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The purpose of this study was the evaluate use of bio-fertilizers to adjustment water shortage stress and improved smooth vetch (Vicia dasycarpa L.) yield under water deficit stress conditions. Thus, A 2-year experiment were performed in an agrisilviculture system of plum orchard in 2016 and 2017. In this study, the single, double and triple combined of Arbuscular mycorrhizal fungi- Rhizophagus intraradices (AMF), Azotobacter chroococcum (Az) and Thiobacillus spp. (Th) on smooth vetch plants were evaluated under rain-fed and supplemental irrigation. The results indicated that irrigated plants had more Fe and Zn nutrients than rain-fed plants. Combined use of AMF + A. chroococcum more improved the forage dry matter digestibility (DMD), total digestible nutrient (TDN), net energy for lactation (NEL), dry matter intake (DMI) and relative feed value (RFV) than plants with single inoculation. In irrigated plants, double and triple combination of AMF with A. chroococcum and/or Thiobacillus spp. improved chlorophyll-a, chlorophyll-b, total chlorophyll, RWC, TSS, AsA, and GSH while lowering proline and MDA. Rain-fed condition reduced grain yield. In conclusion, synthesis non-enzymatic antioxidant because of the combined use of bio-fertilizers (AMF, Az and Th) can reduce ROS damage and improve water deficit resistance and yield in smooth vetch rain-fed plants.

This study investigated the effect of organic fertilizers on vegetative growth and the physiological and antioxidant activity characteristics of thyme plants grown under stress. A factorial experiment was conducted according to randomized complete block design with 12 combinations and 3 replications in the 2018 growing season. The experiment factors were the implementation of organic fertilizers at 4 levels (vermicompost, manure compost, animal manure, and control) and irrigation regime at 3 levels (Irr1, Irr2, and Irr3, respectively, irrigation after 60, 90, and 120 mm evaporation from A pan). The results showed that With delayed irrigation, the chlorophyll a and b contents, total chlorophyll, and carotenoid decreased, while the application of low water stress enhanced the amount of oil and the oil yield with the respective highest values of 2.61% and 3.68 g/m under mild stress conditions. Nonetheless, higher values for the aforementioned properties were noted with the application of vermicompost. Water deficit decreased nutrient uptake (K, P, and N) and relative water content, biological yield, and seed yield of thyme, indicating that thyme was sensitive to drought, and organic fertilizers application improved nutrient uptake (K, P, and N) and relative water content, biological yield and seed yield of the plant within irrigation levels. The activities of catalase, superoxide dismutase and ascorbate peroxidase were reduced under organic fertilizers such as vermicompost and manure compost as compared with control under drought stress. The plants of thyme showed a good response to organic fertilizers under water deficit circumstances, with vermicompost being the most effective.

As opposed to remarkable advances in the cell therapy industry, research reveal inexplicable difficulties associated with preserving and post-thawing cell death. Post cryopreservation apoptosis is a common occurrence that has attracted the attention of scientists to use apoptosis inhibitors. Transporting cells without compromising their survival and function is crucial for any experimental cell-based therapy. Preservation of cells allows the safe transportation of cells between distances and improves quality control testing in clinical and research applications. The vitality of transported cells is used to evaluate the efficacy of transportation strategies. For many decades, the conventional global methods of cell transfer were not only expensive but also challenging and had adverse effects. The first determination of some projects is optimizing cell survival after cryopreservation. The new generation of cryopreservation science wishes to find appropriate and alternative methods for cell transportation to ship viable cells at an ambient temperature without dry ice or in media-filled flasks. The diversity of cell therapies demands new cell shipping methodologies and cryoprotectants. In this review, we tried to summarize novel improved cryopreservation methods and alternatives to cryopreservation with safe and viable cell shipping at ambient temperature, including dry preservation, hypothermic preservation, gel-based methods, encapsulation methods, fibrin microbeads, and osmolyte solution compositions.

Variants of MTC result from different mutations in exons of the RET gene. RET proto-oncogene is activated by a DNA rearrangement and it is one of the first tyrosine kinase receptor (RTK) proteins found to play a role in neoplasia. Early detection using genetic screening has become the gold standard of therapy, followed by prophylactic thyroidectomy. RET-kinase inhibitors have been developed recently for the treatment of MTC and are currently at various phases of pre- and clinical trials. Numerous autosomal dominantly inherited mutations have been demonstrated to activate RET constitutively. These mutations in separate populations are believed to be correlated with a rather heterogeneous prototype across countries. As such, one objective of this study was to demonstrate a geographical pattern of RET mutations in various populations. Advances in RET genetic screening have facilitated for the rapid recognition of hereditary MTCs and prophylactic thyroidectomy for relatives who may not show signs of the disease. In this chapter, we will discuss oncogenic RET signaling, RET inhibitors and the major RET mutations found in MTC and the necessity of RET genetic screening for the early diagnosis of MTC patients, using American Thyroid Association guidelines and genotype-phenotype correlation.

