild und Sprache interaktiv in vernetzende Artikulationsformen treten. In den entstandenen Collagen kommen Aspekte von Ästhetik, Digitalität und Macht in eindrücklicher Weise zum Tragen.
Polariton condensation into vortex states in the synthetic magnetic field of a strained honeycomb lattice
Authors: Lledó Cristóbal , Carusotto Iacopo , Szymanska Marzena
Published: February 2022

Photonic materials are a rapidly growing platform for studying condensed matter physics with light, where the exquisite control capability is allowing us to learn about the relation between microscopic dynamics and macroscopic properties. One of the most interesting aspects of condensed matter is the interplay between interactions and the effect of an external magnetic field or rotation, responsible for a plethora of rich phenomena---Hall physics and quantized vortex arrays. At first sight, however, these effects for photons seem vetoed: they do not interact with each other and they are immune to magnetic fields and rotations. Yet in specially devised structures these effects can be engineered. Here, we propose the use of a synthetic magnetic field induced by strain in a honeycomb lattice of resonators to create a non-equilibrium Bose-Einstein condensate of light-matter particles (polaritons) in a rotating state, without the actual need for external rotation nor reciprocity-breaking elements. We show that thanks to the competition between interactions, dissipation and a suitably designed incoherent pump, the condensate spontaneously becomes chiral by selecting a single Dirac valley of the honeycomb lattice, occupying the lowest Landau level and forming a vortex array. Our results offer a new platform where to study the exciting physics of arrays of quantized vortices with light and pave the way to explore the transition from a vortex-dominated phase to the photonic analogue of the fractional quantum Hall regime.
Impact of public debt profile on economic growth: Evidence from Nigeria
Authors: O. Aiyedogbon John , Zhuravka Fedir , Korneyev Maxim , Banchuk-Petrosova Olena , Kravchenko Olena
Published: February 2022

An excessive increase in public debt characterizes the contemporary development of the global economic and financial system. The paper aims to examine the short- and long-run impact of state debt on economic growth in Nigeria. The model was estimated using an autoregressive distributed lag (ARDL) bounds testing method to co-integration for the long-run investigation. At the same time, the contemporaneous dynamics were explored using an unrestricted error correction model. The data were collected from the Central Bank of Nigeria’s statistical bulletins and annual reports, and it spanned the years from 1990 to 2020. The study uncovers evidence of a long-term link between the study variables. In addition, the study finds that all the explanatory is statistically significant. Specifically, economic growth is significant and negatively responsive to changes in external debt by 0.19% and debt servicing by 0.07%, contrary to its positive response to changes in domestic debt and exchange rate by 0.27% and 0.18%, respectively. The paper, therefore, recommends that government may consider more domestic borrowings to foreign borrowings that should only be resorted to when it is indispensable. Moreover, the government should also strive to balance loan servicing and the economic sustainability.
Regionalization of catchment hydrological model parameters for global water resources simulations
Authors: Qi Wen-yan , Chen Jie , Li Lu , Xu Chong-Yu , Li Jingjing , Xiang Yiheng , Zhang Shaobo
Published: February 2022

Parameter regionalization of hydrological models is one of the most commonly used methods for hydrological prediction over ungauged catchments. Although there were many regional studies, there is no clear conclusion on the best-performing regionalization method for global hydrological modelling. The objective of this study is to determine an appropriate global-scale regionalization scheme (GSRS) for global hydrological modelling. To this end, the performance of five regionalization methods with two different average options, two weighting approaches, and seven efficiency thresholds (i.e. Kling-Gupta efficiency (KGE) values to measure hydrological model performances) was compared over thousands of catchments based on four conceptual hydrological models. Results of nine global models from the Global Earth Observation for Integrated Water Resource Assessment (EartH2Observe) project were selected to validate the accuracy of GSRS in estimating global runoff. The results show that: (1) Spatial proximity method with the Inverse Distance Weighting method and the output average option offers the best regionalization result when using the KGE ≥ 0.5 as an efficiency threshold for all four hydrological models, (2) the regionalization-based global hydrological simulation schemes (RGHSs), i.e. the proposed GSRS combining with four hydrological models, consistently performs better than the nine global models from EartH2Observe project in the estimation of runoff for most catchments, with varying degrees of improvement in the median, upper and lower quartiles, and whiskers of each performance metric, and (3) the global long-term annual water resources estimated by RGHSs range between 42,592 and 46,810 km3/yr.
Research on partition strategy of an urban water supply network based on optimized hierarchical clustering algorithm
Authors: Xia Wei , Wang Shi , Shi Mingjun , Xia Qing , Jin Wenting
Published: February 2022