Long noncoding RNAs are characterized as noncoding transcripts longer than 200 nucleotides in response to a variety of functions within the cells. They are involved in almost all cellular mechanisms so as epigenetics. Given that epigenetics is an important phenomenon, which participates in the biology of complex diseases, many valuable studies have been performed to demonstrate the control status of lncRNAs and epigenetics. DNA methylation and histone modifications as epigenetic mechanisms can regulate the expression of lncRNAs by affecting their coding genes. Reciprocally, the three-dimensional structure of lncRNAs could mechanistically control the activity of epigenetic-related enzymes. Dysregulation in the mutual interaction between epigenetics and lncRNAs is one of the hallmarks of cancer. These mechanisms are either directly or indirectly involved in various cancer properties such as proliferation, apoptosis, invasion, and metastasis. For instance, lncRNA HOTAIR plays a role in regulating the expression of many genes by interacting with epigenetic factors such as DNA methyltransferases and EZH2, and thus plays a role in the initiation and progression of various cancers. Conversely, the expression of this lncRNA is also controlled by epigenetic factors. Therefore, focusing on this reciprocated interaction can apply to cancer management and the identification of prognostic, diagnostic, and druggable targets. In the current review, we discuss the reciprocal relationship between lncRNAs and epigenetic mechanisms to promote or prevent cancer progression and find new potent biomarkers and targets for cancer diagnosis and therapy.

The most serious hallmark step of carcinogenesis is oxidative stress, which induces cell DNA damage. Although in normal conditions ROS are important second messengers, in pathological conditions such as cancer, due to imbalanced redox enzyme expression, oxidative stress can occur. Recent studies with firmly established evidence suggest an interdependence between oxidative stress and thyroid cancer based on thyroid hormone synthesis. Indeed, a reduced antioxidant defense system might play a part in several steps of progression in thyroid cancer. Based on studies that have been conducted previously, future drug designs for targeting enzymatic ROS sources, as a single agent or in combination, have to be tested. Polyphenols represent the potential for modulating biological events in thyroid cancer, including antioxidative activity. Targeting enzymatic ROS sources, without affecting the physiological redox state, might be an important purpose. As regards the underlying chemopreventive mechanisms of natural compounds that have been discussed in other cancer models, the confirmation of the influence of polyphenols on thyroid cancer is inconclusive and rarely available. Therefore, there is a need for further scientific investigations into the features of the antioxidative effects of polyphenols on thyroid cancer. The current review illustrates the association between some polyphenols and the key enzymes that take place in oxidation reactions in developing thyroid cancer cells. This review gives the main points of the enzymatic ROS sources act and redox signaling in normal physiological or pathological contexts and supplies a survey of the currently available modulators of TPO, LOX, NOX, DUOX, Nrf2, and LPO derived from polyphenols.

The trial aimed to study the effects of different levels of humic acid on the antioxidant activity of garden thyme. The study was conducted at the experimental fields of the Agronomy Department, Faculty of Agriculture, Urmia University, West Azerbaijan, Iran, and used randomized complete block design with four replications. Three different humic acid doses; 200 kg ha−1, 400 kg ha−1 and 600 kg ha−1, and control with no humic acid were the treatments. Total phenolic content, total flavonoid content, DPPH (1,1-diphenyl 2-picryl hydroxyl) radical scavenging activity, nitric oxide radical scavenging activity, and chain-breaking activity were determined. According to the results, the effect of different levels of humic acid in the first harvest on total flavonoid content and nitric oxide radical scavenging was significant whereas, in the second harvest, total phenols content, total flavonoids content, DPPH radical scavenging activity, and chain-breaking activity were significant. The maximum total phenolic content, and nitric oxide radical scavenging activity were obtained in the control treatment. The highest total flavonoid content, DPPH radical scavenging activity, and chain-breaking activity were obtained in the application of 400 kg ha−1 and 600 kg ha−1 humic acid.

Mg-based biomaterials are commonly used as biodegradable orthopedic implants (e.g., bone regeneration applications). However, achieving high biocompatibility and corrosion resistance has remained a challenge to be tackled. In this work, to investigate various fabricated coatings (with and without pre- anodizing), five categories of samples are considered: (a) bare Mg alloy (Mg), (b) Anodized Mg alloy (Mg-A), (c) CS-coated Mg alloy (Mg-C), (d) CS-coated anodized Mg alloy (Mg-AC), and (e) CS-CNT-coated anodized Mg alloy (Mg-ACC). These samples were characterized by using Field Emission Scanning Electron Microscopes (FE-SEM), Energy Dispersive Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FT-IR), and Raman Spectroscopy. The adhesion within the coated samples was compared. Then, the effects of the coatings were evaluated by comparing wettability, corrosion behavior, and biocompatibility for bare and coated samples. The adhesion test showed that the coatings exhibited higher adhesion for Mg-AC and Mg-ACC compared to Mg-C. Desired wettability was achieved as the contact angles of coated samples were in the range of 55°– 65°. Electrochemical impedance and polarization as well as immersion tests showed higher corrosion resistance for coated samples. The composite coated sample showed improved cell adhesion since the osteoblast cells covered almost the entire surface of the sample. Moreover, osteoblast cell viability for the sample was around 40% higher than that of the bare sample. Graphical abstract

Contrary to remarkable advances within the cell therapy industry, scientists expose dissatisfied challenges associated with the preservation and post-thaw cell death globally. Post cryopreservation apoptosis is normally observed in cultures and scientists are focusing on incorporation of apoptosis inhibitors. Impressive transport of cells without affecting their survival and function is a crucial and pivotal factor in any practical cell-based therapies. Preservation of cells permits the transportation of cells between distances, as well as improvement of safety and quality control testing in clinical and research applications. The prosperity of transportation methods is evaluated through the viability and proliferation percentages of the transported cell. For many decades, the conventional methods of transferring cells globally having adverse effects and speculated to be a challenging and expensive method. The main purpose of some studies is the optimization of cell survival after cryopreservation. In the new generation of cryopreservation science, various experiments wish to discover suitable and alternative methods for cell transportation to ship viable cells at ambient temperature without dry ice or in media filled flasks. In this review we try to represent a summary of the detection of recent studies including dry preservation, hypothermic preservation, agarose-gel based method, polymer based cryogel matrix, encapsulation method, fibrin microbeads, osmolyte solution composition, collagen-based scaffold, natural zwitterionic betaine, bio-inspired cryo-ink that have been performed alternative, effective and economic methods for shipping viable cells at ambient temperature.

Biomaterial-based drug delivery systems (DDSs) for GBM drug delivery are classified as organic, inorganic and cell-based nanoparticles.

Background: Although statins decrease mortality in coronary artery disease, the effect of high-dose statins and duration of therapy post-percutaneous coronary intervention (PCI) is not well addressed. Aim: To determine the effective dose of statin to prevent major adverse cardiovascular events (MACEs), such as acute coronary syndrome, stroke, myocardial infarction, revascularisation and cardiac death, after PCI in patients with chronic coronary syndrome. Methods: In this randomised, double-blind clinical trial, all chronic coronary syndrome patients with a recent history of PCI were randomly divided into two groups after 1 month of high-dose rosuvastatin therapy. Over the next year, the first group received rosuvastatin 5 mg daily (moderate intensity), while the second received rosuvastatin 40 mg daily (high intensity). Participants were evaluated in terms of high-sensitivity C-reactive protein and MACEs. Results: The 582 eligible patients were divided into group 1 (n=295) and group 2 (n=287). There was no significant difference between the two groups in terms of sex, age, hypertension, diabetes, smoking, previous history of PCI or history of coronary artery bypass grafting (p>0.05). There were no statistically significant differences in MACE and high-sensitivity C-reactive protein after 1 year between the two groups (p=0.66). Conclusion: The high-dose group had lower LDL levels. However, given the lack of association between high-intensity statins and MACEs in the first year after PCI among chronic coronary syndrome patients, the use of moderate-intensity statins may be as effective as high-intensity statins, and treatment based on LDL targets may suffice.