The partitioning of the urban water supply network can significantly enhance water supply quality. Nonetheless, the bulk of the recently deployed partition approaches overlooked the question of whether the district's fluctuation regulation of flow data is consistent. When the district is modified, it most likely leads to an increase in pressure at a node. To tackle the problem, the flow data from a city's water supply network was evaluated in this article. The random forest approach was also used to extract time-domain characteristics from flow data, and the water supply network split was optimized using the random forest-hierarchical clustering (RF-HC) strategy. Finally, the results were examined and compared. The results suggest that the RF-HC-based water supply network partition technique can better meet the aim of consistent flow changes in the district, as well as offer a theoretical foundation and technological support for the optimal dispatch of press concerning the water supply network.
Discharge modeling in compound channels with non-prismatic floodplains using GMDH and MARS models
Authors: Yonesi Hojjat Allah , Parsaie Abbas , Arshia Azadeh , Shamsi Zahra
Published: February 2022

In this study, modeling of discharge was performed in compound open channels with non-prismatic floodplains (CCNPF) using soft computation models including multivariate adaptive regression splines (MARS) and group method of data handling (GMDH), and then their results were compared with the multilayer perceptron neural networks (MLPNN). In addition to the total discharge, the discharge separation between the floodplain and main channel was modeled and predicted. The parameters of relative roughness coefficient, the relative area of flow cross-section, relative hydraulic radius, bed slope, the relative width of water surface, relative depth, convergence or divergence angle, relative longitudinal distance as inputs, and discharge were considered as models output. The results demonstrated that the statistical indices of MARS, GMDH, and MLPNN models in the testing stage are R2 = 0.962(RMSE = 0.003), 0.930(RMSE = 0.004), and 0.933(RMSE = 0.004) respectively. Examination of statistical error indices shows that all the developed models have the appropriate accuracy to estimate the flow discharge in CCNPF. Examination of the structure of developed GMDH and MARS models demonstrated that the relative parameters: roughness, area, hydraulic radius, flow aspect ratio, depth, and angle of convergence or divergence of floodplain have the greatest impact on modeling and estimation of discharge.
Degradation of Oxirane Ring for Epoxidation of Palm Oleic Acid
via In Situ Performic Acid
Authors: Azmi Intan Suhada , Wahi Nurul Fathia , Jalil Mohd Jumain
Published: February 2022

Background:

The world’s raw material consumption has shifted from the use nonrenewable
materials to renewable materials.

Method:

In this study, the epoxidation of palm oleic acid was carried out by in situ performic
acid to produce epoxidized palm oleic acid. Since the epoxide ring is highly reactive, the degradation
of the oxirane was examined by using hydrogen peroxide, formic acid, and water.

Results:

A mathematical model was developed by using the numerical integration of the 4th order
Runge-Kutta method and the results showed that there is a good agreement between the
simulation and experimental data, validating the kinetic model. As a result, the degradation is
highly effective in acidic conditions such as hydrogen peroxide and formic acid, which leads to
the formation of side products such as diol and α-glycol. The kinetic rate (k) parameters obtained
by using ode45 function in MATLAB software is k11= 6.6442, k12= 7.0185, k2= 0.1026, for epoxidation
of palm oleic acid, and k3 = 0.0347, k4= 0.0154, k5= 0.142, in degradation process.

Conclusion:

The minimum error of the simulation is 0.17311.
Anticonvulsant Enaminones: With Emphasis on Methyl 4-[(p-Chloro­phenyi)Amino]-6-Methyi-2-0xocyclohex-3-En-1-0ate(ADD 196022)
Authors: Edafiogho I. O. , Alexander M. S. , Moore J. A. , Farrar V. A. , Scott K. R.
Published: February 2022

Enaminones, enamines of B-dicarbonyl compounds have been known for many years. Their main therapeutic utility was as prodrugs for various amines, stabilizing these active compounds principally in basic media. Our laboratory discovered a series of enamines of cyclic 1,3-diketo esters which were stable and possessed significant anticonvulsant activity. The most notable compound was methyl 4- [(p­ chlorophenyl)amino)-6-methyl-2-oxocyclohex-3-en-1-oate, 15, desig­ nated ADD 196022 by the Anti-convulsant Drug Development (ADD) Program of the National Institutes of Health. Compound 15 displayed an
intraperitoneal (ip) EDso of 26.2 mg/kg and a TDso of 254.8 mg/kg in the mouse and an oral (po)
EDso of 5.8 mg/kg and a TDso of >380 mg/kg in the rat. The protective indices (TDso/EDso) were 9.7 in the mouse and >65.6 in the rat, respectively. This data compared favorably to phenytoin and carbamazepine. In addition, 15 demonstrated oral effectiveness in the rat corneal kindling model, providing an EDso of 34.2 mg/kg. Quantitative structure-activity studies in this series successfully utilized the Craig Plot method (Craig, P. N.J. Med Chern. 1971, 14,
680; Craig, P. N.J. Med Chern. 1972, 15, 144). High field NMR , molecular modeling studies
and CLOGP were also employed to assess the potential interactions of these compounds and phenytoin in its relationship to potential anticonvulsant activity. Each of these factors is discussed.
Quinolone Congeners As Mammalian Topoisomerase-11 Inhibitors
Authors: Radl Stanislav , Daxt Scott
Published: February 2022

The development of the quinolone antibacterials has clearly demonstrated that inhibition of topoisomerase activity can constitute an effective means by which to induce selective pathogen cell death. These agents disrupt normal bacterial gyrase protein-DNA substrate interactions and lead to the formation of a ternary "cleavable complex" which results in a bactericidp.l therapeutic mode of action. However, certain structural 'subsets'
of quinolones have been shown to be toxic to mammalian cells as a result of competing inhibition of mammalian topoisomerase II activity. The investigation of these congeners has revealed that rather simple molecular modifications to the basic quinolone pharmacophore can potentiate activity against mammalian proteins. Structure-activity relationships have been elucidated in an attempt to selectively target the action of mammalian topoisomerase as a means for anticancer chemotherapy.
Inhibitors of Cyclooxygenase and 5-Lipoxygenase
Authors: Mantri Padmaja , Witiak Donald T.
Published: February 2022

Prostaglandin H synthase (PGH synthase) and 5-Lipoxygenase (5-LO) are important enzymes that catalyze the formation of putative intermediates involved in the inflammatory process. The mechanism by which PGH synthase and 5-LO convert their common substrate arachidonic acid (AA) into prostaglandins, thromboxanes and leukotrienes is discussed. Recent advances on competitive, mechanism-based and reversible non­ competitive inhibitors of PGH synthase are described. Further discussed are
classes of compounds which inhibit 5-LO, including compounds structurally related to 5-LO substrate or product, agents acting on 5-LO activating protein (FLAP), iron chelators and antioxidants.
β-Aianyi-L-histidinato Zinc: A Potent Activator in Bone Formation
Authors: Yamaguchit Masayoshi
Published: February 2022

It is known that zinc is essential for the growth of human and many animals. Bone has one of the highest zinc concentrations of all tissues. Bone growth retardation is a common finding in various conditions associated with zinc deficiency, seggesting a physiological role of zinc in the growth and calcification of bone tissue. Bone zinc content is decreased by development with aging, skeletal unloading and postmenopausal conditions. Thus zinc deficiency may play a pathophysiological role in the deterioration of bone metabolism. In fact, zinc has been demonstrated to
have a stimulatory effect on bone formation and mineralization due to promoting bone cellular protein synthesis. AHZ is a new zinc compand, in which zinc is chelated to -alanyi-L­ histidine (L-carnosine). This compound can stimulate bone formation and mineralization in weanling and aged rats, and it has a direct anabolic effect in culture system of bone tissue and bone-forming cells (osteoblastic cells). The stimulatory effect of AHZ on bone formation was more intensive than that of zinc sulfate, showing that the mode of AHZ action differs from that of zinc sulfate. AHZ has a stimulating effect on proliferation and differentiation in osteoblastic cells due to a newly synthesized protein components. It is confirmed that bone-forming effect of AHZ is a greater than that of various bone-regulating hormones and other factors. The oral administration of AHZ has a fine restorative effect on osteopenia with various pathophysiological conditions. AHZ may be new drug in therapy of osteoporosis. Clinical studies are in progress.
Glyceride Conjugates as Drug Carriers
Authors: Lambert D. M. , Scriba G. K.  E. , Gallez B. , Poupaert J.  H. , Dumont P.
Published: February 2022