Aims: Extensive evidence demonstrated that epigenetic modifications play a crucial role in the development of thyroid malignancies. The onset of DNA methylation sequencing technologies has provided a more comprehensive understanding of biological development of tumorigenesis. This cross-sectional study aimed to investigate the methylation degree of a large region of tissue inhibitor of metalloproteinase 3 (TIMP3) promoter, including 15 CpG islands, and its association with BRAF V600E mutation in thyroid nodules. Methods Thyroid specimens from 64 patients met the eligibility criteria, consisting of 28 PTC, 9 FTC, and 27 benign subjects. Exon 15 of the BRAF gene was genotyped using sequencing. The expression of TIMP3 was evaluated using the real-time qRT-PCR method. The bisulfite sequencing PCR technique was used to estimate the promoter methylation status. Results The BRAF V600E mutation was found in 46.2% of PTC and none of FTC cases. TIMP3 mRNA level was reduced in both PTC and FTC tumoral tissues compared to the adjacent non-tumoral tissues (ANT) (p = 0.02 and p = 0.03, respectively). Moreover, a reduction of TIMP3 expression was observed in FTC tissues compared to the benign samples (p = 0.04). It is noteworthy that significant hypermethylation was found in TIMP3 promoter in both PTC and FTC tissues compared to the ANT and benign samples (p BRAF mutation was associated with TIMP3 expression and total methylation in PTC. There was also a significant correlation between the expression and total methylation status in ANT and tumoral tissues of PTC and FTC cases (p TIMP3 promoter's methylation individually may be beneficial in differentiating benign and malignant thyroid tissues. According to the reversibility of DNA methylation, these events may be considered potential targets for demethylation treatments.

In the early inflation period, due to the highest accessible energy, the quantum effects of gravity are essentially considerable and the generalized uncertainty principle (GUP) can be examined. In this paper, we first calculate the slow-roll parameter of the power-law inflation according to physical and co-moving momentum. Then, considering the two proposed algebras for the GUP, we show that considering a minimum length for corrections cannot satisfy the slow-roll condition and inflation, in this case, will not terminate gracefully. By simultaneously considering both minimum length and maximum momentum, inflation will terminate gracefully but it can never start from a pure de Sitter state and will necessarily start from a quasi-de Sitter state.

Purpose This paper aims to investigate the impact of anodizing time and heat treatment on morphology, phase and corrosion resistance of formed coating. To characterize the anodic oxide layer, X-ray diffraction (XRD) patterns and scanning electron microscopy (SEM) that was equipped with energy dispersive spectroscopy (EDS) was hired. The corrosion behavior of oxide-coated samples was estimated by electrochemical polarization test in simulated body fluid (SBF). Design/methodology/approach Anodic oxidation method is applied to reinforce the corrosion and biological properties of biomaterials in the biomedical industry. In this paper, the alkaline NaOH (1 M) electrolyte was used for AZ31 magnesium alloy anodizing accompanied by heat treatment in the air. Findings It can be concluded that the best corrosion resistance belongs to the 10 min anodic oxidized sample and among the heat-treated samples the 30 min anodized sample represented the lowest corrosion rate. Originality/value In this study, to the best of the authors’ knowledge for the first time, this paper describes the effect of anodizing process time on NaOH (1 M) electrolyte at 3 V on corrosion behavior of magnesium AZ31 alloy with an alternate method to change the phase composition of the formed oxide layer. The morphology and composition of the obtained anodic oxide layer were investigated under the results of SEM, EDS and XRD. The corrosion behavior of the oxide coatings layer fabricated on the magnesium-based substrate was studied by the potentiodynamic polarization test in the SBF solution.

Background Gene silence via methylation of the CpG island is the most common epigenetic modification in cancer. Aberrant DNA methylation interferes with active transcription and is also significantly associated with poor tumor differentiation and prognosis. Given the highly significant role of NIS in thyroid cancer differentiation, this cross-sectional study aimed to investigate the DNA methylation pattern in seven CpG islands (CpG1-7 including + 846, +918, + 929, +947, + 953, +955, and + 963, respectively) of the NIS promoter in patients diagnosed with PTC, FTC, and MNG compared with the matched non-tumoral tissues. Methods Thyroid specimens from 64 patients met the eligibility criteria, consisting of 28 PTCs, 9 FTCs, and 27 benign MNG cases. The expression of NIS mRNA was tested by qRT-PCR. The bisulfite sequencing PCR technique was performed was performed to evaluate the promoter methylation pattern of the NIS gene. Sequencing results were received in chromatograph, FASTA, SEQ, and pdf formats and were analyzed using Chromas. The methylation percentage at each position and for each sample was calculated by mC/ (mC + C) formula for all examined CpGs; following that, the methylation percentage was also calculated at each CpG site. Results NIS mRNA levels decreased in tissue samples of patients with PTC (P = 0.04) and FTC (P = 0.03) compared to their matched non-tumoral tissues. The methylation of NIS promoter was not common in PTC samples, but it was frequent in FTC (P NIS promoter between FTC tumoral and MNG tissues (76.34 ± 3.12 vs 40.43 ± 8.42, P = 0.004, 69.63 ± 3.03 vs 23.29 ± 6.84, P = 0.001 and 50.33 ± 5.65 vs 24 ± 6.89, P = 0.030, respectively). There was no significant correlation between the expression and methylation status of NIS in PTC and FTC tumoral tissues. Conclusion Perturbation in NIS promoter’s methylation individually may have a potential utility in differentiating MNG and FTC tissues. The absence of a distinct methylation pattern implies the importance of other epigenetic processes, which may alter the production of NIS mRNA. In addition, according to the reversibility of DNA methylation, it is anticipated that the design of particular targeted demethylation medicines will lead to a novel cancer therapeutic strategy.