Drug-lipid conjugates have been prepared in order to confer the attached drugs to the metabolic pathways of natural lipids. The drug can be covalently bound either to a fatty acid or to a glyceride. In glycerides, one or two fatty acid moieties have been replaced by a drug realizing pseudoglycerides. These pseudoglycerides exhibited some physicochemi­
cal properties and absorption characteristics similar to those of natural triglycerides resulting in a different pharmacokinetic and/or pharmacodynamic profile compared that of the parent drug. Non-steroidal anti-inflammatory drugs such as aspirin, indomethacin, ibuprofen, naproxen and aclofenac were covalently bound to diglycerides in order to reduce the ulcerogenicity of the compounds. Employing the absorption process of dietary fat, pseudoglycerides have been used for the targeting of the lymphatic route in order to avoid the first-pass metabolism of a drug (L-DOPA) and I or to target the lymphatic system for the treatment of lymphatic metastasis (chlorambucil, melphalan) or filiariasis (melphalan and GABA). Pseudoglycerides and other glyceride-like structures have been evaluated in order to increase the intestinal absorption of poorly water-soluble drugs such as phenytoin. An improvement of the blood-brain barrier penetration of GABA covalently bound to glycerides has been reported in the 80's, A similar approach was followed for L-dopa, glycine, valproate, and the enkephalinase inhibitor thiorphan including amide bio-isosteres of glycerides. Radioiodinated agents containing fluoride and nitroxyl moieties were coupled to glycerides and fatty acids as potential hepatographic agents in
nuclear medicine, 19F- and 1H-nuclear magnetic resonance imaging, respectively. A variety of phospholipid-linked cytotoxic nucleosides and nucleoside analogues such as ara-C, AZT and acyclovir have been prepared. Compared to the parent drugs the phospholipid analogs exhibited increased antineoplastic activity in vitro and in vivo. The conjugates were also active against tumors and viruses that were resistant against the drug itself.
Sanguinarine Represses the Growth and Metastasis of Non-small Cell Lung Cancer
by Facilitating Ferroptosis
Authors: Xu Rongzhong , Wu Jianchun , Luo Yingbin , Wang Yuli , Tian Jianhui , Teng Wenjing , Zhang Bo , Fang Zhihong , Li Yan
Published: February 2022

Aim of the study:

Ethnopharmacological relevance: Sanguinarine (SAG), a natural benzophenanthridine
alkaloid derived from the root of Sanguinaria canadensis Linn. (Bloodroot), possesses a potential anticancer
activity. Lung carcinoma is the chief cause of malignancy-related mortality in China. Non-small cell lung carcinoma
(NSCLC) is the main subtype of lung carcinoma and accounts for about eighty-five percent of this disease.
Current treatment in controlling and curing NSCLC remains deficient.

Aim:

The role and underlying mechanism of SAG in repressing the growth and metastasis of NSCLC were
explored.

Materials and Methods:

The role of SAG in regulating the proliferation and invasion of NSCLC cells was
evaluated in vitro and in a xenograft model. After treatment with SAG, Fe2+ concentration, reactive oxygen species
(ROS) levels, malondialdehyde (MDA), and glutathione (GSH) content in NSCLC cells were assessed to
evaluate the effect of SAG on facilitating ferroptosis.

Results:

SAG exhibited a dose- and time-dependent cytotoxicity in A549 and H3122 cells. SAG treatment
effectively repressed the growth and metastasis of NSCLC in a xenograft model. We, for the first time, verified
that SAG triggered ferroptosis of NSCLC cells, as evidenced by increased Fe2+ concentration, ROS level, and
MDA content, and decreased GSH content. Mechanistically, SAG decreased the protein stability of glutathione
peroxide 4 (GPX4) through E3 ligase STUB1-mediated ubiquitination and degradation of endogenous GPX4.
GPX4 overexpression restored the proliferation and invasion of NSCLC cells treated with SAG through inhibiting
ferroptosis.

Conclusions:

SAG inhibits the growth and metastasis of NSCLC by regulating STUB1/GPX4-dependent
ferroptosis.
Venous Thromboembolism Following Major Abdominal Surgery for Cancer: A
Guide for the Surgical Intern
Authors: Theochari Christina A. , Theochari Nikoletta A. , Mylonas Konstantinos S. , Papaconstantinou Dimitrios , Giannakodimos Ilias , Spartalis Eleftherios , Patelis Nikolaos , Schizas Dimitrios
Published: February 2022

Background:

Venous thromboembolism (VTE) is a term used to compositely describe deep vein
thrombosis (DVT) and pulmonary embolism (PE). Overall, the incidence of VTE after major abdominal and
pelvic surgery has been reported to be between 10% and 40%.