Background Gene silence via methylation of the CpG islands is cancer's most common epigenetic modification. Given the highly significant role of NIS in thyroid cancer (TC) differentiation, this cross-sectional study aimed to investigate the DNA methylation pattern in seven CpG islands (CpG1-7 including +846, +918, +929, +947, +953, +955, and +963, respectively) of the NIS promoter in patients diagnosed with papillary (PTC), follicular (FTC), and multinodular goiter (MNG). Additionally, a systematic review of the literature was conducted to compare our results with studies concerning methylation of the NIS gene promoter. Methods Thyroid specimens from 64 patients met the eligibility criteria, consisting of 28 PTC, 9 FTC, and 27 benign MNG cases. The mRNA of NIS was tested by qRT-PCR. The bisulfite sequencing PCR (BSP) technique was performed to evaluate the promoter methylation pattern of the NIS gene. Sequencing results were received in chromatograph, FASTA, SEQ, and pdf formats and were analyzed using Chromas. The methylation percentage at each position and for each sample was calculated by mC/(mC+C) formula for all examined CpGs; following that, the methylation percentage was also calculated at each CpG site. Besides, a literature search was conducted without restricting publication dates. Nine studies met the eligibility criteria after removing duplicates, unrelated articles, and reviews. Results NIS mRNA levels decreased in tumoral tissues of PTC (P = 0.04) and FTC (P = 0.03) patients compared to their matched non-tumoral ones. The methylation of NIS promoter was not common in PTC samples, but it was frequent in FTC (P NIS promoter between FTC and MNG tissues (76.34 ± 3.12 vs 40.43 ± 8.42, P = 0.004, 69.63 ± 3.03 vs 23.29 ± 6.84, P = 0.001 and 50.33 ± 5.65 vs 24 ± 6.89, P = 0.030, respectively). There was no significant correlation between the expression and methylation status of NIS in PTC and FTC tissues. Conclusion Perturbation in NIS promoter’s methylation individually may have a potential utility in differentiating MNG and FTC tissues. The absence of a distinct methylation pattern implies the importance of other epigenetic processes, which may alter the production of NIS mRNA. In addition, according to the reversibility of DNA methylation, it is anticipated that the design of particular targeted demethylation medicines will lead to a novel cancer therapeutic strategy.

Slow-burning inflammation at the lesion rim is connected to the expansion of chronic multiple sclerosis (MS) lesions. However, the underlying processes causing expansion are not clearly realized. In this context, the current study used a bioinformatics approach to identify the expression profiles and related lncRNA-associated ceRNA regulatory axes in the periplaque region in MS patients. Expression data (GSE52139) from periplaque regions in the secondary progressive MS spinal cord and controls were downloaded from the Gene Expression Omnibus database (GEO), which has details on mRNAs and lncRNAs. Using the R software’s limma package, the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were found. The RNA interactions were also found using the DIANA-LncBase, miRTarBase, and HMDD databases. The Pearson correlation coefficient was used to determine whether there were any positive correlations between DEmRNAs and DElncRNAs in the ceRNA network. Finally, lncRNA-associated ceRNA axes were created based on co-expression and connections between DElncRNA, miRNA, and DEmRNA. We used the Enrichr tool to enrich the biological process, molecular function, and pathways for DEmRNAs and DElncRNAs. A network of DEmRNAs’ protein-protein interactions was developed, and the top five hub genes were found using Cytoscape and STRING. The current study indicates that 15 DEmRNAs, including FOS, GJA1, NTRK2, CTNND1, and SP3, are connected to the MS ceRNA network. Additionally, four DElncRNAs (such as TUG1, ASB16-AS1, and LINC01094) that regulated the aforementioned mRNAs by sponging 14 MS-related miRNAs (e.g., hsa-miR-145-5p, hsa-miR-200a-3p, hsa-miR-20a-5p, hsa-miR-22-3p, hsa-miR-23a-3p, hsa-miR-27a-3p, hsa-miR-29b-3p, hsa-miR-29c-3p, hsa-miR-34a-5p) were found. In addition, the analysis of pathway enrichment revealed that DEmRNAs were enriched in the pathways for the “MAPK signaling pathway”, “Kaposi sarcoma-associated herpesvirus infection”, “Human immunodeficiency virus one infection”, “Lipid and atherosclerosis”, and “Amphetamine addiction”. Even though the function of these ceRNA axes needs to be investigated further, this study provides research targets for studying ceRNA-mediated molecular mechanisms related to periplaque demyelination in MS.

In this research, transient liquid phase (TLP) bonding of IN718 and SS316L dissimilar alloys was carried out using MBF-20 amorphous interlayer. The effects of bonding temperature and time ranging f...

High blood pressure (BP) is a risk factor for hypertensive disease during pregnancy. Exposure to multiple toxic air pollutants can affect BP in pregnancy but has been rarely studied. We evaluated trimester-specific associations between air pollution exposure and systolic (SBP) and diastolic BP (DBP). Ozone (O3), sulfur dioxide (SO2), carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter less than 10 and 2.5 μm in aerodynamic diameter (PM10, PM2.5) in the Pregnancy Research on Inflammation, Nutrition, & City Environment: Systematic Analyses (PRINCESA) study. Multipollutant generalized linear regression models with each pollutant and O3 were fit. Due to nonlinear pollution/BP associations, results are presented for “below the median” or “above the median”, where the beta estimate is the change in BP at a pollutant’s median versus BP at the pollutant’s minimum or maximum, respectively. Associations varied across trimesters and pollutants, and deleterious associations (higher blood pressure with higher pollution) were found only at pollutant values below the median: for SBP with NO2 in the second and third trimesters, and PM2.5 during the third trimester, and for DBP, PM2.5, and NO2 in the second and third trimesters. Findings suggest that minimizing prenatal exposure to air pollution may reduce the risks of changes in BP.

Increased expression of Hypoxia-inducible factor-1α (HIF-1α) in the tumor microenvironment, mainly due to tumor growth, plays a major role in the growth of cancer. Tumor cells induce the expression of cyclooxygenase 2 (COX2) and its product, prostaglandin E2 (PGE2), through overexpression of HIF-1α. It has been shown that ligation of PGE2 with its receptor, EP4, robustly promotes cancer progression. HIF-1α/COX2/PGE2/EP4 signaling pathways appear to play an important role in tumor growth. Therefore, we decided to block the expansion of cancer cells by blocking the initiator (HIF-1α) and end (EP4) of this pathway. In this study, we used hyaluronate (HA), and trimethyl chitosan (TMC) recoated superparamagnetic iron oxide nanoparticles (SPIONs) loaded with HIF-1α-silencing siRNA and the EP4 antagonist (E7046) to treat cancer cells and assessed the effect of combination therapy on cancer progression. The results showed that optimum physicochemical characteristics of NPs (size 126.9 nm, zeta potential 27 mV, PDI

Common capabilities of thyroid malignant cells are accelerating metabolism and increasing glucose uptake to optimize energy supply for growth. In tumor cells, keeping the power load required for cell survival is essential and glucose transporters are capable of promoting this task. GLUT-1 and GLUT3 are promising goals for the development of anti-cancer strategies. The lack of oncosuppressors has dominant effect on the membrane expression of GLUT1 and glucose uptake. Overexpression of hypoxia-inducing factors, in thyroid cancer, modulates the expression of some glucose transporter genes. Although the physiology of the thyroid gland has been excellently explained, metabolic regulation in thyroid cancer is inevitable. In this section, we investigated the proliferation pathways of pivotal regulators and signal molecules around GLUT regulation in thyroid cancer, including PTEN, p53, MicroRNA, iodide, BRAF, HIF-1, PI3K-Akt, TSH, c-Myc, and AMPK. Impaired energy regulation and cell metabolism are the most critical symptoms of most cancers. As a result, understanding the mechanisms of glucose transport in the normal and pathological tissues of the thyroid may be very crucial and offer tremendous insights into the science of analysis and remedy of thyroid disease.