Objective:

The aim of this study is to estimate the incidence of post-operative VTE in patients undergoing major
abdominal surgery for cancer, to identify risk factors associated with VTE, and to assess available thromboprophylaxis
tools.

Methods:

A Medline and Cochrane literature search from database inception until February 1st, 2021 was performed
according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses)
guidelines.

Results:

Thirty-one studies met our eligibility criteria and were included in the current review. In total, 435,492
patients were identified and the overall incidence of VTE was 2.19% (95% CI: 1.82-2.38). Τhe following risk
factors were associated with VTE: smoking, advanced age (>70 years), a history of diabetes mellitus, American
Society of Anesthesiologists’ (ASA) classification of Physical Health class III or IV, a history of cardiovascular
or pulmonary disease, a history of DVT or PE, elevated plasma fibrinogen level, c-reactive protein (CRP) level,
cancer stage III or IV, postoperative acute respiratory distress syndrome (ARDS), prolonged postoperative hospital
stay, previous steroid use, history of Inflammatory Bowel Disease (IBD), heart failure and neoadjuvant
and adjuvant chemotherapy.

Conclusion:

VTE remains an important complication after major abdominal surgery for cancer and seems to
increase mortality rates.
Transcription Factors and Regulators Pathway-focused Genes Expression
Analysis in Patients with Different Forms of Thyroid Pathology
Authors: Kamyshna Iryna , Kamyshnyi Aleksandr
Published: February 2022

Background:

Autoimmune thyroiditis (AIT), a T cell-mediated organ-specific disorder,
and transcription factors have a critical role in the regulation of immune responses, especially in the
fate of T-helper cells.

Objective:

This study aims to investigate changes in the gene expression profile of transcription
factors and regulators in patients with different forms of thyroid pathology.

Methods:

We used the pathway-specific real-time PCR array (Neurotrophins and Receptors RT2
Profiler PCR Array, QIAGEN, Germany) to identify and verify transcription factors and regulators
pathway-focused genes expression in peripheral white blood cells of patients with postoperative
hypothyroidism, hypothyroidism as a result of AIT and AIT with elevated serum and antithyroglobulin
(anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies.

Results:

It was shown that in patients with postoperative hypothyroidism FOS, NR1I2, STAT4, and
TP53 significantly increased their expression, whereas the expression of STAT1, STAT2, and
STAT3 decreased. In patients with hypothyroidism as a result of AIT, we have found increased expression
of NR1I2, STAT2, and STAT3. In contrast, the expression of STAT1 and TP53 decreased.
FOS and STAT4 mRNAs did not change their expression. In patients with AIT and elevated serum
anti-Tg and anti-TPO antibodies, the expression of FOS and NR1I2 reduced, whereas the mRNA
level of STAT3 increased. STAT1, STAT2, and STAT4 mRNAs did not change their expression.
MYC did not change its expression in all groups of patients.

Conclusions:

The results of this study demonstrate that autoimmune thyroiditis and hypothyroidism
affect the mRNA-level expression of transcription factors and regulators genes in a gene-specific
manner and that these changes to genes expression can be one of the triggers of autoimmune
inflammation progression in the thyroid gland.
Cancer Immunotherapy: An Overview of Small Molecules as Inhibitors of the Immune Checkpoint PD-1/PD-L1 (2015-2021)
Authors: Taliani Sabrina , Baglini Emma , Salerno Silvia , Barresi Elisabetta , Marzo Tiziano , Settimo Federico Da
Published: February 2022

In 2018, James Allison and Tasuku Honjo received the Nobel Prize in physiology or medicine to discover tumor therapy by inhibition of negative immune regulation. Immunotherapy stimulates T-cells to fight cancer cells by blocking different immune checkpoint pathways. The interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 (Programmed cell death ligand 1) is one of the main pathways. Of note, interfering with this pathway is already exploited in clinical cancer therapy, demonstrating that it is one of the key factors involved in the immune escape mechanism of cancer. The development of monoclonal antibodies (mAbs) that possess the ability to inhibit the interactions between PD-1/PD-L1 has radically made the difference in cancer immunotherapy. Yet, due to the many drawbacks of this therapy, the research shifted its efforts towards the development of novel small molecules. This may constitute hope and an arduous challenge in fighting cancer. This paper reviews the recent primary literature concerning the development of novel small molecules able to block the interaction between PD-1 and its ligand PD-L1.
Developments in the Antitumor Activity, Mechanisms of Action, Structural Modifications, and Structure-Activity Relationships of Steroidal Saponins
Authors: Huang Xuefeng , An Renfeng , Zhang Wenjin
Published: February 2022

Steroidal saponins, a class of natural products formed by the combination of spirosteranes with sugars, are widely distributed in plants and have various biological activities, such as antitumor, anti-inflammatory, anti-bacterial, anti-Alzheimer's, anti-oxidation, etc. Particularly, extensive research on the antitumor property of steroidal saponins has been conducted. Steroidal sapogenins, the aglycones of steroidal saponins, also have attracted much attention due to a vast range of pharmacological activities similar to steroidal saponins. In the past few years, structural modifications on the aglycones and sugar chains of steroidal saponins have been carried out and some achievements have been made. In this mini-review, the antitumor activity, action mechanisms, and structural modifications, along with the structure-activity relationships of steroidal saponins and their derivatives, are summarized.
In vitro Delivery of HIV-1 Nef-Vpr DNA Construct Using the Human
Antimicrobial Peptide LL-37
Authors: Bolhassani Azam , Rouhollah Fatemeh , Nikyar Arash , Heshmati Masoumeh
Published: February 2022

Background and Objectives:

DNA-based therapeutic vaccines have been proposed as a
promising strategy for the treatment of established HIV infections. However, these vaccines are often
associated with certain shortcomings, such as poor immunogenicity and low transfection efficiency. In
this study, we investigated the ability of LL-37 to deliver a potential immunogenic fusion construct
comprising HIV-1 nef and vpr genes into a mammalian cell line.

Methods:

First, the pEGFP-N1 eukaryotic expression vector harboring the HIV-1 nef-vpr fusion was
produced free of endotoxin on a large scale. Then, DNA/LL-37 complexes were prepared by coincubation
of pEGFP-nef-vpr with LL-37 for 45 minutes at different nitrogen to phosphate (N/P) ratios.
The formation of DNA/peptide complexes was investigated by gel retardation assay. Next, the stability
and morphological characteristics of the nanoparticles were evaluated. The toxicity of LL-37 and the
nanoparticles in HEK-293T cells were assessed by MTT assay. The transfection efficiency of the
DNA/LL-37 complexes was studied by fluorescence microscopy, flow cytometry, and western blot
analysis.

Results:

LL-37 formed stable complexes with pEGFP-nef-vpr (diameter of 150-200 nm) while providing
good protection against nucleolytic and proteolytic degradation. The peptide significantly affected
cell viability even at low concentrations. However, the LL-37/DNA complexes had no significant cytotoxic
effect. Treatment of cells with pEGFP-N1/LL-37 and pEGFP-nef-vpr/LL-37 resulted in transfection
of 36.32% ± 1.13 and 25.55% ± 2.07 of cells, respectively.

Conclusion:

Given these findings and the important immunomodulatory and antiviral activities of LL-
37, the use of this peptide can be further exploited in the development of novel gene delivery strategies
and vaccine design.
A Literature Review of Pulmonary Arterial Hypertension (PAH)
Authors: Panchal Ashima , Panchal Jigar , Jain Sonika , Dwivedi Jaya
Published: February 2022

In 1891, German doctor E. Romberg was the first to report PAH. It is widespread throughout the world, but it is particularly problematic in India and other developing countries. Pulmonary arterial hypertension (PAH) is characterised by an increase in pulmonary arterial pres-sure as well as the emergence of progressive symptoms, such as a loss of functional ability, short-ness of breath, and fatigue.
Blood flows from the right side of the heart to the lungs through the pulmonary arteries. Pulmonary arterial pressure refers to the pressure in the arteries of the lungs (PAH). It necessitates immediate treatment because high blood pressure in the lungs causes the right side of the heart to work much harder, increasing the risk of heart failure. This article aimed to provide brief information about the prevalence, pathology, classification, and different therapies of PAH.
Fangchinoline Inhibited Proliferation of Neoplastic B-lymphoid Cells and
Alleviated Sjögren’s Syndrome-like Responses in NOD/Ltj Mice via the
Akt/mTOR Pathway
Authors: Shao Yanxiong , Yu Chuangqi , Fu Jiayao , Zhan Tianle , Ye Lei
Published: February 2022

Backgound:

Fangchinoline is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra S. Moore that is conventionally used as an analgesic, antirheumatic, and antihypertensive drug in China. However, the application of Fanchinoline in Sjögren syndrome (SS) remains unreported.