Thick thermal barrier coatings (TTBCs) with vertical cracks deposited by air plasma spray (APS) and solution precursor plasma spray (SPPS) techniques have been widely investigated to achieve good thermal insulation along with reasonable service life. In this study, synthesized unpyrolyzed YSZ powder was air plasma sprayed in order to produce segmentation crack TTBCs. The microstructure and hardness of the deposits were then compared with those of the conventional TTBCs and dense vertically cracked (DVC)TTBCs. In this regard, spraying parameters were optimized to achieve deposits with the appropriate amount of unpyrolyzed particles in them to assist inducing vertical cracks in the deposited layers. The effect of the unpyrolyzed particles on microstructure, porosity, and microhardness of plasma sprayed coatings were also evaluated and compared. The new fabricated coating showed a bimodal structure combining non-molten sub-micron size particles and conventional splats along with segmentation cracks with higher amount of porosity and lower hardness compared to those of the DVC coatings. The results implied that, depositing unpyrolyzed powder by APS, as a new approach for achieving segmentation crack TTBCs, is very promising.

This study investigates the effectiveness of the reduction policies of the apparent and real losses of non-revenue water. For this purpose, using technique for order of preference by similarity to ideal solution (TOPSIS) model, a decision matrix is proposed, involving apparent and real losses risk reduction values induced by the implementation of each non-revenue water reduction policy. First, decision criteria, including technical, economic, and social criteria, were selected and introduced. Then, the technical criterion was calculated using a fuzzy Bayesian model. In the following, using group decision-making and analytic hierarchy process method, the criteria were weighted. In the next step, the bests of decision criteria were determined by the TOPSIS method. This method was applied in the water distribution network of district 4 of Tehran, Iran. The results indicated that the most basic non-revenue water reduction policy by risk-based group decision-making is to identify unauthorized connections in the apparent water loss sector and increase the speed and quality of maintenance and repairs in the real water loss sector.

A numerical calculation to study the effect of laser pulse polarization on the strength of the axial wakefield in a magnetized plasma has been presented. The influence of different laser polarization, including linear (ordinary wave), elliptic (extraordinary wave), and right- and left-hand circular polarization on the wake wave amplitude, has been evaluated for various values of laser and plasma frequency at a fixed cyclotron frequency. Comparing the results, it is found that an extraordinary laser wave can excite the largest wake wave amplitude. The upper-hybrid wakefield is in the order of $E_{w}\approx 70~$ GV/m, which, under appropriate conditions, is generated by an elliptic Gaussian laser pulse with a relatively low intensity ( $a_{0}=0.3$ ).

This paper is devoted to a comparative study on the isothermal oxidation of thick thermal barrier coating (TTBC) with and without segmented cracks produced by atmospheric plasma spray (APS) process. Accordingly, the growth of thermally grown oxide (TGO) and its effect on the degradation of the coating were investigated. Thick top coat in both segmented crack and conventional thick TBC reduced the double layered TGO growth rate slightly. The segmented crack thick TBC demonstrated longer isothermal oxidation life in comparison with that of the conventional thick TBC at 1100 °C. The dominant failure mechanism was spallation due to lateral cracking within the TGO and/or within TBC near the TGO layer, called mixed failure. Stress, and consequently strain, induced on the TTBC due to progressive TGO growth, seems to be primarily responsible for the crack initiation and propagation leading to the coating failure. Increment of elastic energy stored within the top coat due to the increasing of TGO thickness, finally causes thick thermal barrier coating failure in high temperature isothermal oxidation.

Hypertension is a highly prevalent disease with serious cardiovascular and renal complications. Many studies have demonstrated a weak correlation between the consumption of calcium (or calcium plus vitamin D) and blood pressure, suggesting that calcium supplements might reduce blood pressure. However, the results to date remain controversial. In this study, we assessed the effect of calcium and vitamin D supplementation on the blood pressure of postmenopausal women with hypertension as a population group in which the use of calcium supplements is prevalent. This triple-blind randomized clinical trial enrolled 98 women of postmenopausal age with hypertension in 2019. The study period was 8 weeks with close follow-up. We used 24-h ambulatory blood pressure monitoring to record the initial and final blood pressure in all participants. The changes in both the mean systolic (p = 0.047) and diastolic blood pressure (p = 0.015) were suggestive of an increase in blood pressure after consuming calcium and vitamin D supplements. Among patients who had been using calcium channel blockers, calcium and vitamin D supplementation caused a notable increase compared to baseline systolic (p = 0.019) and diastolic blood pressures (p = 0.001). The present results differ from those of previous studies. This suggests that calcium supplementation for postmenopausal women with hypertension requires the close observation of blood pressure to prevent any further increase, especially in women who are being treated with calcium channel blockers (clinicaltrial.gov registration: NCT04618952).

BackgroundInducible T cell co-stimulator (ICOS) deficiency has been categorized as a combined immunodeficiency often complicated by enteropathies, autoimmunity, lymphoproliferation, and malignancy. We report seven new patients and four novelICOSmutations resulting in a common variable immunodeficiency (CVID)–like phenotype and show that dysregulated IL-12 release, reduced cytotoxic T lymphocyte–associated protein 4 (CTLA4) expression, and skewing towards a Th1-dominant phenotype are all associated with inflammatory complications in this condition.MethodsA combination of whole exome and Sanger sequencing was used to identify novel mutations. Standard clinical and immunological evaluation was performed. FACS and ELISA-based assays were used to study cytokine responses and ICOS/ICOSL/CTLA4 expression following stimulation of whole blood and PBMCs with multiple TLR ligands, anti-CD3, and PHA.ResultsFour novel ICOS mutations included homozygous c.323_332del, homozygous c.451C>G, and compound heterozygous c.58+1G>A/c.356T>C. The predominant clinical phenotype was that of antibody deficiency associated with inflammatory complications in 4/7 patients. Six out of seven patients were treated with immunoglobulin replacement and one patient died from salmonella sepsis. All patients who were tested showed reduced IL-10 and IL-17 cytokine responses, normal IL-1β, IL6, and TNF release following LPS stimulation and highly elevated IL-12 production in response to combined LPS/IFNγ stimulation. This was associated with skewing of CD4+T cells towards Th1 phenotype and increased expression of ICOSL on monocytes. Lastly, reduced CTLA4 expression was found in 2 patients. One patient treated with ustekinumab for pancytopenia due to granulomatous bone marrow infiltration failed to respond to this targeted therapy.ConclusionsICOS deficiency is associated with defective T cell activation, with simultaneously enhanced stimulation of monocytes. The latter is likely to result from a lack of ICOS/ICOSL interaction which might be necessary to provide negative feedback which limits monocytes activation.

The present study aims to investigate the effect of friction stir processing (FSP) conditions on the corrosion characteristic of AZ31B magnesium alloy. Specimens made of AZ31B alloy were friction stir processed under various processing conditions, and their microstructure and corrosion behavior were studied. The corrosion behavior was studied by potentiodynamic polarization, electrochemical impedance spectroscopy (EIS), and immersion test in 3.5% sodium chloride (NaCl) solution. The results showed a substantial improvement in the corrosion resistance of the friction stir processed AZ31B alloy. The improvement is likely a result of more stable corrosion products and microstructure refinement formed after friction sir processing. Keywords: Magnesium, Friction stir processing, Corrosion, Polarization, EIS

Dry tribological behaviors of commercial pure (Cp) titanium and Cp titanium diffusion coated with equiatomic NiTi intermetallic layer were studied and compared at room temperature. Wear tests were performed by a pin on disk tribometer using 52100 steel pins, under various normal loads of 10, 20, and 40 N. worn surfaces were examined by scanning electron microscope, equipped with EDS analyzer. The wear rates of the coated materials were lower than those of the Cp titanium at all loads. This was mainly attributed to the higher hardness of the NiTi intermetallic layer compared to that of the untreated titanium. Furthermore, under an applying load of 10 N, a tribological layer was formed which could protect the surface from severe wear. The results also demonstrated a lower coefficient of friction in the treated specimens compared to those of the Cp materials.

Background Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. Methods We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. Results In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. Conclusion Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy. Graphical Abstract

Background: Coronary artery disease (CAD) is the leading cause of death in the world. To prevent CAD we need to assess the risk of future CAD. Systems for risk assessment has its own limitations. In this study we assessed ankle-brachial index (ABI) as a screening tool for CAD.Method: Between 2019 and 2020, we conducted a large cross-sectional population-based study of 4207 new patients referred to cardiovascular Clinic. The patients underwent selective coronary angiography via radial artery approach by an expert interventional cardiologist. ABI was calculated for all patients. We compared ABI with the results of coronary angiography to determine the specificity and sensitivity of ABI as a screening tool for CAD. Results: Abnormal ABI was significantly more frequent in patients with proven severe CAD (893, 54.8%) than in patients with proven mild CAD (33, 4.7%) or no CAD (94, 5.3%). The specificity of ABI was 95.3%, and its sensitivity was 54.8%. ABI was associated with risk factors such as smoking, male gender, hypertension, diabetes mellitus and dyslipidemia. There was no relationship between abnormal inter-arm systolic pressure difference and severity of CAD, but it showed a significant association with abnormal ABI.Conclusion: ABI can be used as a screening test to rule out CAD with 95.3% specificity. We need to consider risk factors other than ABI to increase screening sensitivity. A multidimensional scoring system should consider risk factors and other noninvasive tests in addition to ABI to develop and ideal screening system for CA. (Clinical trial registration number NCT04667832)