Objective:

This study aimed to identify the potential role of Fangchinoline in the treatment of SS via altering Akt/mTOR signaling.

Methods:

First, we examined levels of p-Akt and p-mTOR in infiltrating lymphocytes of labial glands from SS patients by immunohistochemistry. Then, the effects of Fangchinoline on Raji cells and Daudi cells were investigated using the CCK-8 assay, propidium iodide (PI)/RNase, and Annexin V/PI staining. Western blotting was used to identify the levels of Akt, p-Akt(ser473), mTOR, and p-mTOR. For in vivo analyses, NOD/Ltj and wild-type ICR mice were treated with a Fangchinoline solution, an LY294002 solution (an inhibitor of the PI3K/Akt/mTOR pathway), or their solvent for 28 days. Then, salivary flow assays and hematoxylin and eosin staining of submandibular glands were performed to determine the severity of SS-like responses in the mice.

Results:

Immunohistochemical staining of labial glands from SS patients showed that activation of p-Akt and p-mTOR in infiltrating lymphocytes might be correlated with SS development. In vitro, Fangchino-line and LY294002 inhibited proliferation, induced cell cycle arrest, and promoted apoptosis in Raji and Daudi cells by altering Akt/mTOR signaling. In vivo, Fangchinoline and LY294002 significantly im-proved the salivary secretion by NOD/Ltj mice and reduced the number of lymphocytic foci in the sub-mandibular glands.

Conclusion:

These results indicated that Fangchinoline could effectively inhibit the proliferation of neo-plastic B-lymphoid cells and reduce SS-like responses in NOD/Ltj mice. Our study highlights the poten-tial value of the clinical application of Fangchinoline for SS treatment.
Highly Efficient, Reusable, Functionalized Pyridinium Salts as a Catalyst for the Simple and Cost-effective Preparation of Tetrahydro [b] Benzopyran Derivatives
Authors: Khiri-Meribout Naima , Benzerka Saida , Redouane Mohamed Abdenour , Debache Abdelmadjid
Published: February 2022

Background:

In this work, a series of pyridinium-based ionic liquids (PBILs) were synthesized.

Methods:

Pyridinium-based ionic liquids (PBILs) were synthesized through a simple method, which was initially evaluated as catalysts for the synthesis of tetrahydro[b]benzopyran derivatives via a one-pot three-component reaction involving aldehydes, malononitrile, and dimedone.

Results:

The PBILs perform well in this condensation reaction, especially 1-methylpyridin-1-ium dimethyl phosphate (MPDMP).

Conclusion:

The advantages of this procedure are good yields, short reaction time, simplicity of implementation, and inexpensive starting materials.
Prawa i wolności obywatelskie w warunkach epidemii COVID-19
Authors: Wąsikowski Adam
Published: February 2022

Podjęcie tematu praw i wolności obywatelskich w warunkach epidemii COVID-19 w dużej mierze podyktowane zostało potrzebą zweryfikowania pojawiających się w przestrzeni publicznej opinii, jakoby rząd polski w tych trudnych czasach poprzez działania prawodawcze godził w podstawowe swobody obywatelskie. Reakcją większości rządzących na świecie wobec rozprzestrzenianie się wirusa SARS-CoV-2 było wprowadzanie odpowiednich regulacji prawnych, mających na celu ograniczenie lub zahamowanie epidemii i władze polskie nie stanowiły tu wyjątku. Niniejsze opracowanie w dużej mierze koncentruje się na omówieniu konkretnych działań prawnych podjętych przez rząd premiera Mateusza Morawieckiego w czasie epidemii, które w opinii wielu ekspertów mogły godzić w prawa i wolności obywatelskie. W artykule zaprezentowane są również przykłady regulacji prawnych wprowadzanych przez polski rząd, które nosiły znamiona wadliwej i niepoprawnej legislacji, co w konsekwencji mogło podważać zasadę demokratycznego państwa prawa. Zauważalne próby zahamowania epidemii COVID-19 wymagały przedsięwzięcia określonych działań prawnych. Poważne wątpliwości budzi jednak sposób ich wprowadzania, zgodność z zasadami stanowienia prawa, a co ważniejsze – godzenie w określone swobody obywatelskie.
Blended learning: A study on Tamil primary schools
Authors:   Faculty of Languages and Communication, Sultan Idris Education University, Tanjung Malim, Malaysia, et al. Ponniah
Published: February 2022

This research was conducted to study the interest of blended learning among the students of Tamil primary schools and to identify the performance on the verse and figurative language (ceiyulum moziyaniyum). Primary schools including Tamil primary schools of Malaysia have implemented blended learning in their teaching and learning process. Both traditional and online learning are blended. Due to the implementation of blended learning in schools, the attitude of students changed and it became a powerful and effective tool for the students to learn. Many types of research on blended learning among primary school students and teachers have been carried out. According to these studies' findings, blended learning in primary schools both in traditional and online learning is essential. The impacts, effects, and environment are focused. Compared with these previous studies, the present study discusses and provides information about the interest and performance of blended learning in primary schools. Moreover, Tamil primary school students are focused on in this study. Further, the findings of this study show that students’ participation in blended learning and their performance are high even during pandemic days. In this study, 4 different Tamil primary schools in Kedah State, Malaysia involved in blended learning were selected. Based on the objectives, the data were analyzed. The findings show that students’ participation in blended learning and their performance are high even during pandemic days.
Tecnologias e educação
Authors: Adams Telmo
Published: February 2022

Este artigo apresenta um estudo a partir da obra de Paulo Freire com o objetivo de identificar e analisar seu aporte para embasar a reflexão crítica sobre as tecnologias. No atual contexto, entende-se que um dos grandes desafios do campo educacional está na compreensão crítica da relação entre tecnologias e educação. Entre as contribuições teóricas do autor estão: a denúncia do falso dilema entre humanismo-tecnologia; a crítica ao tecnicismo, à ideologização, ao pragmatismo neoliberal; e a necessária vigilância ética frente ao utilitarismo consumista que domina a ciência e a tecnologia na lógica do mercado capitalista. Conclui-se que as contribuições de Paulo Freire continuam extremamente atuais para a compreensão dessa temática, contribuindo com referências éticas para avalizar os sentidos da tecnologia no campo educativo; e, ao mesmo tempo, indica critérios para evitar o tecnocentrismo que dicotomiza humanismo e tecnologia.
Cuentos de Tío Conejo: El pequeño gigante de las sabanas
Authors: Pérez Salgado Antonio
Published: February 2022

Escribir de Tío conejo es escribir de la niñez de los latinoamericanos. Desde México hasta Argentina, este singular personaje perteneciente a la tradición de los cuentos orales refleja el imaginario y la cosmogonía de nosotros como pueblo. Son incontables las generaciones que hemos crecido con él, y es ideal para acercar al niño a la lectura creadora. Tío Conejo es heredero de la picaresca hispana, por ello es un personaje con desventaja física – como un antihéroe –, pero con una inteligencia superior a sus eternos contrincantes. Su astucia simboliza las diversas formas de los pueblos para defenderse y burlarse de los poderosos. Sin embargo, esta picardía también es la capacidad creativa para salir de las constantes situaciones de peligro y no debe confundirse con acciones que se riñen con la ética. Este debe ser un tema tratado con cuidado y esmero cuando sea leído y compartido, Tío Conejo siempre se defiende, nunca ataca si no está en peligro, y siempre trata de ser justo.
Indicators to achieve a better positioning of Ecuadorian scientific journals
Authors: Santiago Padilla Victor , Ramos Gil Yalitza Therly
Published: February 2022

Ecuador's scientific journals are not in a good position worldwide, as seen in the small number of journals indexed in impact databases. This research was carried out due to the current and prevailing need to improve the performance level of national scientific journals at the international level. This work sought to generate the information necessary for Ecuadorian scientific journals to have a greater scope considering the criteria for indexing in the Scopus, Clarivate Web of Science, Scielo, and Redalyc databases. This was determined based on the hypothesis: Failure to comply with the indicators for international scientific databases makes Ecuadorian journals not part of these collections. We identified differences between public and private institutions and the status of communication journals in compliance with the same criteria. We analyzed 55 Ecuadorian scientific journals already indexed in Latindex. The analysis was carried out by creating matrices that made it possible to quantify the fulfillment of the criteria, implementing a categorization of Yes for the journals that meet the indicator or NO for those that do not. Similarly, interviews were conducted with editors of the Ecuadorian journals with the best indexing to triangulate the information discussed in this research. The research showed that, although most magazines meet the vast majority of indexing criteria, the main problems are the geographic and institutional diversity of the editors and authors in the journals.